bluuebunny/crossref_metadata_2025 huggingface dataset:
Plasma Deposited Polyoxazoline Films Integration Into Spiral Microfluidics for the Targeted Capture of Size Selected Cells
Authors: Gheorghiu Alexandru A. , Muguet Ines , Chakiris James , Chan Kit Man , Priest Craig , Macgregor Melanie
Published: May 2021

Biomolecules readily and irreversibly bind to plasma deposited Polyoxazoline thin films in physiological conditions. The unique reactivity of these thin films toward antibodies is driving the development of immunosensing platforms for applications in cancer diagnostics. However, in order for these coatings to be used as advanced immunosensors, they need to be incorporated into microfluidic devices that are sealed via plasma bonding. In this work, the thickness, chemistry and reactivity of the polyoxazoline films were assessed following plasma activation. Films deposited from methyl and isopropenyl oxazoline precursors were integrated into spiral microfluidic devices and biofunctionalized with prostate cancer specific antibodies. Using microbeads as model particles, the design of the spiral microfluidic was optimised to enable the size-based isolation of cancer cells. The device was tested with a mixed cell suspension of healthy and malignant prostate cells. The results showed that, following size-specific separation in the spiral, selective capture was achieved on the immunofunctionalised PPOx surface. This proof of concept study demonstrates that plasma deposited polyoxazoline can be used for immunosensing in plasma bonded microfluidic devices.
Plasma Metabolomics of Acute Coronary Syndrome Patients Based on Untargeted Liquid Chromatography–Mass Spectrometry
Authors: Zhong Wei , Deng Qiaoting , Deng Xunwei , Zhong Zhixiong , Hou Jingyuan
Published: May 2021

Background: Acute coronary syndrome (ACS) is the main cause of death and morbidity worldwide. The present study aims to investigate the altered metabolites in plasma from patients with ACS and sought to identify metabolic biomarkers for ACS.

Methods: The plasma metabolomics profiles of 284 ACS patients and 130 controls were carried out based on an untargeted liquid chromatography coupled with tandem mass spectrometry (LC-MS) approach. Multivariate statistical methods, pathway enrichment analysis, and univariate receiver operating characteristic (ROC) curve analysis were performed.

Results: A total of 328 and 194 features were determined in positive and negative electrospray ionization mode in the LC-MS analysis, respectively. Twenty-eight metabolites were found to be differentially expressed, in ACS patients relative to controls (p < 0.05). Pathway analysis revealed that these metabolites are mainly involved in synthesis and degradation of ketone bodies, phenylalanine metabolism, and arginine and proline metabolism. Furthermore, a diagnostic model was constructed based on the metabolites identified and the areas under the curve (AUC) for 5-oxo-D-proline, creatinine, phosphatidylethanolamine lyso 16:0, and LPC (20:4) range from 0.764 to 0.844. The higher AUC value of 0.905 was obtained for the combined detection of phosphatidylethanolamine lyso 16:0 and LPC (20:4).

Conclusions: Differential metabolic profiles may be useful for the effective diagnosis of ACS and may provide additional insight into the molecular mechanisms underlying ACS.
Phenotypic Variability of a Pathogenic PKP2 Mutation in an Italian Family Affected by Arrhythmogenic Cardiomyopathy and Juvenile Sudden Death: Considerations From Molecular Autopsy to Sport Restriction
Authors: Leone Maria Pia , Palumbo Pietro , Saenen Johan , Mastroianno Sandra , Castellana Stefano , Amico Cesare , Mazza Tommaso , Potenza Domenico Rosario , Petracca Antonio , Castori Marco , Carella Massimo , Di Stolfo Giuseppe
Published: May 2021

Background: Arrhythmogenic cardiomyopathy (ACM) is a genetic disorder with an estimated prevalence between 1:2,000 and 1:5,000 and is characterized by the fibrofatty replacement of cardiomyocytes that predisposes to malignant arrhythmias, heart failure, and sudden cardiac death. The diagnosis is based on the 2010 Task Force Criteria including family history, electrocardiographic traits and arrhythmogenic pattern, specific gene mutations, and structural and/or histological abnormalities. Most ACMs display an autosomal dominant mode of inheritance often with incomplete penetrance and variable expressivity. Genetic screening of patients with ACM identifies pathogenic or likely pathogenic variants, prevalently in genes encoding the cardiac desmosome (PKP2, DSP, DSC2, DSG2, and JUP) or less frequently in non-desmosomal genes (CTNNA3, PLN, TMEM43, RYR2, SCN5A, CDH2, and DES).

Methods: In the present study, we performed molecular autopsy in a boy who died suddenly during physical exertion. In addition to post-mortem examination, a DNA sample was analyzed with next-generation sequencing (NGS).

Results: The genetic analysis revealed the presence of pathogenic heterozygous c.314del (p.Pro105Leufs*7) frameshift variant in the PKP2 gene. Cascade screening of family members allowed us to identify 12 mutation carriers and to intervene on subjects at risk, many of whom were athletes.

