bluuebunny/crossref_metadata_2025 huggingface dataset:
BAHASA DAN IDENTITAS DALAM STUDENT HIDJO: TINJAUAN SOSIOLOGI SASTRA
Authors: Galuh Sakti Bandini
Published: January 2022

Abstrak

Dunia sastra Indonesia sebelum kemerdekaan cukup unik. Ditinjau dari segi bahasa, ada dua jenis sastra Indonesia yang beredar di Hindia Belanda, yaitu karya sastra yang menggunakan bahasa Melayu Tinggi dan Bahasa Melayu Pasar. Masing-masing bahasa mewakili ideologi tertentu. Tulisan ini membahas penggunaan bahasa dalam Student Hidjo karya Mas Marco Kartodikromo dan kaittannya dengan identitas, ditinjau dari sudut pandang sosiologi sastra. Dari penelitian ini terlihat bahwa penggunaan bahasa Melayu Rendah yang dicampur bahasa Belanda di dalam Student Hidjo tidak hanya menunjukkan identitas tokoh sebagai intelektualis muda, tapi juga sebagai bentuk perlawanan Mas Marco terhadap kolonialisme.

Kata Kunci: Student Hidjo, Mas Marco, Bahasa, identitas, sosiologi sastra.

 

Abstract

The world of Indonesian literature before independence was unique. In terms of language, there are two types of Indonesian literature circulating in the Dutch East Indies, literary works that use the High Malay and the Pasar/low Malay. Each language represents a certain ideology. This paper discusses the use of language in Mas Marco Kartodikromo's Student Hidjo and its relation to identity from the sociology of literature. From this research, it can be seen that the use of Low Malay mixed with Dutch in Student Hidjo not only shows the identity of the character as a young intellectual but also as a form of Mas Marco's resistance to colonialism.

Keyword: Student Hidjo, Mas Marco, language, identity, sociology of literature
Assessment of Particulate Matter Levels in Homes with Children
Authors: Rabou Ali Al , Wichman Christopher , Caputo-Rennels Nicole , Achutan Chandran
Published: January 2022

Children’s exposure to particulate matter (PM) is of great interest because it can cause adverse health effects, including asthma, and decreased lung function. The purpose of this study was to determine the levels of PM in low socio-economic status homes in Omaha, Nebraska. Between October 2018 and September 2019, we collected ambient air PM samples from 30 homes, of which 70% had at least one asthmatic child. Samples were collected at the 2-foot level and the 4-foot level to approximate the breathing zones of toddlers and older children, respectively. We also asked the study participants questions related to indoor air quality (IAQ). Indoor PM levels ranged from 4.28 to 72.81 μg/m3. There was a significant association between IAQ and the furnace filter status (dirty or clean) (p = 0.023, OR = 7.5 [95% confidence interval: 1.40, 39.84]). We found that IAQ status suggests a significant association with the level of housekeeping (p = 0.05, OR = 4.76 [95% confidence interval: 0.95, 23.86]). Indoor PM levels varied significantly between 2 feet and 4 feet (p < 0.05). PM levels could differ substantially depending on the furnace filter’s status. In addition, exposure to PM can significantly depend on the child’s height.
COVID-19 Mortality, Diabetes, and Obesity: The Impact of Health Inequity
Authors: J. Fos Peter , Honoré Peggy , Kellum Katrina
Published: January 2022

Early in the COVID-19 pandemic, minorities experienced the greatest burden of infection and death. These disparities were studied and related to the disproportionate distribution of comorbidities among minority, especially diabetes and obesity in non-Hispanic Blacks. Additionally, health equity has been linked to health disparities of chronic disease and COVID-19 infection. The same effect of the social determinants of health on chronic diseases in minorities is now seen in the COVID-19 pandemic. This study, which is a follow-up of research in the early stages of the pandemic, is focused on determining if the disparity in mortality is still present in the second year of the COVID-19 pandemic. Data were collected for state health departments in Georgia, Louisiana, Michigan and Mississippi on mortality due to COVID-19 infection. Mortality and case-fatality rates were collected for each state and selected counties in the study states. Mortality and case-fatality rates were determined according to race, comparing non-Hispanic Whites with non-Hispanic Blacks. The prevalence of diabetes and obesity was evaluated in relation to mortality and case-fatality rates. Results of this study indicate that the disparity between non-Hispanic Whites and non-Hispanic Blacks continues to be observed in the second year of the COVID-19 pandemic. Non-Hispanic Blacks, in the study states and counties, have higher mortality and case-fatality rates than non-Hispanic Whites. This difference ranges from nearly 1.2% greater in Georgia to 71% greater in Michigan. In the study counties with diabetes prevalence of ≥12.0% and obesity prevalence of ≥38.0% had the highest mortality rates. This study indicates that the effect of health inequities must be addressed for both chronic diseases and COVID-19.
Post-Licensure RN to BSN Nursing Students: Maintaining Collaboration and Engagement via Technology with Community-based Agencies
Authors: Grace Amendola Mary , Jackson Laura
Published: January 2022

Academic learning software is vital when conducting online post-licensure RN to BSN courses, especially when maintaining collaboration and engagement with community-based agencies. This paper will discuss Osprey Impact as an example of a possible solution to streng then collaborative partnerships between RN to BSN students and their chosen community-based agency, by streamlining the process of logging and tracking community clinical hours using this software. This online interface also tracks the progression of the RNs community/public health promotion projects with their community-based agency and faculty. The University of North Florida School of Nursing (UNF) and its Center for Instruction and Research Technology worked together to solve the problem through technology.
Print Mass Media Strategies in Central Java and Yogyakarta Provinces to Survive the Disruption Era
Authors: Kristiana Dewi Danar , Rachman Ace Sriati , Sediyaningsih Sri , Priono M , Windyaningrum Rachmawati
Published: January 2022

