bluuebunny/crossref_metadata_2025 huggingface dataset:
Salinity Fluctuation on the Genetic Regulatory Mechanisms of the Crustacean, Charybdis japonica
Authors: Shui Bonian , Wang Yuju , Lou Fangrui , Han Zhiqiang
Published: July 2022

The intertidal salinity fluctuations provide pose a significant physical challenge for the crustaceans that live here. In the present study, Charybdis japonica was selected as the research species to explore the genetic regulatory mechanisms of intertidal crustaceans responding to salinity fluctuations. We cultured C. japonica s with three salinity gradients (the salinity of 15‰, 25‰, and 35‰) and 68.90 Gb clean transcriptome reads were obtained by RNA-seq. All clean reads were then de novo assembled to 41,058 unigene with a mean length of 1,179.39 bp and an N50 length of 2,033 bp. Furthermore, a total of 18,100 (24.74%) unigenes were successfully matched with the sequences from at least one database. We further analyzed the transcriptome structure of C. japonica and a total of 26,853 CDSs and 12,190 SSRs were predicted. The gene expression levels of C. japonica at 25‰ were used as control, and 204 and 5,392 DEGs were found at the salinity of 35‰ and 15‰, respectively. Based on the annotated information of DEGs, we speculated that C. japonicas were subjected to greater stress under the salinity of 35‰ and isotonic intracellular regulation was activated. Furthermore, neuronal activity, oxidation response, intracellular regulatory activity and osmotic regulation-related genes were speculated to be critical genes for C. japonica to cope with salinity fluctuations. The present results will provide fundamental information for revealing the salinity fluctuation-related genetic regulatory mechanisms of C. japonica and other intertidal crustaceans, and then help us predict how future salinity changes will affect the survival of crustaceans.
Flow Pathways of Abyssal Water in the Yap Trench and Adjacent Channels and Basins
Authors: Liu Xuehai , Liu Yongzhi , Cao Wei , Li Dong
Published: July 2022

Abyssal flow pathways in the Yap Trench and adjacent regions were investigated by computing geostrophic flows and analyzing water properties. Using boundary values of potential temperature, salinity, oxygen, and silicate, the upper and lower Circumpolar Deep Waters (UCPW, LCPW) were identified as the main abyssal water masses in the trench. At the western East Mariana Basin, some of the LCPW enters the southern Mariana Trench, and the remainder reaches the northern basin and then partly turns to the northern Mariana Trench, eventually joining the southern trench. At the Yap-Mariana Junction, some LCPW enters the West Mariana Basin, and the remainder passes the region east of the Yap Trench and then flows or subsides to the northern and southern trenches, respectively. In the northern trench, the LCPW flows north into the West Mariana Basin. The UCPW enters the northern Yap Trench via the East Mariana Basin and the Mariana Trench, reaches the sill of the Yap Trench via the East Caroline Basin and a narrow channel, and enters the southern trench via the East/West Caroline and Philippine Basins. The UCPW and LCPW circulate anticlockwise in the southern trench and in the northern region of it, respectively. The LCPW may be driven by the downwelling in the trench.
A T3SS Regulator Mutant HY9901 ΔaraC of Vibrio alginolyticus Decreased the Expression of HopPmaJ and Provided Protection to Danio rerio as a Live-Attenuated Vaccine
Authors: Wang Junlin , Zeng Fuyuan , Feng Haiyun , Chen Liangchuan , Zhang Weijie , Xiao Xing , Monaghan Sean J. , Jian Jichang , Pang Huanying , Wang Na
Published: July 2022

Vibrio alginolyticus, a zoonotic bacterial pathogen, expresses a type III secretion system (T3SS) that is critical for pathogen virulence and disease development. In this study, the mutant HY9901 ΔaraC was obtained from the laboratory and its biological characteristics were analyzed. The swimming ability of ΔaraC decreased and exhibited a 2,600 times reduction in virulence to zebrafish. However, ΔaraC showed no difference in growth and extracellular protease activity compared to wild type. Biofilm-forming ability was improved at 24 h, but no difference was observed at other time points. The results of drug sensitivity testing showed that compared with the wild-type HY9901 strain, ΔaraC was sensitive to amikacin, tetracycline, neomycin, minocycline, and gentamicin. The transcription levels of T3SS effector proteins HopPmaJ, VopS, VcrV, and VopN were analyzed by qRT-PCR. The results showed that ΔaraC had significantly upregulated the mRNA expression of VopS, VcrV, and VopN, but significantly downregulated the mRNA expression of HopPmaJ at each stage compared with HY9901. Western blotting and the β-galactosidase reporter gene experiment also showed that the deletion of araC gene significantly downregulated the expression of HopPmaJ. Finally, the relative percent survival (RPS) rate of grouper inoculated by intramuscular (IM) injection of HY9901 ΔaraC was 61.3% after being challenged with HY9901. Real-time qPCR analysis showed that vaccination of HY9901 ΔaraC could enhance the expression of immune-related genes, including gata-1, il6, IgM, il-1β, and lyz in liver and spleen, indicating that ΔaraC applied as a live-attenuated vaccine effectively induced an immune response in the zebrafish. This study provides evidence for the subsequent development of an effective live-attenuated V. alginolyticus vaccine.
Uncertainty Quantification of a High-Throughput Profilometry-Based Indentation Plasticity Test of Al 7075 T6 Alloy
Authors: Tallman Aaron E. , Paul Tanaji , John Denny , Agarwal Arvind
Published: July 2022

