bluuebunny/crossref_metadata_2025 huggingface dataset:
Endothelial YAP/TAZ Signaling in Angiogenesis and Tumor Vasculature
Authors: Hooglugt Aukie , van der Stoel Miesje M. , Boon Reinier A. , Huveneers Stephan
Published: February 2021

Solid tumors are dependent on vascularization for their growth. The hypoxic, stiff, and pro-angiogenic tumor microenvironment induces angiogenesis, giving rise to an immature, proliferative, and permeable vasculature. The tumor vessels promote tumor metastasis and complicate delivery of anti-cancer therapies. In many types of tumors, YAP/TAZ activation is correlated with increased levels of angiogenesis. In addition, endothelial YAP/TAZ activation is important for the formation of new blood and lymphatic vessels during development. Oncogenic activation of YAP/TAZ in tumor cell growth and invasion has been studied in great detail, however the role of YAP/TAZ within the tumor endothelium remains insufficiently understood, which complicates therapeutic strategies aimed at targeting YAP/TAZ in cancer. Here, we overview the upstream signals from the tumor microenvironment that control endothelial YAP/TAZ activation and explore the role of their downstream targets in driving tumor angiogenesis. We further discuss the potential for anti-cancer treatments and vascular normalization strategies to improve tumor therapies.
Landscape Profiling Analysis of DPP4 in Malignancies: Therapeutic Implication for Tumor Patients With Coronavirus Disease 2019
Authors: Shu Lingling , Liu Yang , Li Jinyuan , Wu Xiaoping , Li Yang , Huang Hanying
Published: February 2021

Severe coronavirus disease 2019 (COVID-19), caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), is characterized by pneumonia, lymphopenia, and cytokine storms. Patients with underlying conditions, and especially cancer patients with impaired immunity, are particularly vulnerable to SARS-CoV-2 infection and complications. Although angiotensin converting enzyme II (ACE2) has been identified as a cellular binding receptor for SARS-CoV-2, immunopathological changes in severe cancer patients support the investigation of additional potential receptors such as dipeptidyl peptidase 4 (DPP4), a key immunoregulator. However, a comprehensive profiling analysis of DPP4 in malignancies remains obscure. In this study, using different datasets, we demonstrated the expression of DPP4 in healthy tissues and pan-cancers, showing the risk of different cancer types towards SARS-CoV-2 infection according to DPP4 expression levels. DPP4 expression was positively correlated with infiltrating levels of various immune cells and showed strong correlations with diverse immune marker sets in pan-cancer patients analyzed by Tumor Immune Estimation Resource (TIMER). These findings suggest that increased DPP4 expression in specific cancer patients might account for the high susceptibility to SARS-CoV-2 infection and the induction of cytokine storms. Due to the critical role of DPP4 in immunometabolism, our results indicate that pharmacological inhibition of DPP4 might provide beneficial therapeutic effects for SARS-CoV-2 treatment together with other strategies in specific tumor patients.
Case Discussion and Literature Review: Cancer Immunotherapy, Severe Immune-Related Adverse Events, Multi-Inflammatory Syndrome, and Severe Acute Respiratory Syndrome Coronavirus 2
Authors: Ragoonanan Dristhi , Khazal Sajad J. , Mejia Rodrigo , Ewing Linette , Durand Jean-Bernard , Bashoura Lara , Tayar Jean , Dailey Garnes Natalie , Petropoulos Demetrios , Tewari Priti , Bhatti Micah , Ahmad Ali Haider , Cortes Jose , Razvi Shehla , McBeth Katrina , Swinford Rita , Shoberu Basirat , Waseemuddin Waseem , Chi Linda , Gill Jonathan B. , Zaky Wafik , Daw Najat , Gutierrez Cristina , Tereffe Welela , Kebriaei Partow , Rezvani Katayoun , Shpall Elizabeth J. , Champlin Richard E. , Mahadeo Kris M.
Published: February 2021

Pediatric, adolescent and young adult (AYA) patients receiving novel cancer immunotherapies may develop associated toxicities with overlapping signs and symptoms that are not always easily distinguished from severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection/clinical sequelae. We describe 2 diagnostically challenging cases of SARS-CoV-2 and Multi-Inflammatory Syndrome-Adult (MIS-A), in patients with a history of acute lymphoblastic leukemia following cellular therapy administration and review evolving characterization of both the natural course of SARS-CoV-2 infection and toxicities experienced in younger cancer immunotherapy patients. Vigilant monitoring for unique presentations and epidemiologic surveillance to promptly detect changes in incidence of either condition may be warranted.
The Association Between Changes in Plasma Short-Chain Fatty Acid Concentrations and Hypertension in Children With Chronic Kidney Disease
Authors: Lu Pei-Chen , Hsu Chien-Ning , Lin I-Chun , Lo Mao-Hung , Yang Ming-Yu , Tain You-Lin
Published: February 2021

Background: Some children with chronic kidney disease (CKD) develop hypertension faster than others. This may be attributable to endothelial dysfunction, among other reasons. Short-chain fatty acids (SCFAs), that is, acetate, butyrate, and propionate, are known for reducing cardiovascular risks via preserving endothelial function. This study aimed to investigate the association between changes in plasma SCFA concentrations and in cardiovascular and endothelial parameters in children with CKD.

Methods: In total, 105 children and adolescents who met the CKD criteria were enrolled in this study, and 65 patients aged >6 years were divided into two groups based on the ambulatory BP measurements. The parameters of plasma SCFAs, endothelial function and morphology, and echocardiography were examined at the index visit and followed up after 1 year.