Conclusions: Molecular autopsy can establish cardiogenetic diagnosis and allow appropriate preventative measures in high-risk relatives.
Intra-Discrete Typing Unit TcV Genetic Variability of Trypanosoma cruzi in Chronic Chagas' Disease Bolivian Immigrant Patients in Barcelona, Spain
Authors: Oliveira Maykon Tavares de , Sulleiro Elena , Silva Maria Cláudia da , Silgado Aroa , de Lana Marta , da Silva João Santana , Molina Israel , Marin-Neto J. Antônio
Published: May 2021

Background:Trypanosoma cruzi has a high rate of biological and genetic variability, and its population structure is divided into seven distinct genetic groups (TcI-TcVI and Tcbat). Due to immigration, Chagas disease (ChD), caused by T. cruzi, has become a serious global health problem including in Europe. Therefore, the aim of this study was to evaluate the existence of genetic variability within discrete typing unit (DTU) TcV of T. cruzi in Bolivian patients with chronic ChD residing in Barcelona, Spain.

Methods: The DNA was extracted from the peripheral blood of 27 patients infected with T. cruzi DTU TcV and the fragments of the genetic material were amplificated through the low stringency single primer-polymerase chain reaction (LSSP-PCR). The data generated after amplification were submitted to bioinformatics analysis.

Results: Of the 27 patients evaluated in the study, 8/27 (29.6%) were male and 19/27 (70.4%) female, 17/27 (62.9%) were previously classified with the indeterminate clinical form of Chagas disease and 10/27 (37.1%) with Chagas cardiomyopathy. The LSSP-PCR detected 432 band fragments from 80 to 1,500 bp. The unweighted pair-group method analysis and principal coordinated analysis data demonstrated the existence of three distinct genetic groups with moderate-high rates of intraspecific genetic variability/diversity that had shared parasite's alleles in patients with the indeterminate and cardiomyopathy forms of ChD.

Conclusions: This study demonstrated the existence of a moderate to high rate of intra-DTU TcV variability in T. cruzi. Certain alleles of the parasite were associated with the absence of clinical manifestations in patients harboring the indeterminate form of ChD. These results support the need to search for increasingly specific targets in the genome of T. cruzi to be correlated with its main biological properties and clinical features in patients with chronic ChD.
A Taxonomy of Critical Dimensions at the Intersection of Learning Analytics and Educational Measurement
Authors: Scalise Kathleen , Wilson Mark , Gochyyev Perman
Published: May 2021

From a measurement perspective, a variety of analytic approaches are fast emerging in the data mining and exploratory analytics branches of the field of data sciences. In particular, for learning analytics, more theory is needed showing how the analytical approaches are related to one another and to their respective purposes when measurement is involved. For example, machine learning acting on process data can yield sets of specific patterns as results, but the critical question from a measurement perspective is: What do these results mean and how can they be used successfully in learning analytics? That is, if the goal is to make an inference regarding some underlying variable or set of elements about a student (or a teacher, school, or other agent or program within an educational setting), what claims are being made regarding the evidence and how can learning analytics contribute? In this paper we introduce techniques that move toward theory extensions that need to be developed at the intersection of learning analytics with measurement technology. For elucidating potential theoretical components from a measurement perspective, we draw on a type of case study research in the computer science domain, specifically employing “use cases.” A use case in computer science describes a scenario of use for software. Different use cases can describe different situations in which software may have utility. Like other multi-case designs, use cases can offer a means of exploring relationships and advancing potential theories by comparing similarities and differences among the cases. Here we explore three LA use case examples that differ purposively in critical ways. Examining their similarities and differences highlights potential dimensions that distinguish among emerging LA use cases at the intersection of data science and measurement technology.
Roles of Gut Microbial Metabolites in Diabetic Kidney Disease
Authors: Fang Qing , Liu Na , Zheng Binjie , Guo Fei , Zeng Xiangchang , Huang Xinyi , Ouyang Dongsheng
Published: May 2021

Diabetes is a highly prevalent metabolic disease that has emerged as a global challenge due to its increasing prevalence and lack of sustainable treatment. Diabetic kidney disease (DKD), which is one of the most frequent and severe microvascular complications of diabetes, is difficult to treat with contemporary glucose-lowering medications. The gut microbiota plays an important role in human health and disease, and its metabolites have both beneficial and harmful effects on vital physiological processes. In this review, we summarize the current findings regarding the role of gut microbial metabolites in the development and progression of DKD, which will help us better understand the possible mechanisms of DKD and explore potential therapeutic approaches for DKD.
Association of Genetic Variants in IGF2-Related Genes With Risk of Metabolic Syndrome in the Chinese Han Population
Authors: Gui Weiwei , Liang Julong , Lin Xihua , Shi Nanjing , Zhu Yiyi , Tan Bowen , Li Hong
Published: May 2021

Aims

To explore associations between polymorphisms of IGF2-related genes including H19, IGF2, IGF2BP2 and IGF2R and Metabolic syndrome (MetS) susceptibility in the Chinese Han population.

Methods

66 subjects with MetS and 257 control subjects were collected for inclusion in a case-control study. PCR-RFLP was used to investigate polymorphisms in the H19, IGF2, IGF2BP2 and IGF2R genes. Elisa was used to detect the serum IGF2 concentrations.

