bluuebunny/crossref_metadata_2025 huggingface dataset:
Genomic Insight Into the Population Structure and Admixture History of Tai-Kadai-Speaking Sui People in Southwest China
Authors: Bin Xiaoyun , Wang Rui , Huang Youyi , Wei Rongyao , Zhu Kongyang , Yang Xiaomin , Ma Hao , He Guanglin , Guo Jianxin , Zhao Jing , Yang Meiqing , Chen Jing , Zhang Xianpeng , Tao Le , Liu Yilan , Huang Xiufeng , Wang Chuan-Chao
Published: September 2021

Sui people, which belong to the Tai-Kadai-speaking family, remain poorly characterized due to a lack of genome-wide data. To infer the fine-scale population genetic structure and putative genetic sources of the Sui people, we genotyped 498,655 genome-wide single-nucleotide polymorphisms (SNPs) using SNP arrays in 68 Sui individuals from seven indigenous populations in Guizhou province and Guangxi Zhuang Autonomous Region in Southwest China and co-analyzed with available East Asians via a series of population genetic methods including principal component analysis (PCA), ADMIXTURE, pairwise Fst genetic distance, f-statistics, qpWave, and qpAdm. Our results revealed that Guangxi and Guizhou Sui people showed a strong genetic affinity with populations from southern China and Southeast Asia, especially Tai-Kadai- and Hmong-Mien-speaking populations as well as ancient Iron Age Taiwan Hanben, Gongguan individuals supporting the hypothesis that Sui people came from southern China originally. The indigenous Tai-Kadai-related ancestry (represented by Li), Northern East Asian-related ancestry, and Hmong-Mien-related lineage contributed to the formation processes of the Sui people. We identified the genetic substructure within Sui groups: Guizhou Sui people were relatively homogeneous and possessed similar genetic profiles with neighboring Tai-Kadai-related populations, such as Maonan. While Sui people in Yizhou and Huanjiang of Guangxi might receive unique, additional gene flow from Hmong-Mien-speaking populations and Northern East Asians, respectively, after the divergence within other Sui populations. Sui people could be modeled as the admixture of ancient Yellow River Basin farmer-related ancestry (36.2–54.7%) and ancient coastal Southeast Asian-related ancestry (45.3–63.8%). We also identified the potential positive selection signals related to the disease susceptibility in Sui people via integrated haplotype score (iHS) and number of segregating sites by length (nSL) scores. These genomic findings provided new insights into the demographic history of Tai-Kadai-speaking Sui people and their interaction with neighboring populations in Southern China.
Prediction of Protein–Protein Interactions in Arabidopsis, Maize, and Rice by Combining Deep Neural Network With Discrete Hilbert Transform
Authors: Pan Jie , Li Li-Ping , You Zhu-Hong , Yu Chang-Qing , Ren Zhong-Hao , Guan Yong-Jian
Published: September 2021

Protein–protein interactions (PPIs) in plants play an essential role in the regulation of biological processes. However, traditional experimental methods are expensive, time-consuming, and need sophisticated technical equipment. These drawbacks motivated the development of novel computational approaches to predict PPIs in plants. In this article, a new deep learning framework, which combined the discrete Hilbert transform (DHT) with deep neural networks (DNN), was presented to predict PPIs in plants. To be more specific, plant protein sequences were first transformed as a position-specific scoring matrix (PSSM). Then, DHT was employed to capture features from the PSSM. To improve the prediction accuracy, we used the singular value decomposition algorithm to decrease noise and reduce the dimensions of the feature descriptors. Finally, these feature vectors were fed into DNN for training and predicting. When performing our method on three plant PPI datasets Arabidopsis thaliana, maize, and rice, we achieved good predictive performance with average area under receiver operating characteristic curve values of 0.8369, 0.9466, and 0.9440, respectively. To fully verify the predictive ability of our method, we compared it with different feature descriptors and machine learning classifiers. Moreover, to further demonstrate the generality of our approach, we also test it on the yeast and human PPI dataset. Experimental results anticipated that our method is an efficient and promising computational model for predicting potential plant–protein interacted pairs.
HIV-Associated Interactions Between Oral Microbiota and Mucosal Immune Cells: Knowledge Gaps and Future Directions
Authors: Coker Modupe O. , Cairo Cristiana , Garzino-Demo Alfredo
Published: September 2021

Even with sustained use of antiretroviral therapy (ART), HIV-infected individuals have an increased risk of systemic comorbid conditions and oral pathologies, including opportunistic infections, oral mucosal inflammation, and gingival and periodontal diseases. The immune-mediated mechanisms that drive this increased risk, in the context of sustained viral suppression, are unclear. HIV infection, even when controlled, alters microbial communities contributing to a chronic low-grade inflammatory state that underlies these non-HIV co-morbidities. The higher prevalence of dental caries, and mucosal and periodontal inflammation reported in HIV-infected individuals on ART is often associated with differentially abundant oral microbial communities, possibly leading to a heightened susceptibility to inflammation. This mini-review highlights current gaps in knowledge regarding the microbe-mediated oral mucosal immunity with HIV infection while discussing opportunities for future research investigations and implementation of novel approaches to elucidate these gaps. Interventions targeting both inflammation and microbial diversity are needed to mitigate oral inflammation-related comorbidities, particularly in HIV-infected individuals. More broadly, additional research is needed to bolster general models of microbiome-mediated chronic immune activation and aid the development of precise microbiota-targeted interventions to reverse or mitigate adverse outcomes.
Precision Engineering of an Anti-HLA-A2 Chimeric Antigen Receptor in Regulatory T Cells for Transplant Immune Tolerance
Authors: Muller Yannick D. , Ferreira Leonardo M. R. , Ronin Emilie , Ho Patrick , Nguyen Vinh , Faleo Gaetano , Zhou Yu , Lee Karim , Leung Kevin K. , Skartsis Nikolaos , Kaul Anupurna M. , Mulder Arend , Claas Frans H. J. , Wells James A. , Bluestone Jeffrey A. , Tang Qizhi
Published: September 2021

