bluuebunny/crossref_metadata_2025 huggingface dataset:
RETRACTED: Comparative Evaluation of the Incidence of Postoperative Pulmonary Complications After Minimally Invasive Valve Surgery vs. Full Sternotomy: A Systematic Review and Meta-Analysis of Randomized Controlled Trials and Propensity Score-Matched Studies
Authors: Mohamed Mohamed Abdulkadir , Ding Shuai , Ali Shah Sayed Zulfiqar , Li Rui , Dirie Najib Isse , Cheng Cai , Wei Xiang
Published: August 2021

Background: Postoperative pulmonary complications remain a leading cause of increased morbidity, mortality, longer hospital stays, and increased costs after cardiac surgery; therefore, our study aims to analyze whether minimally invasive valve surgery (MIVS) for both aortic and mitral valves can improve pulmonary function and reduce the incidence of postoperative pulmonary complications when compared with the full median sternotomy (FS) approach.

Methods: A comprehensive systematic literature research was performed for studies comparing MIVS and FS up to February 2021. Randomized controlled trials (RCTs) and propensity score-matching (PSM) studies comparing early respiratory function and pulmonary complications after MIVS and FS were extracted and analyzed. Secondary outcomes included intra- and postoperative outcomes.

Results: A total of 10,194 patients from 30 studies (6 RCTs and 24 PSM studies) were analyzed. Early mortality differed significantly between the groups (MIVS 1.2 vs. FS 1.9%; p = 0.005). Compared with FS, MIVS significantly lowered the incidence of postoperative pulmonary complications (odds ratio 0.79, 95% confidence interval [0.67, 0.93]; p = 0.004) and improved early postoperative respiratory function status (mean difference −24.83 [−29.90, −19.76]; p < 0.00001). Blood transfusion amount was significantly lower after MIVS (p < 0.02), whereas cardiopulmonary bypass time and aortic cross-clamp time were significantly longer after MIVS (p < 0.00001).

Conclusions: Our study showed that minimally invasive valve surgery decreases the incidence of postoperative pulmonary complications and improves postoperative respiratory function status.
Black Sea Methane Flares From the Seafloor: Tracking Outgassing by Using Passive Acoustics
Authors: Longo Manfredi , Lazzaro Gianluca , Caruso Cinzia Giuseppina , Radulescu Vlad , Radulescu Raluca , Sciré Scappuzzo Sergio Simone , Birot Dominique , Italiano Francesco
Published: August 2021

The Black Sea bottom is well known to be earth’s largest anaerobic methane source, hosting a huge amount of cold seeps releasing significant volumes of methane of both thermogenic and biogenic origin. Taking into account the well-known effects of methane concerning global warming, including the warming up of the oceans, an effective monitoring of its output from the Black Sea is nowadays an essential target for interdisciplinary studies. We discuss the results achieved during monitoring campaigns aimed to detect and track methane flares from the seafloor of the Romanian sector of the Black Sea, in order to better constrain the possible mechanisms responsible for its injection from the marine sediments, through the water column, into the atmosphere. In the mainframe of the ENVRI-Plus project, we deployed a multidisciplinary seafloor observatory for short, mid and long time monitoring and collected samples of the water column. The multidisciplinary seafloor observatory was equipped with probes for passive acoustic signals, dissolved CH4 and chemical-physical parameters. The collected data showed a high concentration of dissolved methane up to values of 5.8 micromol/L. Passive acoustics data in the frequencies range 40–2,500 Hz allow us to discriminate different degassing mechanisms and degassing styles. The acoustic energy associated with gas bubbling is interpreted as a consequence of the gas dynamics along the water column while the acoustic range 2–20 Hz reveals vibration mechanisms generated by gas dynamic’s along the cracks and inside the sediments.
Accuracy Evaluation of Altimeter-Derived Gravity Field Models in Offshore and Coastal Regions of China
Authors: Li Qianqian , Bao Lifeng , Wang Yong
Published: August 2021

Satellite radar altimetry has made unique contributions to global and coastal gravity field recovery. This paper starts with a general introduction followed by the progress of satellite radar altimetry technology. Then, the methods of marine gravity field recovery and dominating gravity models are described briefly. Finally, typical gravity models are compared with shipboard gravity measurements to evaluate their accuracies in offshore and coastal regions of China. The root mean squares of deviations between gravity models and shipboard gravity are all more than 7 mGal in offshore regions and within the range of 9.5–10.2 mGal in coastal regions. Further analysis in coastal regions indicates that the new gravity models with new satellite missions including Jason-2, SARAL/Altika, and Envisat data have relatively higher accuracy, especially SARAL/Altika data, significantly improving the coastal gravity field. Accuracies are low in areas with strong currents, showing that tide correction is very important for altimetry-derived marine gravity recovery as well as shipboard measurements in coastal gravity field determination. Moreover, as an external check, shipboard gravity data need more operations to improve their precision, such as higher instrument accuracy and finer data processing.
Detection of Urinary Exosomal HSD11B2 mRNA Expression: A Useful Novel Tool for the Diagnostic Approach of Dysfunctional 11β-HSD2-Related Hypertension
Authors: De Santis Domenica , Castagna Annalisa , Danese Elisa , Udali Silvia , Martinelli Nicola , Morandini Francesca , Veneri Mariangela , Bertolone Lorenzo , Olivieri Oliviero , Friso Simonetta , Pizzolo Francesca
Published: August 2021

Objective

Apparent mineralocorticoid excess (AME) is an autosomal recessive disorder caused by the 11β-hydroxysteroid dehydrogenase type 2 (11β-HSD2) enzyme deficiency, traditionally assessed by measuring either the urinary cortisol metabolites ratio (tetrahydrocortisol+allotetrahydrocortisol/tetrahydrocortisone, THF+5αTHF/THE) or the urinary cortisol/cortisone (F/E) ratio. Exosomal mRNA is an emerging diagnostic tool due to its stability in body fluids and its biological regulatory function. It is unknown whether urinary exosomal HSD11B2 mRNA is related to steroid ratio or the HSD11B2 662 C>G genotype (corresponding to a 221 A>G substitution) in patients with AME and essential hypertension (EH).