Results

Females carrying the GG and AG genotypes of rs680 (IGF2) exhibited a lower risk of MetS, compared with those harboring AA (adjusted OR = 0.388, p = 0.027), while GG and AG genotypes were associated with lower fasting glucose and HbA1c. In males, the Waist-to-Hip Ratio (WHR) and the level of TG were significantly higher in GG and AG genotypes than in the AA genotype of rs680 in IGF2. Levels of HDL-c were lower in men with GG and AG genotypes compared with those carrying the AA genotype. Serum IGF2 concentrations did not change among different genotypes. Finally, multifactor dimensionality reduction (MDR) analysis identified interactions between four polymorphisms: rs3741279 (H19), rs680 (IGF2), rs1470579 (IGF2BP2) and rs629849 (IGF2R).

Conclusions

Our study suggests that IGF2-related genes including H19, IGF2, IGF2BP2 and IGF2R genes may play pivotal roles in the development of MetS.
Effects of Fracturing Parameters on Fracture Unevenness During Large-Stage Multi-Cluster Fracturing in Horizontal Wells
Authors: Yong Rui , Zhou Fu-Jian , Li Ming-Hui , Song Yi , Zhou Xiao-Jin , Zhao Zhi-Heng , Li Ben , Qin Shi-Yong
Published: May 2021

Horizontal wellswith multi-cluster fracturing technology is an effective approach to exploit unconventional hydrocarbon reservoirs. The on-site diagnosis results indicate that multi-cluster fractures always tend to propagate unevenly due to stressinterference, therefore it is very essential to study the effect of fracturing parameters on fracture propagation unevenness. In this paper, the unconventional fracturing model (UFM, Unconventional Fracturing Model) is used to study the effect of multi-cluster fracturing parameters on fracture unevenness in a large stage. This model has been validated with the actual fracturing case on-site in the Longmaxi shale. The investigated parameters include completion parameters (cluster spacing, number of perforations per cluster), pumping parameters (fluid injection intensity and proppant injection intensity). Our simulation results show that firstly reducing fracture spacing will increase stress interference, andhydraulic fractures exhibit a “radial” pattern. Secondly, reducing the perforation number of a single cluster can promote the more uniform propagation of multi-cluster fractures. Thirdly, increasing the fluid injection intensity will increase the fracture length, but will also increase the fracture unevenness. Besides, the injection strength of the proppant has a little effect on the average fracture length and the unevenness of the fracture length. Finally, setting a reasonable cluster spacing and injection fluid strength can obtain a more uniform fracture propagation. Meanwhile reducing the number of perforations per cluster can also reach the goal of propagating evenly. This paper provides a certain reference for the optimization of multi-cluster fracturing parameters in large-stage and multi-cluster wells.
TRPM2, PDLIM5, BCL3, CD14, GBA Genes as Feasible Markers for Premature Coronary Heart Disease Risk
Authors: Prasongsukarn Kriengchai , Dechkhajorn Wilanee , Benjathummarak Surachet , Maneerat Yaowapa
Published: May 2021

Background: Beyond non-genetic risk factors, familial hypercholesterolemia (FH) plays a major role in the development of CHD. FH is a genetic disorder characterized by heritable and severely elevated levels of low-density lipoprotein (LDL) cholesterol, which can lead to premature cardiovascular disease, particularly familial coronary heart disease (FH-CHD).

Method: To explore genes indicating a risk of familial (premature) coronary heart disease (FH-CHD) development in FH, 30 Thai male volunteers were enrolled: 7 healthy controls (N), 6 patients with hypercholesterolemia (H), 4 with FH, 10 with CHD, and 3 with FH-CHD. Transcriptome data were investigated using next-generation sequencing analysis in whole blood (n = 3). Genes that were significantly expressed in both FH and FH-CHD, but not in N, H, and CHD groups, were selected and functionally analyzed.

Results: The findings revealed that 55 intersecting genes were differentially expressed between FH and FH-CHD groups. Ten of the 55 genes (MAPK14, TRPM2, STARD8, PDLIM5, BCL3, BLOC1S5, GBA, RBMS1, CD14, and CD36 were selected for validation. These 10 genes play potential roles in chronic inflammation and are involved in pathways related to pathogenesis of CHD. Using quantitative real-time PCR, we evaluated the mRNA expression of the selected genes in all 30 volunteers. TRPM2, PDLIM5, BCL3 were significantly upregulated and GBA was significantly downregulated in both FH and FH-CHD compared with the N, H, and CHD groups.

Conclusion: our preliminary investigation reveals that the TRPM2, PDLIM5, BCL3, and GBA genes may have potential for further development as predictive markers for FH-CHD.
Characterizing Genetic Regulatory Elements in Ovine Tissues
Authors: Davenport Kimberly M. , Massa Alisha T. , Bhattarai Suraj , McKay Stephanie D. , Mousel Michelle R. , Herndon Maria K. , White Stephen N. , Cockett Noelle E. , Smith Timothy P. L. , Murdoch Brenda M. ,   on behalf of The Ovine FAANG Project Consortium
Published: May 2021

