bluuebunny/crossref_metadata_2025 huggingface dataset:
Association of Inflammation-Related Gene Polymorphisms With Susceptibility and Radiotherapy Sensitivity in Head and Neck Squamous Cell Carcinoma Patients in Northeast China
Authors: Li Ying , Zhu Li , Yao Hongmin , Zhang Ye , Kong Xiangyu , Chen Liping , Song Yingqiu , Mu Anna , Li Xia
Published: June 2021

Background

Inflammation-related gene polymorphisms are some of the most important determinants for cancer susceptibility, clinical phenotype diversity, and the response to radiotherapy and chemotherapy. However, the relationship between these polymorphisms and head and neck squamous cell carcinoma (HNSCC) remains unclear. The aim of this study was to investigate the role of inflammation-related gene polymorphisms in the developmental risk and radiotherapy sensitivity of HNSCC.

Methods

The Matrix-Assisted Laser Desorption Ionization Time of Flight (MALDI-TOF) genotyping system was used to genotype 612 individuals from a Chinese population for 28 inflammation-related gene polymorphisms.

Results

The protein kinase B (AKT1) rs1130233 TT, dominance model (CT+TT vs. CC), recessive model (TT vs. CT+CC), and rs2494732 CC genotypes were associated with reduced risk of HNSCC (P=0.014; P=0.041; P=0.043). The polymeric immunoglobulin receptor (PIGR) rs291097 GA, dominance model (GA+AA vs. GG), and rs291102 dominance model (GA+AA vs. GG) were associated with increased risk of HNSCC (P=0.025; P=0.025; P=0.040). The interleukin-4 receptor-α (IL-4RA) rs1801275 AA genotype was significantly correlated with increased radiotherapy sensitivity of HNSCC patients (P=0.030). In addition, age ≤ 60 years, non-smoker status, and normal levels of squamous cell carcinoma antigen (SCC) were found to be associated with increased radiotherapy sensitivity of HNSCC patients (P=0.033; P=0.033; P=0.030).

Conclusion

The AKT1 rs1130233, AKT1 rs2494732, PIGR rs291097, and PIGR rs291102 polymorphisms were significantly related to the risk of HNSCC. The IL-4RA rs1801275 polymorphism, age ≤ 60 years, non-smoker status, and normal levels of SCC were significantly associated with increased radiotherapy sensitivity of HNSCC.
An Essential NRP1-Mediated Role for Tagln2 in Gastric Cancer Angiogenesis
Authors: Jin Hongwei , Zheng Wei , Hou Jingjing , Peng Huifang , Zhuo Huiqin
Published: June 2021

Knowledge about the precise biological role and underlying mechanism of Tagln2 in tumor progression is relatively limited, especially in angiogenesis focused on tumor derived endothelial cells (ECs) has rarely been reported. Here, the function, molecular mechanism and potential clinical value of Tagln2 in gastric cancer (GC) angiogenesis were investigated. GC tissue microarrays were used to assess the expression of Tagln2 in ECs. The relationships between expression and clinicopathological features were analyzed to evaluate the clinical value of Tagln2. Gain- and loss-of-function approaches were performed in ECs to investigate the functions of Tagln2 in angiogenesis. A combination of angiogenesis antibody array, RNA-Seq analyses and a series of in vitro experiments were performed to reveal the proangiogenic mechanism mediated by NRP1. Immunohistochemistry performed on an independent tissue chip (n=75) revealed significant upregulation of Tagln2 in tumor-derived ECs which were specifically immunolabeled with CD34. Additionally, high Tagln2 levels correlated significantly with the presence of lymph node as well as distant metastases. Gain- and loss-of-function approaches highlighted the function of Tagln2 in promoting EC proliferation, motility, and capillary-like tube formation and in reducing apoptosis. Tagln2 upregulation led to significantly increased mRNA and protein levels of NRP1 and subsequently activated the NRP1/VEGFR2 and downstream MAPK signaling pathways. These data indicate the importance of Tagln2 in angiogenesis, as a potential therapeutic target, and as a candidate prognostic marker in GC.
Lovastatin Inhibits EMT and Metastasis of Triple-Negative Breast Cancer Stem Cells Through Dysregulation of Cytoskeleton-Associated Proteins
Authors: Zheng Chanjuan , Yan Shichao , Lu Lu , Yao Hui , He Guangchun , Chen Sisi , Li Ying , Peng Xiaojun , Cheng Zhongyi , Wu Mi , Zhang Qiuting , Li Guifei , Fu Shujun , Deng Xiyun
Published: June 2021