The quantification of spatially variable mechanical response in structural materials remains a challenge. Additive manufacturing methods result in increased spatial property variations—the effect of which on component performance is of key interest. To assist iterative design of additively manufactured prototypes, lower-cost benchtop test methods with high precision and accuracy will be necessary. Profilometry-based indentation plastometry (PIP) promises to improve upon the instrumented indentation test in terms of the measurement uncertainty. PIP uses an isotropic Voce hardening model and inverse numerical methods to identify plasticity parameters. The determination of the baseline uncertainty of PIP test is fundamental to its use in characterizing spatial material property variability in advanced manufacturing. To quantify the uncertainty of the PIP test, ninety-nine PIP tests are performed on prepared portions of a traditionally manufactured Al 7075 plate sample. The profilometry data and the Voce parameter predictions are examined to distinguish contributions of noise, individual measurement uncertainty, and additional set-wide variations. Individual measurement uncertainty is estimated using paired profilometry measurements that are taken from each indentation. Principal component analysis is used to analyze and model the measurement uncertainty. The fitting procedure used within the testing device software is employed to examine the effect of profile variations on plasticity predictions. The expected value of the error in the plasticity parameters is given as a function of the number of tests taken, to support rigorous use of the PIP method. The modeling of variability in the presence of measurement uncertainty is discussed.
Learning Causal Effects From Observational Data in Healthcare: A Review and Summary
Authors: Shi Jingpu , Norgeot Beau
Published: July 2022

Causal inference is a broad field that seeks to build and apply models that learn the effect of interventions on outcomes using many data types. While the field has existed for decades, its potential to impact healthcare outcomes has increased dramatically recently due to both advancements in machine learning and the unprecedented amounts of observational data resulting from electronic capture of patient claims data by medical insurance companies and widespread adoption of electronic health records (EHR) worldwide. However, there are many different schools of learning causality coming from different fields of statistics, some of them strongly conflicting. While the recent advances in machine learning greatly enhanced causal inference from a modeling perspective, it further exacerbated the fractured state in this field. This fractured state has limited research at the intersection of causal inference, modern machine learning, and EHRs that could potentially transform healthcare. In this paper we unify the classical causal inference approaches with new machine learning developments into a straightforward framework based on whether the researcher is most interested in finding the best intervention for an individual, a group of similar people, or an entire population. Through this lens, we then provide a timely review of the applications of causal inference in healthcare from the literature. As expected, we found that applications of causal inference in medicine were mostly limited to just a few technique types and lag behind other domains. In light of this gap, we offer a helpful schematic to guide data scientists and healthcare stakeholders in selecting appropriate causal methods and reviewing the findings generated by them.
Acute Ankle Sprain Management: An Umbrella Review of Systematic Reviews
Authors: Gaddi Diego , Mosca Angelo , Piatti Massimiliano , Munegato Daniele , Catalano Marcello , Di Lorenzo Giorgia , Turati Marco , Zanchi Nicolò , Piscitelli Daniele , Chui Kevin , Zatti Giovanni , Bigoni Marco
Published: July 2022

Even though ankle sprains are among the most frequent musculoskeletal injuries seen in emergency departments, management of these injuries continues to lack standardization. Our objective was to carry out an umbrella review of systematic reviews to collect the most effective evidence-based treatments and to point out the state-of-the-art management for this injury. PubMed, Scopus, Web of Science, and the Cochrane library were searched from January 2000 to September 2020. After removing duplicates and applying the eligibility criteria, based on titles and abstracts, 32 studies were screened. At the end of the process, 24 articles were included in this umbrella review with a mean score of 7.7/11 on the AMSTAR quality assessment tool. We found evidence supporting the effectiveness of non-surgical treatment in managing acute ankle sprain; moreover, functional treatment seems to be preferable to immobilization. We also found evidence supporting the use of paracetamol or opioids as effective alternatives to non-steroidal anti-inflammatory drugs to reduce pain. Furthermore, we found evidence supporting the effectiveness of manipulative and supervised exercise therapy to prevent re-injury and restore ankle dorsiflexion.
DNA Methylation: A Target in Neuropathic Pain
Authors: Jiang Wei , Tan Xuan-Yu , Li Jia-Ming , Yu Peng , Dong Ming
Published: July 2022

Neuropathic pain (NP), caused by an injury or a disease affecting the somatosensory nervous system of the central and peripheral nervous systems, has become a global health concern. Recent studies have demonstrated that epigenetic mechanisms are among those that underlie NP; thus, elucidating the molecular mechanism of DNA methylation is crucial to discovering new therapeutic methods for NP. In this review, we first briefly discuss DNA methylation, demethylation, and the associated key enzymes, such as methylases and demethylases. We then discuss the relationship between NP and DNA methylation, focusing on DNA methyltransferases including methyl-CpG-binding domain (MBD) family proteins and ten-eleven translocation (TET) enzymes. Based on experimental results of neuralgia in animal models, the mechanism of DNA methylation-related neuralgia is summarized, and useful targets for early drug intervention in NP are discussed.
The Risk of Major Adverse Cardiovascular Events in Ankylosing Spondylitis Patients With a History of Acute Anterior Uveitis: A Nationwide, Population Based Cohort Study
Authors: Bai Yi-Chiao , Liu Chin-Hsiu , Leong Pui-Ying , Lai Kuo-Lung , Chen Hsin-Hua , Wei James Cheng-Chung
Published: July 2022

Background

To investigate the association between a history of acute anterior uveitis (AAU) and the risk of major adverse cardiovascular events (MACE) among patients with ankylosing spondylitis (AS).