The emergence of the internet, which has the power of convergence and multiplatform, terminates the information boundaries. The information flow streaming through the internet creates numerous changes in various lifelines. One of the changes that are experienced is the information shift from print to online. This condition significantly affects print media companies, where customers and advertisers in newspapers begin migrating to a new platform, the internet. It becomes a big challenge for print media in addition to production costs that increase every year. In this era, if the print media do not immediately take action to adapt and innovate, it will be difficult to survive. Observing this development, it is essential to research to determine the strategies implemented by print media companies that currently exist to survive the disruption era. This study implemented a qualitative research method. This study’s results indicate that the print media's survival strategies are innovation, collaboration, maintaining good relationships with customers, and strengthening the journalistic content production to be more attractive.
Quantitative Dissection of the Proximal Ciona brachyury Enhancer
Authors: Shimai Kotaro , Veeman Michael
Published: January 2022

A major goal in biology is to understand the rules by which cis-regulatory sequences control spatially and temporally precise expression patterns. Here we present a systematic dissection of the proximal enhancer for the notochord-specific transcription factor brachyury in the ascidian chordate Ciona. The study uses a quantitative image-based reporter assay that incorporates a dual-reporter strategy to control for variable electroporation efficiency. We identified and mutated multiple predicted transcription factor binding sites of interest based on statistical matches to the JASPAR binding motif database. Most sites (Zic, Ets, FoxA, RBPJ) were selected based on prior knowledge of cell fate specification in both the primary and secondary notochord. We also mutated predicted Brachyury sites to investigate potential autoregulation as well as Fos/Jun (AP1) sites that had very strong matches to JASPAR. Our goal was to quantitatively define the relative importance of these different sites, to explore the importance of predicted high-affinity versus low-affinity motifs, and to attempt to design mutant enhancers that were specifically expressed in only the primary or secondary notochord lineages. We found that the mutation of all predicted high-affinity sites for Zic, FoxA or Ets led to quantifiably distinct effects. The FoxA construct caused a severe loss of reporter expression whereas the Ets construct had little effect. A strong Ets phenotype was only seen when much lower-scoring binding sites were also mutated. This supports the enhancer suboptimization hypothesis proposed by Farley and Levine but suggests that it may only apply to some but not all transcription factor families. We quantified reporter expression separately in the two notochord lineages with the expectation that Ets mutations and RBPJ mutations would have distinct effects given that primary notochord is induced by Ets-mediated FGF signaling whereas secondary notochord is induced by RBPJ/Su(H)-mediated Notch/Delta signaling. We found, however, that ETS mutations affected primary and secondary notochord expression relatively equally and that RBPJ mutations were only moderately more severe in their effect on secondary versus primary notochord. Our results point to the promise of quantitative reporter assays for understanding cis-regulatory logic but also highlight the challenge of arbitrary statistical thresholds for predicting potentially important sites.
Gemcitabine-Resistant Biomarkers in Bladder Cancer are Associated with Tumor-Immune Microenvironment
Authors: Song Yuxuan , Du Yiqing , Qin Caipeng , Liang Haohong , Yang Wenbo , Lin Jiaxing , Ding Mengting , Han Jingli , Xu Tao
Published: January 2022

To identify key biomarkers in gemcitabine (GEM)-resistant bladder cancer (BCa) and investigate their associations with tumor-infiltrating immune cells in a tumor immune microenvironment, we performed the present study on the basis of large-scale sequencing data. Expression profiles from the Gene Expression Omnibus GSE77883 dataset and The Cancer Genome Atlas BLCA dataset were analyzed. Both BCa development and GEM-resistance were identified to be immune-related through evaluating tumor-infiltrating immune cells. Eighty-two DEGs were obtained to be related to GEM-resistance. Functional enrichment analysis demonstrated they were related to regulation of immune cells proliferation. Protein–protein interaction network selected six key genes (CAV1, COL6A2, FABP4, FBLN1, PCOLCE, and CSPG4). Immunohistochemistry confirmed the down-regulation of the six key genes in BCa. Survival analyses revealed the six key genes were significantly associated with BCa overall survival. Correlation analyses revealed the six key genes had high infiltration of most immune cells. Gene set enrichment analysis further detected the key genes might regulate GEM-resistance through immune response and drug metabolism of cytochrome P450. Next, microRNA-gene regulatory network identified three key microRNAs (hsa-miR-124-3p, hsa-miR-26b-5p, and hsa-miR-192-5p) involved in GEM-resistant BCa. Connectivity Map analysis identified histone deacetylase inhibitors might circumvent GEM-resistance. In conclusion, CAV1, COL6A2, FABP4, FBLN1, PCOLCE, and CSPG4 were identified to be critical biomarkers through regulating the immune cell infiltration in an immune microenvironment of GEM-resistance and could act as promising treatment targets for GEM-resistant muscle-invasive BCa.
1,3,4-Thiadiazole Scaffold: As Anti-Epileptic Agents
Authors: Anthwal Tulika , Nain Sumitra
Published: January 2022