Results: We observed that 27.69% of 65 patients developed hypertension during the study period. Plasma acetate increased by 22.75 μM in the stable group (P < 0.001), whereas there was no change in the worsened BP group. The index higher plasma butyrate was positively correlated with worsened BP (adjusted odd ratio, 1.381; P = 0.013). At the follow-up, plasma butyrate decreased by 2.12 and 4.41 μM in the stable and worsened BP groups, respectively (P < 0.001). In 105 subjects, higher index plasma propionate was positively correlated with decreasing ejection fraction (adjusted odd ratio, 1.281; P = 0.046).

Conclusions: Plasma acetate seemed to play a role in preventing hypertension in children with CKD. However, the index plasma propionate and butyrate concentrations seemed to imply the development of cardiovascular problems in our 1-year study.
Case Report: Eosinophilic Myenteric Ganglionitis in a Child With Hirschsprung's Disease: A Challenge in Pseudo-Obstruction
Authors: D'Auria Enza , Calcaterra Valeria , Maestri Luciano , Meroni Milena , Selvaggio Giorgio Giuseppe Orlando , Villanacci Vincenzo , Nebuloni Manuela , Pelizzo Gloria
Published: February 2021

Introduction: The presentation of eosinophilic myenteric ganglionitis (EMG) can be similar to that of Hirschsprung's disease (HD). In a limited number of cases of pediatric patients, the diagnosis of both EMG and HD are reported. A case of pseudo-obstruction in EMG occurring in a child with HD diagnosis is discussed with literature review.

Case Presentation: A boy aged 2 years and 6 months presented with intractable constipation and abdominal distension. Histological HD diagnosis was carried out and transanal Soave pullthrough was performed. At the age of 3 years and 2 months, an infectious enterocolitis occurred. One month later, he presented with constipation, marked abdominal distension and melena. Full thickness colonic biopsies revealed eosinophilic myenteric ganglionitis. Specific IgE tests were positive for several foods. Dietary exclusion was adopted with resolution of clinical symptoms and histologic remission.

Conclusion: EMD may occur in patients with HD. At the onset, EMD may be associated with functional intestinal obstruction. The use of an elimination diet proved effective for the relief of symptoms. Long term follow-up is mandatory to define the timing of the reintroduction of foods.
Point-of-Care Ultrasound May Reduce Misdiagnosis of Pediatric Intussusception
Authors: Hsiao Hsiang-Ju , Wang Chao-Jan , Lee Chien-Chung , Hsin Yi-Chen , Yau Sze-Yuen , Chen Shih-Yen , Lo Wan-Chak , Wu Patricia-Wanping , Chen Chyi-Liang , Chang Yi-Jung
Published: February 2021

Aim: Intussusception, the most common abdominal emergency in early childhood, is frequently misdiagnosed at initial presentation. The effect of using point-of-care ultrasonography (POCUS) by emergency medicine physicians on pediatric intussusception misdiagnosis rate remains unclear. Here, we summarize outcomes and misdiagnoses before and after training junior and senior physicians on using POCUS for diagnosing intussusception and compared their performance levels.

Materials and Methods: This observational cohort analysis included patients with suspected intussusception who visited a pediatric emergency department (ED) between January 2017 and December 2019. All enrolled patients were evaluated by junior (<10-year experience) or senior attending physicians. Misdiagnosis was defined as a finding of negative air reduction or confirmation of diagnosis on ED revisit or admission. The misdiagnosis rates and outcomes before and after POCUS training for intussusception diagnosis were evaluated and performance of the junior and senior physicians was compared.

Results: Of the 167 enrolled patients, 130 were confirmed to have intussusception by air reduction. Misdiagnosis rate was significantly lower in the post-training patient group after training than in the pre-training patient group (43.7 vs. 12.7%, P < 0.001). After training, fewer misdiagnoses were made by the junior (59.1 vs. 25.9%, P = 0.003) and senior (31.7 vs. 0%, P < 0.001) physicians. In the post-training patient group, the door-to-reduction time and rate of ultrasonography consultation with an expert also decreased significantly (118.2 ± 124.5 vs. 198 ± 250.2 min, P = 0.006). Abdominal pain (80.9%) was the most common symptom of intussusception, followed by vomiting (58.3%), fever (17.8%), bloody stool (15.4%), and diarrhea (14.2%). Even after training, the presenting symptoms of intussusception often leading junior physicians to misdiagnosis were diarrhea and fever.

Conclusions: A brief POCUS training leads to decreased misdiagnosis rates in both the senior and junior physicians. Junior physicians should increase their awareness regarding diarrhea and fever being the presenting symptoms of intussusception, particularly in early childhood. Combining clinical judgment and POCUS results forms the core principle of the evaluation of children with intussusception.
Differential Expression Profiles and Functional Analysis of Long Non-coding RNAs in Children With Dilated Cardiomyopathy
Authors: Cai Dongxiao , Han Bo , Sun Wei , Zhang Li , Wang Jing , Jiang Diandong , Jia Hailin
Published: February 2021

Aim: To evaluate the expression profile of long non-coding RNAs (lncRNAs) in different left ventricular function of dilated cardiomyopathy (DCM) in children and explore their possible functions.

Methods: The lncRNA microarray experiment was used to determine the differential expression profile of lncRNA in three children with DCM and three healthy volunteers. The functional analysis and the construction of the lncRNA-mRNA interaction network were carried out to study the biological functions. Quantitative real-time polymerase chain reaction (qRT-PCR) analysis was used to verify the microarray data.