The Ovine Functional Annotation of Animal Genomes (FAANG) project, part of the broader livestock species FAANG initiative, aims to identify and characterize gene regulatory elements in domestic sheep. Regulatory element annotation is essential for identifying genetic variants that affect health and production traits in this important agricultural species, as greater than 90% of variants underlying genetic effects are estimated to lie outside of transcribed regions. Histone modifications that distinguish active or repressed chromatin states, CTCF binding, and DNA methylation were used to characterize regulatory elements in liver, spleen, and cerebellum tissues from four yearling sheep. Chromatin immunoprecipitation with sequencing (ChIP-seq) was performed for H3K4me3, H3K27ac, H3K4me1, H3K27me3, and CTCF. Nine chromatin states including active promoters, active enhancers, poised enhancers, repressed enhancers, and insulators were characterized in each tissue using ChromHMM. Whole-genome bisulfite sequencing (WGBS) was performed to determine the complement of whole-genome DNA methylation with the ChIP-seq data. Hypermethylated and hypomethylated regions were identified across tissues, and these locations were compared with chromatin states to better distinguish and validate regulatory elements in these tissues. Interestingly, chromatin states with the poised enhancer mark H3K4me1 in the spleen and cerebellum and CTCF in the liver displayed the greatest number of hypermethylated sites. Not surprisingly, active enhancers in the liver and spleen, and promoters in the cerebellum, displayed the greatest number of hypomethylated sites. Overall, chromatin states defined by histone marks and CTCF occupied approximately 22% of the genome in all three tissues. Furthermore, the liver and spleen displayed in common the greatest percent of active promoter (65%) and active enhancer (81%) states, and the liver and cerebellum displayed in common the greatest percent of poised enhancer (53%), repressed enhancer (68%), hypermethylated sites (75%), and hypomethylated sites (73%). In addition, both known and de novo CTCF-binding motifs were identified in all three tissues, with the highest number of unique motifs identified in the cerebellum. In summary, this study has identified the regulatory regions of genes in three tissues that play key roles in defining health and economically important traits and has set the precedent for the characterization of regulatory elements in ovine tissues using the Rambouillet reference genome.
Machine Learning Assisted Prediction of Prognostic Biomarkers Associated With COVID-19, Using Clinical and Proteomics Data
Authors: Sardar Rahila , Sharma Arun , Gupta Dinesh
Published: May 2021

With the availability of COVID-19-related clinical data, healthcare researchers can now explore the potential of computational technologies such as artificial intelligence (AI) and machine learning (ML) to discover biomarkers for accurate detection, early diagnosis, and prognosis for the management of COVID-19. However, the identification of biomarkers associated with survival and deaths remains a major challenge for early prognosis. In the present study, we have evaluated and developed AI-based prediction algorithms for predicting a COVID-19 patient’s survival or death based on a publicly available dataset consisting of clinical parameters and protein profile data of hospital-admitted COVID-19 patients. The best classification model based on clinical parameters achieved a maximum accuracy of 89.47% for predicting survival or death of COVID-19 patients, with a sensitivity and specificity of 85.71 and 92.45%, respectively. The classification model based on normalized protein expression values of 45 proteins achieved a maximum accuracy of 89.01% for predicting the survival or death, with a sensitivity and specificity of 92.68 and 86%, respectively. Interestingly, we identified 9 clinical and 45 protein-based putative biomarkers associated with the survival/death of COVID-19 patients. Based on our findings, few clinical features and proteins correlate significantly with the literature and reaffirm their role in the COVID-19 disease progression at the molecular level. The machine learning–based models developed in the present study have the potential to predict the survival chances of COVID-19 positive patients in the early stages of the disease or at the time of hospitalization. However, this has to be verified on a larger cohort of patients before it can be put to actual clinical practice. We have also developed a webserver CovidPrognosis, where clinical information can be uploaded to predict the survival chances of a COVID-19 patient. The webserver is available at http://14.139.62.220/covidprognosis/.
Association Between Environmental Factors and Asthma Using Mendelian Randomization: Increased Effect of Body Mass Index on Adult-Onset Moderate-to-Severe Asthma Subtypes
Authors: Ha Tae-Woong , Jung Hae-Un , Kim Dong Jun , Baek Eun Ju , Lee Won Jun , Lim Ji Eun , Kim Han Kyul , Kang Ji-One , Oh Bermseok
Published: May 2021

Although asthma is one of the most common chronic diseases throughout all age groups, its etiology remains unknown, primarily due to its heterogeneous characteristics. We examined the causal effects of various environmental factors on asthma using Mendelian randomization and determined whether the susceptibility to asthma due to the causal effect of a risk factor differs between asthma subtypes, based on age of onset, severity of asthma, and sex. We performed Mendelian randomization analyses (inverse variance weighted, weighted median, and generalized summary-data-based Mendelian randomization) using UK Biobank data to estimate the causal effects of 69 environmental factors on asthma. Additional sensitivity analyses (MR-Egger regression, Cochran’s Q test, clumping, and reverse Mendelian randomization) were performed to ensure minimal or no pleiotropy. For confirmation, two-sample setting analyses were replicated using BMI SNPs that had been reported by a meta-genome-wide association study in Japanese and European (GIANT) populations and a genome-wide association study in control individuals from the UK Biobank. We found that BMI causally affects the development of asthma and that the adult-onset moderate-to-severe asthma subtype is the most susceptible to causal inference by BMI. Further, it is likely that the female subtype is more susceptible to BMI than males among adult asthma cases. Our findings provide evidence that obesity is a considerable risk factor in asthma patients, particularly in adult-onset moderate-to-severe asthma cases, and that weight loss is beneficial for reducing the burden of asthma.
Case Report: Identification of a de novo Microdeletion 1q44 in a Patient With Seizures and Developmental Delay
Authors: Tung Yiehen , Lu Haiying , Lin Wenxin , Huang Tingting , Kim Samuel , Hu Guo , Zhang Gang , Zheng Guo
Published: May 2021

Objective: 1q44 microdeletion syndrome is difficult to diagnose due to the wide phenotypic spectrum and strong genetic heterogeneity. We explore the correlation between the chromosome microdeletions and phenotype in a child with 1q44 microdeletion syndrome, we collected the clinical features of the patient and combined them with adjacent copy number variation (CNV) regions previously reported.