Methods

We identified 38,691 newly diagnosed AS patients between 2003 and 2013 from the Taiwan National Health Insurance Research Database. The exposure group was defined as people with uveitis diagnosis by ophthalmologist before AS diagnosis date. The incidence of MACE in patients with AS according to the International Classification of Diseases, Ninth Revision. We randomly selected a comparison group without a history of AAU at a 1:4 ratio matched by age, sex, and index year in relation to the risk of developing MACE. We used cox proportional hazard regression model to compare the risk of MACE between groups, shown as adjusted hazard ratios (aHRs) with 95% confidence intervals (CI). Further subgroup analysis and sensitivity tests were also performed.

Results

There were 3,544 patients in the AAU group and 14,176 patients in the non-AAU group. The aHR of MACE for the AAU group was 0.79 (95% CI = 0.57–1.10) at a 1:4 ratio for age, sex and index year. Sensitivity analyses using various adjustment variables showed consistent results. Cox proportional hazard regression model demonstrated that use of non-steroidal anti-inflammatory drugs (NSAIDs) was associated with an increased risk of MACE in this cohort (HR = 3.44; 95% CI = 2.25–5.25).

Conclusion

This cohort study showed that subjects with AAU was not associated with the risk of MACE among AS patients, compared to non-AAU controls.
In silico Identification of Immune Cell-Types and Pathways Involved in Chronic Spontaneous Urticaria
Authors: Prosty Connor , Gabrielli Sofianne , Ben-Shoshan Moshe , Le Michelle , Giménez-Arnau Ana M. , Litvinov Ivan V. , Lefrançois Philippe , Netchiporouk Elena
Published: July 2022

Background

The immunopathogenesis of chronic spontaneous urticaria (CSU) is poorly understood, but recent research suggests that patients can be divided into autoallergic and autoimmune subtypes. Given that not all patients can be controlled with current treatment regimens, including anti-IgE monoclonal antibodies, a better understanding of the immune pathways involved in CSU may enable the repurposing of monoclonal antibodies used for other dermatologic diseases (e.g., Th2 and Th17 inhibitors). Therefore, we investigated the implicated immune cells and pathways by reanalyzing publicly available transcriptomic data.

Methods

Microarray data of CSU and healthy control (HC) skin and blood were obtained from the Gene Expression Omnibus (GSE72542, GSE57178). Differentially expressed genes were defined as a false discovery rate <0.05 and a |log2 fold change| ≥1. Pathway analyses were conducted using ToppGene and KEGG. Cell-type enrichment was determined by CIBERSORT and xCell and was correlated with clinical characteristics.

Results

Th2 (IL-4/13 signaling) and Th17-related (IL-17/23 signaling) pathways were upregulated in lesional compared to non-lesional and HC samples. In non-lesional versus lesional samples, CIBERSORT analysis revealed increased regulatory T-cells (Treg) and resting mast cells. xCell analysis established that Th1 and Th2 scores were not significantly different between lesional and HC samples. However, Th2 scores in both lesional and non-lesional samples correlated positively with disease severity. Few differentially expressed genes and pathways were identified between CSU and HC blood samples.

Conclusion

Our results support the involvement of Th2 and Th17-related genes and pathways in CSU. Th2 scores associate with disease severity, which indicates the clinical relevance of these findings. Increased resting mast cell and Treg scores in non-lesional samples may suggest local suppression of wheal formation. Moreover, disease activity seemed to be restricted to the skin as there were limited findings from blood. Larger studies using next-generation sequencing will be helpful to confirm these results.
MMF/MPA Is the Main Mediator of a Delayed Humoral Response With Reduced Antibody Decline in Kidney Transplant Recipients After SARS-CoV-2 mRNA Vaccination
Authors: Stumpf Julian , Siepmann Torsten , Schwöbel Jörg , Glombig Grit , Paliege Alexander , Steglich Anne , Gembardt Florian , Kessel Friederike , Kröger Hannah , Arndt Patrick , Sradnick Jan , Frank Kerstin , Klimova Anna , Mauer René , Tonn Torsten , Hugo Christian
Published: July 2022

Kidney transplant recipients (KTR) show significantly lower seroconversion rates after SARS-CoV-2 mRNA vaccination compared to dialysis patients (DP). Mycophenolate mofetil or mycophenolic acid (MMF/MPA) in particular has been identified as a risk factor for seroconversion failure. While the majority of all KTR worldwide receive MMF/MPA for immunosuppressive therapy, its impact on antibody decline in seroconverted KTR still remains unclear. In an observational study (NCT04799808), we investigated whether 132 seroconverted KTR (anti-spike S1 IgG or IgA positive after 2 vaccinations) show a more rapid antibody decline with MMF/MPA than those without this medication. A total of 2 months after mRNA vaccination, average anti-spike S1 IgG levels of KTR with MMF/MPA were lower than without (p = 0.001), while no differences between these two groups were observed after 6 months (p = 0.366). Similar results were obtained for anti-RBD IgG antibodies (T2 p = 0.003 and T3 p = 0.135). The probability of severe IgG decline with MMF/MPA was three times lower than without (p = 0.003, OR 0.236, 95% CI 0.091–0.609). In the multivariate analysis, neither immunosuppressants, such as calcineurin inhibitors, mTOR inhibitors (mTOR-I; mechanistic target of rapamycin), glucocorticoids, nor vaccine type, sex, or age showed a significant influence on IgG titer decline between 2 and 6 months. For the decision on additional booster vaccinations, we consider immunosurveillance to be needed as an integral part of renal transplant follow-up after SARS-CoV-2 mRNA vaccination. Not only the lack of seroconversion but also the peak and titer decline of the specific IgG and RBD IgG antibody formation after two mRNA vaccinations is significantly influenced by MMF/MPA.
First Report of blaCTX–M–167, blaSHV–1, and blaTEM–1B Carrying Klebsiella pneumonia Showing High-Level Resistance to Carbapenems
Authors: Li Shirong , Shen Siquan , Ding Li , Han Renru , Guo Yan , Yin Dandan , Guan Ming , Hu Fupin
Published: July 2022