Results: There were 369 up-regulated lncRNAs identified in the DCM patients (fold change >2, P < 0.05), and 505 down-regulated lncRNAs. Based on target gene prediction and co-expression network construction, 9 differentially expressed lncRNAs were selected for the PCR to verify the accuracy of the microarray data, of which 5 were up-regulated and 4 were down-regulated, and finally proved that 7 of them were consistent with the trend of microarray data results. Four of these lncRNAs had significant differences between the patients with poor cardiac function and patients with improved left ventricle function.

Conclusion: LncRNAs may play an important role in pediatric DCM and may provide a new perspective for the pathogenesis, diagnosis, and treatment of this disease.
Impaired Oligodendrocyte Development Following Preterm Birth: Promoting GABAergic Action to Improve Outcomes
Authors: Shaw Julia C. , Crombie Gabrielle K. , Palliser Hannah K. , Hirst Jonathan J.
Published: February 2021

Preterm birth is associated with poor long-term neurodevelopmental and behavioral outcomes, even in the absence of obvious brain injury at the time of birth. In particular, behavioral disorders characterized by inattention, social difficulties and anxiety are common among children and adolescents who were born moderately to late preterm (32–37 weeks' gestation). Diffuse deficits in white matter microstructure are thought to play a role in these poor outcomes with evidence suggesting that a failure of oligodendrocytes to mature and myelinate axons is responsible. However, there remains a major knowledge gap over the mechanisms by which preterm birth interrupts normal oligodendrocyte development. In utero neurodevelopment occurs in an inhibitory-dominant environment due to the action of placentally derived neurosteroids on the GABAA receptor, thus promoting GABAergic inhibitory activity and maintaining the fetal behavioral state. Following preterm birth, and the subsequent premature exposure to the ex utero environment, this action of neurosteroids on GABAA receptors is greatly reduced. Coinciding with a reduction in GABAergic inhibition, the preterm neonatal brain is also exposed to ex utero environmental insults such as periods of hypoxia and excessive glucocorticoid concentrations. Together, these insults may increase levels of the excitatory neurotransmitter glutamate in the developing brain and result in a shift in the balance of inhibitory: excitatory activity toward excitatory. This review will outline the normal development of oligodendrocytes, how it is disrupted under excitation-dominated conditions and highlight how shifting the balance back toward an inhibitory-dominated environment may improve outcomes.
Impact of Ethnicity on COVID-19 Related Hospitalizations in Children During the First Pandemic Wave in Northern Italy
Authors: Baronio Roberto , Savaré Lucia , Ruggiero Jessica , Crotti Beatrice , Mazza Angelo , Marseglia Gian Luigi , Dodi Icilio , Cavalli Claudio , Schumacher Richard Fabian
Published: February 2021

There is increasing evidence that black people and other minorities have a higher incidence of severe COVID-19 disease, but little is known about the situation of children, especially in Europe. In general children are less infected and if so, frequently show mild or asymptomatic disease, making conclusions difficult. We collected data on SARS-CoV-2 associated hospitalizations in a well-defined population of 550,180 children up to 15 years in five hub-centers during the “first wave” at the heart of the pandemic in Northern Italy. Among the 451,053 Italian citizens 80 were hospitalized as compared to 31 out of 99,127 foreign citizens, giving a significantly higher risk (odds ratio 1.76; 95% CI: 1.16–2.66) for the foreign children. The risk was highest for children of African ethnicity as compared to Italians with an odds ratio of 2.76 (95% CI: 1.56–4.87). None of the patients deceased. There was no significant difference in age (thou infants regardless of ethnicity had a 10-fold higher risk), sex, length of hospitalization or comorbidities, namely overweight. As bureaucratic, cultural and information barriers mostly affect preventive and adult services and considering that in contrast to other countries, in Italy pediatric care is guaranteed free of (out-of-pocket) charge to all people <16 years, and hospitals are densely spaced, access to health care seems to be a minor problem. Thus, other possible root causes are discussed. We believe that this is an unbiased starting point to understand and overcome the reasons for the higher risk those children experience.
Integrated Network Pharmacology and Metabonomics to Reveal the Myocardial Protection Effect of Huang-Lian-Jie-Du-Tang on Myocardial Ischemia
Authors: Li Li , Dai Weixing , Li Wenting , Zhang Yumao , Wu Yanqin , Guan Chenfeng , Zhang Anye , Huang Hui , Li Yuzhen
Published: February 2021

Myocardial ischemia (MI) is one of the most common cardiovascular diseases with high incidence and mortality. Huang-Lian-Jie-Du-Tang (HLJDT) is a classic traditional Chinese prescription to clear “heat” and “poison”. In this study, we used a deliberate strategy integrating the methods of network pharmacology, pharmacodynamics, and metabonomics to investigate the molecular mechanism and potential targets of HLJDT in the treatment of MI. Firstly, by a network pharmacology approach, a global view of the potential compound-target-pathway network based on network pharmacology was constructed to provide a preliminary understanding of bioactive compounds and related targets of HLJDT for elucidating its molecular mechanisms in MI. Subsequently, in vivo efficacy of HLJDT was validated in a rat model. Meanwhile, the corresponding metabonomic profiles were used to explore differentially induced metabolic markers thus providing the metabolic mechanism of HLJDT in treating MI. The results demonstrated the myocardial protection effect of HLJDT on ischemia by a multicomponent-multitarget mode. This study highlights the reliability and effectiveness of a network pharmacology-based approach that identifies and validates the complex of natural compounds in HLJDT for illustrating the mechanism for the treatment of MI.
Vortioxetine Prevents Lipopolysaccharide-Induced Memory Impairment Without Inhibiting the Initial Inflammatory Cascade
Authors: Alboni S. , Benatti C. , Colliva C. , Radighieri G. , Blom J. M. C. , Brunello N. , Tascedda F.
Published: February 2021

