bluuebunny/crossref_metadata_2025 huggingface dataset:
Case Report: Neonatal Cholestasis as Early Manifestation of Primary Adrenal Insufficiency
Authors: Di Dato Fabiola , Capalbo Donatella , Mirra Rita , Del Vecchio Blanco Francesca , Salerno Mariacarolina , Iorio Raffaele
Published: November 2021

Neonatal cholestasis (NC) may be due to multiple surgical and non-surgical causes, some of which are potentially fatal. The list of potential causes of NC is long, and the systematic search for each of them is challenging in infants, especially when overt signs of underlying disease are lacking. Endocrinological diseases as causes of NC are rare and sometimes misdiagnosed. We report the case of an infant with prolonged cholestatic jaundice due to adrenal insufficiency suspected because of a single episode of hypoglycemia occurring at birth in the absence of clinical signs of adrenal impairment. Clinical exome analysis identified a new homozygous variant in MC2R gene as a putative responsible for familial glucocorticoid deficiency (FGD). Adrenal insufficiency should always be considered in all cholestatic infants, even in the absence of specific symptoms, since early recognition and treatment is essential to prevent life-threatening events.
Progress and Research Trends on Catha edulis (Vahl) Endl. (Catha edulis): A Review and Bibliometric Analysis
Authors: Ye Shuang , Hu Jin , Liu Zilong , Liang Man
Published: November 2021

Catha edulis (Vahl) Endl., known as Catha edulis or Khat is a traditional and regional plant for chewing, smoking and drinking, that has posed a worldwide public health problem due to its recent emerging abused consumption. In the face of the massive use of Catha edulis, we reviewed related publications to analyze the progress and research trends through bibliometric methods. After screening, a total of 514 scientific publications published from 1997 to 2020 were included by systematic retrieval from the Web of Science (WoS) database. According to further scientometric analysis, the annual number of publications output kept rising in most of the years. Ethiopia and the United States of America (USA) have been devoting significant contributions to the field. Though the research emphasis had been the chemical composition and pharmacological and toxicological effects for several years, the hot spots were transferred; the mechanism investigations of Catha edulis have been the focus in recent years, which might be continued in the future. Furthermore, co-operations of multi-disciplinary researchers are needed to minimize abuse harms and maximize the medicinal benefits of Catha edulis to human beings.
Dose Tailoring of Vancomycin Through Population Pharmacokinetic Modeling Among Surgical Patients in Pakistan
Authors: Munir Muhammad Muaaz , Rasheed Huma , Khokhar Muhammad Imran , Khan Rizwan Rasul , Saeed Hafiz Asad , Abbas Mateen , Ali Mohsin , Bilal Rabiea , Nawaz Hafiz Awais , Khan Abdul Muqeet , Qamar Shaista , Anjum Syed Muneeb , Usman Muhammad
Published: November 2021

Background:Vancomycin is a narrow therapeutic agent, and it is necessary to optimize the dose to achieve safe therapeutic outcomes. The purpose of this study was to identify the significant covariates for vancomycin clearance and to optimize the dose among surgical patients in Pakistan.

Methods:Plasma concentration data of 176 samples collected from 58 surgical patients treated with vancomycin were used in this study. A population pharmacokinetic model was developed on NONMEM®using plasma concentration–time data. The effect of all available covariates was evaluated on the pharmacokinetic parameters of vancomycin by stepwise covariate modeling. The final model was evaluated using bootstrap, goodness-of-fit plots, and visual predictive checks.

Results:The pharmacokinetics of vancomycin followed a one-compartment model with first-order elimination. The vancomycin clearance (CL) and volume of distribution (Vd) were 2.45 L/h and 22.6 l, respectively. Vancomycin CL was influenced by creatinine clearance (CRCL) and body weight of the patients; however, no covariate was significant for its effect on the volume of distribution. Dose tailoring was performed by simulating dosage regimens at a steady state based on the CRCL of the patients. The tailored doses were 400, 600, 800, and 1,000 mg for patients with a CRCL of 20, 60, 100, and 140 ml/min, respectively.