Aim of the Study

To detect and quantify HSD11B2 mRNA from urinary exosomes in samples from family members affected by AME and EH, and to evaluate the relationship between exosomal HSD11B2 mRNA, steroid ratio, 662C>G genotype, and hypertension.

Methods

In this observational case–control study, urinary steroid ratios and biochemical parameters were measured. Urinary exosomes were extracted from urine and exosomal HSD11B2 mRNA was quantified by Droplet Digital PCR (ddPCR). B2M (β-2 microglobulin) gene was selected as the reference housekeeping gene.

Results

Among family members affected by AME, exosomal urinary HSD11B2 mRNA expression was strictly related to genotypes. The two homozygous mutant probands showed the highest HSD11B2 mRNA levels (median 169, range 118–220 copies/µl) that progressively decreased in 221 AG heterozygous with hypertension (108, range 92–124 copies/µl), 221 AG heterozygous normotensives (23.35, range 8–38.7 copies/µl), and wild-type 221 AA subjects (5.5, range 4.5–14 copies/µl). Heterozygous hypertensive subjects had more HSD11B2 mRNA than heterozygous normotensive subjects. The F/E urinary ratio correlated with HSD11B2 mRNA copy number (p < 0.05); HSD11B2 mRNA strongly decreased while THF+5αTHF/THE increased in the two probands after therapy. In the AME family, HSD11B2 copy number correlated with both F/E and THF+5αTHF/THE ratios, whereas in EH patients, a high F/E ratio reflected a reduced HSD11B2 mRNA expression.

Conclusions

HSD11B2 mRNA is detectable and quantifiable in urinary exosomes; its expression varies according to the 662 C>G genotype with the highest levels in homozygous mutant subjects. The HSD11B2 mRNA overexpression in AME could be due to a compensatory mechanism of the enzyme impairment. Exosomal mRNA is a useful tool to investigate HSD11B2 dysregulation in hypertension.
Method to Evaluate the Impact of Integration of PMSG on Stability of Synchronous Generator Shaft Under Weak Grid Connection
Authors: Zhang Tianyi , Wang Haifeng
Published: August 2021

With the continuous growth in the amount of wind power accessed by the AC grid, the impact of the grid connection of wind-power generators with the power system has gradually increased. In this study, the subsynchronous oscillation of a synchronous generator (SG) shaft caused by the integration of direct-drive permanent-magnet synchronous generators (PMSGs) was investigated. The mechanism governing the effect of the connection strength between the PMSG and AC power system on the stability of the generator shaft system was analyzed based on the complex torque coefficient method. When the connection strength between the PMSG and AC power system weakens, the same voltage variation that occurs at the point of common coupling of the PMSG stimulates more intense power fluctuations in the PMSG, and the electrical damping injected by the PMSG into the SG increases considerably. This may cause the oscillation mode dominated by the generator shaft system to move to the right half of the complex plane, thereby reducing the stability of the generator shaft system. In addition, the evaluation process of the influence of the PMSG on the SG shaft system was summarized, and the proposed method can determine the stability of the AC power system after the integration of the PMSG. Finally, the effectiveness of the proposed method was validated via study cases, and conclusions were drawn. This method is expected to serve as a useful tool for the risk assessment of subsynchronous oscillations in wind farms.
Impacts of Land Surface Conditions and Land Use on Dust Events in the Inner Mongolian Grasslands, China
Authors: Yong Mei , Shinoda Masato , Nandintsetseg Banzragch , Bi Lige , Gao Hailin , Wang Yingshun
Published: August 2021

Aeolian processes in temperate grasslands (TGs) are unique because the plant growth–decay cycle, soil water, and land-use interactions affect the seasonal and inter-annual changes in dust events. Land-use types in Inner Mongolian TGs are unique (settled grazing and grass mowing) compared with those in Mongolian TGs. Since 2003, land use has been controlled by grassland protection legislation, which is intended to prevent desertification and dust storms. In this study, we used process-based ecosystem (DAYCENT) and statistical modeling, along with dust event observations from March to June of 1981–2015, to (1) identify critical land surface factors controlling dust emissions (vegetation components, live grass, standing dead grass, litter, and soil moisture) at typical and desert steppe sites in Inner Mongolia and (2) estimate the impact of controlled land-use legislation on dust events. The DAYCENT model realistically simulated the dynamics of the observed vegetation components and soil moisture in 2005–2015. At both sites, similar significant correlations were obtained between spring dust events and wind speed or a combination of all surface factors that retained anomalies (memory) from the preceding year. Among the surface factors, vegetation was a critical factor that suppressed dust in Inner Mongolian TGs, similar to that in Mongolian TGs. In the desert steppe, standing dead grass had the strongest memory and was significantly correlated with dust events, whereas no significant correlations were observed in the typical steppe. This suggests that, in a typical steppe region, heavy grazing and mowing result in few dead grasses, thereby inhibiting the prevention of dust events. Moreover, the simulations of dust events under controlled (light grazing) and uncontrolled (heavy grazing) land-use conditions demonstrated that the grassland protection legislation reduced the occurrence of dust events in typical and desert steppe sites by 25 and 40%, respectively, since 2003.
The Importance of Alaska for Climate Stabilization, Resilience, and Biodiversity Conservation
Authors: Vynne Carly , Dovichin Erin , Fresco Nancy , Dawson Natalie , Joshi Anup , Law Beverly E. , Lertzman Ken , Rupp Scott , Schmiegelow Fiona , Trammell E. Jamie
Published: August 2021