A wide range of biological activities is exhibited by 1,3,4-thiadiazole moiety such as antidiabetic, anticancer, anti-inflammatory, anticonvulsant, antiviral, antihypertensive, and antimicrobial. To date, drugs such as butazolamide, and acetazolamide. Several modifications have been done in the 1,3,4-thiadiazole moiety which showed good potency as anticonvulsant agents which are highly effective and have less toxicity. After in-depth literature survey in this review, we have compiled various derivatives of 1,3,4-thiadiazole scaffold as anticonvulsant agents.
Deep Learning Analysis of Cardiac MRI in Legacy Datasets: Multi-Ethnic Study of Atherosclerosis
Authors: Suinesiaputra Avan , Mauger Charlène A. , Ambale-Venkatesh Bharath , Bluemke David A. , Dam Gade Josefine , Gilbert Kathleen , Janse Markus H. A. , Hald Line Sofie , Werkhoven Conrad , Wu Colin O. , Lima Joao A. C. , Young Alistair A.
Published: January 2022

The Multi-Ethnic Study of Atherosclerosis (MESA), begun in 2000, was the first large cohort study to incorporate cardiovascular magnetic resonance (CMR) to study the mechanisms of cardiovascular disease in over 5,000 initially asymptomatic participants, and there is now a wealth of follow-up data over 20 years. However, the imaging technology used to generate the CMR images is no longer in routine use, and methods trained on modern data fail when applied to such legacy datasets. This study aimed to develop a fully automated CMR analysis pipeline that leverages the ability of machine learning algorithms to enable extraction of additional information from such a large-scale legacy dataset, expanding on the original manual analyses. We combined the original study analyses with new annotations to develop a set of automated methods for customizing 3D left ventricular (LV) shape models to each CMR exam and build a statistical shape atlas. We trained VGGNet convolutional neural networks using a transfer learning sequence between two-chamber, four-chamber, and short-axis MRI views to detect landmarks. A U-Net architecture was used to detect the endocardial and epicardial boundaries in short-axis images. The landmark detection network accurately predicted mitral valve and right ventricular insertion points with average error distance <2.5 mm. The agreement of the network with two observers was excellent (intraclass correlation coefficient >0.9). The segmentation network produced average Dice score of 0.9 for both myocardium and LV cavity. Differences between the manual and automated analyses were small, i.e., <1.0 ± 2.6 mL/m2 for indexed LV volume, 3.0 ± 6.4 g/m2 for indexed LV mass, and 0.6 ± 3.3% for ejection fraction. In an independent atlas validation dataset, the LV atlas built from the fully automated pipeline showed similar statistical relationships to an atlas built from the manual analysis. Hence, the proposed pipeline is not only a promising framework to automatically assess additional measures of ventricular function, but also to study relationships between cardiac morphologies and future cardiac events, in a large-scale population study.
Leukocyte Telomere Length Shortening Implies Plaque Instability and Major Adverse Cardiovascular Events in Patients With Angiographically Intermediate Lesions
Authors: Zhang Alian , Fan Li , Bao Xiaolu , Xu Zuojun , Yin Zhaofang , Zhuo Yang , Zhang Junfeng , Gu Jun , Chang Alex C. Y. , Fan Yuqi , Wang Changqian
Published: January 2022

Background

Telomere shortening, an indicator of aging, is associated with age-related diseases. This study aims to investigate the association between leukocyte telomere length (LTL) and thin-capped fibroatheromata (TCFA) and the impact of using LTL cutoff to determine the incidence of major adverse cardiovascular events (MACEs) in patients with angiographically intermediate coronary lesions.

Methods

This was a signal-center retrospective study focusing on patients who underwent coronary angiography and optical coherence tomography (OCT). The degree of coronary stenosis was assessed by angiography. The presence of TCFA was determined by OCT imaging. A total of 156 patients with angiographically intermediate coronary lesions were enrolled.

Results

Leukocyte telomere lengths were significantly shorter in the TCFA group compared with non-TCFA group [11.95 (10.56, 15.21) kb vs. 13.81 (12.06, 16.11) kb, p = 0.003]. The short-LTL group and long-LTL group were divided according to the optimal cut-off value which was determined by the receiver operating characteristic (ROC) curve analysis. Logistic regression model revealed that short-LTL was independently associated with TCFA incidence (odds ratio [OR] 4.387, 95% CI: 1.902–10.120, p = 0.001) after adjusting for confounding factors. Over a 24-months follow-up, the MACE incidence among patients with short-LTL was significantly higher than those in the long-LTL group (12.5 vs. 2.0%, p = 0.006 by log-rank test). Multivariable cox regression analysis indicated that short-LTL (hazard ratio [HR] 9.716, 95% CI: 1.995–47.319, p = 0.005) was an independent prognostic factor of MACE incidence in angiographically intermediate coronary lesions patients.

Conclusions

Short-LTL was independently associated with the incidence of TCFA and may serve as a prognostic factor for MACE risk on top of conventional risk factors.
Investigating Stress Transfer Between the Tuz Gölü Fault Zone and Hasan Dağ Volcano (Turkey)
Authors: Hedger Emily , Gottsmann Jo
Published: January 2022