Conclusion:Vancomycin CL is influenced by CRCL and body weight of the patient. This model can be helpful for the dose tailoring of vancomycin based on renal status in Pakistani patients.
Combination Therapy With Rapamycin and Low Dose Imatinib in Pulmonary Hypertension
Authors: Shi Yinan , Gu Chenxin , Zhao Tongtong , Jia Yangfan , Bao Changlei , Luo Ang , Guo Qiang , Han Ying , Wang Jian , Black Stephen M. , Desai Ankit A. , Tang Haiyang
Published: November 2021

Rationale: Enhanced proliferation and distal migration of human pulmonary arterial smooth muscle cells (hPASMCs) both contribute to the progressive increases in pulmonary vascular remodeling and resistance in pulmonary arterial hypertension (PAH). Our previous studies revealed that Rictor deletion, to disrupt mTOR Complex 2 (mTORC2), over longer periods result in a paradoxical rise in platelet-derived growth factor receptor (PDGFR) expression in PASMCs. Thus, the purpose of this study was to evaluate the role of combination therapy targeting both mTOR signaling with PDGFR inhibition to attenuate the development and progression of PAH.

Methods and Results: Immunoblotting analyses revealed that short-term exposure to rapamycin (6h) significantly reduced phosphorylation of p70S6K (mTORC1-specific) in hPASMCs but had no effect on the phosphorylation of AKT (p-AKT S473, considered mTORC2-specific). In contrast, longer rapamycin exposure (>24 h), resulted in differential AKT (T308) and AKT (S473) phosphorylation with increases in phosphorylation of AKT at T308 and decreased phosphorylation at S473. Phosphorylation of both PDGFRα and PDGFRβ was increased in hPASMCs after treatment with rapamycin for 48 and 72 h. Based on co-immunoprecipitation studies, longer exposure to rapamycin (24–72 h) significantly inhibited the binding of mTOR to Rictor, mechanistically suggesting mTORC2 inhibition by rapamycin. Combined exposure of rapamycin with the PDGFR inhibitor, imatinib significantly reduced the proliferation and migration of hPASMCs compared to either agent alone. Pre-clinical studies validated increased therapeutic efficacy of rapamycin combined with imatinib in attenuating PAH over either drug alone. Specifically, combination therapy further attenuated the development of monocrotaline (MCT)- or Hypoxia/Sugen-induced pulmonary hypertension (PH) in rats as demonstrated by further reductions in the Fulton index, right ventricular systolic pressure (RVSP), pulmonary vascular wall thickness and vessel muscularization, and decreased proliferating cell nuclear antigen (PCNA) staining in PASMCs.

Conclusion: Prolonged rapamycin treatment activates PDGFR signaling, in part, via mTORC2 inhibition. Combination therapy with rapamycin and imatinib may be a more effective strategy for the treatment of PAH.
Control of Tissue Fibrosis by 5-Methoxytryptophan, an Innate Anti-Inflammatory Metabolite
Authors: Wu Kenneth K
Published: November 2021

Tissue fibrosis causes debilitating human diseases such as liver cirrhosis, heart failure, chronic kidney disease and pulmonary insufficiency. It is a dynamic process orchestrated by specific subsets of monocyte-macrophages, fibroblasts, pericytes and hepatic stellate cells. Fibrosis is linked to tissue inflammation. Pro-inflammatory macrophages promote fibrosis by driving myofibroblast differentiation and macrophage myofibroblast transition. Myofibroblasts express α-smooth muscle cell actin (α-SMA) and secrete extracellular matrix (ECM) proteins notably collagen I and III. Deposition of ECM proteins at injury sites and interstitial tissues distorts normal structure and impairs vital functions. Despite advances in the mechanisms of fibrosis at cellular, molecular and genetic levels, prevention and treatment of fibrotic diseases remain poorly developed. Recent reports suggest that 5-methoxytryptophan (5-MTP) is effective in attenuating injury-induced liver, kidney, cardiac and pulmonary fibrosis. It inhibits macrophage activation and blocks fibroblast differentiation to myofibroblasts. Furthermore, it inhibits hepatic stellate cell differentiation into myofibroblasts. As 5-MTP is an endogenous molecule derived from tryptophan catabolism via tryptophan hydroxylase pathway, it is well-suited as a lead compound for developing new anti-fibrotic drugs. This article provides an overview of 5-MTP synthesis, and a critical review of its anti-fibrotic activities. Its mechanisms of actions and potential therapeutic value will be discussed.
Jintiange Capsules Ameliorate Osteoarthritis by Modulating Subchondral Bone Remodeling and Protecting Cartilage Against Degradation
Authors: Zhuang Chenyang , Wang Zixiang , Chen Weisin , Wang Hanquan , Tian Bo , Lin Hong
Published: November 2021