Alaska is globally significant for its large tracts of intact habitats, which support complete wildlife assemblages and many of the world’s healthiest wild fisheries, while also storing significant amounts of carbon. Alaska has 1/3 of United States federal lands, the bulk of the United States’ intact and wild lands, and over half of the country’s total terrestrial ecosystem carbon on federal lands. Managing Alaska’s public lands for climate and biodiversity conservation purposes over the next 30–50 years would provide meaningful and irreplaceable climate benefits for the United States and globe. Doing so via a co-management approach with Alaska’s 229 federally recognized tribes is likely not only to be more effective but also more socially just. This paper lays out the scientific case for managing Alaska’s public lands for climate stabilization and resilience and addresses three primary questions: Why is Alaska globally meaningful for biodiversity and climate stabilization? Why should Alaska be considered as a key element of a climate stabilization and biodiversity conservation strategy for the United States? What do we need to know to better understand the role of Alaska given future scenarios? We summarize evidence for the role Alaska’s lands play in climate stabilization, as well as what is known about the role of land management in influencing carbon storage and sequestration. Finally, we summarize priority research that is needed to improve understanding of how policy and management prescriptions are likely to influence the role Alaska plays in global climate stabilization and adaptation.
Intracellular Accumulation of IFN-λ4 Induces ER Stress and Results in Anti-Cirrhotic but Pro-HCV Effects
Authors: Onabajo Olusegun O. , Wang Fang , Lee Mei-Hsuan , Florez-Vargas Oscar , Obajemu Adeola , Tanikawa Chizu , Vargas Joselin M. , Liao Shu-Fen , Song Ci , Huang Yu-Han , Shen Chen-Yang , Banday A. Rouf , O’Brien Thomas R. , Hu Zhibin , Matsuda Koichi , Prokunina-Olsson Ludmila
Published: August 2021

IFNL3/IFNL4 polymorphisms are inversely associated with the risk of chronic hepatitis C virus (HCV) infection and cirrhosis, two major risk factors for developing hepatocellular carcinoma (HCC). To further explore these inverse associations and their molecular underpinnings, we analyzed IFNL3/IFNL4 polymorphisms represented by the IFNL4 genotype (presence of rs368234815-dG or rs12979860-T alleles) in HCV patients: 2969 from Japan and 2931 from Taiwan. IFNL4 genotype was associated with an increased risk of HCV-related HCC (OR=1.28, 95%CI=1.07-1.52, P=0.0058) in the general population of Japanese patients, but not in Taiwanese patients who achieved treatment-induced viral clearance. IFNL4 genotype was also associated with a decreased risk of cirrhosis (OR=0.66, 95%CI=0.46-0.93, P=0.018, in Taiwanese patients). We then engineered HepG2 cells to inducibly express IFN-λ4 in the presence or absence of interferon lambda receptor 1 (IFNLR1). Induction of IFN-λ4 resulted in its intracellular accumulation, mainly in lysosomes and late endosomes, and increased ER stress, leading to apoptosis and reduced proliferation. We identified the very-low-density lipoprotein receptor (VLDLR), which facilitates HCV entry into hepatocytes, as a transcript induced by IFN-λ4 but not IFN-λ3. Our results suggest that the molecular mechanisms underlying the anti-cirrhotic but pro-HCV associations observed for IFNL3/IFNL4 polymorphisms are, at least in part, contributed by intracellular accumulation of IFN-λ4 causing ER stress in hepatic cells.
Baricitinib Attenuates Autoimmune Phenotype and Podocyte Injury in a Murine Model of Systemic Lupus Erythematosus
Authors: Lee Jaeseon , Park Youngjae , Jang Se Gwang , Hong Seung-Min , Song Young-Seok , Kim Min-Jun , Baek SeungYe , Park Sung-Hwan , Kwok Seung-Ki
Published: August 2021

Objective

Baricitinib, a selective inhibitor for janus kinase (JAK) 1 and JAK2, is approved for use in rheumatoid arthritis. Systemic lupus erythematosus (SLE) is recently regarded as a potential candidate targeted by JAK inhibitors because of the relationship between its pathogenesis and JAK/signal transducer and activator of transcription (STAT) pathway-mediated cytokines such as type I interferons. The objective of this study was to determine whether baricitinib could effectively ameliorate SLE using a murine model

Methods

To investigate effects of baricitinib on various autoimmune features, especially renal involvements in SLE, eight-week-old MRL/Mp-Faslpr (MRL/lpr) mice were used as a lupus-prone animal model and treated with baricitinib for eight weeks. Immortalized podocytes and primary podocytes and B cells isolated from C57BL/6 mice were used to determine the in vitro efficacy of baricitinib.