The prevalence of carbapenem-resistant Klebsiella pneumoniae is increasing. Although carbapenemase production is the main resistance mechanism of K. pneumonia to carbapenems, there are still some reports of non-carbapenemase-producing K.pneumoniae showing high-level resistance to carbapenems. In this study, we had also isolated a carbapenemase-negative carbapenem-resistant K. pneumoniae L204 from a patient with an asymptomatic urinary tract infection. Species identification was performed using MALDI-TOF MS, and carbapenemase-encoding genes were detected using both NG-test carba-5 and whole-genome sequencing. Antimicrobial susceptibility testing was performed by the broth microdilution method according to CLSI guidance. The results of antimicrobial susceptibility testing indicated that K. pneumoniae L204 was resistant to meropenem (MIC = 16 mg/L) and imipenem (MIC = 4 mg/L), but susceptible to ceftazidime-avibactam (MIC = 8 mg/L). Through whole-genome sequencing, several resistance genes had been identified, including blaTEM–1B, blaCTX–M–167, blaSHV–1, aac(6’)-1b-cr, qnrS, aadA16, tet(A), fosA, sul1, and mph(A). The efflux pump inhibition testing showed that the efflux pump was not involved in the resistance mechanism to carbapenems. The result of the conjugation experiment indicated that the plasmid with blaCTX–M–167 and blaSHV–1 was transferrable. The sodium dodecyl sulfate-polyacrylamide gel electrophoresis (SDS-PAGE) demonstrated that K. pneumoniae L204 only contained outer membrane porin OmpK35.
Expression, Characterization, Fermentation, Immobilization, and Application of a Novel Esterase Est804 From Metagenomic Library in Pesticide Degradation
Authors: Chen Cuihua , Yu Gen , Guo Zhenyu , Yang Qihao , Su Wenfeng , Xie Qingfen , Yang Guandong , Ren Yifei , Li He
Published: July 2022

Esterase, as a type of powerful catabolic enzyme for the degradation of pyrethroid pesticides (PYRs), appears promising in improving the quality of crops and the environment contaminated by pesticide residues. The purpose of this research is to provide a detailed introduction to the enzymatic properties, optimal production and immobilization conditions, and the degradation ability of Est804 for PYRs. The study on enzymatic properties indicated that Est804 was an alkaline esterase with an optimal pH of 8.0 and a broad optimal temperature in the range of 35−50°C. The optimal activity of free Est804 was calculated to be 112.812 U, and the specific enzyme activity was 48.97 U/mg. The kinetic parameters of Est804 were Km = 0.613 mM, kcat = 12,371 s–1, and Vm = 0.095 mM/min. The results of the fermentative optimization demonstrated that the optimal conditions included 1.5% of inoculation amount, 30 mL of liquid volume, 28°C of the fermentation temperature, and 18 h of the fermentation time. The optimal medium consists of 15.87 g of yeast powder, 8.00 g of glycerol, and 9.57 g of tryptone in 1 L of liquid. The optimized enzyme activity was 1.68-fold higher than that before optimization. Immobilized Est804 exhibited the highest activity under the optimum preparation conditions, including 0.35 g of chitosan dosage, 0.4 mL of an enzyme, and 4 h at 40°C for adsorption. The degradation rates of Cypermethrin (CYP), fenpropathrin (FE), and lambda-cyhalothrin (LCT) by Est804 within 30 min were 77.35%, 84.73%, and 74.16%, respectively. The present study indicated that Est804 possesses great potential for the treatment of pesticide residues on crops and environmental remediation, conducive to the development of SGNH family esterase against pyrethroid accumulation.
Survival and Replication of Zika Virus in Diapause Eggs of Aedes Albopictus From Beijing, China
Authors: Zhang Qianghui , Jiang Yuting , Li Chaojie , Gao Jian , Zhao Teng , Zhang Hengduan , Li Chunxiao , Xing Dan , Dong Yande , Zhao Tongyan , Guo Xiaoxia
Published: July 2022