Triple-negative breast cancer (TNBC) is more aggressive and has poorer prognosis compared to other subtypes of breast cancer. Epithelial-to-mesenchymal transition (EMT) is a process in which epithelial cells transform into mesenchymal-like cells capable of migration, invasion, and metastasis. Recently, we have demonstrated that lovastatin, a 3-hydroxy-3-methylglutaryl-coenzyme A reductase inhibitor and a lipid-lowering drug, could inhibit stemness properties of cancer stem cells (CSCs) derived from TNBC cell in vitro and in vivo. This study is aimed at investigating whether lovastatin inhibits TNBC CSCs by inhibiting EMT and suppressing metastasis and the mechanism involved. In the present study, we found that lovastatin dysregulated lysine succinylation of cytoskeleton-associated proteins in CSCs derived from TNBC MDA-MB-231 cell. Lovastatin inhibited EMT as demonstrated by down-regulation of the protein levels of Vimentin and Twist in MDA-MB-231 CSCs in vitro and vivo and by reversal of TGF-β1-induced morphological change in MCF10A cells. Lovastatin also inhibited the migration of MDA-MB-231 CSCs. The disruption of cytoskeleton in TNBC CSCs by lovastatin was demonstrated by the reduction of the number of pseudopodia and the relocation of F-actin cytoskeleton. Combination of lovastatin with doxorubicin synergistically inhibited liver metastasis of MDA-MB-231 CSCs. Bioinformatics analysis revealed that higher expression levels of cytoskeleton-associated genes were characteristic of TNBC and predicted survival outcomes in breast cancer patients. These data suggested that lovastatin could inhibit the EMT and metastasis of TNBC CSCs in vitro and in vivo through dysregulation of cytoskeleton-associated proteins.
Aggressiveness of Care at the End-of-Life in Cancer Patients and Its Association With Psychosocial Functioning in Bereaved Caregivers
Authors: Tönnies Justus , Hartmann Mechthild , Jäger Dirk , Bleyel Caroline , Becker Nikolaus , Friederich Hans-Christoph , Haun Markus W.
Published: June 2021

Study Registration

https://www.drks.de/drks_web/navigate.do?navigationId=trial.HTML&TRIAL_ID=DRKS00022837,DRKS00022837.

Background

Intensified oncological treatment for advanced cancer patients at the end-of-life has been specified as aggressiveness of care (AOC) and increased over the past decades. The aims of this study were to 1) determine the frequency of AOC in Central Europe, and 2) investigate differences in mental health outcomes in bereaved caregivers depending on whether the decedent had experienced AOC or not.

Materials and methods

We conducted a cross-sectional study in a large tertiary comprehensive cancer care center in Germany. Bereaved caregivers provided information about (a) treatment within the last month of life of the deceased cancer patient and (b) their own mental health status, i.e., decision regret, complicated grief, depression, and anxiety. After multiple imputation of missing data, differences in mental health outcomes between AOC-caregivers and non-AOC-caregivers were analyzed in a multivariate analysis of variances.

Results

We enrolled 298 bereaved caregivers of deceased cancer patients. AOC occurred in 30.9% of all patients. In their last month of life, 20.0% of all patients started a new chemotherapy regimen, and 13.8% received ICU-treatment. We found differences in mental health outcomes between bereaved AOC- and non-AOC-caregivers. Bereaved AOC caregivers experienced significantly more decision regret compared to non-AOC caregivers (Cohen’s d = 0.49, 95% CI [0.23, 0.76]).

Conclusion

AOC occurs frequently in European health care and is associated with poorer mental health outcomes in bereaved caregivers. Future cohort studies should substantiate these findings and explore specific trajectories related to AOC. Notwithstanding, shared-decision making at end-of-life should increasingly account for both patients’ and caregivers’ preferences.
Identifying Critical States of Complex Diseases by Single-Sample Jensen-Shannon Divergence
Authors: Yan Jinling , Li Peiluan , Gao Rong , Li Ying , Chen Luonan
Published: June 2021

Motivation

The evolution of complex diseases can be modeled as a time-dependent nonlinear dynamic system, and its progression can be divided into three states, i.e., the normal state, the pre-disease state and the disease state. The sudden deterioration of the disease can be regarded as the state transition of the dynamic system at the critical state or pre-disease state. How to detect the critical state of an individual before the disease state based on single-sample data has attracted many researchers’ attention.

Methods

In this study, we proposed a novel approach, i.e., single-sample-based Jensen-Shannon Divergence (sJSD) method to detect the early-warning signals of complex diseases before critical transitions based on individual single-sample data. The method aims to construct score index based on sJSD, namely, inconsistency index (ICI).

Results

This method is applied to five real datasets, including prostate cancer, bladder urothelial carcinoma, influenza virus infection, cervical squamous cell carcinoma and endocervical adenocarcinoma and pancreatic adenocarcinoma. The critical states of 5 datasets with their corresponding sJSD signal biomarkers are successfully identified to diagnose and predict each individual sample, and some “dark genes” that without differential expressions but are sensitive to ICI score were revealed. This method is a data-driven and model-free method, which can be applied to not only disease prediction on individuals but also targeted drug design of each disease. At the same time, the identification of sJSD signal biomarkers is also of great significance for studying the molecular mechanism of disease progression from a dynamic perspective.
The Application of Combined Immune Checkpoint Inhibitor Modalities in Previously Treated Non-Small Cell Lung Cancer Patients and the Associations Thereof With the Lung Immune Prognostic Index
Authors: Zhang Ting , Yang Xue , Zhao Jing , Xia Lixia , Wang Qiyuan , Jin Rui , Zhou Lingxiao , Zhang Bin , Zhao Jun , Li Huijie , Li Wen , Xia Yang
Published: June 2021

Background

Immune checkpoint inhibitor (ICI) monotherapy remains the standard of care for patients with previously treated non-small cell lung cancer. However, few reports have compared the clinical benefits of second-line ICIs alone with those of ICIs combined with other therapies, including anti-angiogenesis therapy or chemotherapy.