Results

Baricitinib remarkably suppressed lupus-like phenotypes of MRL/lpr mice, such as splenomegaly, lymphadenopathy, proteinuria, and systemic autoimmunity including circulating autoantibodies and pro-inflammatory cytokines. It also modulated immune cell populations and effectively ameliorated renal inflammation, leading to the recovery of the expression of structural proteins in podocytes. According to in vitro experiments, baricitinib treatment could mitigate B cell differentiation and restore disrupted cytoskeletal structures of podocytes under inflammatory stimulation by blocking the JAK/STAT pathway.

Conclusions

The present study demonstrated that baricitinib could effectively attenuate autoimmune features including renal inflammation of lupus-prone mice by suppressing aberrant B cell activation and podocyte abnormalities. Thus, baricitinib as a selective JAK inhibitor could be a promising therapeutic candidate in the treatment of SLE.
Single-Cell Analysis of the Neonatal Immune System Across the Gestational Age Continuum
Authors: Peterson Laura S. , Hedou Julien , Ganio Edward A. , Stelzer Ina A. , Feyaerts Dorien , Harbert Eliza , Adusumelli Yamini , Ando Kazuo , Tsai Eileen S. , Tsai Amy S. , Han Xiaoyuan , Ringle Megan , Houghteling Pearl , Reiss Jonathan D. , Lewis David B. , Winn Virginia D. , Angst Martin S. , Aghaeepour Nima , Stevenson David K. , Gaudilliere Brice
Published: August 2021

Although most causes of death and morbidity in premature infants are related to immune maladaptation, the premature immune system remains poorly understood. We provide a comprehensive single-cell depiction of the neonatal immune system at birth across the spectrum of viable gestational age (GA), ranging from 25 weeks to term. A mass cytometry immunoassay interrogated all major immune cell subsets, including signaling activity and responsiveness to stimulation. An elastic net model described the relationship between GA and immunome (R=0.85, p=8.75e-14), and unsupervised clustering highlighted previously unrecognized GA-dependent immune dynamics, including decreasing basal MAP-kinase/NFκB signaling in antigen presenting cells; increasing responsiveness of cytotoxic lymphocytes to interferon-α; and decreasing frequency of regulatory and invariant T cells, including NKT-like cells and CD8+CD161+T cells. Knowledge gained from the analysis of the neonatal immune landscape across GA provides a mechanistic framework to understand the unique susceptibility of preterm infants to both hyper-inflammatory diseases and infections.
Rewilding of Protected Areas Enhances Resilience of Marine Ecosystems to Extreme Climatic Events
Authors: Sheehan E. V. , Holmes L. A. , Davies B. F. R. , Cartwright A. , Rees A. , Attrill M. J.
Published: August 2021

Marine protected areas (MPAs) are employed as tools to manage human impacts, especially fishing pressure. By excluding the most destructive activities MPAs can rewild degraded areas of seabed habitat. The potential for MPAs to increase ecosystem resilience from storms is, however, not understood, nor how such events impact seabed habitats. Extreme storm disturbance impact was studied in Lyme Bay MPA, Southwest United Kingdom, where the 2008 exclusion of bottom-towed fishing from the whole site allowed recovery of degraded temperate reef assemblages to a more complex community. Severe storm impacts in 2013–2014 resulted in major damage to the seabed so that assemblages in the MPA were more similar to sites where fishing continued than at any point since the designation of the MPA; the communities were not dominated by species resistant to physical disturbance. Nevertheless, annual surveys since 2014 have demonstrated that the initial recovery of MPA assemblages was much quicker than that seen following the cessation of chronic towed fishing impact in 2008. Likewise, General Additive Mixed Effect Models (GAMMs) showed that inside the MPA increases in diversity metrics post-Storm were greater and more consistent over time than post-Bottom-Towed Fishing. As extreme events are likely to become more common with climate change, wave exposure observations indicated that 29% of coastal reef MPAs around the United Kingdom may be exposed to comparable wave climate extremes, and may be similarly impacted. This paper therefore provides an insight into the likely extent and magnitude of ecological responses of seabed ecosystems to future extreme disturbance events.
Circulation Pathways and Exports of Arctic River Runoff Influenced by Atmospheric Circulation Regimes
Authors: Wang Qiang , Danilov Sergey , Sidorenko Dmitry , Wang Xuezhu
Published: August 2021

River runoff supplies the Arctic Ocean with a large amount of freshwater and land-derived material, so it is important for both the physical and biogeochemical marine environment. In this study, we used wind perturbation simulations to elucidate the response of the circulation pathways and exports of Arctic river runoff to different atmospheric circulation regimes. Specifically, wind perturbations representing the negative and positive phases of the Arctic Oscillation and Beaufort High modes were imposed over the Arctic Ocean separately in different sensitivity experiments. In addition, some combinations of the two modes were also considered in sensitivity experiments. By comparing these experiments with a control simulation, we revealed the impact of different wind perturbations. The atmospheric circulation regimes influence the Arctic surface geostrophic currents through changing the halosteric height, which is associated with the changes in spatial distribution of surface freshwater. The circulation pathways of river runoff, and Pacific and Atlantic derived surface waters are mainly determined by the surface geostrophic currents. The positive (negative) Arctic Oscillation reduces (increases) freshwater storage and sea surface height in the Makarov and Eurasian basins, thus strengthening (weakening) the cyclonic circulation and weakening (strengthening) the anticyclonic circulation; Accordingly, the Eurasian runoff leaves the Siberian shelf at more eastern (western) locations, and has an enhanced export through the Fram Strait (Canadian Arctic Archipelago). The positive (negative) Beaufort High increases (reduces) freshwater storage and sea surface height in the Amerasian Basin, thus strengthening (weakening) the anticyclonic circulation; Accordingly, the Eurasian runoff export through the Fram Strait and the Mackenzie River runoff export through the Canadian Arctic Archipelago are reduced (increased). The positive Arctic Oscillation increases freshwater available to the Beaufort Gyre, which can be efficiently accumulated there in the presence of a positive Beaufort High forcing. The impact of the Beaufort High mode on the location of the Transpolar Drift Stream and runoff circulation pathways is stronger with a positive Arctic Oscillation than with a neutral Arctic Oscillation state. Our results also showed that Eurasian runoff can only have a relatively small contribution to freshwater accumulation in the Beaufort Gyre region.
Genomic Investigation of Antimicrobial-Resistant Salmonella enterica Isolates From Dead Chick Embryos in China
Authors: Elbediwi Mohammed , Tang Yanting , Shi Dawei , Ramadan Hazem , Xu Yaohui , Xu Sihong , Li Yan , Yue Min
Published: August 2021