Faulting, magmatism and volcanism are intrinsically linked by plate tectonics. Fault slip imparts stress changes to the surrounding crust and other faults and fractures. Volcano-tectonic hazard assessment in areas with long recurrence intervals of volcanic and tectonic activity requires an assessment of current stress levels. Here we investigate stress transfer between the Akhisar-Kiliç fault segment (AKFS) of the seismically active Tuz Gölü fault zone in the Central Anatolian Volcanic Province and the active Hasan Dağ volcanic complex. Current stress accumulation by protracted gradual slip on the AKFS since its most recent rupture (5.45 ka±0.16 BP) is quantified using the Coulomb Failure Stress change (ΔCFS). We calculate currently accrued ΔCFS magnitudes of between 2.5±0.2 and 15±0.5 MPa on the fault plane for published lower and upper-bound estimates of right-lateral slip rates, respectively. These changes are sufficient to promote failure of the segment. The M5.1 September 20, 2020 earthquake SW of Hasan Dağ occurred in a volume predicted by this study to have undergone fault unclamping by gradual slip along the AKFS. We also show that gradual slip of the AKFS contributes to the progressive unclamping of fractures and transtensional opening of potential magma pathways oriented perpendicularly to the AKFS both above and below Hasan Dağ’s magma reservoir, while pathways oriented parallel to the AKFS are being clamped. Earthquake moment magnitudes of between Mw5.94 and Mw6.76 due to hypothetical partial or complete rupture of the segment exacerbate these trends. The spatial pattern of Coulomb failure stress changes on Hasan Dağ’s magma reservoir is predominantly controlled by the location of rupture relative to the reservoir with the magnitude of the earthquake playing a subordinate role. We explore implications of our findings for the assessment of interconnected seismo-volcanic hazards and associated risks.
Study on Evaluation and Prediction of the Degree of Surface Damage Caused by Coal Mining
Authors: Xie Xiaoshen , Hou Enke , Long Tianwen , Feng Dong , Hou Pengfei , Wei Qiming , Li Yang , Liu Jiangbin
Published: January 2022

Surface damage caused by coal mining is one of the problems perplexing ecological environment restorations in coal mining areas. Accurately evaluating and predicting the degree of surface damage induced by coal mining with reasonable and correct indexes are of great significance to the restoration and treatment of the ecological environment. In this paper, these methods including the unmanned aerial vehicle aerial photography and manual measurement were used to investigate the development characteristics of surface damage caused by 2# coal seam mining in Yangchangwan Coal Mine. The results showed that with the change of mining conditions, the characteristics of surface cracks change obviously, which can be adopted to indicate the degree of surface damage. Thus, based on the results of the investigation, the classification standard of surface damage degree was established based on the evaluation indexes including density of crack, drop height of surface crack, crack width, maximum surface subsidence, and geological disaster caused by cracks and the damage characteristics of buildings. The evaluation method and process of surface damage degree also were given. Based on the ratio of the buried depth to the thickness of the coal seam (H/M), ratio of the thickness of overlying bedrock to the thickness of the coal seam, the thickness of loose layers (Ms), geomorphology, distance to faults, and distance to folds, the prediction model of surface damage degree was built on the GIS platform. The weight coefficient of each prediction index was obtained by the analytic hierarchy process (AHP) method. The surface damage degree map of 2# coal seam in Yangchangwan Coal Mine was divided into four classes: very minor, minor, moderate, and serious, which provides a relatively applicable method for the prediction of surface damage degree in Yangchangwan Coal Mine and its adjacent mining areas.
PBK/TOPK Inhibitor Suppresses the Progression of Prolactinomas
Authors: Zhu Kejing , Cheng Xueting , Wang Shuman , Zhang Hong , Zhang Yu , Wang Xiong , Chen Yonggang , Wu Jinhu
Published: January 2022

Background

Prolactinoma is the most common type of pituitary tumors, and its resultant tumor occupying and hormone disturbance greatly damage the health of patients. In this study, we investigated a protein kinase-PDZ Binding Kinase (PBK)/T-LAK Cell-Originated Protein Kinase (TOPK) as a candidate protein regulating prolactin (PRL) secretion and tumor growth of prolactinomas.

Methods

Downloaded prolactinoma transcriptome dataset from Gene Expression Omnibus (GEO) database, and screened differentially expressed genes (DEGs) between normal pituitary tissues and prolactinoma tissues. Then, Gene ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) enrichment analyses of DEGs were performed, a protein-protein interaction (PPI) network was constructed and the hub genes were identified. After a literature search, TOPK was presumed as an candidate target regulating the prolactinoma. We found a specific inhibitor of TOPK to investigate its effects on the proliferation, migration, apoptosis and PRL secretion of pituitary tumor cells. Finally, the regulation of TOPK inhibitor on its downstream target-p38 Mitogen Activated Protein Kinase (p38 MAPK) was detected to explore the potential mechanism.

Results

A total of 361 DEGs were identified, and 20 hub genes were screened out. TOPK inhibitor HI-TOPK-032 could suppress the proliferation & migration and induce apoptosis of pituitary tumor cells in vitro, and reduce PRL secretion and tumor growth in vivo. HI-TOPK-032 also inhibited the phosphorylation level of the downstream target p38 MAPK, suggesting that TOPK inhibitors regulate the development of prolactinoma by mediating p38 MAPK.