Methods

Patients with previously treated advanced non-small cell lung cancer who received ICIs were retrospectively reviewed. The progression-free survival (PFS), overall survival, objective response rate, disease control rate, and safety were assessed. Complete blood cell counts and serum lactate dehydrogenase (LDH) levels were measured before and after ICI treatment.

Results

Of 120 patients, 75 were treated with ICI monotherapy, 26 with ICIs plus anti-angiogenic therapy (ICI+A), and 19 with ICIs plus chemotherapy (ICI+C). The objective response rate was significantly higher in the ICI+C group (57.9%) than ICI monotherapy (26.3%) and ICI+A (31.8%) groups. The depth of response was significantly greater in the ICI+C (-35.1%) than ICI+A (−2.04%) and ICI monotherapy (3.963%) groups. ICI+C afforded a better PFS compared with the ICI monotherapy and ICI+A groups (8.5 vs. 4.6 and 4.1 months, respectively). Notably, the pre- and post-treatment peripheral neutrophil/lymphocyte ratios and serum LDH levels were negatively correlated with the PFS of the entire cohort. More importantly, the pretreatment lung immune prognostic index (neutrophil/lymphocyte ratio ≥ 4 and LDH level ≥ upper limit of normal) satisfactorily predicted the responses to ICI-based strategies. Adverse events (AEs) occurred in 65.3%, 92.3%, and 94.7% of patients in the ICI monotherapy, ICI+A, and ICI+C groups, respectively. Grade 3–5 AEs were more common in the combination therapy groups (ICI+A, 19.2%; ICI+C, 21%; ICI monotherapy, 4%).

Conclusion

In second-line settings and beyond, ICIs combined with chemotherapy prolonged survival, with tolerable AEs. Addition of anti-angiogenic agents to ICIs did not afford any additional benefits. Further prospective studies are warranted.
Implementation of a Framelet-Based Spectral Reconstruction for Multi-Slice Spiral CT
Authors: Li Xin , Zhang Yanbo , Mao Shuwei , Zhu Jiehua , Ye Yangbo
Published: June 2021

Spectral CT utilizes spectral information of X-ray sources to reconstruct energy-resolved X-ray images and has wide medical applications. Compared with conventional energy-integrated CT scanners, however, spectral CT faces serious technical difficulties in hardware, and hence its clinical use has been expensive and limited. The goal of this paper is to present a software solution and an implementation of a framelet-based spectral reconstruction algorithm for multi-slice spiral scanning based on a conventional energy-integrated CT hardware platform. In the present work, we implement the framelet-based spectral reconstruction algorithm using compute unified device architecture (CUDA) with bowtie filtration. The platform CUDA enables fast execution of the program, while the bowtie filter reduces radiation exposure. We also adopt an order-subset technique to accelerate the convergence. The multi-slice spiral scanning geometry with these additional features will make the framelet-based spectral reconstruction algorithm more powerful for clinical applications. The method provides spectral information from just one scan with a standard energy-integrating detector and produces color CT images, spectral curves of the attenuation coefficient at every point inside the object, and photoelectric images, which are all valuable imaging tools in cancerous diagnosis. The proposed algorithm is tested with a Catphan phantom and real patient data sets for its performance. In experiments with the Catphan 504 phantom, the synthesized color image reveals changes in the level of colors and details and the yellow color in Teflon indicates a special spectral property which is invisible in regular CT reconstruction. In experiments with clinical images, the synthesized color images provide some extra details which are helpful for clinical diagnosis, for example, details about the renal pelvis and lumbar join. The numerical studies indicate that the proposed method provides spectral image information which can reveal fine structures in clinical images and that the algorithm is efficient regarding to the computational time. Thus, the proposed algorithm has a great potential in practical application.
Temperature and Soil Moisture Stress Modulate the Host Defense Response in Chickpea During Dry Root Rot Incidence
Authors: Sharath Chandran U. S. , Tarafdar Avijit , Mahesha H. S. , Sharma Mamta
Published: June 2021

Dry root rot caused by the necrotrophic phytopathogenic fungus Rhizoctonia bataticola is an emerging threat to chickpea production in India. In the near future, the expected increase in average temperature and inconsistent rainfall patterns resultant of changing climatic scenarios are strongly believed to exacerbate the disease to epidemic proportions. The present study aims to quantify the collective role of temperature and soil moisture content (SMC) on disease progression in chickpea under controlled environmental conditions. In our study, we could find that both temperature and soil moisture played a decisive role in influencing the dry root rot disease scenario. As per the disease susceptibility index (DSI), a combination of high temperature (35°C) and low SMC (60%) was found to elicit the highest disease susceptibility in chickpea. High pathogen colonization was realized in chickpea root tissue at all time-points irrespective of genotype, temperature, and SMC. Interestingly, this was in contrast to the DSI where no visible symptoms were recorded in the roots or foliage during the initial time-points. For each time-point, the colonization was slightly higher at 35°C than 25°C, while the same did not vary significantly with respect to SMC. Furthermore, the differential expression study revealed the involvement of host defense-related genes like endochitinase and PR-3-type chitinase (CHI III) genes in delaying the dry root rot (DRR) disease progression in chickpea. Such genes were found to be highly active during the early stages of infection especially under low SMC.
Biochemical and Genetic Approaches Improving Nitrogen Use Efficiency in Cereal Crops: A Review
Authors: Sandhu Nitika , Sethi Mehak , Kumar Aman , Dang Devpriya , Singh Jasneet , Chhuneja Parveen
Published: June 2021