Zika virus (ZIKV) has emerged as a globally important arbovirus. The virus is primarily transmitted to humans through the bite of an infective Aedes albopictus in temperate area. Vertical transmission of ZIKV by Ae. albopictus is determined and has been suggested to be a means by which the virus could persist in nature. Ae. albopictus undergoes a well-characterized photoperiodic diapause. Viruses are harbored by overwintering mosquitoes in diapause that contributes to the resurgence of vertebrate diseases in the following spring, yet little is known about the impact of diapause on the regulation of viral replication and survival. The purpose of this study is to determine that Ae. albopictus in Beijing are highly susceptible to ZIKV (92.3%), and viable virus is passed to their organs of progeny via vertical transmission. Moreover, diapause eggs (diapause incidence 97.8%) had significantly lower minimum infection rates and filial infection rates of the first gonotrophic cycle than those of the second gonotrophic cycle in the short-day photoperiod group. Regarding the development of diapause eggs, the minimum infection rates and ZIKV RNA copy number increased significantly, suggesting that virus RNA replication occurred in the diapause eggs. Meanwhile, eggs from the ZIKV-infected mosquitoes had a significantly lower hatching rate compared with uninfected mosquitoes, implying an intriguing interaction between diapause eggs and virus. The findings here suggest that vertical transmission of ZIKV from diapause eggs to progeny may have a critical epidemiological role in the dissemination and maintenance of ZIKV circulating in the vector.
Effects of Cellulase and Lactiplantibacillus plantarum on the Fermentation Parameters, Nutrients, and Bacterial Community in Cassia alata Silage
Authors: Xian Zhenyu , Wu Jiaqi , Deng Ming , Wang Meng , Tian Hanchen , Liu Dewu , Li Yaokun , Liu Guangbin , Sun Baoli , Guo Yongqing
Published: July 2022

Silage Cassia alata (CA) can alleviate feed shortage in some areas to a certain extent and reduce feed costs. The present research evaluated the effect of cellulase (CE) and Lactiplantibacillus plantarum (LP) on the fermentation parameters, nutrients, and bacterial community of CA silage. Chopped CA was ensiled with three different treatments, namely, no inoculant (CK), CE, and LP, and the indexes were determined on the 2nd, 6th, 14th, and 30th days of silage fermentation. The fermentation parameters indicate that the pH value of the three groups decreased and then increased with the ensilage process, and the lowest value was observed on the 14th day. The CK and LP groups attained the highest value on the 30th day, while the CE group attained the highest value on the 2nd day. Additionally, the pH value and NH3-N content were significantly lower (P < 0.05) in the CE and LP groups than in the CK group. In terms of nutrients, crude protein (CP) contents significantly increased (P < 0.05) in the CE and LP groups on the 30th day. The neutral detergent fiber (NDF) and acid detergent fiber (ADF) contents of the CE group were significantly and negatively associated with fermentation time, and the water-soluble carbohydrate (WSC) contents of the three groups were significantly lower during ensiling. In comparison with the CK group, the NDF and ADF contents were significantly reduced (P < 0.05), and the WSC content increased (P < 0.05) in the CE group on day 30. Sequencing analysis of bacterial communities showed that Lactobacillus became the most dominant genus in the ensilage process. Moreover, both CE and LP groups increased the abundance of Lactobacillus and decreased that of Klebsiella, Weissella, and Acetobacter in comparison to the CK group, in which LP had a better effect. CE and LP could further improve the silage quality of CA, and LP had a more significant effect in reconstructing the bacterial community in the silage environment.
Humanization of Yeasts for Glycan-Type End-Products
Authors: Li Xingjuan , Shen Jianlie , Chen Xingqiang , Chen Lei , Wan Shulin , Qiu Xingtao , Chen Ke , Chen Chunmiao , Tan Haidong
Published: July 2022

Yeasts are often considered microorganisms for producing human therapeutic glycosylated end-products at an industrial scale. However, the products with non-humanized glycans limited their usage. Therefore, various methods to develop humanized glycosylated end-products have been widely reported in yeasts. To make full use of these methods, it is necessary to summarize the present research to find effective approaches to producing humanized products. The present research focuses on yeast species selection, glycosyltransferase deletion, expression of endoglycosidase, and expression of proteins with galactosylated and or sialylated glycans. Nevertheless, the yeasts will have growth defects with low bioactivity when the key enzymes are deleted. It is necessary to express the corresponding repairing protein. Compared with N-glycosylation, the function of yeast protein O-glycosylation is not well-understood. Yeast proteins have a wide variety of O-glycans in different species, and it is difficult to predict glycosylation sites, which limits the humanization of O-glycosylated yeast proteins. The future challenges include the following points: there are still many important potential yeasts that have never been tried to produce glycosylated therapeutic products. Their glycosylation pathway and related mechanisms for producing humanized glycosylated proteins have rarely been reported. On the other hand, the amounts of key enzymes on glycan pathways in human beings are significantly more than those in yeasts. Therefore, there is still a challenge to produce a large body of humanized therapeutic end-products in suitable yeast species, especially the protein with complex glycans. CRISPR-Cas9 system may provide a potential approach to address the important issue.
High-Altitude Drives the Convergent Evolution of Alpha Diversity and Indicator Microbiota in the Gut Microbiomes of Ungulates
Authors: Wang Xibao , Wu Xiaoyang , Shang Yongquan , Gao Ying , Li Ying , Wei Qinguo , Dong Yuehuan , Mei Xuesong , Zhou Shengyang , Sun Guolei , Liu Lixian , Lige Bi , Zhang Zhihao , Zhang Honghai
Published: July 2022