Infusion of regulatory T cells (Tregs) engineered with a chimeric antigen receptor (CAR) targeting donor-derived human leukocyte antigen (HLA) is a promising strategy to promote transplant tolerance. Here, we describe an anti-HLA-A2 CAR (A2-CAR) generated by grafting the complementarity-determining regions (CDRs) of a human monoclonal anti-HLA-A2 antibody into the framework regions of the Herceptin 4D5 single-chain variable fragment and fusing it with a CD28-ζ signaling domain. The CDR-grafted A2-CAR maintained the specificity of the original antibody. We then generated HLA-A2 mono-specific human CAR Tregs either by deleting the endogenous T-cell receptor (TCR) via CRISPR/Cas9 and introducing the A2-CAR using lentiviral transduction or by directly integrating the CAR construct into the TCR alpha constant locus using homology-directed repair. These A2-CAR+TCRdeficient human Tregs maintained both Treg phenotype and function in vitro. Moreover, they selectively accumulated in HLA-A2-expressing islets transplanted from either HLA-A2 transgenic mice or deceased human donors. A2-CAR+TCRdeficient Tregs did not impair the function of these HLA-A2+ islets, whereas similarly engineered A2-CAR+TCRdeficientCD4+ conventional T cells rejected the islets in less than 2 weeks. A2-CAR+TCRdeficient Tregs delayed graft-versus-host disease only in the presence of HLA-A2, expressed either by co-transferred peripheral blood mononuclear cells or by the recipient mice. Altogether, we demonstrate that genome-engineered mono-antigen-specific A2-CAR Tregs localize to HLA-A2-expressing grafts and exhibit antigen-dependent in vivo suppression, independent of TCR expression. These approaches may be applied towards developing precision Treg cell therapies for transplant tolerance.
Neuroimmune and Mu-Opioid Receptor Alterations in the Mesocorticolimbic System in a Sex-Dependent Inflammatory Pain-Induced Alcohol Relapse-Like Rat Model
Authors: Cuitavi Javier , Lorente Jesús David , Campos-Jurado Yolanda , Polache Ana , Hipólito Lucía
Published: September 2021

Evidence concerning the role of alcohol-induced neuroinflammation in alcohol intake and relapse has increased in the last few years. It is also proven that mu-opioid receptors (MORs) mediate the reinforcing properties of alcohol and, interestingly, previous research suggests that neuroinflammation and MORs could be related. Our objective is to study neuroinflammatory states and microglial activation, together with adaptations on MOR expression in the mesocorticolimbic system (MCLS) during the abstinence and relapse phases. To do so, we have used a sex-dependent rat model of complete Freund’s adjuvant (CFA)-induced alcohol deprivation effect (ADE). Firstly, our results confirm that only CFA-treated female rats, the only experimental group that showed relapse-like behavior, exhibited specific alterations in the expression of phosphorylated NFκB, iNOS, and COX2 in the PFC and VTA. More interestingly, the analysis of the IBA1 expression revealed a decrease of the microglial activation in PFC during abstinence and an increase of its expression in the relapse phase, together with an augmentation of this activation in the NAc in both phases that only occur in female CFA-treated rats. Additionally, the expression of IL1β also evidenced these dynamic changes through these two phases following similar expression patterns in both areas. Furthermore, the expression of the cytokine IL10 showed a different profile than that of IL1β, indicating anti-inflammatory processes occurring only during abstinence in the PFC of CFA-female rats but neither during the reintroduction phase in PFC nor in the NAc. These data indicate a downregulation of microglial activation and pro-inflammatory processes during abstinence in the PFC, whereas an upregulation can be observed in the NAc during abstinence that is maintained during the reintroduction phase only in CFA-female rats. Secondly, our data reveal a correlation between the alterations observed in IL1β, IBA1 levels, and MOR levels in the PFC and NAc of CFA-treated female rats. Although premature, our data suggest that neuroinflammatory processes, together with neural adaptations involving MOR, might play an important role in alcohol relapse in female rats, so further investigations are warranted.
Interleukin-17A Drives IL-19 and IL-24 Expression in Skin Stromal Cells Regulating Keratinocyte Proliferation
Authors: Xu Xiaofei , Prens Errol , Florencia Edwin , Leenen Pieter , Boon Luis , Asmawidjaja Patrick , Mus Anne-Marie , Lubberts Erik
Published: September 2021