Conclusion

Our study of identification and functional validation of TOPK suggests that this candidate can be a promising molecular target for prolactinoma treatment.
Fluoride-Controlled Riboswitch-Based Dampening of Gene Expression for Cloning Potent Promoters
Authors: Korniakova Vesta , Devinck Aurélie , Groleau Marie-Christine , Déziel Eric , Perreault Jonathan
Published: January 2022

Bioreporter systems based on detectable enzyme activity, such as that of beta-galactosidase or luciferase, are key in novel bacterial promoter discovery and study. While these systems permit quantification of gene expression, their use is limited by the toxicity of the expressed reporter enzymes in a given host. Indeed, the most potent promoters may be overlooked if their activity causes a lethal overproduction of the reporter genes when screening for transcriptional activity of potential promoter sequences with the luxCDABE cassette. To overcome this limitation, a variation of the mini-CTX-lux plasmid has been designed which allows reduction of promoter activity via the addition of an adjacent fluoride riboswitch. The riboswitch adds a layer of regulation between the promoter and the reporter gene, allowing cloning of stronger promoters by weakening expression, while giving the potential to induce with fluoride to provide a good signal for weaker promoters, thus circumventing limitations associated with reporter toxicity. We noticed the riboswitch potential portability issues between species, suggesting caution when using riboswitches non-native to the species where it is being used. This study introduces a new molecular biology tool which will allow for the identification of previously unverifiable or uncharacterized potent promoters and also provides a cloning vector for translational fusion with luciferase in a plasmid compatible with many species such as from the genera Burkholderia and Pseudomonas.
Comprehensive Analysis to Identify the Encoded Gens of Sodium Channels as a Prognostic Biomarker in Hepatocellular Carcinoma
Authors: Yan Yan , He Wen , Chen Yonghua , Li Qiang , Pan Jiahao , Yuan Yunfei , Zeng Weian , Chen Dongtai , Xing Wei
Published: January 2022

The SCN family as the encoded gens of sodium channels has been proven to participate in development of cancers including hepatocellular carcinoma (HCC), but the prognostic value of the SCN family is unclear. The results of the UALCAN database had showed that SCN2A/4A/5A/8A mRNA were highly expressed in tumour tissues, while SCN1A/7A/11A mRNA were expressed at low levels (p < 0.05), furthermore, the expression of SCN4A and SCN7A had the similar levels in microarray analysis result. The pan-tumour analysis showed that SCN7A expression was stably lower in tumours than SCN4A expression by TIMER. Both SCN4A and SCN7A were related to tumour grade, nodal metastatic status, histological subtype, patient race, individual cancer stages and TP53 mutation status to varying degrees. The Kaplan–Meier plotter demonstrated that high SCN4A mRNA expression was correlated with better overall survival (OS), disease-specific survival (DSS) and progression-free survival (PFS) and that high expression of SCN7A mRNA was associated with better OS; however, in Asians, higher SCN4A was correlated with better OS and DSS, and higher SCN7A was well correlated with better OS, recurrence-free survival (RFS), DSS and PFS. Analysis of data from cBioPortal showed that mutation of SCN7A was related to RFS and PFS. The protein expression of SCN4A and SCN7A had been detected by Immunohistochemistry. Univariate survival analysis revealed that high SCN7A protein expression was significantly linked to better OS (p = 0.001) and RFS (p = 0.003). Moreover, SCN7A displayed as an independent prognostic factor by multivariate analysis. In addition, a lower methylation level indicated a poor outcome. Pathway and functional enrichment analysis predicted a relationship between SCN7A and the PI3K pathway. In conclusion, there are significant and stable changes in SCN4A and SCN7A expression in HCC. SCN7A expression has better prognostic value and might participate in HCC progression.
Transcriptome and Metabolome Integration Provides New Insights Into the Regulatory Networks of Tibetan Pig Alveolar Type II Epithelial Cells in Response to Hypoxia
Authors: Yang Yanan , Yuan Haonan , Liu Xuanbo , Wang Zhengwen , Li Yongqing , Ren Yue , Gao Caixia , Jiao Ting , Cai Yuan , Zhao Shengguo
Published: January 2022

Tibetan pigs show a widespread distribution in plateau environments and exhibit striking physiological and phenotypic differences from others pigs for adaptation to hypoxic conditions. However, the regulation of mRNAs and metabolites as well as their functions in the alveolar type II epithelial (ATII) cells of Tibetan pigs remain undefined. Herein, we carried out integrated metabolomic and transcriptomic profiling of ATII cells between Tibetan pigs and Landrace pigs across environments with different oxygen levels to delineate their signature pathways. We observed that the differentially accumulated metabolites (DAMs) and differentially expressed genes (DEGs) profiles displayed marked synergy of hypoxia-related signature pathways in either Tibetan pigs or Landrace pigs. A total of 1,470 DEGs shared between normoxic (TN, ATII cells of Tibetan pigs were cultured under 21% O2; LN, ATII cells of Landrace pigs were cultured under 21% O2) and hypoxic (TL, ATII cells of Tibetan pigs were cultured under 2% O2; LL, ATII cells of Landrace pigs were cultured under 2% O2) groups and 240 DAMs were identified. Functional enrichment assessment indicated that the hypoxia-related genes and metabolites were primarily involved in glycolysis and aldosterone synthesis and secretion. We subsequently constructed an interaction network of mRNAs and metabolites related to hypoxia, such as guanosine-3′, 5′-cyclic monophosphate, Gly-Tyr, and phenylacetylglycine. These results indicated that mitogen-activated protein kinase (MAPK) signaling, aldosterone synthesis and secretion, and differences in the regulation of MCM and adenosine may play vital roles in the better adaptation of Tibetan pigs to hypoxic environments relative to Landrace pigs. This work provides a new perspective and enhances our understanding of mRNAs and metabolites that are activated in response to hypoxia in the ATII cells of Tibetan pigs.
A Mouse Immunogenicity Model for the Evaluation of Meningococcal Conjugate Vaccines
Authors: Arunachalam Arun B. , Vile Stacey , Rosas Angel
Published: January 2022