Nitrogen is an essential nutrient required in large quantities for the proper growth and development of plants. Nitrogen is the most limiting macronutrient for crop production in most of the world’s agricultural areas. The dynamic nature of nitrogen and its tendency to lose soil and environment systems create a unique and challenging environment for its proper management. Exploiting genetic diversity, developing nutrient efficient novel varieties with better agronomy and crop management practices combined with improved crop genetics have been significant factors behind increased crop production. In this review, we highlight the various biochemical, genetic factors and the regulatory mechanisms controlling the plant nitrogen economy necessary for reducing fertilizer cost and improving nitrogen use efficiency while maintaining an acceptable grain yield.
Raman Spectroscopy Can Distinguish Glyphosate-Susceptible and -Resistant Palmer Amaranth (Amaranthus palmeri)
Authors: Singh Vijay , Dou Tianyi , Krimmer Mark , Singh Shilpa , Humpal Dillon , Payne William Z. , Sanchez Lee , Voronine Dmitri V. , Prosvirin Andrey , Scully Marlan , Kurouski Dmitry , Bagavathiannan Muthukumar
Published: June 2021

The non-judicious use of herbicides has led to a widespread evolution of herbicide resistance in various weed species including Palmer amaranth, one of the most aggressive and troublesome weeds in the United States. Early detection of herbicide resistance in weed populations may help growers devise alternative management strategies before resistance spreads throughout the field. In this study, Raman spectroscopy was utilized as a rapid, non-destructive diagnostic tool to distinguish between three different glyphosate-resistant and four -susceptible Palmer amaranth populations. The glyphosate-resistant populations used in this study were 11-, 32-, and 36-fold more resistant compared to the susceptible standard. The 5-enolpyruvylshikimate-3-phosphate synthase (EPSPS) gene copy number for these resistant populations ranged from 86 to 116. We found that Raman spectroscopy could be used to differentiate herbicide-treated and non-treated susceptible populations based on changes in the intensity of vibrational bands at 1156, 1186, and 1525 cm–1 that originate from carotenoids. The partial least squares discriminant analysis (PLS-DA) model indicated that within 1 day of glyphosate treatment (D1), the average accuracy of detecting herbicide-treated and non-treated susceptible populations was 90 and 73.3%, respectively. We also found that glyphosate-resistant and -susceptible populations of Palmer amaranth can be easily detected with an accuracy of 84.7 and 71.9%, respectively, as early as D1. There were relative differences in the concentration of carotenoids in plants with different resistance levels, but these changes were not significant. The results of the study illustrate the utility of Raman spectra for evaluation of herbicide resistance and stress response in plants under field conditions.
Transcriptome Analysis Reveals Putative Target Genes of APETALA3-3 During Early Floral Development in Nigella damascena L.
Authors: Deveaux Yves , Conde e Silva Natalia , Manicacci Domenica , Le Guilloux Martine , Brunaud Véronique , Belcram Harry , Joets Johann , Soubigou-Taconnat Ludivine , Delannoy Etienne , Corti Hélène , Balzergue Sandrine , Caius Jose , Nadot Sophie , Damerval Catherine
Published: June 2021

Even though petals are homoplastic structures, their identity consistently involves genes of the APETALA3 (AP3) lineage. However, the extent to which the networks downstream of AP3 are conserved in species with petals of different evolutionary origins is unknown. In Ranunculaceae, the specificity of the AP3-III lineage offers a great opportunity to identify the petal gene regulatory network in a comparative framework. Using a transcriptomic approach, we investigated putative target genes of the AP3-III ortholog NdAP3-3 in Nigella damascena at early developmental stages when petal identity is determined, and we compared our data with that from selected eudicot species. We generated a de novo reference transcriptome to carry out a differential gene expression analysis between the wild-type and mutant NdAP3-3 genotypes differing by the presence vs. absence of petals at early stages of floral development. Among the 1,620 genes that were significantly differentially expressed between the two genotypes, functional annotation suggested a large involvement of nuclear activities, including regulation of transcription, and enrichment in processes linked to cell proliferation. Comparing with Arabidopsis data, we found that highly conserved genes between the two species are enriched in homologs of direct targets of the AtAP3 protein. Integrating AP3-3 binding site data from another Ranunculaceae species, Aquilegia coerulea, allowed us to identify a set of 18 putative target genes that were conserved between the three species. Our results suggest that, despite the independent evolutionary origin of petals in core eudicots and Ranunculaceae, a small conserved set of genes determines petal identity and early development in these taxa.
Perspectives on Applications of Hierarchical Gene-To-Phenotype (G2P) Maps to Capture Non-stationary Effects of Alleles in Genomic Prediction
Authors: Powell Owen M. , Voss-Fels Kai P. , Jordan David R. , Hammer Graeme , Cooper Mark
Published: June 2021