Osteoarthritis (OA) is the most prevalent joint disease worldwide, making it a major cause of pain and disability. Identified as a chronic and progressive disease, effective treatment at the early stages of OA has become critical to its management. Jintiange (Jtg) capsules are a traditional Chinese medicine produced from multiple organic components of various animal bones and routinely used to treat osteoporosis in China. However, the effect of Jtg on subchondral bone and cartilage degeneration in OA remains unknown. The purpose of the present study was to investigate the biomolecular role and underlying mechanisms of Jtg in OA progression. Herein, we found that Jtg inhibited receptor activator of nuclear factor-κB ligand (RANKL)-induced osteoclast formation and it functions through the NF-κB signaling pathway. Jtg also inhibited chondrocyte apoptosis via reducing the reactive oxygen species concentration in these cells. Moreover, in vivo evaluation revealed that Jtg significantly attenuates subchondral bone remodeling and cartilage destruction in anterior cruciate ligament transection (ACLT) mouse models. Taken together, our data demonstrate that Jtg inhibits osteoclast differentiation in subchondral bone and chondrocyte apoptosis in cartilage, supporting its potential therapeutic value for treating OA.
Statistical Study of Small-Scale Interplanetary Magnetic Flux Ropes in the Vicinity of the Heliospheric Current Sheet
Authors: Liu Qiang , Zhao Yan , Zhao Guoqing
Published: November 2021

The small-scale interplanetary magnetic flux ropes (SIMFRs) are common magnetic structures in the interplanetary space, yet their origination is still an open question. In this article, we surveyed 63 SIMFRs found within 6-day window around the heliospheric current sheet (HCS) and investigated their axial direction, as well as the local normal direction of the HCS. Results showed that the majority (48/63) of the SIMFRs were quasi-parallel to the associated HCS (i.e., the axial direction of SIMFRs was quasi-perpendicular to the normal direction of the associated HCS). They also showed that the SIMFRs quasi-parallel to the associated HCS statistically had shorter duration than the cases quasi-perpendicular. The results indicate that most of these SIMFRs may be generated in the nearby HCSs.
Remote Hind-Limb Ischemia Mechanism of Preserved Ejection Fraction During Heart Failure
Authors: Homme Rubens P. , Zheng Yuting , Smolenkova Irina , Singh Mahavir , Tyagi Suresh C.
Published: November 2021

During acute heart failure (HF), remote ischemic conditioning (RIC) has proven to be beneficial; however, it is currently unclear whether it also extends benefits from chronic congestive, cardiopulmonary heart failure (CHF). Previous studies from our laboratory have shown three phases describing CHF viz. (1) HF with preserved ejection fraction (HFpEF), (2) HF with reduced EF (HFrEF), and (3) HF with reversed EF. Although reciprocal organ interaction, ablation of sympathetic, and calcium signaling genes are associated with HFpEF to HFrEF, the mechanism is unclear. The HFrEF ensues, in part, due to reduced angiogenesis, coronary reserve, and leakage of endocardial endothelial (EE) and finally breakdown of the blood-heart barrier (BHB) integrity. In fact, our hypothesis states that a change in phenotype from compensatory HFpEF to decompensatory HFrEF is determined by a potential decrease in regenerative, proangiogenic factors along with a concomitant increase in epigenetic memory, inflammation that combinedly causes oxidative, and proteolytic stress response. To test this hypothesis, we created CHF by aorta-vena-cava (AV) fistula in a group of mice that were subsequently treated with that of hind-limb RIC. HFpEF vs. HFrEF transition was determined by serial/longitudinal echo measurements. Results revealed an increase in skeletal muscle musclin contents, bone-marrow (CD71), and sympathetic activation (β2-AR) by RIC. We also observed a decrease in vascular density and attenuation of EE-BHB function due to a corresponding increase in the activity of MMP-2, vascular endothelial growth factor (VEGF), caspase, and calpain. This decrease was successfully mitigated by RIC-released skeletal muscle exosomes that contain musclin, the myokine along with bone marrow, and sympathetic activation. In short, based on proteome (omics) analysis, ∼20 proteins that appear to be involved in signaling pathways responsible for the synthesis, contraction, and relaxation of cardiac muscle were found to be the dominant features. Thus, our results support that the CHF phenotype causes dysfunction of cardiac metabolism, its contraction, and relaxation. Interestingly, RIC was able to mitigate many of the deleterious changes, as revealed by our multi-omics findings.
KCNQ and KCNE Isoform-Dependent Pharmacology Rationalizes Native American Dual Use of Specific Plants as Both Analgesics and Gastrointestinal Therapeutics
Authors: Abbott Geoffrey W. , Redford Kaitlyn E. , Yoshimura Ryan F. , Manville Rían W. , Moreira Luiz , Tran Kevin , Arena Grey , Kookootsedes Alexandra , Lasky Emma , Gunnison Elliot
Published: November 2021