Convergent evolution is an important sector of evolutionary biology. High-altitude environments are one of the extreme environments for animals, especially in the Qinghai Tibet Plateau, driving the inquiry of whether, under broader phylogeny, high-altitude factors drive the convergent evolution of Artiodactyla and Perissodactyla gut microbiomes. Therefore, we profiled the gut microbiome of Artiodactyla and Perissodactyla at high and low altitudes using 16S rRNA gene sequencing. According to cluster analyses, the gut microbiome compositions of high-altitude Artiodactyla and Perissodactyla were not grouped together and were far from those of low-altitude Artiodactyla and Perissodactyla. The Wilcoxon’s test in high-altitude ungulates showed significantly higher Sobs and Shannon indices than in low-altitude ungulates. At the phylum level, Firmicutes and Patescibacteria were significantly enriched in the gut microbiomes of high-altitude ungulates, which also displayed a higher Firmicutes/Bacteroidetes value than low-altitude ungulates. At the family level, Ruminococcaceae, Christensenellaceae, and Saccharimonadaceae were significantly enriched in the gut microbiomes of high-altitude ungulates. Our results also indicated that the OH and FH groups shared two significantly enriched genera, Christensenellaceae_R_7_group and Candidatus_Saccharimonas. These findings indicated that a high altitude cannot surpass the order level to drive the convergent evolution of ungulate gut microbiome composition but can drive the convergent evolution of alpha diversity and indicator microbiota in the gut microbiome of ungulates. Overall, this study provides a novel perspective for understanding the adaptation of ungulates to high-altitude environments.
Benchmarking of ATAC Sequencing Data From BGI’s Low-Cost DNBSEQ-G400 Instrument for Identification of Open and Occupied Chromatin Regions
Authors: Naval-Sanchez Marina , Deshpande Nikita , Tran Minh , Zhang Jingyu , Alhomrani Majid , Alsanie Walaa , Nguyen Quan , Nefzger Christian M.
Published: July 2022

Background: Chromatin falls into one of two major subtypes: closed heterochromatin and euchromatin which is accessible, transcriptionally active, and occupied by transcription factors (TFs). The most widely used approach to interrogate differences in the chromatin state landscape is the Assay for Transposase-Accessible Chromatin using sequencing (ATAC-seq). While library generation is relatively inexpensive, sequencing depth requirements can make this assay cost-prohibitive for some laboratories.

Findings: Here, we benchmark data from Beijing Genomics Institute’s (BGI) DNBSEQ-G400 low-cost sequencer against data from a standard Illumina instrument (HiSeqX10). For comparisons, the same bulk ATAC-seq libraries generated from pluripotent stem cells (PSCs) and fibroblasts were sequenced on both platforms. Both instruments generate sequencing reads with comparable mapping rates and genomic context. However, DNBSEQ-G400 data contained a significantly higher number of small, sub-nucleosomal reads (>30% increase) and a reduced number of bi-nucleosomal reads (>75% decrease), which resulted in narrower peak bases and improved peak calling, enabling the identification of 4% more differentially accessible regions between PSCs and fibroblasts. The ability to identify master TFs that underpin the PSC state relative to fibroblasts (via HOMER, HINT-ATAC, TOBIAS), namely, foot-printing capacity, were highly similar between data generated on both platforms. Integrative analysis with transcriptional data equally enabled direct recovery of three published 3-factor combinations that have been shown to induce pluripotency.

Conclusion: Other than a small increase in peak calling sensitivity for DNBSEQ-G400 data (BGI), both platforms enable comparable levels of open chromatin identification for ATAC-seq library sequencing, yielding similar analytical outcomes, albeit at low-data generation costs in the case of the BGI instrument.
Implementing a Scoring Function Based on Interaction Fingerprint for Autogrow4: Protein Kinase CK1δ as a Case Study
Authors: Pavan Matteo , Menin Silvia , Bassani Davide , Sturlese Mattia , Moro Stefano
Published: July 2022

In the last 20 years, fragment-based drug discovery (FBDD) has become a popular and consolidated approach within the drug discovery pipeline, due to its ability to bring several drug candidates to clinical trials, some of them even being approved and introduced to the market. A class of targets that have proven to be particularly suitable for this method is represented by kinases, as demonstrated by the approval of BRAF inhibitor vemurafenib. Within this wide and diverse set of proteins, protein kinase CK1δ is a particularly interesting target for the treatment of several widespread neurodegenerative diseases, such as Alzheimer’s disease, Parkinson’s disease, and amyotrophic lateral sclerosis. Computational methodologies, such as molecular docking, are already routinely and successfully applied in FBDD campaigns alongside experimental techniques, both in the hit-discovery and in the hit-optimization stage. Concerning this, the open-source software Autogrow, developed by the Durrant lab, is a semi-automated computational protocol that exploits a combination between a genetic algorithm and a molecular docking software for de novo drug design and lead optimization. In the current work, we present and discuss a modified version of the Autogrow code that implements a custom scoring function based on the similarity between the interaction fingerprint of investigated compounds and a crystal reference. To validate its performance, we performed both a de novo and a lead-optimization run (as described in the original publication), evaluating the ability of our fingerprint-based protocol to generate compounds similar to known CK1δ inhibitors based on both the predicted binding mode and the electrostatic and shape similarity in comparison with the standard Autogrow protocol.
The Impact of Hidden Structure on Aggregate Disassembly by Molecular Chaperones
Authors: Shoup Daniel , Roth Andrew , Puchalla Jason , Rye Hays S.
Published: July 2022