IL-17A has been shown to be up-regulated in psoriasis lesions and is central to psoriasis pathogenesis. IL-19, along with other IL-20 subfamily cytokines such as IL-20 and IL-24, is induced by IL-17A and contributes especially to epidermal hyperplasia in psoriasis. However, the regulation, cellular sources of IL-19 and whether targeting of IL-17A by biologics influence IL-19 expression is not completely understood. To investigate the regulation of IL-19 by IL-17A in psoriasis, the imiquimod-induced psoriasis mouse (IMQ) model was used. Enhanced expression of IL-17A in the IMQ model was achieved by anti-IL-10 antibody treatment. Assessments of skin inflammation macroscopically, by histology and flow cytometry, all confirmed increased psoriatic symptoms. Interestingly, depletion of IL-10 markedly upregulated IL-23/IL-17 pathway related cytokines followed by a significant increase in IL-19 and IL-24. The up-regulation of IL-19 and IL-24, but not IL-17A, coincided with increased keratinocyte proliferation. To investigate the cellular source and effects of biologics on IL-19, human skin fibroblasts from healthy controls and psoriasis patients were cultured alone or co-cultured with activated memory CD4+ T cells. Besides IL-1β, IL-17A induced direct expression of IL-19 and IL-24 in skin fibroblasts and keratinocytes. Importantly, intrinsic higher expression of IL-19 in psoriatic skin fibroblasts was observed in comparison to healthy skin fibroblasts. Neutralization of IL-17A in the human skin fibroblast-T cell co-culture system significantly suppressed IL-19 and IL-24 expression. Together, our data show that IL-17A-induced IL-19 and IL-24 expression in skin stromal cells contribute to keratinocyte proliferation.
TRPing on Cell Swelling - TRPV4 Senses It
Authors: Toft-Bertelsen Trine L. , MacAulay Nanna
Published: September 2021

The transient receptor potential vanilloid 4 channel (TRPV4) is a non-selective cation channel that is widely expressed and activated by a range of stimuli. Amongst these stimuli, changes in cell volume feature as a prominent regulator of TRPV4 activity with cell swelling leading to channel activation. In experimental settings based on abrupt introduction of large osmotic gradients, TRPV4 activation requires co-expression of an aquaporin (AQP) to facilitate such cell swelling. However, TRPV4 readily responds to cell volume increase irrespectively of the molecular mechanism underlying the cell swelling and can, as such, be considered a sensor of increased cell volume. In this review, we will discuss the proposed events underlying the molecular coupling from cell swelling to channel activation and present the evidence of directversusindirect swelling-activation of TRPV4. With this summary of the current knowledge of TRPV4 and its ability to sense cell volume changes, we hope to stimulate further experimental efforts in this area of research to clarify TRPV4’s role in physiology and pathophysiology.
Bacterial Outer Membrane Vesicles as Antibiotic Delivery Vehicles
Authors: Collins Shannon M. , Brown Angela C.
Published: September 2021

Bacterial outer membrane vesicles (OMVs) are nanometer-scale, spherical vehicles released by Gram-negative bacteria into their surroundings throughout growth. These OMVs have been demonstrated to play key roles in pathogenesis by delivering certain biomolecules to host cells, including toxins and other virulence factors. In addition, this biomolecular delivery function enables OMVs to facilitate intra-bacterial communication processes, such as quorum sensing and horizontal gene transfer. The unique ability of OMVs to deliver large biomolecules across the complex Gram-negative cell envelope has inspired the use of OMVs as antibiotic delivery vehicles to overcome transport limitations. In this review, we describe the advantages, applications, and biotechnological challenges of using OMVs as antibiotic delivery vehicles, studying both natural and engineered antibiotic applications of OMVs. We argue that OMVs hold great promise as antibiotic delivery vehicles, an urgently needed application to combat the growing threat of antibiotic resistance.
Impaired Antibody-Dependent Cellular Cytotoxicity in a Spanish Cohort of Patients With COVID-19 Admitted to the ICU
Authors: Vigón Lorena , García-Pérez Javier , Rodríguez-Mora Sara , Torres Montserrat , Mateos Elena , Castillo de la Osa María , Cervero Miguel , Malo De Molina Rosa , Navarro Cristina , Murciano-Antón María Aránzazu , García-Gutiérrez Valentín , Planelles Vicente , Alcamí José , Pérez-Olmeda Mayte , Coiras Mayte , López-Huertas María Rosa
Published: September 2021

SARS-CoV-2 infection causes COVID-19, ranging from mild to critical disease in symptomatic subjects. It is essential to better understand the immunologic responses occurring in patients with the most severe outcomes. In this study, parameters related to the humoral immune response elicited against SARS-CoV-2 were analysed in 61 patients with different presentations of COVID-19 who were recruited in Hospitals and Primary Healthcare Centres in Madrid, Spain, during the first pandemic peak between April and June 2020. Subjects were allocated as mild patients without hospitalization, severe patients hospitalized or critical patients requiring ICU assistance. Critical patients showed significantly enhanced levels of B cells with memory and plasmablast phenotypes, as well as higher levels of antibodies against SARS-CoV-2 with neutralization ability, which were particularly increased in male gender. Despite all this, antibody-dependent cell-mediated cytotoxicity was defective in these individuals. Besides, patients with critical COVID-19 also showed increased IgG levels against herpesvirus such as CMV, EBV, HSV-1 and VZV, as well as detectable CMV and EBV viremia in plasma. Altogether, these results suggest an enhanced but ineffectual immune response in patients with critical COVID-19 that allowed latent herpesvirus reactivation. These findings should be considered during the clinical management of these patients due to the potential contribution to the most severe disease during SARS-CoV-2 infection.
LOX-1-Expressing Immature Neutrophils Identify Critically-Ill COVID-19 Patients at Risk of Thrombotic Complications
Authors: Combadière Behazine , Adam Lucille , Guillou Noëlline , Quentric Paul , Rosenbaum Pierre , Dorgham Karim , Bonduelle Olivia , Parizot Christophe , Sauce Delphine , Mayaux Julien , Luyt Charles-Edouard , Boissonnas Alexandre , Amoura Zahir , Pourcher Valérie , Miyara Makoto , Gorochov Guy , Guihot Amélie , Combadière Christophe
Published: September 2021

Background

Lymphopenia and the neutrophil/lymphocyte ratio may have prognostic value in COVID-19 severity.