Vortioxetine is a novel multimodal antidepressant that modulates a wide range of neurotransmitters throughout the brain. Preclinical and clinical studies have shown that vortioxetine exerts positive effects on different cognitive domains and neuroprotective effects. Considering the key role of microglial cells in brain plasticity and cognition, we aimed at investigating the effects of pretreatment with vortioxetine in modulating behavioral and molecular effects induced by an immune challenge: peripheral injection of lipopolysaccharide (LPS). To this purpose, C57BL/6J male mice were first exposed to a 28-day standard diet or vortioxetine-enriched diet, which was followed by an acute immune challenge with LPS. Sickness symptoms and depressive-like behaviors (anhedonia and memory impairment) were tested 6 and 24 h after exposure to LPS, respectively. Moreover, the expressions of markers of immune activation and M1/M2 markers of microglia polarization were measured in the dorsal and ventral parts of the hippocampus. The pretreatment with vortioxetine did not affect both LPS-induced sickness behavior and anhedonia but prevented the deficit in the recognition memory induced by the immune challenge. At the transcriptional level, chronic exposure to vortioxetine did not prevent LPS-induced upregulation of proinflammatory cytokines 6 h after the immune challenge but rather seemed to potentiate the immune response to the challenge also by affecting the levels of expression of markers of microglia M1 phenotype, like cluster of differentiation (CD)14 and CD86, in an area-dependent manner. However, at the same time point, LPS injection significantly increased the expression of the M2 polarization inducer, interleukin 4, only in the hippocampus of animals chronically exposed to vortioxetine. These results demonstrate that a chronic administration of vortioxetine specifically prevents LPS-induced memory impairment, without affecting acute sickness behavior and anhedonia, and suggest that hippocampal microglia may represent a cellular target of this novel antidepressant medication. Moreover, we provide a useful model to further explore the molecular mechanisms specifically underlying cognitive impairments following an immune challenge.
Is Cannabidiol During Neurodevelopment a Promising Therapy for Schizophrenia and Autism Spectrum Disorders?
Authors: Loss Cássio Morais , Teodoro Lucas , Rodrigues Gabriela Doná , Moreira Lucas Roberto , Peres Fernanda Fiel , Zuardi Antonio Waldo , Crippa José Alexandre , Hallak Jaime Eduardo Cecilio , Abílio Vanessa Costhek
Published: February 2021

Schizophrenia and autism spectrum disorders (ASD) are psychiatric neurodevelopmental disorders that cause high levels of functional disabilities. Also, the currently available therapies for these disorders are limited. Therefore, the search for treatments that could be beneficial for the altered course of the neurodevelopment associated with these disorders is paramount. Preclinical and clinical evidence points to cannabidiol (CBD) as a promising strategy. In this review, we discuss clinical and preclinical studies on schizophrenia and ASD investigating the behavioral, molecular, and functional effects of chronic treatment with CBD (and with cannabidivarin for ASD) during neurodevelopment. In summary, the results point to CBD's beneficial potential for the progression of these disorders supporting further investigations to strengthen its use.
Exercise Training as Therapeutic Approach in Cancer Cachexia: A Review of Potential Anti-inflammatory Effect on Muscle Wasting
Authors: Leal Luana G. , Lopes Magno A. , Peres Sidney B. , Batista Miguel L.
Published: February 2021

Cachexia is a multifactorial inflammatory syndrome with high prevalence in cancer patients. It is characterized by a metabolic chaos culminating in drastic reduction in body weight, mainly due to skeletal muscle and fat depletion. Currently, there is not a standard intervention for cachexia, but it is believed that a dynamic approach should be applied early in the course of the disease to maintain or slow the loss of physical function. The present review sought to explain the different clinical and experimental applications of different models of exercise and their contribution to a better prognosis of the disease. Here the advances in knowledge about the application of physical training in experimental models are elucidated, tests that contribute substantially to elucidate the cellular and biochemical mechanisms of exercise in different ways, as well as clinical trials that present not only the impacts of exercise in front cachexia but also the challenges of its application in clinical practice.
CFTR Correctors and Antioxidants Partially Normalize Lipid Imbalance but not Abnormal Basal Inflammatory Cytokine Profile in CF Bronchial Epithelial Cells
Authors: Veltman Mieke , De Sanctis Juan B. , Stolarczyk Marta , Klymiuk Nikolai , Bähr Andrea , Brouwer Rutger W. , Oole Edwin , Shah Juhi , Ozdian Tomas , Liao Jie , Martini Carolina , Radzioch Danuta , Hanrahan John W. , Scholte Bob J.
Published: February 2021