Methods: We collected the full medical history of the patient and summarized her clinical symptoms. Whole-exome sequencing (WES) and CapCNV analysis were performed with DNA extracted from both the patient's and her parents' peripheral blood samples. Fluorescent quantitative PCR (q-PCR) was performed for the use of verification to the CNV regions.

Results: A 28.7 KB microdeletion was detected in the 1q44 region by whole-exome sequencing and low-depth whole-genome sequencing. The deleted region included the genes COX20 and HNRNPU. As verification, karyotype analysis showed no abnormality, and the results of qPCR were consistent with that of whole-exome sequencing and CapCNV analysis.

Conclusion: The patient was diagnosed with 1q44 microdeletion syndrome with clinical and genetic analysis. Analyzing both whole-exome sequencing and CapCNV analysis can not only improve the diagnostic rate of clinically suspected syndromes that present with intellectual disability (ID) and multiple malformations but also support further study of the correlation between CNVs and clinical phenotypes. This study lays the foundation for the further study of the pathogenesis of complex diseases.
Adaptive Differences in Gene Expression in Farm-Impacted Seedbeds of the Native Blue Mussel Mytilus chilensis
Authors: Yévenes Marco , Núñez-Acuña Gustavo , Gallardo-Escárate Cristian , Gajardo Gonzalo
Published: May 2021

The study of adaptive population differences is relevant for evolutionary biology, as it evidences the power of selective local forces relative to gene flow in maintaining adaptive phenotypes and their underlying genetic determinants. However, human-mediated hybridization through habitat translocations, a common and recurrent aquaculture practice where hybrids could eventually replace local genotypes, risk populations’ ability to cope with perturbations. The endemic marine mussel Mytilus chilensis supports a booming farming industry in the inner sea of Chiloé Island, southern Chile, which entirely relies on artificially collected seeds from natural beds that are translocated to ecologically different fattening centers. A matter of concern is how farm-impacted seedbeds will potentially cope with environmental shifts and anthropogenic perturbations. This study provides the first de novo transcriptome of M. chilensis; assembled from tissue samples of mantles and gills of individuals collected in ecologically different farm-impacted seedbeds, Cochamó (41°S) and Yaldad (43°S). Both locations and tissue samples differentially expressed transcripts (DETs) in candidate adaptive genes controlling multiple fitness traits, involved with metabolism, genetic and environmental information processing, and cellular processes. From 189,743 consensus contigs assembled: 1,716 (Bonferroni pvalue ≤ 0.05) were DETs detected in different tissues of samples from different locations, 210 of them (fold change ≥ | 100|) in the same tissue of samples from a different location, and 665 (fold change ≥ | 4|) regardless of the tissue in samples from a different location. Site-specific DETs in Cochamó (169) and Yaldad (150) in candidate genes controlling tolerance to temperature and salinity shifts, and biomineralization exhibit a high number of nucleotide genetic variants with regular occurrence (frequency > 99%). This novel M. chilensis transcriptome should help assessing and monitoring the impact of translocations in wild and farm-impacted mussel beds in Chiloé Island. At the same time, it would help designing effective managing practices for conservation, and translocation traceability.
Ribosomal Protein L13 Participates in Innate Immune Response Induced by Foot-and-Mouth Disease Virus
Authors: Guan Junyong , Han Shichong , Wu Jin’en , Zhang Yun , Bai Manyuan , Abdullah Sahibzada Waheed , Sun Shiqi , Guo Huichen
Published: May 2021

In addition to ribosomal protein synthesis and protein translation, ribosomal proteins also participate in tumorigenesis and tumor progression, immune responses, and viral replication. Here, we show that ribosomal protein L13 (RPL13) participates in the antiviral immune response induced by foot-and-mouth disease virus (FMDV), inhibiting FMDV replication. The overexpression of RPL13 promoted the induction and activation of the promoters of the nuclear factor-κB (NF-κB) and interferon-β (IFN-β) genes, and the expression and protein secretion of the antiviral factor IFN-β and proinflammatory cytokine interleukin-6 (IL-6). The knockdown of RPL13 had the opposite effects. We also found that the FMDV 3Cpro protease interacts with RPL13, and that its activity reduces the expression of RPL13, thus antagonizing the RPL13-mediated antiviral activity. This study extends our knowledge of the extraribosomal functions of ribosomal proteins and provides new scientific information on cellular antiviral defenses and virus-antagonizing mechanisms.
Tackling Chronic Kidney Transplant Rejection: Challenges and Promises
Authors: Lai Xingqiang , Zheng Xin , Mathew James M. , Gallon Lorenzo , Leventhal Joseph R. , Zhang Zheng Jenny
Published: May 2021