The identification of an appropriate animal model for use in the development of meningococcal vaccines has been a challenge as humans are the only natural host for Neisseria meningitidis. Small animal models have been developed and are widely used to study the efficacy or immunogenicity of vaccine formulations generated against various diseases. Here, we describe the development and optimization of a mouse model for assessing the immunogenicity of candidate tetravalent meningococcal polysaccharide (MenACYW-TT) protein conjugate vaccines. Three inbred (BALB/c [H-2d], C3H/HeN [H-2k], or C57BL/6 [H-2b]) and one outbred (ICR [H-2g7]) mouse strains were assessed using serial two-fold dose dilutions (from 2 µg to 0.03125 µg per dose of polysaccharide for each serogroup) of candidate meningococcal conjugate vaccines. Groups of 10 mice received two doses of the candidate vaccine 14 days apart with serum samples obtained 14 days after the last dose for the evaluation of serogroup-specific anti-polysaccharide IgG by ELISA and bactericidal antibody by serum bactericidal assay (SBA). C3H/HeN and ICR mice had a more dose-dependent antibody response to all four serogroups than BALB/c and C57Bl/6 mice. In general, ICR mice had the greatest antibody dose-response range (both anti-polysaccharide IgG and bactericidal antibodies) to all four serogroups and were chosen as the model of choice. The 0.25 µg per serogroup dose was chosen as optimal since this was in the dynamic range of the serogroup-specific dose-response curves in most of the mouse strains evaluated. We demonstrate that the optimized mouse immunogenicity model is sufficiently sensitive to differentiate between conjugated polysaccharides, against unconjugated free polysaccharides and, to degradation of the vaccine formulations. Following optimization, this optimized mouse immunogenicity model has been used to assess the impact of different conjugation chemistries on immunogenicity, and to screen and stratify various candidate meningococcal conjugate vaccines to identify those with the most desirable profile to progress to clinical trials.
Regulation of Algal Bloom Hotspots Under Mega Estuarine Constructions in the Changjiang River Estuary
Authors: He Yanru , Wang Yihe , Wu Hui
Published: January 2022

Massive large-scale engineering projects have been built in river estuaries around the world, but their effects on environments in the surrounding coastal waters were less emphasized compared to those due to the watershed projects. In this study, we used the Changjiang River Estuary as an example to show that a significant consequence can be resulted in such a situation. Through analyzing the harmful algal bloom events data and the chlorophyll satellite data, we investigate the spatiotemporal variations of algal blooms in the estuary and its adjacent water. The results indicate that the location of algal bloom hotspot changed over the period of the estuarine constructions. Furthermore, using a well-validated numerical model, we explored the mechanisms responsible for such an ecosystem regime shift. It was found that after the estuarine constructions were built, the surface chlorophyll maximum was attenuated and part of it migrated landward north of the river mouth but was strengthened south of the river mouth and extended seaward. Alternations of the nutrient concentration distribution and turbidity distribution induced by river plume deviation are responsible for the redistribution of the high chlorophyll concentration area. By contrast, the direct impact of the Three Gorges Dam through changing the runoff and sediments flux, which has been highlighted in numerous studies, was less important than expected. Given the fact that Three Gorges Dam and mega estuarine constructions were built in a similar period, any observed regime shift of hydrodynamic and ecological status outside the estuary should be interpreted with particular caution.
Magnetic-Optic Effect-Based Topological State: Realization and Application
Authors: Wang Xinyue , Zhao Wen , Zhang Hongyu , Elshahat Sayed , Lu Cuicui
Published: January 2022

The topological state in photonics was first realized based on the magnetic-optic (MO) effect and developed rapidly in recent years. This review summarizes various topological states. First, the conventional topological chiral edge states, which are accomplished in periodic and aperiodic systems based on the MO effect, are introduced. Some typical novel topological states, including valley-dependent edge states, helical edge states, antichiral edge states, and multimode edge states with large Chern numbers in two-dimensional and Weyl points three-dimensional spaces, have been introduced. The manifest point of these topological states is the wide range of applications in wave propagation and manipulation, to name a few, one-way waveguides, isolator, slow light, and nonreciprocal Goos–Hänchen shift. This review can bring comprehensive physical insights into the topological states based on the MO effect and provides reference mechanisms for light one-way transmission and light control.
Candida Infection as an Early Sign of Subsequent Sjögren's Syndrome: A Population-Based Matched Cohort Study
Authors: Chen Chia-Lun , Chang Fang-Cherng , Hung Yao-Min , Chou Mei-Chia , Yip Hei-Tung , Chang Renin , Wei James Cheng-Chung
Published: January 2022

Background

Candida infection is prevalent in patients with Sjögren's syndrome (SjS), which usually takes years to reach diagnosis. Is the link a two-way street? The role of Candida infection before SjS has not been examined clearly. This study was conducted to provide epidemiological evidence regarding the relationship between the first acquisition of Candida infection and subsequent SjS.

Methods

Totally, 23,494 individuals newly diagnosed with Candida infection were enrolled from 2000, to 2012. Controls (N = 93,976) were selected at a 1:4 ratio through propensity score matched (PSM) using the greedy algorithm. Exposure was defined according to the International Classification of Diseases, Ninth Revision, Clinical Modification (ICD-9-CM) codes.

Main Outcomes and Measures

SjS was recorded in the Registry for Catastrophic Illness Patients Database (RCIPD). Cox proportional hazard model was used to analyze the association and sensitivity analyses for cross-validation.