A deficiency in cystic fibrosis transmembrane conductance regulator (CFTR) function in CF leads to chronic lung disease. CF is associated with abnormalities in fatty acids, ceramides, and cholesterol, their relationship with CF lung pathology is not completely understood. Therefore, we examined the impact of CFTR deficiency on lipid metabolism and pro-inflammatory signaling in airway epithelium using mass spectrometric, protein array. We observed a striking imbalance in fatty acid and ceramide metabolism, associated with chronic oxidative stress under basal conditions in CF mouse lung and well-differentiated bronchial epithelial cell cultures of CFTR knock out pig and CF patients. Cell-autonomous features of all three CF models included high ratios of ω-6- to ω-3-polyunsaturated fatty acids and of long- to very long-chain ceramide species (LCC/VLCC), reduced levels of total ceramides and ceramide precursors. In addition to the retinoic acid analog fenretinide, the anti-oxidants glutathione (GSH) and deferoxamine partially corrected the lipid profile indicating that oxidative stress may promote the lipid abnormalities. CFTR-targeted modulators reduced the lipid imbalance and oxidative stress, confirming the CFTR dependence of lipid ratios. However, despite functional correction of CF cells up to 60% of non-CF in Ussing chamber experiments, a 72-h triple compound treatment (elexacaftor/tezacaftor/ivacaftor surrogate) did not completely normalize lipid imbalance or oxidative stress.

Protein array analysis revealed differential expression and shedding of cytokines and growth factors from CF epithelial cells compared to non-CF cells, consistent with sterile inflammation and tissue remodeling under basal conditions, including enhanced secretion of the neutrophil activator CXCL5, and the T-cell activator CCL17. However, treatment with antioxidants or CFTR modulators that mimic the approved combination therapies, ivacaftor/lumacaftor and ivacaftor/tezacaftor/elexacaftor, did not effectively suppress the inflammatory phenotype.

We propose that CFTR deficiency causes oxidative stress in CF airway epithelium, affecting multiple bioactive lipid metabolic pathways, which likely play a role in CF lung disease progression. A combination of anti-oxidant, anti-inflammatory and CFTR targeted therapeutics may be required for full correction of the CF phenotype.
Spatial Genetic Structure and Demographic History of the Dominant Forest Oak Quercus fabri Hance in Subtropical China
Authors: Chen Xiao-Dan , Yang Jia , Guo Yu-Fan , Zhao Yue-Mei , Zhou Tao , Zhang Xiao , Ju Miao-Miao , Li Zhong-Hu , Zhao Gui-Fang
Published: February 2021

Oak trees (QuercusL.) are important models for estimating abiotic impacts on the population structure and demography of long life span tree species. In this study, we generated genetic data for 17 nuclear microsatellite loci in 29 natural populations ofQuercus fabrito estimate the population genetic structure. We also integrated approximate Bayesian computation (ABC) and ecological niche analysis to infer the population differentiation processes and demographic history of this oak species. The genetic analyses indicated two genetic clusters across the 29 populations collected, where most approximately corresponded to the intraspecific differentiation among populations from western and eastern China, whereas admixed populations were mainly found in central mountains of China. The best model obtained from hierarchical ABC simulations suggested that the initial intraspecific divergence ofQ. fabripotentially occurred during the late Pliocene (ca.3.99 Ma) to form the two genetic clusters, and the admixed population group might have been generated by genetic admixture of the two differentiated groups atca.53.76 ka. Ecological analyses demonstrated clear differentiation among theQ. fabripopulation structures, and association estimations also indicated significant correlations between geography and climate with the genetic variation in this oak species. Our results suggest abiotic influences, including past climatic changes and ecological factors, might have affected the genetic differentiation and demographic history ofQ. fabriin subtropical China.
Lead Toxicity in Cereals: Mechanistic Insight Into Toxicity, Mode of Action, and Management
Authors: Aslam Muhammad , Aslam Ayesha , Sheraz Muhammad , Ali Basharat , Ulhassan Zaid , Najeeb Ullah , Zhou Weijun , Gill Rafaqat Ali
Published: February 2021

Cereals are the major contributors to global food supply, accounting for more than half of the total human calorie requirements. Sustainable availability of quality cereal grains is an important step to address the high-priority issue of food security. High concentrations of heavy metals specifically lead (Pb) in the soil negatively affect biochemical and physiological processes regulating grain quality in cereals. The dietary intake of Pb more than desirable quantityviafood chain is a major concern for humans, as it can predispose individuals to chronic health issues. In plant systems, high Pb concentrations can disrupt several key metabolic processes such as electron transport chain, cellular organelles integrity, membrane stability index, PSII connectivity, mineral metabolism, oxygen-evolving complex, and enzymatic activity. Plant growth-promoting rhizobacteria (PGPR) has been recommended as an inexpensive strategy for remediating Pb-contaminated soils. A diverse group ofAscomycetesfungi, i.e., dark septate endophytes is successfully used for this purpose. A symbiotic relationship between endophytes and host cereal induces Pb tolerance by immobilizing Pb ions. Molecular and cellular modifications in plants under Pb-stressed environments are explained by transcription factor families such as bZIP, ERF, and GARP as a regulator. The role of metal tolerance protein (MTP), natural resistance-associated macrophage protein (NRAMP), and heavy metal ATPase in decreasing Pb toxicity is well known. In the present review, we provided the contemporary synthesis of existing data regarding the effects of Pb toxicity on morpho-physiological and biochemical responses of major cereal crops. We also highlighted the mechanism/s of Pb uptake and translocation in plants, critically discussed the possible management strategies and way forward to overcome the menace of Pb toxicity in cereals.
Exogenous DA-6 Improves the Low Night Temperature Tolerance of Tomato Through Regulating Cytokinin
Authors: Lu Jiazhi , Guan Pengxiao , Gu Jiamao , Yang Xiaolong , Wang Feng , Qi Mingfang , Li Tianlai , Liu Yufeng
Published: February 2021