Salmonella spp. is recognized as an important zoonotic pathogen. The emergence of antimicrobial resistance in Salmonella enterica poses a great public health concern worldwide. While the knowledge on the incidence and the characterization of different S. enterica serovars causing chick embryo death remains obscure in China. In this study, we obtained 45 S. enterica isolates from 2,139 dead chick embryo samples collected from 28 breeding chicken hatcheries in Henan province. The antimicrobial susceptibility assay was performed by the broth microdilution method and the results showed that 31/45 (68.8%) isolates were multidrug-resistant (≥3 antimicrobial classes). Besides the highest resistance rate was observed in the aminoglycoside class, all the isolates were susceptible to chloramphenicol, azithromycin, and imipenem. Furthermore, genomic characterization revealed that S. Enteritidis (33.33%; 15/45) was a frequent serovar that harbored a higher number of virulence factors compared to other serovars. Importantly, genes encoding β-lactamases were identified in three serovars (Thompson, Enteritidis, and Kottbus), whereas plasmid-mediated quinolone resistance genes (qnrB4) were detected in certain isolates of S. Thompson and the two S. Kottbus isolates. All the examined isolates harbored the typical virulence factors from Salmonella pathogenicity islands 1 and 2 (SPI-1 and SPI-2). Additionally, a correlation analysis between the antimicrobial resistance genes, phenotype, and plasmids was conducted among Salmonella isolates. It showed strong positive correlations (r < 0.6) between the different antimicrobial-resistant genes belonging to certain antimicrobial classes. Besides, IncF plasmid showed a strong negative correlation (r > −0.6) with IncHI2 and IncHI2A plasmids. Together, our study demonstrated antimicrobial-resistant S. enterica circulating in breeding chicken hatcheries in Henan province, highlighting the advanced approach, by using genomic characterization and statistical analysis, in conducting the routine monitoring of the emerging antimicrobial-resistant pathogens. Our findings also proposed that the day-old breeder chicks trading could be one of the potential pathways for the dissemination of multidrug-resistant S. enterica serovars.
A Novel, Small Cysteine-Rich Effector, RsSCR10 in Rhizoctonia solani Is Sufficient to Trigger Plant Cell Death
Authors: Niu Xianyu , Yang Guijing , Lin Hui , Liu Yao , Li Ping , Zheng Aiping
Published: August 2021

The necrotrophic phytopathogen Rhizoctonia solani (R. solani) is a fungus that causes disease in a wide range of plant species. Fungal genomes encode abundant, small cysteine-rich (SCR) secreted proteins, and the probable importance of these to pathogenesis has been highlighted in various pathogens. However, there are currently no reports of an R. solani SCR-secreted protein with evidential elicitor activity. In this study, the molecular function of 10 SCR-secreted protein genes from R. solani was explored by agroinfiltration into Nicotiana benthamiana (N. benthamiana) leaves, and a novel SCR protein RsSCR10 was identified that triggered cell death and oxidative burst in tobacco. RsSCR10 comprises 84 amino acids, including a signal peptide (SP) of 19 amino acids that is necessary for RsSCR10 to induce tobacco cell death. Elicitation of cell death by RsSCR10 was dependent on Hsp90 but not on RAR1, proving its effector activity. Two cysteine residues have important effects on the function of RsSCR10 in inducing cell death. Furthermore, RsSCR10 showed cross-interaction with five rice molecules, and the inferred functions of these rice proteins suggest they are instrumental in how the host copes with adversity. Overall, this study demonstrates that RsSCR10 is a potential effector that has a critical role in R. solani AG1 IA-host interactions.
Multi-Strain Tropical Bacillus spp. as a Potential Probiotic Biocontrol Agent for Large-Scale Enhancement of Mariculture Water Quality
Authors: Ren Wei , Wu Haiwu , Guo Cong , Xue Bingqing , Long Hao , Zhang Xiang , Cai Xiaoni , Huang Aiyou , Xie Zhenyu
Published: August 2021

Graphical Abstract

Multi-strain tropical Bacillus spp. as a potential probiotic biocontrol agent for large-scale enhancement of mariculture water quality.
Loss of the ClpXP Protease Leads to Decreased Resistance to Cell-Envelope Targeting Antimicrobials in Bacillus anthracis Sterne
Authors: Zou Lang , Evans Christopher R. , Do Vuong D. , Losefsky Quinn P. , Ngo Diem Q. , McGillivray Shauna M.
Published: August 2021