Objective

We investigated neutrophil subsets and functions in blood and bronchoalveolar lavage (BAL) of COVID-19 patients on the basis of patients’ clinical characteristics.

Methods

We used a multiparametric cytometry profiling based to mature and immature neutrophil markers in 146 critical or severe COVID-19 patients.

Results

The Discovery study (38 patients, first pandemic wave) showed that 80% of Intensive Care Unit (ICU) patients develop strong myelemia with CD10−CD64+ immature neutrophils (ImNs). Cellular profiling revealed three distinct neutrophil subsets expressing either the lectin‐like oxidized low‐density lipoprotein receptor‐1 (LOX‐1), the interleukin-3 receptor alpha (CD123), or programmed death-ligand 1 (PD-L1) overrepresented in ICU patients compared to non-ICU patients. The proportion of LOX-1- or CD123-expressing ImNs is positively correlated with clinical severity, cytokine storm (IL-1β, IL-6, IL-8, TNFα), acute respiratory distress syndrome (ARDS), and thrombosis. BALs of patients with ARDS were highly enriched in LOX-1-expressing ImN subsets and in antimicrobial neutrophil factors. A validation study (118 patients, second pandemic wave) confirmed and strengthened the association of the proportion of ImN subsets with disease severity, invasive ventilation, and death. Only high proportions of LOX-1-expressing ImNs remained strongly associated with a high risk of severe thrombosis independently of the plasma antimicrobial neutrophil factors, suggesting an independent association of ImN markers with their functions.

Conclusion

LOX-1-expressing ImNs may help identifying COVID-19 patients at high risk of severity and thrombosis complications.
Coxiella burnetii Whole Cell Vaccine Produces a Th1 Delayed-Type Hypersensitivity Response in a Novel Sensitized Mouse Model
Authors: Fratzke Alycia P. , Gregory Anthony E. , van Schaik Erin J. , Samuel James E.
Published: September 2021

Q-VAX®, a whole cell, formalin-inactivated vaccine, is the only vaccine licensed for human use to protect against Coxiella burnetii, the cause of Q fever. Although this vaccine provides long-term protection, local and systemic reactogenic responses are common in previously sensitized individuals which prevents its use outside of Australia. Despite the importance of preventing these adverse reactions to develop widely accepted, novel vaccines against C. burnetii, little is understood about the underlying cellular mechanisms. This is mostly attributed to the use of a guinea pig reactogenicity model where complex cellular analysis is limited. To address this, we compared three different mouse strains develop a model of C. burnetii whole cell vaccine reactogenic responses. SKH1 and C57Bl/6, but not BALBc mice, develop local granulomatous reactions after either infection- or vaccine-induced sensitization. We evaluated local and systemic responses by measuring T cell populations from the vaccination site and spleen during elicitation using flow cytometry. Local reaction sites showed influx of IFNγ+ and IL17a+ CD4 T cells in sensitized mice compared with controls and a reduction in IL4+ CD4 T cells. Additionally, sensitized mice showed a systemic response to elicitation by an increase in IFNγ+ and IL17a+ CD4 T cells in the spleen. These results indicate that local and systemic C. burnetii reactogenic responses are consistent with a Th1 delayed-type hypersensitivity. Our experiments provide insights into the pathophysiology of C. burnetii whole cell vaccine reactogenicity and demonstrate that C57Bl/6 and SKH1 mice can provide a valuable model for evaluating the reactogenicity of novel C. burnetii vaccine candidates.
Capture, Culture and Release of Postlarvae Fishes: Proof-of-Concept as a Tool Approach to Support Reef Management
Authors: Cortés-Useche Camilo , Reyes-Gamboa Williams , Cabrera-Pérez José Luís , Calle-Triviño Johanna , Cerón-Flores Ana , Raigoza-Figueras Rodolfo , Yathiraj Roshni , Arias-González Jesús Ernesto
Published: September 2021

The changing world presents negative impacts on marine ecosystems and has led to the development of diversified tools to support reef restoration. Harnessing restoration to achieve success needs innovative techniques that also address the restoration of reef fish assemblages, contributing to the conservation of biodiversity and ecosystem functions and also tackle the cost-effectiveness through impact-driven solutions. Here, we propose a proof-of-concept for enhancing fish populations on reefs using: (1) postlarvae capture, (2) aquarium culture, and (3) release to reef sites. We conducted field studies in the Mexican Caribbean to analyze for the first time, the possibility of using the capture and aquarium culture of postlarvae fish species and release of juveniles as a tool for the potential recovery of reef biodiversity resilience. We tested the potential of postlarvae capture using two distinct night light traps (BOX and collect by artificial reef ecofriendly traps, C.A.R.E.) in three sampling sites with different distances from shoreline and depth. We collected 748 postlarvae reef fishes from eight orders, 20 families, and 40 species.Acanthuridae, Pomacentridae, Monacanthidae, andTetraodontidaecomprised the highest species number of postlarvae families. We also set up a pilot release experiment withStegastes partitususing two trials (32 and 1 day after capture) and propose analysis to determine appropriate reef sites to release the cultured juveniles and to aid ecological planning. We present the results of the pilot release experiment withS. partitus, showing that there is a positive effect in survivorship during the capture (80%) and release (76–100%) procedures into suitable habitat and good chance that more studies will bring novelty to the field. Although trials carried out with more species relevant to restoration will be needed. The use of these techniques can be a great opportunity to improve the research of restoration efforts in the Caribbean region with fish-depleted coral reefs with vulnerable food webs, especially at local scales and supporting other management strategies.
Multi-Variate Analyses of Coral Mortality From the 2014–2015 Stony Coral Tissue Loss Disease Outbreak Off Miami-Dade County, Florida
Authors: Spadafore Rachele , Fura Ryan , Precht William F. , Vollmer Steven V.
Published: September 2021