Indigenous peoples of the Americas are proficient in botanical medicine. KCNQ family voltage-gated potassium (Kv) channels are sensitive to a variety of ligands, including plant metabolites. Here, we screened methanolic extracts prepared from 40 Californian coastal redwood forest plants for effects on Kv current and membrane potential in Xenopus oocytes heterologously expressing KCNQ2/3, which regulates excitability of neurons, including those that sense pain. Extracts from 9 of the 40 plant species increased KCNQ2/3 current at –60 mV by ≥threefold (maximally, 15-fold by Urtica dioica) and/or hyperpolarized membrane potential by ≥-3 mV (maximally, –11 mV by Arctostaphylos glandulosa). All nine plants have traditionally been used as both analgesics and gastrointestinal therapeutics. Of two extracts tested, both acted as KCNQ-dependent analgesics in mice. KCNQ2/3 activation at physiologically relevant, subthreshold membrane potentials by tannic acid, gallic acid and quercetin provided molecular correlates for analgesic action of several of the plants. While tannic acid also activated KCNQ1 and KCNQ1-KCNE1 at hyperpolarized, negative membrane potentials, it inhibited KCNQ1-KCNE3 at both negative and positive membrane potentials, mechanistically rationalizing historical use of tannic acid-containing plants as gastrointestinal therapeutics. KCNE dependence of KCNQ channel modulation by plant metabolites therefore provides a molecular mechanistic basis for Native American use of specific plants as both analgesics and gastrointestinal aids.
Sleeve Gastrectomy Ameliorates Diabetes-Induced Cardiac Hypertrophy Correlates With the MAPK Signaling Pathway
Authors: Xu Qian , Ding Huanxin , Li Songhan , Dong Shuohui , Li Linchuan , Shi Bowen , Zhong Mingwei , Zhang Guangyong
Published: November 2021

Background: Cardiac hypertrophy as a main pathological manifestation of diabetic cardiomyopathy (DCM), is a significant complication of diabetes. Bariatric surgery has been proven to relieve DCM; however, whether it can alleviate diabetes-induced cardiac hypertrophy is undefined.

Methods: Diabetic and obese rats were performed sleeve gastrectomy (SG) after having diabetes for 16weeks. The rats were euthanized 8weeks after SG. Metabolic parameters, heart function parameters, myocardial glucose uptake, morphometric and histological changes, and the expression level of mitogen-activated protein kinases (MAPKs) were determined and compared among the control group (CON group), diabetes mellitus group (DM group), sham operation group (SHAM group), and SG group.

Results: Compared with the SHAM group, the blood glucose, body weight, insulin resistance, and other metabolic parameters were significantly improved in the SG group. There was also a marked improvement in myocardial morphometric and histological parameters after SG. Furthermore, the myocardial glucose uptake and heart function were reversed after SG. Additionally, the phosphorylation of MAPKs was inhibited after SG, including p38 MAPKs, c-Jun N-terminal kinases (JNKs), and extracellular signal-regulated kinases 1/2 (ERK1/2). The expression of DUSP6, which dephosphorylates ERK1/2, was upregulated after SG. These findings suggest that SG ameliorated diabetes-induced cardiac hypertrophy correlates with the MAPK signaling pathway.