The ClpX ATPase is critical for resistance to cell envelope targeting antibiotics in Bacillus anthracis, however, it is unclear whether this is due to its function as an independent chaperone or as part of the ClpXP protease. In this study, we demonstrate that antibiotic resistance is due to formation of the ClpXP protease through construction of a ClpX complementation plasmid that is unable to interact with ClpP. Additionally, we genetically disrupted both clpP genes, clpP1 and clpP2, found in B. anthracis Sterne and find that the loss of either increases susceptibility to cell envelope targeting antimicrobials, although neither has as strong of a phenotype as loss of clpX and neither clpP gene is essential for virulence in a G. mellonella model of infection. Lastly, we looked at changes to cell envelope morphology that could contribute to increased antibiotic sensitivity. We find no difference in cell charge or cell lysis, although we do see increased hydrophobicity in the ΔclpX strain, decreased cellular density and slightly thinner cells walls. We also see significant cell division defects in ΔclpX, although only when cells are grown in the mammalian cell culture medium, RPMI. We conclude that the intrinsic resistance of B. anthracis to cell wall active antimicrobials is dependent on formation of the ClpXP protease and that this could be due, at least in part, to the role of ClpX in regulating cell envelope morphology.
Glucotoxicity Activation of IL6 and IL11 and Subsequent Induction of Fibrosis May Be Involved in the Pathogenesis of Islet Dysfunction
Authors: Lu Liqin , Zhuang Lili , Shen Ximei , Yang Liyong
Published: August 2021

Background: Islet dysfunction is the main pathological process of type 2 diabetes mellitus (T2DM). Fibrosis causes islet dysfunction, but the current mechanism is still unclear. Here, bioinformatics analysis identified gene clusters closely related to T2DM and differentially expressed genes related to fibrosis, and animal models verified the roles of these genes.

Methods: Human islet transcriptomic datasets were obtained from the Gene Expression Omnibus (GEO), and weighted gene coexpression network analysis (WGCNA) was applied to screen the key gene modules related to T2DM and analyze the correlations between the modules and clinical characteristics. Enrichment analysis was performed to identify the functions and pathways of the key module genes. WGCNA, protein-protein interaction (PPI) analysis and receiver operating characteristic (ROC) curve analysis were used to screen the hub genes. The hub genes were verified in another GEO dataset, the islets of high-fat diet (HFD)-fed Sprague-Dawley rats were observed by H&E and Masson’s trichrome staining, the fibrotic proteins were verified by immunofluorescence, and the hub genes were tested by immunohistochemistry.

Results: The top 5,000 genes were selected according to the median absolute deviation, and 18 modules were analyzed. The yellow module was highly associated with T2DM, and its positive correlation with glycated hemoglobin (HbA1c) was significantly stronger than that with body mass index (BMI). Enrichment analysis revealed that extracellular matrix organization, the collagen-containing extracellular matrix and cytokine−cytokine receptor interaction might influence T2DM progression. The top three hub genes, interleukin 6 (IL6), IL11 and prostaglandin-endoperoxide synthase 2 (PTGS2), showed upregulated expression in T2DM. In the validation dataset, IL6, IL11, and PTGS2 levels were upregulated in T2DM, and IL6 and PTGS2 expression was positively correlated with HbA1c and BMI; however, IL11 was positively correlated only with HbA1c. In HFD-fed Sprague-Dawley rats, the positive of IL6 and IL11 in islets was stronger, but PTGS2 expression was not significantly altered. The extent of fibrosis, irregular cellular arrangement and positive actin alpha 2 (ACTA2) staining in islets was significantly greater in HFD-fed rats than in normal diet-fed rats.

Conclusion: Glucotoxicity is a major factor leading to increased IL6 and IL11 expression, and IL6-and IL11-induced fibrosis might be involved in islet dysfunction.
Cardiometabolic Modification of Amyloid Beta in Alzheimer’s Disease Pathology
Authors: Hefner Marleigh , Baliga Vineet , Amphay Kailinn , Ramos Daniela , Hegde Vijay
Published: August 2021

In recent years, several studies have suggested that cardiometabolic disorders, such as diabetes, obesity, hypertension, and dyslipidemia, share strong connections with the onset of neurodegenerative disorders such as Parkinson’s and Alzheimer’s disease (AD). However, establishing a definitive link between medical disorders with coincident pathophysiologies is difficult due to etiological heterogeneity and underlying comorbidities. For this reason, amyloid β (Aβ), a physiological peptide derived from the sequential proteolysis of amyloid precursor protein (APP), serves as a crucial link that bridges the gap between cardiometabolic and neurodegenerative disorders. Aβ normally regulates neuronal synaptic function and repair; however, the intracellular accumulation of Aβ within the brain has been observed to play a critical role in AD pathology. A portion of Aβ is believed to originate from the brain itself and can readily cross the blood-brain barrier, while the rest resides in peripheral tissues that express APP required for Aβ generation such as the liver, pancreas, kidney, spleen, skin, and lungs. Consequently, numerous organs contribute to the body pool of total circulating Aβ, which can accumulate in the brain and facilitate neurodegeneration. Although the accumulation of Aβ corresponds with the onset of neurodegenerative disorders, the direct function of periphery born Aβ in AD pathophysiology is currently unknown. This review will highlight the contributions of individual cardiometabolic diseases including cardiovascular disease (CVD), type 2 diabetes (T2D), obesity, and non-alcoholic fatty liver disease (NAFLD) in elevating concentrations of circulating Aβ within the brain, as well as discuss the comorbid association of Aβ with AD pathology.
Automated Neuron Tracing Using Content-Aware Adaptive Voxel Scooping on CNN Predicted Probability Map
Authors: Huang Qing , Cao Tingting , Chen Yijun , Li Anan , Zeng Shaoqun , Quan Tingwei
Published: August 2021