Genomic prediction of complex traits across environments, breeding cycles, and populations remains a challenge for plant breeding. A potential explanation for this is that underlying non-additive genetic (GxG) and genotype-by-environment (GxE) interactions generate allele substitution effects that are non-stationary across different contexts. Such non-stationary effects of alleles are either ignored or assumed to be implicitly captured by most gene-to-phenotype (G2P) maps used in genomic prediction. The implicit capture of non-stationary effects of alleles requires the G2P map to be re-estimated across different contexts. We discuss the development and application of hierarchical G2P maps that explicitly capture non-stationary effects of alleles and have successfully increased short-term prediction accuracy in plant breeding. These hierarchical G2P maps achieve increases in prediction accuracy by allowing intermediate processes such as other traits and environmental factors and their interactions to contribute to complex trait variation. However, long-term prediction remains a challenge. The plant breeding community should undertake complementary simulation and empirical experiments to interrogate various hierarchical G2P maps that connect GxG and GxE interactions simultaneously. The existing genetic correlation framework can be used to assess the magnitude of non-stationary effects of alleles and the predictive ability of these hierarchical G2P maps in long-term, multi-context genomic predictions of complex traits in plant breeding.
Candidate Gene Analysis for Nitrogen Absorption and Utilization in Japonica Rice at the Seedling Stage Based on a Genome-Wide Association Study
Authors: Xin Wei , Wang Jingguo , Li Jia , Zhao Hongwei , Liu Hualong , Zheng Hongliang , Yang Luomiao , Wang Chao , Yang Fan , Chen Jiahui , Zou Detang
Published: June 2021

Over-application of nitrogen (N) fertilizer in fields has had a negative impact on both environment and human health. Domesticated rice varieties with high N use efficiency (NUE) reduce fertilizer requirements, enabling sustainable agriculture. Genome-wide association study (GWAS) analysis of N absorption and utilization traits under low and high N conditions was performed to obtain 12 quantitative trait loci (QTLs) based on genotypic data including 151,202 single-nucleotide polymorphisms (SNPs) developed by re-sequencing 267 japonica rice varieties. Eighteen candidate genes were obtained by integrating GWAS and transcriptome analyses; among them, the functions of OsNRT2.4, OsAMT1.2, and OsAlaAT genes in N transport and assimilation have been identified, and OsJAZ12 and OsJAZ13 also play important roles in rice adaptation to abiotic stresses. A NUE-related candidate gene, OsNAC68, was identified by quantitative real-time PCR (qRT-PCR) analyses. OsNAC68 encodes a NAC transcription factor and has been shown to be a positive regulator of the drought stress response in rice. Overexpression of OsNAC68 significantly increased rice NUE and grain yield under deficient N conditions, but the difference was not significant under sufficient N conditions. NUE and grain yield significantly decreased under both N supply conditions in the osbnac68 mutant. This study provides crucial insights into the genetic basis of N absorption and utilization in rice, and a NUE-related gene, OsNAC68, was cloned to provide important resources for rice breeding with high NUE and grain yield.
Identification of a Sulfatase that Detoxifies Glucosinolates in the Phloem-Feeding Insect Bemisia tabaci and Prefers Indolic Glucosinolates
Authors: Manivannan Abinaya , Israni Bhawana , Luck Katrin , Götz Monika , Seibel Elena , Easson Michael L. A. E. , Kirsch Roy , Reichelt Michael , Stein Beate , Winter Stephan , Gershenzon Jonathan , Vassão Daniel Giddings
Published: June 2021

Cruciferous plants in the order Brassicales defend themselves from herbivory using glucosinolates: sulfur-containing pro-toxic metabolites that are activated by hydrolysis to form compounds, such as isothiocyanates, which are toxic to insects and other organisms. Some herbivores are known to circumvent glucosinolate activation with glucosinolate sulfatases (GSSs), enzymes that convert glucosinolates into inactive desulfoglucosinolates. This strategy is a major glucosinolate detoxification pathway in a phloem-feeding insect, the silverleaf whitefly Bemisia tabaci, a serious agricultural pest of cruciferous vegetables. In this study, we identified and characterized an enzyme responsible for glucosinolate desulfation in the globally distributed B. tabaci species MEAM1. In in vitro assays, this sulfatase showed a clear preference for indolic glucosinolates compared with aliphatic glucosinolates, consistent with the greater representation of desulfated indolic glucosinolates in honeydew. B. tabaci might use this detoxification strategy specifically against indolic glucosinolates since plants may preferentially deploy indolic glucosinolates against phloem-feeding insects. In vivo silencing of the expression of the B. tabaci GSS gene via RNA interference led to lower levels of desulfoglucosinolates in honeydew. Our findings expand the knowledge on the biochemistry of glucosinolate detoxification in phloem-feeding insects and suggest how detoxification pathways might facilitate plant colonization in a generalist herbivore.
Molecular Traits and Functional Analysis of the CLAVATA3/Endosperm Surrounding Region-Related Small Signaling Peptides in Three Species of Gossypium Genus
Authors: Lin Huan , Wang Wei , Chen Xiugui , Sun Zhenting , Han Xiulan , Wang Shuai , Li Yan , Ye Wuwei , Yin Zujun
Published: June 2021