Environmental compliance monitoring associated with the Port Miami dredging project (2013–2015), designed to assess the impact of project-generated sediments on the local coral community, fortuitously captured a thermal bleaching event and the first reports of an emergent, highly contagious, white-plague-like coral disease outbreak in the fall of 2014. The disease, now termed stony coral tissue loss disease (SCTLD), has decimated reefs throughout Florida and is now spreading across the Caribbean. The high prevalence of disease, the number of affected species, and the high mortality of corals affected suggests SCTLD may be the most lethal coral disease ever recorded. Previous analyses of the dredge monitoring data have reached mixed conclusions about the relative impact of dredging on coral mortality and has often parsed out disease susceptible individuals to isolate the impacts of dredging only. We use multi-variate analyses, including time-based survival analyses, to examine the timing and impacts of dredging, coral bleaching, and disease on local coral mortality. By examining the status of corals monthly from the October 2013 to July 2015 observational period, we found that coral mortality was not significantly affected by a coral’s proximity to the dredge site or sediment burial. Instead, coral mortality was most strongly impacted by disease and the emergence of SCTLD during the monitoring period. During the 2-year monitoring period, 26.3% of the monitored corals died, but the only conditions significantly affected by the dredge were partial burial and partial mortality. The strongest link to mortality was due to disease, which impacted coral species differently depending on their susceptibility to SCTLD. The focus on disturbances associated with dredging created a circumstance where the greater impacts of this emergent disease were downplayed, leading to a false narrative of the resulting mortality on the local coral communities. The results of this study reveal that while local events such as a dredging project do have quantifiable effects and can be harmful to corals, regional and global threats that result in mass coral mortality such as thermal stress and disease represent an existential threat to coral reefs and must be urgently addressed.
Influence of Salinity and Temperature Gradients on the Variability of the North Brazil Undercurrent
Authors: Liu Hao , Wei Zexun , Richter Ingo , Nie Xunwei , Li Chuanshun
Published: September 2021

The North Brazil Undercurrent (NBUC) is a narrow (<1°) northward western boundary current in the tropical South Atlantic Ocean. It carries a large volume of water (>16 Sv) and plays an important role in the Atlantic Meridional Overturning Circulation and the South Atlantic Subtropical Cell. Strong salinity and temperature fronts occur over the NBUC region. The role of temperature and salinity gradients on the genesis of NBUC variability has never been explored. This study uses three high-resolution (≤0.1°) and one low-resolution (=0.25°) model outputs to explore the linear trend of NBUC transport and its variability on annual and interannual time scales. We find that the linear trend and interannual variability of the geostrophic NBUC transport show large discrepancies among the datasets. Thus, the linear trend and variability of the geostrophic NBUC are associated with model configuration. We also find that the relative contributions of salinity and temperature gradients to the geostrophic shear of the NBUC are not model dependent. Salinity-based and temperature-based geostrophic NBUC transports tend to be opposite-signed on all time scales. Despite the limited salinity and temperature profiles, the model results are consistent with the in-situ observations on the annual cycle and interannual time scales. This study shows the relationship of salinity-based and temperature-based geostrophic NBUC variations in the annual and interannual variability and trend among different models and highlights the equal important roles of temperature and salinity in driving the variability of NBUC transport.
Modeling of Rolling Force for Thick Plate of Multicomponent Alloys and Its Application on Thickness Prediction
Authors: Zhang Shun Hu , Xin Jia Lin , Che Li Zhi
Published: September 2021

During the rolling process of thick plate, the nonlinear specific plastic power that derived from the non-linear Mises yield criterion is difficult to be integrated, which has restricted the establishment of a rolling force model. To solve this problem, a new yield criterion is firstly established, and then used to derive a linear specific plastic power. Meanwhile, a kinematically admissible velocity field whose horizontal velocity component obeys the Logistic function is proposed to describe the metal flow of the deformed plate. On these bases, the rolling energy items including the internal deformation power of the deformed body, friction power on the contact surface, and shear power on the entry and exit sections are integrated successively, and the rolling force model is established. It is proved that the model can predict the rolling force well when compared with the actual data of multicomponent alloys. Besides, the formula for predicting the outlet thickness is ultimately given upon this derived model, and a good agreement is also found between the predicted values and the actual ones, since the absolute errors between them are within 0.50 mm.
Primary Hyperoxaluria Type 1 Disease Manifestations and Healthcare Utilization: A Multi-Country, Online, Chart Review Study
Authors: Wang Xiangling , Danese David , Brown Thomas , Baldwin Jessica , Sajeev Gautam , Cook Erin E. , Wang Yao , Xu Chunyi , Yang Hongbo , Moritz Michael L.
Published: September 2021

Background: Primary hyperoxaluria type 1 (PH1) is a rare genetic disease that can result in irreversible damage to the kidneys and, eventually, extrarenal organs. While kidney failure is a known consequence of PH1, few studies to date have characterized clinical consequences of PH1 prior to kidney failure, and data on healthcare resource use outcomes across different stages of disease severity in PH1 are also limited. To help fill this knowledge gap, this study characterized the clinical and healthcare resource use (HRU) burden in patients with PH1 with varying stages of kidney disease.