Conclusion: These results showed that diabetes-induced cardiac hypertrophy was ameliorated after SG was closely related to the inhibition of the MAPK signaling pathway and upregulation of DUSP6. Therefore, this study provides a novel strategy for treating diabetes-induced cardiac hypertrophy.
Role of Auxin and Nitrate Signaling in the Development of Root System Architecture
Authors: Hu Qi-Qi , Shu Jian-Qin , Li Wen-Min , Wang Guang-Zhi
Published: November 2021

The plant root is an important storage organ that stores indole-3-acetic acid (IAA) from the apical meristem, as well as nitrogen, which is obtained from the external environment. IAA and nitrogen act as signaling molecules that promote root growth to obtain further resources. Fluctuations in the distribution of nitrogen in the soil environment induce plants to develop a set of strategies that effectively improve nitrogen use efficiency. Auxin integrates the information regarding the nitrate status inside and outside the plant body to reasonably distribute resources and sustainably construct the plant root system. In this review, we focus on the main factors involved in the process of nitrate- and auxin-mediated regulation of root structure to better understand how the root system integrates the internal and external information and how this information is utilized to modify the root system architecture.
Transcriptomic Analysis Reveals the Positive Role of Abscisic Acid in Endodormancy Maintenance of Leaf Buds of Magnolia wufengensis
Authors: Wu Kunjing , Duan Xiaojing , Zhu Zhonglong , Sang Ziyang , Zhang Yutong , Li Haiying , Jia Zhongkui , Ma Luyi
Published: November 2021

Magnolia wufengensis(Magnoliaceae) is a deciduous landscape species, known for its ornamental value with uniquely shaped and coloured tepals. The species has been introduced to many cities in south China, but low temperatures limit the expansion of this species in cold regions. Bud dormancy is critical for plants to survive in cold environments during the winter. In this study, we performed transcriptomic analysis of leaf buds using RNA sequencing and compared their gene expression during endodormancy, endodormancy release, and ecodormancy. A total of 187,406 unigenes were generated with an average length of 621.82 bp (N50 = 895 bp). In the transcriptomic analysis, differentially expressed genes involved in metabolism and signal transduction of hormones especially abscisic acid (ABA) were substantially annotated during dormancy transition. Our results showed that ABA at a concentration of 100 μM promoted dormancy maintenance in buds ofM. wufengensis. Furthermore, the expression of genes related to ABA biosynthesis, catabolism, and signalling pathway was analysed by qPCR. We found that the expression ofMwCYP707A-1-2was consistent with ABA content and the dormancy transition phase, indicating thatMwCYP707A-1-2played a role in endodormancy release. In addition, the upregulation ofMwCBF1during dormancy release highlighted the enhancement of cold resistance. This study provides new insights into the cold tolerance ofM. wufengensisin the winter from bud dormancy based on RNA-sequencing and offers fundamental data for further research on breeding improvement ofM. wufengensis.
Titanium Application Increases Phosphorus Uptake Through Changes in Auxin Content and Root Architecture in Soybean (Glycine Max L.)
Authors: Hussain Sajad , Shafiq Iram , Skalicky Milan , Brestic Marian , Rastogi Anshu , Mumtaz Maryam , Hussain Muzammil , Iqbal Nasir , Raza Muhammad Ali , Manzoor Sumaira , Liu Weiguo , Yang Wenyu
Published: November 2021