Protein aggregation, or the uncontrolled self-assembly of partially folded proteins, is an ever-present danger for living organisms. Unimpeded, protein aggregation can result in severe cellular dysfunction and disease. A group of proteins known as molecular chaperones is responsible for dismantling protein aggregates. However, how protein aggregates are recognized and disassembled remains poorly understood. Here we employ a single particle fluorescence technique known as Burst Analysis Spectroscopy (BAS), in combination with two structurally distinct aggregate types grown from the same starting protein, to examine the mechanism of chaperone-mediated protein disaggregation. Using the core bi-chaperone disaggregase system from Escherichia coli as a model, we demonstrate that, in contrast to prevailing models, the overall size of an aggregate particle has, at most, a minor influence on the progression of aggregate disassembly. Rather, we show that changes in internal structure, which have no observable impact on aggregate particle size or molecular chaperone binding, can dramatically limit the ability of the bi-chaperone system to take aggregates apart. In addition, these structural alterations progress with surprising speed, rendering aggregates resistant to disassembly within minutes. Thus, while protein aggregate structure is generally poorly defined and is often obscured by heterogeneous and complex particle distributions, it can have a determinative impact on the ability of cellular quality control systems to process protein aggregates.
Fibrinogen in Alzheimer’s Disease, Parkinson’s Disease and Lewy Body Dementia: A Mendelian Randomization Study
Authors: Zhang Hanyu , Zhou Zengyuan
Published: July 2022

Fibrinogen is reportedly associated with neurodegenerative diseases (NDs), but the underlying causality remains controversial. Using Mendelian randomization (MR), this study aimed to assess the causal association between fibrinogen and Alzheimer’s disease (AD), Parkinson’s disease (PD), and Lewy body dementia (LBD). Genetic variants associated with fibrinogen and γ-fibrinogen were selected and used as instrumental variables. The effect estimates of the main analysis were obtained by inverse-variance weighting (IVW), complemented by sensitivity analyses to verify model assumptions, and multivariable MR was conducted to control for potential pleiotropic effect. Two-step MR was performed to assess the causal association through mediators. The main analysis suggested no causal association between genetically predicted plasma fibrinogen and γ-fibrinogen levels and the risk of AD, PD, and LBD. The effect estimates did not change in the follow-up sensitivity analyses and MVMR. However, the two-step MR analysis provides evidence that fibrinogen may contribute to the risk of AD via CRP levels. There was an inverse effect of adult height levels on the risk of AD. Our results support the effects of fibrinogen on the risk of AD through increasing plasma CRP levels. Our study found no evidence to support the effects of genetically determined fibrinogen and γ-fibrinogen levels on the risk of PD and LBD. Additionally, our findings suggested an inverse association between genetically determined adult height levels and the risk of AD. Future studies are needed to elucidate the underlying mechanisms and their clinical applications.
Spatial-Temporal Attention Mechanism and Graph Convolutional Networks for Destination Prediction
Authors: Li Cong , Zhang Huyin , Wang Zengkai , Wu Yonghao , Yang Fei
Published: July 2022

Urban transportation destination prediction is a crucial issue in the area of intelligent transportation, such as urban traffic planning and traffic congestion control. The spatial structure of the road network has high nonlinearity and complexity, and also, the traffic flow is dynamic due to the continuous changing of the traffic environment. Thus, it is very important to model the spatial relation and temporal dependence simultaneously to simulate the true traffic conditions. Most of the existing destination prediction methods have limited ability to model large-scale spatial data that changes dynamically with time, so they cannot obtain satisfactory prediction results. This paper proposes a human-in-loop Spatial-Temporal Attention Mechanism with Graph Convolutional Network (STAGCN) model to explore the spatial-temporal dependencies for destination prediction. The main contributions of this study are as follows. First, the traffic network is represented as a graph network by grid region dividing, then the spatial-temporal correlations of the traffic network can be learned by convolution operations in time on the graph network. Second, the attention mechanism is exploited for the analysis of features with loop periodicity and enhancing the features of key nodes in the grid. Finally, the spatial and temporal features are combined as the input of the Long-Short Term Memory network (LSTM) to further capture the spatial-temporal dependences of the traffic data to reach more accurate results. Extensive experiments conducted on the large scale urban real dataset show that the proposed STAGCN model has achieved better performance in urban car-hailing destination prediction compared with the traditional baseline models.
Acute Kidney Injury and Intestinal Dysbiosis
Authors: Chávez-Iñiguez Jonathan Samuel , Villegas-Gutiérrez Luz Yareli , Gallardo-González Alejandro Martínez
Published: July 2022

Within the multiple communication pathways of the intestine-kidney axis, one of the most important pathways is the interaction between the commensals of the intestinal microbiome, through the production of short-chain fatty acids, and the segments of the nephron. These interactions maintain a perfect environmental balance. During AKI, there are negative repercussions in all organs, and the systemic interconnection is related in part to the intense inflammation and the uremic environment that this syndrome generates. For example, in the intestine, the microbiome is severely affected, with a decrease in benign bacteria that promote anti-inflammatory effects and an increase in negative, pro-inflammatory bacteria. This scenario of intestinal dysbiosis widens the inflammatory loop that favors worsening kidney function and the probability of dying. It is possible that the manipulation of the intestinal microbiome with probiotics, prebiotics and symbiotics is a reasonable therapeutic goal for AKI.
Evaluation of the Reddesa Chart, a New Red Desaturation Testing Method, for Optic Neuritis Screening and Grading in Clinical Routine
Authors: Bruegger Dominik , Koth Anna-Lucia , Dysli Muriel , Goldblum David , Abegg Mathias , Tschopp Markus , Tappeiner Christoph
Published: July 2022

Background:

Optic neuritis usually leads to reduced color sensitivity. Most often, the change of red color, the so-called red desaturation, is tested in clinical routine. The aim of this study was to test the feasibility of the Reddesa chart, a new red desaturation test based on polarization, as a screening method for optic neuropathy.