Neuron tracing, as the essential step for neural circuit building and brain information flow analyzing, plays an important role in the understanding of brain organization and function. Though lots of methods have been proposed, automatic and accurate neuron tracing from optical images remains challenging. Current methods often had trouble in tracing the complex tree-like distorted structures and broken parts of neurite from a noisy background. To address these issues, we propose a method for accurate neuron tracing using content-aware adaptive voxel scooping on a convolutional neural network (CNN) predicted probability map. First, a 3D residual CNN was applied as preprocessing to predict the object probability and suppress high noise. Then, instead of tracing on the binary image produced by maximum classification, an adaptive voxel scooping method was presented for successive neurite tracing on the probability map, based on the internal content properties (distance, connectivity, and probability continuity along direction) of the neurite. Last, the neuron tree graph was built using the length first criterion. The proposed method was evaluated on the public BigNeuron datasets and fluorescence micro-optical sectioning tomography (fMOST) datasets and outperformed current state-of-art methods on images with neurites that had broken parts and complex structures. The high accuracy tracing proved the potential of the proposed method for neuron tracing on large-scale.
Echo State Networks for Estimating Exteroceptive Conditions From Proprioceptive States in Quadruped Robots
Authors: Calandra Mario , Patanè Luca , Sun Tao , Arena Paolo , Manoonpong Poramate
Published: August 2021

We propose a methodology based on reservoir computing for mapping local proprioceptive information acquired at the level of the leg joints of a simulated quadruped robot into exteroceptive and global information, including both the ground reaction forces at the level of the different legs and information about the type of terrain traversed by the robot. Both dynamic estimation and terrain classification can be achieved concurrently with the same reservoir computing structure, which serves as a soft sensor device. Simulation results are presented together with preliminary experiments on a real quadruped robot. They demonstrate the suitability of the proposed approach for various terrains and sensory system fault conditions. The strategy, which belongs to the class of data-driven models, is independent of the robotic mechanical design and can easily be generalized to different robotic structures.
Fold Change Detection in Visual Processing
Authors: Borba Cezar , Kourakis Matthew J. , Schwennicke Shea , Brasnic Lorena , Smith William C.
Published: August 2021

Visual processing transforms the complexities of the visual world into useful information. Ciona, an invertebrate chordate and close relative of the vertebrates, has one of the simplest nervous systems known, yet has a range of visuomotor behaviors. This simplicity has facilitated studies linking behavior and neural circuitry. Ciona larvae have two distinct visuomotor behaviors – a looming shadow response and negative phototaxis. These are mediated by separate neural circuits that initiate from different clusters of photoreceptors, with both projecting to a CNS structure called the posterior brain vesicle (pBV). We report here that inputs from both circuits are processed to generate fold change detection (FCD) outputs. In FCD, the behavioral response scales with the relative fold change in input, but is invariant to the overall magnitude of the stimulus. Moreover, the two visuomotor behaviors have fundamentally different stimulus/response relationships – indicative of differing circuit strategies, with the looming shadow response showing a power relationship to fold change, while the navigation behavior responds linearly. Pharmacological modulation of the FCD response points to the FCD circuits lying outside of the visual organ (the ocellus), with the pBV being the most likely location. Consistent with these observations, the connectivity and properties of pBV interneurons conform to known FCD circuit motifs, but with different circuit architectures for the two circuits. The negative phototaxis circuit forms a putative incoherent feedforward loop that involves interconnecting cholinergic and GABAergic interneurons. The looming shadow circuit uses the same cholinergic and GABAergic interneurons, but with different synaptic inputs to create a putative non-linear integral feedback loop. These differing circuit architectures are consistent with the behavioral outputs of the two circuits. Finally, while some reports have highlighted parallels between the pBV and the vertebrate midbrain, suggesting a common origin for the two, others reports have disputed this, suggesting that invertebrate chordates lack a midbrain homolog. The convergence of visual inputs at the pBV, and its putative role in visual processing reported here and in previous publications, lends further support to the proposed common origin of the pBV and the vertebrate midbrain.
The Concept of Symmetry and the Theory of Perception
Authors: Pizlo Zygmunt , de Barros J. Acacio
Published: August 2021

Perceptual constancy refers to the fact that the perceived geometrical and physical characteristics of objects remain constant despite transformations of the objects such as rigid motion. Perceptual constancy is essential in everything we do, like recognition of familiar objects and scenes, planning and executing visual navigation, visuomotor coordination, and many more. Perceptual constancy would not exist without the geometrical and physical permanence of objects: their shape, size, and weight. Formally, perceptual constancy and permanence of objects are invariants, also known in mathematics and physics as symmetries. Symmetries of the Laws of Physics received a central status due to mathematical theorems of Emmy Noether formulated and proved over 100 years ago. These theorems connected symmetries of the physical laws to conservation laws through the least-action principle. We show how Noether's theorem is applied to mirror-symmetrical objects and establishes mental shape representation (perceptual conservation) through the application of a simplicity (least-action) principle. This way, the formalism of Noether's theorem provides a computational explanation of the relation between the physical world and its mental representation.
Seizure Forecasting Using a Novel Sub-Scalp Ultra-Long Term EEG Monitoring System
Authors: Stirling Rachel E. , Maturana Matias I. , Karoly Philippa J. , Nurse Ewan S. , McCutcheon Kate , Grayden David B. , Ringo Steven G. , Heasman John M. , Hoare Rohan J. , Lai Alan , D'Souza Wendyl , Seneviratne Udaya , Seiderer Linda , McLean Karen J. , Bulluss Kristian J. , Murphy Michael , Brinkmann Benjamin H. , Richardson Mark P. , Freestone Dean R. , Cook Mark J.
Published: August 2021