Phosphorus (P) is an essential macronutrient needed for plant growth, development, and production. A deficiency of P causes a severe impact on plant development and productivity. Several P-based fertilizers are being used in agriculture but limited uptake of P by the plant is still a challenge to be solved. Titanium (Ti) application increases the nutrient uptake by affecting the root growth; however, the role of Ti in plant biology, specifically its application under low light and phosphorus stress, has never been reported. Therefore, a pot study was planned with foliar application of Ti (in a different concentration ranging from 0 to 1,000 mg L–1) under different light and P concentrations. The result indicated that under shade and low P conditions the foliar application of Ti in different concentrations significantly improves the plant growth parameters such as root length, root surface area, root dry matter, and shoot dry matters. The increase was observed to be more than 100% in shade and low P stressed soybean root parameter with 500 mg L–1 of Ti treatment. Ti was observed to improve the plant growth both in high P and low P exposed plants, but the improvement was more obvious in Low P exposed plants. Auxin concentration in stressed and healthy plant roots was observed to be slightly increased with Ti application. Ti application was also observed to decrease rhizosphere soil pH and boosted the antioxidant enzymatic activities with an enhancement in photosynthetic efficiency of soybean plants under shade and P stress. With 500 mg L–1 of Ti treatment, the photosynthetic rate was observed to improve by 45% under shade and P stressed soybean plants. Thus, this work for the first time indicates a good potential of Ti application in the low light and P deficient agricultural fields for the purpose to improve plant growth and development parameters.
Genome-Wide DNA Polymorphism Analysis and Molecular Marker Development for the Setaria italica Variety “SSR41” and Positional Cloning of the Setaria White Leaf Sheath Gene SiWLS1
Authors: Zhang Hui , Tang Sha , Schnable James C. , He Qiang , Gao Yuanzhu , Luo Mingzhao , Jia Guanqing , Feng Baili , Zhi Hui , Diao Xianmin
Published: November 2021

Genome-wide DNA polymorphism analysis and molecular marker development are important for forward genetics research and DNA marker-assisted breeding. As an ideal model system for Panicoideae grasses and an important minor crop in East Asia, foxtail millet (Setaria italica) has a high-quality reference genome as well as large mutant libraries based on the “Yugu1” variety. However, there is still a lack of genetic and mutation mapping tools available for forward genetics research on S. italica. Here, we screened another S. italica genotype, “SSR41”, which is morphologically similar to, and readily cross-pollinates with, “Yugu1”. High-throughput resequencing of “SSR41” identified 1,102,064 reliable single nucleotide polymorphisms (SNPs) and 196,782 insertions/deletions (InDels) between the two genotypes, indicating that these two genotypes have high genetic diversity. Of the 8,361 high-quality InDels longer than 20 bp that were developed as molecular markers, 180 were validated with 91.5% accuracy. We used “SSR41” and these developed molecular markers to map the white leaf sheath gene SiWLS1. Further analyses showed that SiWLS1 encodes a chloroplast-localized protein that is involved in the regulation of chloroplast development in bundle sheath cells in the leaf sheath in S. italica and is related to sensitivity to heavy metals. Our study provides the methodology and an important resource for forward genetics research on Setaria.
Functional Analysis of the “Green Revolution” Gene Photoperiod-1 and Its Selection Trends During Bread Wheat Breeding
Authors: Wu Yongzhen , Liu Jiahui , Hu Guimei , Xue Huixian , Xu Huiyuan , Zhao Chunhua , Qin Ran , Cui Fa , Sun Han
Published: November 2021

Flowering is central to the transformation of plants from vegetative growth to reproductive growth. The circadian clock system enables plants to sense the changes in the external environment and to modify the growth and development process at an appropriate time. Photoperiod-1 (Ppd-1), which is controlled by the output signal of the circadian clock, has played an important role in the wheat “Green Revolution.” In the current study, we systematically studied the relationship between Ppd-1 haplotypes and both wheat yield- and quality-related traits, using genome-wide association analysis and transgenic strategies, and found that highly appropriate haplotypes had been selected in the wheat breeding programs. Genome-wide association analysis showed that Ppd-1 is associated with significant differences in yield-related traits in wheat, including spike length (SL), heading date (HD), plant height (PH), and thousand-grain weight (TGW). Ppd-1-Hapl-A1 showed increased SL by 4.72–5.93%, whereas Ppd-1-Hapl-B1 and Ppd-1-Hapl-D1 displayed earlier HD by 0.58–0.75 and 1.24–2.93%, respectively, decreased PH by 5.64–13.08 and 13.62–27.30%, respectively, and increased TGW by 4.89–10.94 and 11.12–21.45%, respectively. Furthermore, the constitutive expression of the Ppd-D1 gene in rice significantly delayed heading date and resulted in reduced plant height, thousand-grain weight, grain width (GW), and total protein content. With reference to 40years of data from Chinese wheat breeding, it was found that the appropriate haplotypes Ppd-1-Hapl-A1, Ppd-1-Hapl-B1, and Ppd-1-Hapl-D1 had all been subjected to directional selection, and that their distribution frequencies had increased from 26.09, 60.00, and 52.00% in landraces to 42.55, 93.62, and 96.23% in wheat cultivars developed in the 2010s. A Ppd-B1 methylation molecular marker was also developed to assist molecular wheat breeding. This research is of significance for fully exploring the function of the Ppd-1 gene and its genetic resource diversity, to effectively use the most appropriate haplotypes and to improve crop yield and sustainability.
A Sugarcane G-Protein-Coupled Receptor, ShGPCR1, Confers Tolerance to Multiple Abiotic Stresses
Authors: Ramasamy Manikandan , Damaj Mona B. , Vargas-Bautista Carol , Mora Victoria , Liu Jiaxing , Padilla Carmen S. , Irigoyen Sonia , Saini Tripti , Sahoo Nirakar , DaSilva Jorge A. , Mandadi Kranthi K.
Published: November 2021