The CLAVATA3/endosperm surrounding region-related (CLE) small peptides are a group of C-terminally encoded and post-translationally modified signal molecules involved in regulating the growth and development of various plants. However, the function and evolution of these peptides have so far remained elusive in cotton. In this study, 55, 56, and 86 CLE genes were identified in the Gossypium raimondii, Gossypium arboreum, and Gossypium hirsutum genomes, respectively, and all members were divided into seven groups. These groups were distinctly different in their protein characteristics, gene structures, conserved motifs, and multiple sequence alignment. Whole genome or segmental duplications played a significant role in the expansion of the CLE family in cotton, and experienced purifying selection during the long evolutionary process in cotton. Cis-acting regulatory elements and transcript profiling revealed that the CLE genes of cotton exist in different tissues, developmental stages, and respond to abiotic stresses. Protein properties, structure prediction, protein interaction network prediction of GhCLE2, GhCLE33.2, and GhCLE28.1 peptides were, respectively, analyzed. In addition, the overexpression of GhCLE2, GhCLE33.2, or GhCLE28.1 in Arabidopsis, respectively, resulted in a distinctive shrub-like dwarf plant, slightly purple leaves, large rosettes with large malformed leaves, and lack of reproductive growth. This study provides important insights into the evolution of cotton CLEs and delineates the functional conservatism and divergence of CLE genes in the growth and development of cotton.
Exogenous 2,4-Epibrassinolide Treatment Maintains the Quality of Carambola Fruit Associated With Enhanced Antioxidant Capacity and Alternative Respiratory Metabolism
Authors: Zhu Xiaoyang , Chen Yuxin , Li Junyi , Ding Xiaochun , Xiao Shuangling , Fan Silin , Song Zunyang , Chen Weixin , Li Xueping
Published: June 2021

Brassinosteroids act by delaying fruit ripening. The effects of different concentrations of 2,4-epibrassinolide (eBL) treatments on carambola fruit ripening were investigated. The results show that treatment of 2.8 mg L–1, eBL with 10 min effectively delays ripening and maintains the quality of carambola fruit. This is achieved by retarding color changes and firmness losses while maintaining high level of soluble protein content and vitamin C, and low organic acid content. eBL-delayed senescence may be due to the inhibition of respiration rate and enhanced antioxidant system. It is noteworthy that eBL treatment markedly reduces the content of fructose-6-phosphate (6-P-F) and enhances the activity of cytochrome oxidase (CCO), and the total activity of glucose-6-phosphate dehydrogenase (G-6-PDH) and 6-phosphate gluconate dehydrogenase (6-PGDH). eBL treatment induces the IAA and GA contents but reduces that of ABA. In general, senescence retardation and quality improvement by eBL treatment may be due to the enhanced antioxidant capacity and altered respiratory pathways.
Agrobacterium VirE2 Protein Modulates Plant Gene Expression and Mediates Transformation From Its Location Outside the Nucleus
Authors: Lapham Rachelle A. , Lee Lan-Ying , Xhako Eder , Gómez Esteban Gañán , Nivya V. M. , Gelvin Stanton B.
Published: June 2021

Agrobacterium effector protein VirE2 is important for plant transformation. VirE2 likely coats transferred DNA (T-DNA) in the plant cell and protects it from degradation. VirE2 localizes to the plant cytoplasm and interacts with several host proteins. Plant-expressed VirE2 can complement a virE2 mutant Agrobacterium strain to support transformation. We investigated whether VirE2 could facilitate transformation from a nuclear location by affixing to it a strong nuclear localization signal (NLS) sequence. Only cytoplasmic-, but not nuclear-localized, VirE2 could stimulate transformation. To investigate the ways VirE2 supports transformation, we generated transgenic Arabidopsis plants containing a virE2 gene under the control of an inducible promoter and performed RNA-seq and proteomic analyses before and after induction. Some differentially expressed plant genes were previously known to facilitate transformation. Knockout mutant lines of some other VirE2 differentially expressed genes showed altered transformation phenotypes. Levels of some proteins known to be important for transformation increased in response to VirE2 induction, but prior to or without induction of their corresponding mRNAs. Overexpression of some other genes whose proteins increased after VirE2 induction resulted in increased transformation susceptibility. We conclude that cytoplasmically localized VirE2 modulates both plant RNA and protein levels to facilitate transformation.
RNA N6-Methyladenosine Responds to Low-Temperature Stress in Tomato Anthers
Authors: Yang Dandan , Xu Huachao , Liu Yue , Li Mengzhuo , Ali Muhammad , Xu Xiangyang , Lu Gang
Published: June 2021

Cold stress is a serious threat to subtropical crop pollen development and induces yield decline. N6-methyladenosine (m6A) is the most frequent mRNA modification and plays multiple physiological functions in plant development. However, whether m6A regulates pollen development is unclear, and its putative role in cold stress response remains unknown. Here, we observed that moderate low-temperature (MLT) stress induced pollen abortion in tomato. This phenotype was caused by disruption of tapetum development and pollen exine formation, accompanied by reduced m6A levels in tomato anther. Analysis of m6A-seq data revealed 1,805 transcripts displayed reduced m6A levels and 978 transcripts showed elevated m6A levels in MLT-stressed anthers compared with those in anthers under normal temperature. These differentially m6A enriched transcripts under MLT stress were mainly related to lipid metabolism, adenosine triphosphatase (ATPase) activity, and ATP-binding pathways. An ATP-binding transcript, SlABCG31, had significantly upregulated m6A modification levels, which was inversely correlated to the dramatically downregulated expression level. These changes correlated with higher abscisic acid (ABA) levels in anthers and disrupted pollen wall formation under low-temperature stress. Our findings characterized m6A as a novel layer of complexity in gene expression regulation and established a molecular link between m6A methylation and tomato anther development under low-temperature conditions.
Psychometric Properties of the Spanish Version of the Cognitive Emotional Regulation Difficulties Questionnaire (CERQ) in Higher Education Students in Times of Covid-19
Authors: Rodríguez-Sabiote Clemente , Ibáñez-Cubillas Pilar , López-Rodríguez Slava , Álvarez-Rodríguez José
Published: June 2021