Low night temperature (LNT) causes environmental stress and has a severe and negative impact on plant growth and productivity. Synthetic elicitors can regulate plant growth and induce defense mechanisms from this type of stress. Here, we evaluated the effect of the exogenous growth regulator diethyl aminoethyl hexanoate (DA-6) in tomato leaf response to LNT stress. Our results showed that exogenous DA-6 activates the expression of chlorophyll synthesis and photosystem-related genes, and results in higher photosynthetic activity and chlorophyll production. Furthermore, DA-6 can regulate the synthesis of endogenous cytokinin (CTK) and the expression of decomposition genes to stabilize chloroplast structure, reduce oxidative damage, and maintain the photochemical activity of tomato leaves under LNT stress. DA-6 maintains a high level of ABA content and induces the expression of CBF genes, indicating that DA-6 may participate in the cold response signaling pathway and induce the expression of downstream low temperature response genes and accumulation of compatible osmolytes. This study unravels a mode of action by which plant growth regulators can improve low temperature tolerance and provides important considerations for their application to alleviate the harmful effects of cold stress.
Rapid and Detailed Characterization of Transgene Insertion Sites in Genetically Modified Plants via Nanopore Sequencing
Authors: Giraldo Paula A. , Shinozuka Hiroshi , Spangenberg German C. , Smith Kevin F. , Cogan Noel O. I.
Published: February 2021

Molecular characterization of genetically modified plants can provide crucial information for the development of detection and identification methods, to comply with traceability, and labeling requirements prior to commercialization. Detailed description of the genetic modification was previously a challenging step in the safety assessment, since it required the use of laborious and time-consuming techniques. In this study an accurate, simple, and fast method was developed for molecular characterization of genetically modified (GM) plants, following a user-friendly workflow for researchers with limited bioinformatic capabilities. Three GM events from a diverse array of crop species—perennial ryegrass, white clover, and canola—were used to test the approach that exploits long-read sequencing by the MinION device, from Oxford Nanopore Technologies. The method delivered a higher degree of resolution of the transgenic events within the host genome than has previously been possible with the standard Illumina short-range sequencing strategies. The flanking sequences, copy number, and presence of backbone sequences, and overall transgene insertion structure were determined for each of the plant genomes, with the additional identification of moderate-sized secondary insertions that would have previously been missed. The proposed workflow takes only about 1 week from DNA extraction to analyzed result, and the method will complement the existing approaches for molecular characterization of GM plants, since it makes the process faster, simpler, and more cost-effective.
Daytime, Not Nighttime, Elevated Atmospheric Carbon Dioxide Exposure Improves Plant Growth and Leaf Quality of Mulberry (Morus alba L.) Seedlings
Authors: Shi Songmei , Qiu Yuling , Wen Miao , Xu Xiao , Dong Xingshui , Xu Chenyang , He Xinhua
Published: February 2021

Almost all elevated atmospheric CO2 concentrations (eCO2) studies have not addressed the potential responses of plant growth to different CO2 in daytime and nighttime. The present study was to determine the impact of daytime and/or nighttime eCO2 on growth and quality of mulberry (Morus alba L.), a perennial multipurpose cash plant. Six-month-old mulberry seedlings were hence grown in environmentally auto-controlled growth chambers under four CO2 concentrations: (1) ambient CO2 (ACO2, 410 μmol mol–1 daytime/460 μmol mol–1 nighttime), (2) sole daytime elevated CO2 (DeCO2, 710 μmol mol–1/460 μmol mol–1), (3) sole nighttime elevated CO2 (NeCO2, 410 μmol mol–1/760 μmol mol–1), and (4) continuous daytime and nighttime elevated CO2 (D + NeCO2, 710 μmol mol–1/760 μmol mol–1). Plant growth characteristics, nutrient uptake, and leaf quality were then examined after 120 days of CO2 exposure. Compared to control, DeCO2 and (D + N)eCO2 increased plant biomass production and thus the harvest of nutrients and accumulation of leaf carbohydrates (starch, soluble sugar, and fatty acid) and N-containing compounds (free amino acid and protein), though there were some decreases in the concentration of leaf N, P, Mg, Fe, and Zn. NeCO2 had no significant effects on leaf yield but an extent positive effect on leaf nutritional quality due to their concentration increase in leaf B, Cu, starch, and soluble sugar. Meanwhile, (D + N)eCO2 decreased mulberry leaf yield and harvest of nutritious compounds for silkworm when compared with DeCO2. The reason may be associated to N, P, Mg, Fe, and Zn that are closely related to leaf pigment and N metabolism. Therefore, the rational application of mineral nutrient (especially N, P, Fe, Mg, and Zn) fertilizers is important for a sustainable mulberry production under future atmosphere CO2 concentrations.
Redistribution of Meiotic Crossovers Along Wheat Chromosomes by Virus-Induced Gene Silencing
Authors: Raz Amir , Dahan-Meir Tal , Melamed-Bessudo Cathy , Leshkowitz Dena , Levy Avraham A.
Published: February 2021