Results

Of 117,470 individuals (106,077 [89%] women), 23,494 individuals (20.0%) had Candida infection and 104 individuals (0.1%) developed SjS. The incidence of SjS was higher in the exposed group compared with the controls (1.92 vs. 0. 98 per 10,000 person-years) with adjusted hazard ratio (aHR) 1.90 (95% CI, 1.25–2.87). The aHRs in subgroups of aged 18–30 years, oral candidiasis and depression were 4.30 (95% CI, 1.60–11.55), 4.70 (4.70–13.93) and 6.34 (2.16–18.66). Sensitivity analyses yield consistent results.

Conclusions

Residents in Taiwan with Candida infection have higher risk of SjS. For early diagnosis of SjS, clinicians are advised to take Candida infection into account in some situation.
Lactic Acid Bacteria Are Prevalent in the Infrabuccal Pockets and Crops of Ants That Prefer Aphid Honeydew
Authors: Zheng Zhou , Zhao Mengqin , Zhang Zhijun , Hu Xin , Xu Yang , Wei Cong , He Hong
Published: January 2022

Ants are evolutionarily successful species and occupy diverse trophic and habitat niches on the earth. To fulfill dietary requirements, ants have established commensalism with both sap-feeding insects and bacteria. In this study, we used high-throughput sequencing of the bacterial 16S rRNA gene to characterize the bacterial composition and structure of the digestive tracts in three species of Formica ants and Lasius niger (Linnaeus)—species that predominantly feed on honeydew secreted by aphids. We found that bacterial communities displayed species- and colony-level signatures, and that bacterial communities in the infrabuccal pockets and crops were different from those in the midguts and hindguts. Lactobacillus and Wolbachia were dominant in the infrabuccal pockets and crops of workers, whereas Wolbachia was dominant in the midguts, hindguts and brood (larvae, pupae and cocoons). To learn more about the dominant Lactobacillus in ants, we assessed its prevalence in a wide range of aphid-tending ants using diagnostic PCR. We found that Lactobacillus was more prevalent in Formicinae than in Myrmicinae species. We also isolated four strains of lactic acid bacteria (Lactobacillus sanfranciscensis, Lactobacillus lindneri, Weissella cibaria and Fructobacillus sp.) from the infrabuccal pockets and crops of aphid-tending ants using a culture-dependent method. Two predominant lactic acid bacterial isolates, Lactobacillus sanfranciscensis (La2) and Weissella cibaria (La3), exhibited abilities in catabolizing sugars (sucrose, trehalose, melezitose and raffinose) known to be constituents of hemipteran honeydew. These findings contribute to further understanding the association between ants, aphids and bacteria, and provide additional information on the function of lactic acid bacteria in ants.
A Recombinant Porcine Reproductive and Respiratory Syndrome Virus Stably Expressing DsRed Protein Based on Bacterial Artificial Chromosome System
Authors: Li Na , Zhang Yiyi , Yao Lunguang , Shi Yunpeng , Zhao Qin , Huang Baicheng , Sun Yani
Published: January 2022

Recombinant viruses possessing reporter proteins as tools are widely applied in investigating viral biology because of the convenience for observation. Previously, we generated a recombinant pathogenic porcine reproductive and respiratory syndrome virus (PRRSV) with enhanced green fluorescent protein (EGFP) reporter for monitoring virus spread and screening of neutralizing antibodies. PRRSV with different kinds of reporters can support more application scenarios. Here, we described a new genetically stable infectious clones of a highly pathogenic PRRSV (HP-PRRSV) harboring the DsRed (a red fluorescent protein isolated from the coral Discosoma) gene. In the recombinant infectious clone, the transcription regulatory sequence 2 (TRS2) of PRRSV was inserted between the open reading frame 7 (ORF7) and 3′UTR to drive the transcription of DsRed gene, which makes it a separate transcription unit in the viral genome. Using the bacterial artificial chromosome (BAC) system and cytomegalovirus (CMV) promoter, the recombinant HP-PRRSV with the DsRed insertion was successfully rescued and showed similar growth and replication patterns compared with the wild-type virus in the MARC-145 cells. In addition, the DsRed protein was stably expressed in the recombinant virus for at least 10 passages with consistent fluorescence intensity and density. Using the recombinant HP-PRRSV with DsRed protein, the virus tracking in MARC-145 was observed by live-cell imaging. Meanwhile, quantification of the DsRed fluorescence positive cells by flow cytometry provides an alternative to standard methods for testing the level of PRRSV infection. This recombinant PRRSV with DsRed fluorescence protein expression could be a useful tool for fundamental research on the viral biology and shows the new design for stable expression of foreign genes in PRRSV.
Mechanistic Insight Into Cadmium- and Zinc-Induced Inactivation of the Candida albicans Pif1 Helicase
Authors: Zhang Bo , Zhang Qintao , Zhu Xinting , Li Dayu , Duan Xiaolei , Jin Jiao , Wang Kejia , Xie Yan , Liu Yang
Published: January 2022