Despite advances in post-transplant management, the long-term survival rate of kidney grafts and patients has not improved as approximately forty percent of transplants fails within ten years after transplantation. Both immunologic and non-immunologic factors contribute to late allograft loss. Chronic kidney transplant rejection (CKTR) is often clinically silent yet progressive allogeneic immune process that leads to cumulative graft injury, deterioration of graft function. Chronic active T cell mediated rejection (TCMR) and chronic active antibody-mediated rejection (ABMR) are classified as two principal subtypes of CKTR. While significant improvements have been made towards a better understanding of cellular and molecular mechanisms and diagnostic classifications of CKTR, lack of early detection, differential diagnosis and effective therapies continue to pose major challenges for long-term management. Recent development of high throughput cellular and molecular biotechnologies has allowed rapid development of new biomarkers associated with chronic renal injury, which not only provide insight into pathogenesis of chronic rejection but also allow for early detection. In parallel, several novel therapeutic strategies have emerged which may hold great promise for improvement of long-term graft and patient survival. With a brief overview of current understanding of pathogenesis, standard diagnosis and challenges in the context of CKTR, this mini-review aims to provide updates and insights into the latest development of promising novel biomarkers for diagnosis and novel therapeutic interventions to prevent and treat CKTR.
Helper T Cells in Idiopathic Membranous Nephropathy
Authors: Zhao Qihan , Dai Haoran , Liu Xianli , Jiang Hanxue , Liu Wenbin , Feng Zhendong , Zhang Na , Gao Yu , Dong Zhaocheng , Zhou Xiaoshan , Du Jieli , Zhang Naiqian , Rui Hongliang , Yuan Li , Liu Baoli
Published: May 2021

Idiopathic membranous nephropathy (IMN) is an autoimmune disease in which the immune system produces an antibody response to its own antigens due to impaired immune tolerance. Although antibodies are derived from plasma cells differentiated by B cells, the T-B cells also contribute a lot to the immune system. In particular, the subsets of helper T (Th) cells, including the dominant subsets such as Th2, Th17, and follicular helper T (Tfh) cells and the inferior subsets such as regulatory T (Treg) cells, shape the immune imbalance of IMN and promote the incidence and development of autoimmune responses. After reviewing the physiological knowledge of various subpopulations of Th cells and combining the existing studies on Th cells in IMN, the role model of Th cells in IMN was explained in this review. Finally, the existing clinical treatment regimens for IMN were reviewed, and the importance of the therapy for Th cells was highlighted.
Global Trends in Research of Macrophages Associated With Acute Lung Injury Over Past 10 Years: A Bibliometric Analysis
Authors: Wang Sheng , Zhou Huanping , Zheng Li , Zhu Wanli , Zhu Lina , Feng Di , Wei Juan , Chen Guannan , Jin Xiaohong , Yang Hao , Shi Xuan , Lv Xin
Published: May 2021

Acute lung injury (ALI) is an intractable disorder associated with macrophages. This bibliometric analysis was applied to identify the characteristics of global scientific output, the hotspots, and frontiers about macrophages in ALI over the past 10 years. We retrieved publications published from 2011 to 2020 and their recorded information from Science Citation Index Expanded (SCI-expanded) of Web of Science Core Collection (WoSCC). Bibliometrix package was used to analyze bibliometric indicators, and the VOSviewer was used to visualize the trend and hotspots of researches on macrophages in ALI. Altogether, 2,632 original articles were reviewed, and the results showed that the annual number of publications (Np) concerning the role of macrophages in ALI kept increasing over the past 10 years. China produced the most papers, the number of citations (Nc) and H-index of the USA ranked first. Shanghai Jiaotong University and INT IMMUNOPHARMACOL were the most prolific affiliation and journal, respectively. Papers published by Matute-Bello G in 2011 had the highest local citation score (LCS). Recently, the keywords “NLRP3” and “extracellular vesicles” appeared most frequently. Besides, researches on COVID-19–induced ALI related to macrophages seemed to be the hotspot recently. This bibliometric study revealed that publications related to macrophages in ALI tend to increase continuously. China was a big producer and the USA was an influential country in this field. Most studies were mainly centered on basic researches in the past decade, and pathways associated with the regulatory role of macrophages in inhibiting and attenuating ALI have become the focus of attention in more recent studies. What is more, our bibliometric analysis showed that macrophages play an important role in COVID-19–induced ALI and may be a target for the treatment of COVID-19.
Functional Homology for Antibody-Dependent Phagocytosis Across Humans and Rhesus Macaques
Authors: Pollara Justin , Tay Matthew Zirui , Edwards R. Whitney , Goodman Derrick , Crowley Andrew R. , Edwards Robert J. , Easterhoff David , Conley Haleigh E. , Hoxie Taylor , Gurley Thaddeus , Jones Caroline , Machiele Emily , Tuyishime Marina , Donahue Elizabeth , Jha Shalini , Spreng Rachel L. , Hope Thomas J. , Wiehe Kevin , He Max M. , Moody M. Anthony , Saunders Kevin O. , Ackerman Margaret E. , Ferrari Guido , Tomaras Georgia D.
Published: May 2021