Meiotic recombination is the main driver of genetic diversity in wheat breeding. The rate and location of crossover (CO) events are regulated by genetic and epigenetic factors. In wheat, most COs occur in subtelomeric regions but are rare in centromeric and pericentric areas. The aim of this work was to increase COs in both “hot” and “cold” chromosomal locations. We used Virus-Induced gene Silencing (VIGS) to downregulate the expression of recombination-suppressing genesXRCC2andFANCMand of epigenetic maintenance genesMET1andDDM1during meiosis. VIGS suppresses genes in a dominant, transient and non-transgenic manner, which is convenient in wheat, a hard-to-transform polyploid. F1 hybrids of a cross between two tetraploid lines whose genome was fully sequenced (wild emmer and durum wheat), were infected with a VIGS vector ∼ 2 weeks before meiosis. Recombination was measured in F2 seedlings derived from F1-infected plants and non-infected controls. We found significant up and down-regulation of CO rates along subtelomeric regions as a result of silencing eitherMET1,DDM1orXRCC2during meiosis. In addition, we found up to 93% increase in COs in XRCC2-VIGS treatment in the pericentric regions of some chromosomes. SilencingFANCMshowed no effect on CO. Overall, we show that CO distribution was affected by VIGS treatments rather than the total number of COs which did not change. We conclude that transient silencing of specific genes during meiosis can be used as a simple, fast and non-transgenic strategy to improve breeding abilities in specific chromosomal regions.
The Photosynthetic Bacterium Rhodopseudomonas palustris Strain PS3 Exerts Plant Growth-Promoting Effects by Stimulating Nitrogen Uptake and Elevating Auxin Levels in Expanding Leaves
Authors: Hsu Shu-Hua , Shen Meng-Wei , Chen Jen-Chih , Lur Huu-Sheng , Liu Chi-Te
Published: February 2021

Rhodopseudomonas palustris strain PS3, a phototrophic bacterium, was originally isolated from a paddy field located in Taipei city, Taiwan, and showed positive effects on the growth of leafy vegetables. The aim of this study was to clarify the mechanism of the beneficial effects exerted by PS3 on plants. An ineffective R. palustris strain, YSC3, isolated from a paddy field located in Yilan County, was used as the negative control for comparative analyses. We cultivated non-heading Chinese cabbage (Brassica rapa var. chinensis) in 1/2 strength Hoagland hydroponic solution, in which nitrate is the main nitrogen source. We evaluated various plant physiological responses to inoculation with different bacterial inoculants. The N use efficiency (NUE) of PS3-inoculated plants was dramatically higher than that of YSC3-inoculated plants. The nitrate uptake efficiency (NUpE) was significantly elevated in plants treated with PS3; however, no excess nitrate accumulation was observed in leaves. We also noticed that the endogenous indole-3-acetic acid (IAA) levels as well as the cell division rate in the leaves of PS3-inoculated plants were significantly higher than those in the leaves of YSC3-inoculated plants. We examined the bacterial transcription of some genes during root colonization, and found that the expression level of IAA synthesis related gene MAO was almost the same between these two strains. It suggests that the elevated endogenous IAA in the PS3-inoculated plants was not directly derived from the exogenous IAA produced by this bacterium. Taken together, we deduced that PS3 inoculation could promote plant growth by enhancing nitrate uptake and stimulating the accumulation of endogenous auxin in young expanding leaves to increase the proliferation of leaf cells during leaf development.
Algae as New Kids in the Beneficial Plant Microbiome
Authors: Lee Sang-Moo , Ryu Choong-Min
Published: February 2021

Previously, algae were recognized as small prokaryotic and eukaryotic organisms found only in aquatic habitats. However, according to a recent paradigm shift, algae are considered ubiquitous organisms, occurring in plant tissues as well as in soil. Accumulating evidence suggests that algae represent a member of the plant microbiome. New results indicate that plants respond to algae and activate related downstream signaling pathways. Application of algae has beneficial effects on plant health, such as plant growth promotion and disease control. Although accumulating evidence suggests that secreted compounds and cell wall components of algae induce physiological and structural changes in plants that protect against biotic and abiotic stresses, knowledge of the underlying mechanisms and algal determinants is limited. In this review, we discuss recent studies on this topic, and highlight the bioprotectant and biostimulant roles of algae as a new member of the plant beneficial microbiome for crop improvement.
Characterization of Mungbean CONSTANS-LIKE Genes and Functional Analysis of CONSTANS-LIKE 2 in the Regulation of Flowering Time in Arabidopsis
Authors: Liu Chenyang , Zhang Qianqian , Zhu Hong , Cai Chunmei , Li Shuai
Published: February 2021

CONSTANS-LIKE (COL) genes play important roles in the regulation of plant growth and development, and they have been analyzed in many plant species. However, few studies have examined COL genes in mungbean (Vigna radiata). In this study, we identified and characterized 31 mungbean genes whose proteins contained B-Box domains. Fourteen were designated as VrCOL genes and were distributed on 7 of the 11 mungbean chromosomes. Based on their phylogenetic relationships, VrCOLs were clustered into three groups (I, II, and III), which contained 4, 6, and 4 members, respectively. The gene structures and conserved motifs of the VrCOL genes were analyzed, and two duplicated gene pairs, VrCOL1/VrCOL2 and VrCOL8/VrCOL9, were identified. A total of 82 cis-acting elements were found in the VrCOL promoter regions, and the numbers and types of cis-acting elements in each VrCOL promoter region differed. As a result, the expression patterns of VrCOLs varied in different tissues and throughout the day under long-day and short-day conditions. Among these VrCOL genes, VrCOL2 showed a close phylogenetic relationship with Arabidopsis thaliana CO and displayed daily oscillations in expression under short-day conditions but not long-day conditions. In addition, overexpression of VrCOL2 accelerated flowering in Arabidopsis under short-day conditions by affecting the expression of the flowering time genes AtFT and AtTSF. Our study lays the foundation for further investigation of VrCOL gene functions.
On the Efficacy of Water Transport in Leaves. A Coupled Xylem-Phloem Model of Water and Solute Transport
Authors: Sakurai Gen , Miklavcic Stanley J.
Published: February 2021