Zinc and cadmium are environmental contaminants that can cause disease by affecting the activity of DNA-repair proteins. In this study, we investigated the effect of Zn2+ and Cd2+ on the Candida albicans Pif1, a DNA-repair helicase that plays a critical role in ensuring genomic stability. We show that Zn2+ and Cd2+ strongly inhibit both the ATPase and the unwinding activities of CaPif1, but have no effect on its DNA binding activity. High concentrations of Cd2+ may bind to the cysteine residues of CaPif1, and its inhibition appears to be difficult to be restored by ethylene diamine tetraacetic acid, while inhibition due to Zn2+ can. When the two ions are at low concentrations, increasing the concentration of ATP in the reaction can appropriately weaken the inhibitory effect of Zn2+, while cysteine can reduce the inhibitory effect of Cd2+. In addition, we found that for both Cd2+ and Zn2+ the inhibition effects were nearly 100 times greater in reduced environments than in non-reducing environments. When heavy metals stimulate the body’s response, the environment of the body becomes less reducing, and thus the tolerance of CaPif1 to heavy metals will be stronger. We propose that CaPif1 may resist the toxicity of heavy metals through this mechanism. Altogether, our results provide new insights into the mechanisms by which heavy metals are toxic to DNA-repair proteins.
Integrative Genomic Analyses of 1,145 Patient Samples Reveal New Biomarkers in Esophageal Squamous Cell Carcinoma
Authors: Zou Binbin , Guo Dinghe , Kong Pengzhou , Wang Yanqiang , Cheng Xiaolong , Cui Yongping
Published: January 2022

Due to the lack of effective diagnostic markers and therapeutic targets, esophageal squamous cell carcinoma (ESCC) shows a poor 5 years survival rate of less than 30%. To explore the potential therapeutic targets of ESCC, we integrated and reanalyzed the mutation data of WGS (whole genome sequencing) or WES (whole exome sequencing) from a total of 1,145 samples in 7 large ESCC cohorts, including 270 ESCC gene expression data. Two new mutation signatures and 20 driver genes were identified in our study. Among them, AP3S1, MUC16, and RPS15 were reported for the first time. We also discovered that the KMT2D was associated with the multiple clinical characteristics of ESCC, and KMT2D knockdown cells showed enhanced cell migration and cell invasion. Furthermore, a few neoantigens were shared between ESCC patients. For ESCC, compared to TMB, neoantigen might be treated as a better immunotherapy biomarker. Our research expands the understanding of ESCC mutations and helps the identification of ESCC biomarkers, especially for immunotherapy biomarkers.
Prediction of Residue-specific Contributions to Binding and Thermal Stability Using Yeast Surface Display
Authors: Ahmed Shahbaz , Bhasin Munmun , Manjunath Kavyashree , Varadarajan Raghavan
Published: January 2022

Accurate prediction of residue burial as well as quantitative prediction of residue-specific contributions to protein stability and activity is challenging, especially in the absence of experimental structural information. This is important for prediction and understanding of disease causing mutations, and for protein stabilization and design. Using yeast surface display of a saturation mutagenesis library of the bacterial toxin CcdB, we probe the relationship between ligand binding and expression level of displayed protein, with in vivo solubility in E. coli and in vitro thermal stability. We find that both the stability and solubility correlate well with the total amount of active protein on the yeast cell surface but not with total amount of expressed protein. We coupled FACS and deep sequencing to reconstruct the binding and expression mean fluorescent intensity of each mutant. The reconstructed mean fluorescence intensity (MFIseq) was used to differentiate between buried site, exposed non active-site and exposed active-site positions with high accuracy. The MFIseq was also used as a criterion to identify destabilized as well as stabilized mutants in the library, and to predict the melting temperatures of destabilized mutants. These predictions were experimentally validated and were more accurate than those of various computational predictors. The approach was extended to successfully identify buried and active-site residues in the receptor binding domain of the spike protein of SARS-CoV-2, suggesting it has general applicability.
Targeting Sensory and Motor Integration for Recovery of Movement After CNS Injury
Authors: Asan Ahmet S. , McIntosh James R. , Carmel Jason B.
Published: January 2022

The central nervous system (CNS) integrates sensory and motor information to acquire skilled movements, known as sensory-motor integration (SMI). The reciprocal interaction of the sensory and motor systems is a prerequisite for learning and performing skilled movement. Injury to various nodes of the sensorimotor network causes impairment in movement execution and learning. Stimulation methods have been developed to directly recruit the sensorimotor system and modulate neural networks to restore movement after CNS injury. Part 1 reviews the main processes and anatomical interactions responsible for SMI in health. Part 2 details the effects of injury on sites critical for SMI, including the spinal cord, cerebellum, and cerebral cortex. Finally, Part 3 reviews the application of activity-dependent plasticity in ways that specifically target integration of sensory and motor systems. Understanding of each of these components is needed to advance strategies targeting SMI to improve rehabilitation in humans after injury.
MicroRNAs Play a Role in Parkinson’s Disease by Regulating Microglia Function: From Pathogenetic Involvement to Therapeutic Potential
Authors: Li Silu , Bi Guorong , Han Shunchang , Huang Rui
Published: January 2022

Parkinson’s disease (PD) is a clinically common neurodegenerative disease of the central nervous system (CNS) characterized by loss of dopamine neurons in the substantia nigra. Microglia (MG), as an innate immune cell in the CNS, are involved in a variety of immunity and inflammatory responses in the CNS. A number of studies have shown that the overactivation of MG is one of the critical pathophysiological mechanisms underlying PD. MicroRNAs (miRNAs) are considered to be an important class of gene expression regulators and are involved in a variety of physiological and pathological mechanisms, including immunity and inflammation. In addition, miRNAs can affect the progress of PD by regulating the expression of various MG genes and the polarization state of the MG. Here, we summarize recent articles and describe the important role of MG pathological polarization in the progression of PD, the diverse mechanisms responsible for how miRNAs regulate MG, and the potential therapeutic prospects of miRNAs for PD. We also propose that the regulation of miRNAs may be a novel protective approach against the pathogenesis of PD.