The Cognitive Emotion Regulation Questionnaire (CERQ) is an instrument developed to assess the cognitive strategies of emotional regulation used by people after experiencing a negative event. The present study aimed to validate the Spanish version of the CERQ in students of the University of Granada (Spain) during the Covid-19 homebound. An online scale was developed and applied based on the Spanish version of the CERQ-S36, consisting of 36 items structured around nine cognitive strategies. Using a mixed sampling, the scale was applied to 450 students from different degree programmes. Regarding the psychometric results of the scale, firstly, in relation to reliability as internal consistency, we found that the scale applied to University students in a Covid-19 setting is highly stable. Secondly, in reference to concurrent criterion validity, we can conclude that the items individually measure the same as the total scale (taken as internal criterion), and thirdly and finally, in relation to construct validation, the two factor analyses implemented, one exploratory and the other confirmatory in nature, conform a factor structure of latent dimensions identical to the original one. In conclusion, the results obtained as a whole suggest that the CERQ-S36 scale could be useful for assessing cognitive coping in University populations in times of crisis. In situations such as the current global emergency due to the presence of Covid-19, the scale is useful for understanding emotional regulation strategies. More studies should be carried out with this scale to find out how emotions influence and what consequences they have on the health and psychological functioning of University students in times of social crisis.
A Deformation-Based Shape Study of the Corpus Callosum in First Episode Schizophrenia
Authors: Huang Weikai , Chen Minhua , Lyu Guiwen , Tang Xiaoying
Published: June 2021

Background: Previous first-episode schizophrenia (FES) studies have reported abnormalities in the volume and mid-sagittal size of the corpus callosum (CC), but findings have been inconsistent. Besides, the CC shape has rarely been analyzed in FES. Therefore, in this study, we investigated FES-related CC shape abnormalities using 198 participants [92 FES patients and 106 healthy controls (HCs)].

Methods: We conducted statistical shape analysis of the mid-sagittal CC curve in a large deformation diffeomorphic metric mapping framework. The CC was divided into the genu, body, and splenium (gCC, bCC, and sCC) to target the key CC sub-regions affected by the FES pathology. Gender effects have been investigated.

Results: There were significant area differences between FES and HC in the entire CC and gCC but not in bCC nor sCC. In terms of the localized shape morphometrics, significant region-specific shape inward-deformations were detected in the superior portion of gCC and the anterosuperior portion of bCC in FES. These global area and local shape morphometric abnormalities were restricted to female FES but not male FES.

Conclusions: gCC was significantly affected in the neuropathology of FES and this finding was specific to female FES. This study suggests that gCC may be a key sub-region that is vulnerable to the neuropathology of FES, specifically in female patients. The morphometrics of gCC may serve as novel and efficient biomarkers for screening female FES patients.
Neighborhood Environments and Utilitarian Walking Among Older vs. Younger Rural Adults
Authors: Lee Chanam , Lee Chunkeun , Stewart Orion T. , Carlos Heather A. , Adachi-Mejia Anna , Berke Ethan M. , Doescher Mark P.
Published: June 2021

Introduction: Walking has the potential to promote health across the life span, but age-specific features of the neighborhood environment (NE), especially in rural communities, linked with walking have not been adequately characterized. This study examines the relationships between NE and utilitarian walking among older vs. younger adults living in US rural towns.

Methods: Data for this cross-sectional study came from telephone interviews in 2011–2012 with 2,140 randomly sampled younger (18–64 years, n = 1,398) and older (65+ years, n = 742) adults, collecting personal and NE perception variables. NE around each participant's home was also measured objectively using geographic information system techniques. Separate mixed-effects logistic regression models were estimated for the two age groups, predicting the odds of utilitarian walking at least once a week.

Results: Perceived presence of crosswalks and pedestrian signals was significantly related to utilitarian walking in both age groups. Among older adults, unattended dogs, lighting at night, and religious institutions were positively while steep slope was negatively associated with their walking. For younger adults, traffic speed (negative, –), public transportation (positive, +), malls (–), cultural/recreational destinations (+), schools (+), and resource production land uses such as farms and mines (–) were significant correlates of utilitarian walking.

Conclusion: Different characteristics of NE are associated with utilitarian walking among younger vs. older adults in US rural towns. Optimal modifications of NE to promote walking may need to reflect these age differences.
Public Policies and One Health in Brazil: The Challenge of the Disarticulation
Authors: Espeschit Isis de Freitas , Santana Clara Marques , Moreira Maria Aparecida Scatamburlo
Published: June 2021