In this paper, we present and use a coupled xylem/phloem mathematical model of passive water and solute transport through a reticulated vascular system of an angiosperm leaf. We evaluate the effect of leaf width-to-length proportion and orientation of second-order veins on the indexes of water transport into the leaves and sucrose transport from the leaves. We found that the most important factor affecting the steady-state pattern of hydraulic pressure distribution in the xylem and solute concentration in the phloem was leaf shape: narrower/longer leaves are less efficient in convecting xylem water and phloem solutes than wider/shorter leaves under all conditions studied. The degree of efficiency of transport is greatly influenced by the orientation of second-order veins relative to the main vein for all leaf proportions considered; the dependence is non-monotonic with efficiency maximized when the angle is approximately 45° to the main vein, although the angle of peak efficiency depends on other conditions. The sensitivity of transport efficiency to vein orientation increases with increasing vein conductivity. The vein angle at which efficiency is maximum tended to be smaller (relative to the main vein direction) in narrower leaves. The results may help to explain, or at least contribute to our understanding of, the evolution of parallel vein systems in monocot leaves.
Target-Site and Non-target-Site Resistance Mechanisms Confer Multiple and Cross- Resistance to ALS and ACCase Inhibiting Herbicides in Lolium rigidum From Spain
Authors: Torra Joel , Montull José María , Taberner Andreu , Onkokesung Nawaporn , Boonham Neil , Edwards Robert
Published: February 2021

Lolium rigidum is one the worst herbicide resistant (HR) weeds worldwide due to its proneness to evolve multiple and cross resistance to several sites of action (SoA). In winter cereals crops in Spain, resistance to acetolactate synthase (ALS)- and acetyl-CoA carboxylase (ACCase)-inhibiting herbicides has become widespread, with farmers having to rely on pre-emergence herbicides over the last two decades to maintain weed control. Recently, lack of control with very long-chain fatty acid synthesis (VLCFAS)-inhibiting herbicides has been reported in HR populations that are difficult to manage by chemical means. In this study, three Spanish populations of L. rigidum from winter cereals were confirmed as being resistant to ALS- and ACCase-inhibiting herbicides, with broad-ranging resistance toward the different chemistries tested. In addition, reduced sensitivity to photosystem II-, VLCFAS-, and phytoene desaturase-inhibiting herbicides were confirmed across the three populations. Resistance to ACCase-inhibiting herbicides was associated with point mutations in positions Trp-2027 and Asp-2078 of the enzyme conferring target site resistance (TSR), while none were detected in the ALS enzyme. Additionally, HR populations contained enhanced amounts of an ortholog of the glutathione transferase phi (F) class 1 (GSTF1) protein, a functional biomarker of non-target-site resistance (NTSR), as confirmed by enzyme-linked immunosorbent assays. Further evidence of NTSR was obtained in dose-response experiments with prosulfocarb applied post-emergence, following pre-treatment with the cytochrome P450 monooxygenase inhibitor malathion, which partially reversed resistance. This study confirms the evolution of multiple and cross resistance to ALS- and ACCase inhibiting herbicides in L. rigidum from Spain by mechanisms consistent with the presence of both TSR and NTSR. Moreover, the results suggest that NTSR, probably by means of enhanced metabolism involving more than one detoxifying enzyme family, confers cross resistance to other SoA. The study further demonstrates the urgent need to monitor and prevent the further evolution of herbicide resistance in L. rigidum in Mediterranean areas.
Will an Implementation of “Joy of Life in Nursing Homes” Have Positive Effect for the Work Culture? A Comparison Between Two Norwegian Municipalities
Authors: André Beate , Heldal Frode , Sjøvold Endre , Haugan Gørill
Published: February 2021

Background

Currently, we are facing a demographic shift to an older population and its consequences worldwide: in the years to come, several older people will need nursing home (NH) care. The work culture is important for care quality in NHs. Some Norwegian municipalities have implemented the Joy of Life Nursing Home (JoLNH) strategy, representing a resource-oriented health-promoting approach. Knowledge about how implementation of the JoLNH approach impacts the work culture is scarce.

Aimss

We hypothesized that the JoLNH strategy impacts positively on the work culture: (1) when comparing measurements at two time points (T1 and T2) and (2) when comparing two municipalities, among which one has implemented the JoLNH and the other has not.

Method

With a 1-year interval, healthcare personnel in 43 NHs located in two large Norwegian municipalities responded to a survey in two waves (T1 and T2). In total, 558 healthcare personnel participated at T1 and 515 at T2. Work culture was assessed by the Systematizing Person–Group Relations Instrument (SPGR).

Findings

The municipality implementing the JOLNH strategy experienced significant increases in SPGR dimensions, representing positive orientations towards a better work culture, whereas those working in the non-JoLNH municipality reported an increase in SPGR dimensions, signifying a worsened work culture.

Discussion

The data indicate that the implemented JoLNH strategy has endorsed positive effects in the work culture. The JoLNH strategy emphasizes on the quality of patient care, which is what healthcare personnel, in general, are much concerned about. Furthermore, attention to task orientation and independent work seem to encourage a better work culture in NHs.

Conclusion

This study suggests that the JoLNH strategy impacts positively on the work culture in Norwegian NHs.