Methods: Nephrologists in the United States, Canada, United Kingdom, France, Germany, and Italy abstracted chart data from patients with PH1 under their care via an online questionnaire. Eligible patients had confirmed PH1 and ≥2 office visits from 2016 to 2019.

Results: A total of 120 patients were analyzed (median age at diagnosis, 17.4 years old, median age at index 19.5 years old, median eGFR at index 45 ml/min/1.73 m2; median follow-up 1.7 years). During follow-up, the most common PH1 manifestations were kidney stones and urinary tract infections (UTIs, both 56.8%), and the most common symptoms were fatigue/weakness (71.7%) and pain (64.6%). With regard to HRU during follow-up, 37.4% required lithotripsy, 31.3% required ureteroscopy, and 9.6% required nephrolithotomy. PH1-related hospitalizations and emergency/urgent care visits were noted for 84.0 and 81.6% of patients, respectively.

Conclusions: The current study demonstrated that patients with PH1 across various stages of kidney disease exhibited a substantial clinical burden, including kidney stones, UTIs, fatigue/weakness, and pain, and required frequent HRU, including kidney stone procedures, hospitalizations, and emergency visits. These findings highlight the significant morbidity and HRU burden in patients with PH1.
Viruses Without Borders: Global Analysis of the Population Structure, Haplotype Distribution, and Evolutionary Pattern of Iris Yellow Spot Orthotospovirus (Family Tospoviridae, Genus Orthotospovirus)
Authors: Tabassum Afsha , Ramesh S. V. , Zhai Ying , Iftikhar Romana , Olaya Cristian , Pappu Hanu R.
Published: September 2021

Iris yellow spot, caused by Iris yellow spot orthotospovirus (IYSV) (Genus: Orthotospovirus, Family: Tospoviridae), is an important disease of Allium spp. The complete N gene sequences of 142 IYSV isolates of curated sequence data from GenBank were used to determine the genetic diversity and evolutionary pattern. In silico restriction fragment length polymorphism (RFLP) analysis, codon-based maximum likelihood studies, genetic differentiation and gene flow within the populations of IYSV genotypes were investigated. Bayesian phylogenetic analysis was carried out to estimate the evolutionary rate. In silico RFLP analysis of N gene sequences categorized IYSV isolates into two major genotypes viz., IYSV Netherlands (IYSVNL; 55.63%), IYSV Brazil (IYSVBR; 38.73%) and the rest fell in neither group [IYSV other (IYSVother; 5.63%)]. Phylogenetic tree largely corroborated the results of RFLP analysis and the IYSV genotypes clustered into IYSVNL and IYSVBR genotypes. Genetic diversity test revealed IYSVother to be more diverse than IYSVNL and IYSVBR. IYSVNL and IYSVBR genotypes are under purifying selection and population expansion, whereas IYSVother showed decreasing population size and hence appear to be under balancing selection. IYSVBR is least differentiated from IYSVother compared to IYSVNL genotype based on nucleotide diversity. Three putative recombinant events were found in the N gene of IYSV isolates based on RDP analysis, however, RAT substantiated two among them. The marginal likelihood mean substitution rate was 5.08 × 10–5 subs/site/year and 95% highest posterior density (HPD) substitution rate between 5.11 × 10–5 and 5.06 × 10–5. Findings suggest that IYSV continues to evolve using population expansion strategies. The substitution rates identified are similar to other plant RNA viruses.
Spread of Mink SARS-CoV-2 Variants in Humans: A Model of Sarbecovirus Interspecies Evolution
Authors: Devaux Christian A. , Pinault Lucile , Delerce Jérémy , Raoult Didier , Levasseur Anthony , Frutos Roger
Published: September 2021

The rapid spread of SARS-CoV-2 variants has quickly spanned doubts and the fear about their ability escape vaccine protection. Some of these variants initially identified in caged were also found in humans. The claim that these variants exhibited lower susceptibility to antibody neutralization led to the slaughter of 17 million minks in Denmark. SARS-CoV-2 prevalence tests led to the discovery of infected farmed minks worldwide. In this study, we revisit the issue of the circulation of SARS-CoV-2 variants in minks as a model of sarbecovirus interspecies evolution by: (1) comparing human and mink angiotensin I converting enzyme 2 (ACE2) and neuropilin 1 (NRP-1) receptors; (2) comparing SARS-CoV-2 sequences from humans and minks; (3) analyzing the impact of mutations on the 3D structure of the spike protein; and (4) predicting linear epitope targets for immune response. Mink-selected SARS-CoV-2 variants carrying the Y453F/D614G mutations display an increased affinity for human ACE2 and can escape neutralization by one monoclonal antibody. However, they are unlikely to lose most of the major epitopes predicted to be targets for neutralizing antibodies. We discuss the consequences of these results for the rational use of SARS-CoV-2 vaccines.
New Estimation of Antibiotic Resistance Genes in Sediment Along the Haihe River and Bohai Bay in China: A Comparison Between Single and Successive DNA Extraction Methods
Authors: Wu Chao , Zhang Guicheng , Xu Wenzhe , Jian Shan , Peng Liyin , Jia Dai , Sun Jun
Published: September 2021