Methods

A total of 20 patients with unilateral optic neuritis and 20 healthy controls were included in this prospective pilot study. Ophthalmological examination included assessment of best corrected visual acuity (BCVA), slit lamp examination, fundoscopy, testing of relative afferent pupillary defect (RAPD) and red desaturation with the red cup test and the Reddesa chart.

Results

The mean BCVA in the optic neuritis group was 0.76 ± 0.36 in the affected eye (95% of eyes with RAPD, 75% of eyes with difference in the Reddesa test) and 1.28 ± 0.24 in the healthy eye, whereas in the control group, BCVA was 1.14 ± 0.11 in the right eye and 1.15 ± 0.14 in the left eye (none of the eyes with RAPD or abnormal Reddesa test). In our study, the Reddesa test showed a positive predictive value of 100% and a negative predictive value of 80% for detecting optic neuritis.

Conclusion

The Reddesa chart allows to quantify red desaturation and has the potential to be implemented as a screening test in clinical routine.
A Novel Patient-Tailored, Cumulative Neurotechnology-Based Therapy for Upper-Limb Rehabilitation in Severely Impaired Chronic Stroke Patients: The AVANCER Study Protocol
Authors: Bigoni Claudia , Zandvliet Sarah B. , Beanato Elena , Crema Andrea , Coscia Martina , Espinosa Arnau , Henneken Tina , Hervé Julie , Oflar Meltem , Evangelista Giorgia G. , Morishita Takuya , Wessel Maximilian J. , Bonvin Christoph , Turlan Jean-Luc , Birbaumer Niels , Hummel Friedhelm C.
Published: July 2022

Effective, patient-tailored rehabilitation to restore upper-limb motor function in severely impaired stroke patients is still missing. If suitably combined and administered in a personalized fashion, neurotechnologies offer a large potential to assist rehabilitative therapies to enhance individual treatment effects. AVANCER (clinicaltrials.govNCT04448483) is a two-center proof-of-concept trial with an individual based cumulative longitudinal intervention design aiming at reducing upper-limb motor impairment in severely affected stroke patients with the help of multiple neurotechnologies. AVANCER will determine feasibility, safety, and effectivity of this innovative intervention. Thirty chronic stroke patients with a Fugl-Meyer assessment of the upper limb (FM-UE) <20 will be recruited at two centers. All patients will undergo the cumulative personalized intervention within two phases: the first uses an EEG-based brain-computer interface to trigger a variety of patient-tailored movements supported by multi-channel functional electrical stimulation in combination with a hand exoskeleton. This phase will be continued until patients do not improve anymore according to a quantitative threshold based on the FM-UE. The second interventional phase will add non-invasive brain stimulation by means of anodal transcranial direct current stimulation to the motor cortex to the initial approach. Each phase will last for a minimum of 11 sessions. Clinical and multimodal assessments are longitudinally acquired, before the first interventional phase, at the switch to the second interventional phase and at the end of the second interventional phase. The primary outcome measure is the 66-point FM-UE, a significant improvement of at least four points is hypothesized and considered clinically relevant. Several clinical and system neuroscience secondary outcome measures are additionally evaluated. AVANCER aims to provide evidence for a safe, effective, personalized, adjuvant treatment for patients with severe upper-extremity impairment for whom to date there is no efficient treatment available.
Neural Synchrony During Naturalistic Information Processing Is Associated With Aerobically Active Lifestyle and Cardiorespiratory Fitness in Cognitively Intact Older Adults
Authors: Eisenstein Tamir , Giladi Nir , Hendler Talma , Havakuk Ofer , Lerner Yulia
Published: July 2022

The functional neural mechanisms underlying the cognitive benefits of aerobic exercise have been a subject of ongoing research in recent years. However, while most neuroimaging studies to date which examined functional neural correlates of aerobic exercise have used simple stimuli in highly controlled and artificial experimental conditions, our everyday life experiences require a much more complex and dynamic neurocognitive processing. Therefore, we have used a naturalistic complex information processing fMRI paradigm of story comprehension to investigate the role of an aerobically active lifestyle in the processing of real-life cognitive-demanding situations. By employing the inter-subject correlation (inter-SC) approach, we have identified differences in reliable stimulus-induced neural responses between groups of aerobically active (n = 27) and non-active (n = 22) cognitively intact older adults (age 65–80). Since cardiorespiratory fitness has previously been suggested to play a key role in the neuroprotective potential of aerobic exercise, we have investigated its dose-response relationship with regional inter-subject neural responses. We found that aerobically active lifestyle and cardiorespiratory fitness were associated with more synchronized inter-subject neural responses during story comprehension in higher order cognitive and linguistic brain regions in the prefrontal and temporo-parietal cortices. In addition, while higher regional inter-SC values were associated with higher performance on a post-listening memory task, this was not translated to a significant between-group difference in task performance. We, therefore, suggest that the modulatory potential of aerobic exercise and cardiorespiratory fitness on cognitive processing may extend beyond simple and highly controlled stimuli to situations in which the brain faces continuous real-life complex information. Additional studies incorporating other aspects of real-life situations such as naturalistic visual stimuli, everyday life decision making, and motor responses in these situations are desired to further validate the observed relationship between aerobic exercise, cardiorespiratory fitness, and complex naturalistic information processing.