Accurate identification of seizure activity, both clinical and subclinical, has important implications in the management of epilepsy. Accurate recognition of seizure activity is essential for diagnostic, management and forecasting purposes, but patient-reported seizures have been shown to be unreliable. Earlier work has revealed accurate capture of electrographic seizures and forecasting is possible with an implantable intracranial device, but less invasive electroencephalography (EEG) recording systems would be optimal. Here, we present preliminary results of seizure detection and forecasting with a minimally invasive sub-scalp device that continuously records EEG. Five participants with refractory epilepsy who experience at least two clinically identifiable seizures monthly have been implanted with sub-scalp devices (Minder®), providing two channels of data from both hemispheres of the brain. Data is continuously captured via a behind-the-ear system, which also powers the device, and transferred wirelessly to a mobile phone, from where it is accessible remotely via cloud storage. EEG recordings from the sub-scalp device were compared to data recorded from a conventional system during a 1-week ambulatory video-EEG monitoring session. Suspect epileptiform activity (EA) was detected using machine learning algorithms and reviewed by trained neurophysiologists. Seizure forecasting was demonstrated retrospectively by utilizing cycles in EA and previous seizure times. The procedures and devices were well-tolerated and no significant complications have been reported. Seizures were accurately identified on the sub-scalp system, as visually confirmed by periods of concurrent conventional scalp EEG recordings. The data acquired also allowed seizure forecasting to be successfully undertaken. The area under the receiver operating characteristic curve (AUC score) achieved (0.88), which is comparable to the best score in recent, state-of-the-art forecasting work using intracranial EEG.
Auxiliary Subunits Regulate the Dendritic Turnover of AMPA Receptors in Mouse Hippocampal Neurons
Authors: Harb Ali , Vogel Nils , Shaib Ali , Becherer Ute , Bruns Dieter , Mohrmann Ralf
Published: August 2021

Different families of auxiliary subunits regulate the function and trafficking of native α-amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid (AMPA) receptors in the central nervous system. While a facilitatory role of auxiliary subunits in ER export and forward trafficking of newly synthesized AMPA receptors is firmly established, it is unclear whether auxiliary subunits also control endosomal receptor turnover in dendrites. Here, we manipulated the composition of AMPA receptor complexes in cultured hippocampal neurons by overexpression of two auxiliary subunits, transmembrane AMPAR regulatory protein (TARP) γ-8 or cysteine knot AMPAR-modulating protein (CKAMP) 44a, and monitored dendritic receptor cycling in live-cell imaging experiments. Receptor surface delivery was assayed using a modified AMPA receptor subunit carrying the pH-dependent fluorophore superecliptic pHluorin (SEP-GluA1), which regains its fluorescence during receptor exocytosis, when transiting from the acidic lumen of transport organelles to the neutral extracellular medium. Strikingly, we observed a dramatic reduction in the spontaneous fusion rate of AMPA receptor-containing organelles in neurons overexpressing either type of auxiliary subunit. An analysis of intracellular receptor distribution also revealed a decreased receptor pool in dendritic recycling endosomes, suggesting that incorporation of TARPγ-8 or CKAMP44a in receptor complexes generally diminishes cycling through the endosomal compartment. To directly analyze dendritic receptor turnover, we also generated a new reporter by N-terminal fusion of a self-labeling HaloTag to an AMPA receptor subunit (HaloTag-GluA1), which allows for selective, irreversible staining of surface receptors. Pulse chase-experiments with HaloTag-GluA1 indeed demonstrated that overexpression of TARPγ-8 or CKAMP44a reduces the constitutive internalization rate of surface receptors at extrasynaptic but not synaptic sites. Thus, our data point to a yet unrecognized regulatory function of TARPγ-8 and CKAMP44a, by which these structurally unrelated auxiliary subunits delay local recycling and increase surface lifetime of extrasynaptic AMPA receptors.
Endocannabinoid Modulation of Nucleus Accumbens Microcircuitry and Terminal Dopamine Release
Authors: Covey Dan P. , Yocky Alyssa G.
Published: August 2021

The nucleus accumbens (NAc) is located in the ventromedial portion of the striatum and is vital to valence-based predictions and motivated action. The neural architecture of the NAc allows for complex interactions between various cell types that filter incoming and outgoing information. Dopamine (DA) input serves a crucial role in modulating NAc function, but the mechanisms that control terminal DA release and its effect on NAc neurons continues to be elucidated. The endocannabinoid (eCB) system has emerged as an important filter of neural circuitry within the NAc that locally shapes terminal DA release through various cell type- and site-specific actions. Here, we will discuss how eCB signaling modulates terminal DA release by shaping the activity patterns of NAc neurons and their afferent inputs. We then discuss recent technological advancements that are capable of dissecting how distinct cell types, their afferent projections, and local neuromodulators influence valence-based actions.