Working the One health strategy in developing countries is a challenge, due to structural weaknesses or deprivation of financial, human, and material resources. Brazil has policies and programs that would allow continuous and systematic monitoring of human, animal, and environmental health, recommending strategies for control and prevention. For animals, there are components of the Epidemiological Surveillance of zoonosis and Animal Health Programs. To guarantee food safety, there are Health Surveillance services and support of the Agropecuary Defense in the inspection of these products, productive environments, and their inputs. Environmental Surveillance Services monitor water and air quality, which may influence health. For human health, these and other services related to Health Surveillance, such as Worker Health and Epidemiological Surveillance, which has a training program responsible for forming professionals groups to respond effectively to emergencies in public health are available. Therefore, Brazil has instruments that may allow integrated planning and intervention based on the One Health initiative. However, the consolidation of this faces several challenges, such as insufficient resources, professional alienation, and lack of the recognition of the importance of animal and environmental health for the maintenance of human and planetary well-being. This culminates in disarticulation, lack of communication, and integration between organizations. Thus, efforts to share attributions and responsibilities must be consolidated, overcoming the verticality of the actions, promoting efficiency and effectiveness. Finally, this perspective aims to describe the government instruments that constitute potential national efforts and the challenges for the consolidation of the One Health initiative in Brazil.
Beirut Ammonium Nitrate Blast: Analysis, Review, and Recommendations
Authors: Al-Hajj Samar , Dhaini Hassan R. , Mondello Stefania , Kaafarani Haytham , Kobeissy Firas , DePalma Ralph G.
Published: June 2021

A massive chemical detonation occurred on August 4, 2020 in the Port of Beirut, Lebanon. An uncontrolled fire in an adjacent warehouse ignited ~2,750 tons of Ammonium Nitrate (AN), producing one of the most devastating blasts in recent history. The blast supersonic pressure and heat wave claimed the lives of 220 people and injured more than 6,500 instantaneously, with severe damage to the nearby dense residential and commercial areas. This review represents one of the in-depth reports to provide a detailed analysis of the Beirut blast and its health and environmental implications. It further reviews prior AN incidents and suggests actionable recommendations and strategies to optimize chemical safety measures, improve emergency preparedness, and mitigate the delayed clinical effects of blast and toxic gas exposures. These recommended actionable steps offer a starting point for government officials and policymakers to build frameworks, adopt regulations, and implement chemical safety protocols to ensure safe storage of hazardous materials as well as reorganizing healthcare system disaster preparedness to improve emergency preparedness in response to similar large-scale disasters and promote population safety. Future clinical efforts should involve detailed assessment of physical injuries sustained by blast victims, with systemic mitigation and possible treatment of late blast effects involving individuals, communities and the region at large.
The Role of Self-Efficacy and Injunctive Norms in Helping Older Adults Decide to Stay Home During the COVID-19 Pandemic
Authors: Macy Jonathan T. , Owens Christopher , Mullis Kristina , Middlestadt Susan E.
Published: June 2021

Purpose: Because older adults are at elevated risk of COVID-19-related adverse health outcomes, and staying at home is an effective strategy to avoid unnecessary exposures, the current formative study used the Reasoned Action Approach (RAA) to identify the beliefs underlying older adults' decision to stay home for the next month.

Methods: The participants (weighted n = 206, age 65-94) for the current study were selected from a nationally representative online survey of US adults from April 10-20, 2020. We used multiple linear regression to estimate the relative contribution of the four RAA global constructs (instrumental attitude, injunctive norms, descriptive norms, and self-efficacy) in explaining intention to stay home after controlling for demographic covariates. We also conducted a content analysis to identify beliefs about advantages, disadvantages, and facilitators of staying home.

Results: After controlling for demographic characteristics, injunctive norms (b = 0.208; SE = 0.059; B = 0.213, p < 0.01) and self-efficacy (b = 0.532; SE = 0.058; B = 0.537, p < 0.001) showed statistically significant independent associations with intention to stay home. The specific beliefs underlying the decision to stay home spanned across health and wellness dimensions and suggested interpersonal, mental health, and leisure/recreational facilitators.

Conclusions: These findings suggest three public health intervention targets. First, self-efficacy building interventions could enhance older adults' perceptions of their ability to stay home to avoid unnecessary exposures. Second, health communication messages to address injunctive norms could emphasize that people important to older adults think they should stay home. Third, for the youngest of the older adults, health communication messages could emphasize the advantages of staying home.
Educational Attainment Decreases the Risk of COVID-19 Severity in the European Population: A Two-Sample Mendelian Randomization Study
Authors: Yoshikawa Masahiro , Asaba Kensuke
Published: June 2021

Observational studies have reported that the severity of COVID-19 depends not only on physical conditions but also on socioeconomic status, including educational level. Because educational attainment (EA), which measures the number of years of schooling, is moderately heritable, we investigated the causal association of EA on the risk of COVID-19 severity using the Mendelian randomization (MR) approach. A two-sample MR analysis was performed using publicly available summary-level data sets of genome-wide association studies (GWASs). A total of 235 single-nucleotide polymorphisms (SNPs) were extracted as instrumental variables for the exposure of EA from the Social Science Genetic Association Consortium GWAS summary data of 766,345 participants of European ancestry. The effect of each SNP on the outcome of COVID-19 severity risk was obtained from the GWAS summary data of 1,059,456 participants of European ancestry gathered from the COVID-19 Host Genetics Initiative. Using inverse variance weighted method, our MR study shows that EA was significantly associated with a lower risk of COVID-19 severity (odds ratio per one standard deviation increase in years of schooling, 0.540; 95% confidence interval, 0.376–0.777, P = 0.0009). A series of sensitivity analyses showed little evidence of bias. In conclusion, we show for the first time using a two-sample MR approach the associations between higher EA and the lower risk of COVID-19 severity in the European population. However, the genetic or epidemiological mechanisms underlying the association between EA and the risk of COVID-19 severity remain unknown, and further studies are warranted to validate the MR findings and investigate underlying mechanisms.