Sediment is thought to be a vital reservoir for antibiotic resistance genes (ARGs). Often, studies describing and comparing ARGs and their potential hosts in sediment are based on single DNA extractions. To date, however, no study has been conducted to assess the influence of DNA extraction efficiency on ARGs in sediment. To determine whether the abundance of ARGs is underestimated, we performed five successive extraction cycles with a widely used commercial kit in 10 sediment samples collected from the Haihe River and Bohai Bay. Our results showed that accumulated DNA yields after five extractions were 1.8–3.1 times higher than that by single DNA extractions. High-throughput sequencing showed that insufficient DNA extraction could generate PCR bias and skew community structure characterization in sediment. The relative abundances of some pathogenic bacteria, such as Enterobacteriales, Lactobacillales, and Streptomycetales, were significantly different between single and successive DNA extraction samples. In addition, real-time fluorescent quantitative PCR (qPCR) showed that ARGs, intI1, and 16S rRNA gene abundance strongly increased with increasing extraction cycles. Among the measured ARGs, sulfonamide resistance genes and multidrug resistance genes were dominant subtypes in the study region. Nevertheless, different subtypes of ARGs did not respond equally to the additional extraction cycles; some continued to have linear growth trends, and some tended to level off. Additionally, more correlations between ARGs and bacterial communities were observed in the successive DNA extraction samples than in the single DNA extraction samples. It is suggested that 3–4 additional extraction cycles are required in future studies when extracting DNA from sediment samples. Taken together, our results highlight that performing successive DNA extractions on sediment samples optimizes the extractable DNA yield and can lead to a better picture of the abundance of ARGs and their potential hosts in sediments.
Putative Riemerella anatipestifer Outer Membrane Protein H Affects Virulence
Authors: Gao Qun , Lu Shuwei , Wang Mingshu , Jia Renyong , Chen Shun , Zhu Dekang , Liu Mafeng , Zhao Xinxin , Yang Qiao , Wu Ying , Zhang Shaqiu , Huang Juan , Mao Sai , Ou Xumin , Sun Di , Tian Bin , Cheng Anchun
Published: September 2021

Riemerella anatipestifer causes serious contagious disease in ducks, geese, and other fowl. However, as a harmful pathogen causing significant economic losses in the poultry industry, R. anatipestifer is still poorly understood for its pathogenesis mechanisms. In a previous study, we developed an indirect ELISA method for detecting R. anatipestifer infection using B739_0832 protein, a putative outer membrane protein H (OmpH) that is conserved among different serotypes of R. anatipestifer. Although OmpH in some pathogenic bacteria, such as Pasteurella, has been reported as a virulence factor, it is still not clear whether B739_0832 protein contributes to the virulence of R. anatipestifer. In this study, we confirmed that B739_0832 protein in R. anatipestifer localizes to the outer membrane. We constructed a B739_0832 deletion mutant strain (ΔB739_0832) and assayed various effects from the deletion of B739_0832. ΔB739_0832 strain had a similar growth rate to wild-type R. anatipestifer CH-1. However, the survival rate of ducklings in 10 days after infection from ΔB739_0832 strain was 50%, whereas no ducklings survived from wild-type R. anatipestifer infection. Furthermore, the median lethal dose (LD50) of the ΔB739_0832 strain was approximately 150 times higher than that of the wild-type strain. Pathology examinations on infected ducklings found that, at 36 h after infection, bacterial loads in blood, liver, and brain tissues from ΔB739_0832-infected ducklings were considerably lower than those from wild-type infected ducklings. These results demonstrate that the B739_0832 protein contributes to the virulence of R. anatipestifer CH-1.
A Valuable Product of Microbial Cell Factories: Microbial Lipase
Authors: Yao Wentao , Liu Kaiquan , Liu Hongling , Jiang Yi , Wang Ruiming , Wang Wei , Wang Tengfei
Published: September 2021

As a powerful factory, microbial cells produce a variety of enzymes, such as lipase. Lipase has a wide range of actions and participates in multiple reactions, and they can catalyze the hydrolysis of triacylglycerol into its component free fatty acids and glycerol backbone. Lipase exists widely in nature, most prominently in plants, animals and microorganisms, among which microorganisms are the most important source of lipase. Microbial lipases have been adapted for numerous industrial applications due to their substrate specificity, heterogeneous patterns of expression and versatility (i.e., capacity to catalyze reactions at the extremes of pH and temperature as well as in the presence of metal ions and organic solvents). Now they have been introduced into applications involving the production and processing of food, pharmaceutics, paper making, detergents, biodiesel fuels, and so on. In this mini-review, we will focus on the most up-to-date research on microbial lipases and their commercial and industrial applications. We will also discuss and predict future applications of these important technologies.
Nuclear Magnetic Resonance Spectroscopy in Clinical Metabolomics and Personalized Medicine: Current Challenges and Perspectives
Authors: Letertre Marine P. M. , Giraudeau Patrick , de Tullio Pascal
Published: September 2021