Analyses of human clinical HIV-1 vaccine trials and preclinical vaccine studies performed in rhesus macaque (RM) models have identified associations between non-neutralizing Fc Receptor (FcR)-dependent antibody effector functions and reduced risk of infection. Specifically, antibody-dependent phagocytosis (ADP) has emerged as a common correlate of reduced infection risk in multiple RM studies and the human HVTN505 trial. This recurrent finding suggests that antibody responses with the capability to mediate ADP are most likely a desirable component of vaccine responses aimed at protecting against HIV-1 acquisition. As use of RM models is essential for development of the next generation of candidate HIV-1 vaccines, there is a need to determine how effectively ADP activity observed in RMs translates to activity in humans. In this study we compared ADP activity of human and RM monocytes and polymorphonuclear leukocytes (PMN) to bridge this gap in knowledge. We observed considerable variability in the magnitude of monocyte and PMN ADP activity across individual humans and RM that was not dependent on FcR alleles, and only modestly impacted by cell-surface levels of FcRs. Importantly, we found that for both human and RM phagocytes, ADP activity of antibodies targeting the CD4 binding site was greatest when mediated by human IgG3, followed by RM and human IgG1. These results demonstrate that there is functional homology between antibody and FcRs from these two species for ADP. We also used novel RM IgG1 monoclonal antibodies engineered with elongated hinge regions to show that hinge elongation augments RM ADP activity. The RM IgGs with engineered hinge regions can achieve ADP activity comparable to that observed with human IgG3. These novel modified antibodies will have utility in passive immunization studies aimed at defining the role of IgG3 and ADP in protection from virus challenge or control of disease in RM models. Our results contribute to a better translation of human and macaque antibody and FcR biology, and may help to improve testing accuracy and evaluations of future active and passive prevention strategies.
Associations Between Antibody Fc-Mediated Effector Functions and Long-Term Sequelae in Ebola Virus Survivors
Authors: Paquin-Proulx Dominic , Gunn Bronwyn M. , Alrubayyi Aljawharah , Clark Danielle V. , Creegan Matthew , Kim Dohoon , Kibuuka Hannah , Millard Monica , Wakabi Salim , Eller Leigh Anne , Michael Nelson L. , Schoepp Randal J. , Hepburn Matthew J. , Hensley Lisa E. , Robb Merlin L. , Alter Galit , Eller Michael A.
Published: May 2021

Antibodies that mediate non-neutralizing functions play an important role in the immune response to Ebola virus (EBOV) and are thought to impact disease outcome. EBOV has also been associated with long term sequelae in survivors, however, the extent to which antibodies that mediate non-neutralizing functions are associated with the development of these sequelae is unknown. Here, the presence of antibodies mediating different effector functions and how they relate to long-term sequelae two years after the 2007 Bundibugyo Ebola virus (BDBV) outbreak was investigated. The majority of survivors demonstrated robust antibody effector functional activity and demonstrated persistent polyfunctional antibody profiles to the EBOV glycoprotein (GP) two years after infection. These functions were strongly associated with the levels of GP-specific IgG1. The odds of developing hearing loss, one of the more common sequelae to BDBV was reduced when antibodies mediating antibody dependent cellular phagocytosis (ADCP), antibody dependent complement deposition (ADCD), or activating NK cells (ADNKA) were observed. In addition, hearing loss was associated with increased levels of several pro-inflammatory cytokines and levels of these pro-inflammatory cytokines were associated with lower ADCP. These results are indicating that a skewed antibody profile and persistent inflammation may contribute to long term outcome in survivors of BDBV infection
Variations of Colored Dissolved Organic Matter in the Mandovi Estuary, Goa, During Spring Inter-Monsoon: A Comparison With COVID-19 Outbreak Imposed Lockdown Period
Authors: Dias Albertina , Kurian Siby , Thayapurath Suresh , Pratihary Anil K.
Published: May 2021

Colored dissolved organic matter (CDOM) is one of the important fractions of dissolved organic matter (DOM) that controls the availability of light in water and plays a crucial role in the cycling of carbon. High CDOM absorption in the Mandovi Estuary (Goa) during spring inter-monsoon (SIM) is largely driven by both in-situ production and anthropogenic activities. Here we have presented the CDOM variation in the estuary during SIM of 2014–2018 and compared it with that of 2020 when the COVID-19 outbreak imposed lockdown was implemented. During 2020, low CDOM absorption was observed at the mid-stream of the estuary as compared to the previous years, which could be attributed to low autochthonous production and less input from anthropogenic activities. On the other hand, high CDOM observed at the mouth during 2020 is linked to autochthonous production, as seen from the high concentrations of chlorophyll a. High CDOM in the upstream region could be due to both autochthonous production and terrestrially derived organic matter. Sentinel-2 satellite data was also used to look at the variations of CDOM in the study region which is consistent with in-situ observations. Apart from this, the concentration of nutrients (NO3–, NH4+, and SiO44–) in 2020 was also low compared to the previous reports. Hence, our study clearly showed the impact of anthropogenic activities on CDOM build-up and nutrients, as the COVID-19 imposed lockdown drastically controlled such activities in the estuary.
Damage Identification on Impact and Lightning Damage of Flax Composite Laminates (Linum usitatissimum) Using Long-Pulse Thermography of a Low-Resolution Infrared Camera
Authors: Anwar Murniwati , Mustapha Faizal , Sultan Mohamed Thariq H. , Halin Izhal A. , Abdullah Mohd N. , Hassim Mohd I. , Mustapha Mazli
Published: May 2021

The demand for composite fiber material is significantly high due to its excellent mechanical properties and its use in various industries. Recently, with the increasing awareness of environmental issues, researchers are now focusing more on eco-friendly and green materials. A biocomposite offers a good balance of strength and stiffness ratio, bending and membrane mechanical properties, balanced thermal distortion stability, reduced weight and cost, improved fatigue resistance, reduced notch sensitivity, and, comparatively, better performance than synthetic composites. Yet, due to the complex anisotropy of the composite material, the inspection and detection of inner defects become a challenge. Long-pulse thermography is one of the non-destructive evaluations (NDEs) used to detect defects in composite materials. However, very limited research has been carried out on the usage of a low-resolution infrared camera to perform defect or damage inspection on flax composite laminates. In this paper, an experimental setup of a long pulse thermography system using low-resolution infrared camera was performed on flax bio-composite to identify impact and lightning damage. The result highlights that with control parameters, a low-resolution infrared camera has the capability to capture the lightning and impact defects of flax biocomposites using the long-pulse thermography system. An image processing method is then applied to the defect to improve the quality of defect detection and reduce background noise.
The Altitude of Coffee Cultivation Causes Shifts in the Microbial Community Assembly and Biochemical Compounds in Natural Induced Anaerobic Fermentations
Authors: Martinez Silvia Juliana , Simão João Batista Pavesi , Pylro Victor Satler , Schwan Rosane Freitas
Published: May 2021

Coffee harvested in the Caparaó region (Minas Gerais, Brazil) is associated with high-quality coffee beans resulting in high-quality beverages. We characterize, microbiologically and chemically, fermented coffees from different altitudes through target NGS, chromatography, and conventional chemical assays. The generaGluconobacterandWeissellawere dominant in coffee’s fruits from altitudes 800 and 1,000 m. Among the Eukaryotic community, yeasts were the most dominant in all altitudes. The most dominant fungal genus wasCystofilobasidium, which inhabits cold environments and resists low temperatures. The content of acetic acid was higher at altitudes 1,200 and 1,400 m. Lactic acid and the genusLeuconostoc(Pearson: 0.93) were positively correlated. The relative concentration of volatile alcohols, especially of 2-heptanol, was high at all altitudes. Bacteria population was higher in coffees from 800 m, while at 1,000 m, fungi richness was favored. The altitude is an important variable that caused shifts in the microbial community and biochemical compounds content, even in coffees belonging to the same variety and cultivated in the same region under SIAF (self-induced anaerobic fermentation) conditions. Coffee from lower altitudes has higher volatile alcohols content, while high altitudes have esters, aldehydes, and total phenolics contents.
Visible-Light-Driven Photocatalytic Water Disinfection Toward Escherichia coli by Nanowired g-C3N4 Film
Authors: Zhang Yizhu , Su Shigang , Zhang Yuanyuan , Zhang Xia , Giusto Paolo , Huang Xiaohua , Liu Jian
Published: May 2021

Graphitic carbon nitride (g-C3N4) as metal-free visible light photocatalyst has recently emerged as a promising candidate for water disinfection. Herein, a nanowire-rich superhydrophilic g-C3N4 film was prepared by a vapor-assisted confined deposition method. With a disinfection efficiency of over 99.99% in 4 h under visible light irradiation, this nanowire-rich g-C3N4 film was found to perform better than conventional g-C3N4 film. Control experiments showed that the disinfection performance of the g-C3N4 film reduced significantly after hydrophobic treatment. The potential disinfection mechanism was investigated through scavenger-quenching experiments, which indicate that H2O2 was the main active specie and played an important role in bacteria inactivation. Due to the metal-free composition and excellent performance, photocatalytic disinfection by nanowire-rich g-C3N4 film would be a promising and cost-effective way for safe drinking water production.
Differential Contributions of Inhibitory Subnetwork to Visual Cortical Modulations Identified via Computational Model of Working Memory
Authors: Nesse William H. , Bahmani Zahra , Clark Kelsey , Noudoost Behrad
Published: May 2021

Extrastriate visual neurons show no firing rate change during a working memory (WM) task in the absence of sensory input, but both αβ oscillations and spike phase locking are enhanced, as is the gain of sensory responses. This lack of change in firing rate is at odds with many models of WM, or attentional modulation of sensory networks. In this article we devised a computational model in which this constellation of results can be accounted for via selective activation of inhibitory subnetworks by a top-down working memory signal. We confirmed the model prediction of selective inhibitory activation by segmenting cells in the experimental neural data into putative excitatory and inhibitory cells. We further found that this inhibitory activation plays a dual role in influencing excitatory cells: it both modulates the inhibitory tone of the network, which underlies the enhanced sensory gain, and also produces strong spike-phase entrainment to emergent network oscillations. Using a phase oscillator model we were able to show that inhibitory tone is principally modulated through inhibitory network gain saturation, while the phase-dependent efficacy of inhibitory currents drives the phase locking modulation. The dual contributions of the inhibitory subnetwork to oscillatory and non-oscillatory modulations of neural activity provides two distinct ways for WM to recruit sensory areas, and has relevance to theories of cortical communication.