Personalized medicine is probably the most promising area being developed in modern medicine. This approach attempts to optimize the therapies and the patient care based on the individual patient characteristics. Its success highly depends on the way the characterization of the disease and its evolution, the patient’s classification, its follow-up and the treatment could be optimized. Thus, personalized medicine must combine innovative tools to measure, integrate and model data. Towards this goal, clinical metabolomics appears as ideally suited to obtain relevant information. Indeed, the metabolomics signature brings crucial insight to stratify patients according to their responses to a pathology and/or a treatment, to provide prognostic and diagnostic biomarkers, and to improve therapeutic outcomes. However, the translation of metabolomics from laboratory studies to clinical practice remains a subsequent challenge. Nuclear magnetic resonance spectroscopy (NMR) and mass spectrometry (MS) are the two key platforms for the measurement of the metabolome. NMR has several advantages and features that are essential in clinical metabolomics. Indeed, NMR spectroscopy is inherently very robust, reproducible, unbiased, quantitative, informative at the structural molecular level, requires little sample preparation and reduced data processing. NMR is also well adapted to the measurement of large cohorts, to multi-sites and to longitudinal studies. This review focus on the potential of NMR in the context of clinical metabolomics and personalized medicine. Starting with the current status of NMR-based metabolomics at the clinical level and highlighting its strengths, weaknesses and challenges, this article also explores how, far from the initial “opposition” or “competition”, NMR and MS have been integrated and have demonstrated a great complementarity, in terms of sample classification and biomarker identification. Finally, a perspective discussion provides insight into the current methodological developments that could significantly raise NMR as a more resolutive, sensitive and accessible tool for clinical applications and point-of-care diagnosis. Thanks to these advances, NMR has a strong potential to join the other analytical tools currently used in clinical settings.
Significance of Parkinson Family Genes in the Prognosis and Treatment Outcome Prediction for Lung Adenocarcinoma
Authors: Li Yanqi , Lu Xiao , Zhang Jiao , Liu Quanxing , Zhou Dong , Deng Xufeng , Qiu Yuan , Chen Qian , Li Manyuan , Yang Guixue , Zheng Hong , Dai Jigang
Published: September 2021

Epidemiological investigations have shown that patients with Parkinson’s disease (PD) have a lower probability of developing lung cancer. Subsequent research revealed that PD and lung cancer share specific genetic alterations. Therefore, the utilisation of PD biomarkers and therapeutic targets may improve lung adenocarcinoma (LUAD) diagnosis and treatment. We aimed to identify a gene-based signature from 25 Parkinson family genes for LUAD prognosis and treatment choice. We analysed Parkinson family gene expression and protein levels in LUAD, utilising multiple databases. Least absolute shrinkage and selection operator (LASSO) regression was used to construct a prognostic model based on the TCGA-LUAD cohort. We validated the model in external GEO cohorts. Immune cell infiltration was compared between risk groups, and GEO data was used to explore the model’s predictive ability for LUAD treatment response. Nearly all Parkinson family genes exhibited significant differential expression between LUAD and normal tissues. LASSO regression confirmed that our seven Parkinson family gene-based signature had excellent prognostic performance for LUAD, as validated in three GEO cohorts. The high-risk group was clearly associated with low tumour immune cell infiltration, suggesting that immunotherapy may not be an optimal treatment choice. This is the first Parkinson family gene-based model for the prediction of LUAD prognosis and treatment outcome. The association of these genes with poor prognosis and low immune infiltration requires further investigation.
Semantic Recollection in Parkinson’s Disease: Functional Reconfiguration and MAPT Variants
Authors: Harrington Deborah L. , Shen Qian , Sadeghi Vida , Huang Mingxiong , Litvan Irene , Wei Xiangyu , Lee Roland R.
Published: September 2021

Decline in semantic cognition in early stages of Parkinson’s disease (PD) is a leading risk factor for future dementia, yet the underlying neural mechanisms are not understood. The present study addressed this gap by investigating the functional connectivity of regions involved in semantic recollection. We further examined whether microtubule-associated protein tau (MAPT) risk variants, which may accelerate cognitive decline, altered the strength of regional functional connections. Cognitively normal PD and healthy elder controls underwent fMRI while performing a fame-discrimination task, which activates the semantic network. Analyses focused on disturbances in fame-modulated functional connectivity in PD for regions that govern semantic recollection and interrelated processes. Group differences were found in multiple connectivity features, which were reduced into principal components that reflected the strength of fame-modulated regional couplings with other brain areas. Despite the absence of group differences in semantic cognition, two aberrant connectivity patterns were uncovered in PD. One pattern was related to a loss in frontal, parietal, and temporal connection topologies that governed semantic recollection in older controls. Another pattern was characterized by functional reconfiguration, wherein frontal, parietal, temporal and caudate couplings were strengthened with areas that were not recruited by controls. Correlations between principal component scores and cognitive measures suggested that reconfigured frontal coupling topologies in PD supported compensatory routes for accessing semantic content, whereas reconfigured parietal, temporal, and caudate connection topologies were detrimental or unrelated to cognition. Increased tau transcription diminished recruitment of compensatory frontal topologies but amplified recruitment of parietal topologies that were unfavorable for cognition. Collectively, the findings provide a new understanding of early vulnerabilities in the functional architecture of regional connectivity during semantic recollection in cognitively normal PD. The findings also have implications for tracking cognitive progression and selecting patients who stand to benefit from therapeutic interventions.