Sugarcane (Saccharum spp.) is a prominent source of sugar and serves as bioenergy/biomass feedstock globally. Multiple biotic and abiotic stresses, including drought, salinity, and cold, adversely affect sugarcane yield. G-protein-coupled receptors (GPCRs) are components of G-protein-mediated signaling affecting plant growth, development, and stress responses. Here, we identified a GPCR-like protein (ShGPCR1) from sugarcane and energy cane (Saccharum spp. hybrids) and characterized its function in conferring tolerance to multiple abiotic stresses. ShGPCR1 protein sequence contained nine predicted transmembrane (TM) domains connected by four extracellular and four intracellular loops, which could interact with various ligands and heterotrimeric G proteins in the cells. ShGPCR1 sequence displayed other signature features of a GPCR, such as a putative guanidine triphosphate (GTP)-binding domain, as well as multiple myristoylation and protein phosphorylation sites, presumably important for its biochemical function. Expression of ShGPCR1 was upregulated by drought, salinity, and cold stresses. Subcellular imaging and calcium (Ca2+) measurements revealed that ShGPCR1 predominantly localized to the plasma membrane and enhanced intracellular Ca2+ levels in response to GTP, respectively. Furthermore, constitutive overexpression of ShGPCR1 in sugarcane conferred tolerance to the three stressors. The stress-tolerance phenotype of the transgenic lines corresponded with activation of multiple drought-, salinity-, and cold-stress marker genes, such as Saccharum spp. LATE EMBRYOGENESIS ABUNDANT, DEHYDRIN, DROUGHT RESPONSIVE 4, GALACTINOL SYNTHASE, ETHYLENE RESPONSIVE FACTOR 3, SALT OVERLY SENSITIVE 1, VACUOLAR Na+/H+ ANTIPORTER 1, NAM/ATAF1/2/CUC2, COLD RESPONSIVE FACTOR 2, and ALCOHOL DEHYDROGENASE 3. We suggest that ShGPCR1 plays a key role in conferring tolerance to multiple abiotic stresses, and the engineered lines may be useful to enhance sugarcane production in marginal environments with fewer resources.
Protein Phosphorylation Changes During Systemic Acquired Resistance in Arabidopsis thaliana
Authors: Zhou Qingfeng , Meng Qi , Tan Xiaomin , Ding Wei , Ma Kang , Xu Ziqin , Huang Xuan , Gao Hang
Published: November 2021

Systemic acquired resistance (SAR) in plants is a defense response that provides resistance against a wide range of pathogens at the whole-plant level following primary infection. Although the molecular mechanisms of SAR have been extensively studied in recent years, the role of phosphorylation that occurs in systemic leaves of SAR-induced plants is poorly understood. We used a data-independent acquisition (DIA) phosphoproteomics platform based on high-resolution mass spectrometry in an Arabidopsis thaliana model to identify phosphoproteins related to SAR establishment. A total of 8011 phosphorylation sites from 3234 proteins were identified in systemic leaves of Pseudomonas syringae pv. maculicola ES4326 (Psm ES4326) and mock locally inoculated plants. A total of 859 significantly changed phosphoproteins from 1119 significantly changed phosphopeptides were detected in systemic leaves of Psm ES4326 locally inoculated plants, including numerous transcription factors and kinases. A variety of defense response-related proteins were found to be differentially phosphorylated in systemic leaves of Psm ES4326 locally inoculated leaves, suggesting that these proteins may be functionally involved in SAR through phosphorylation or dephosphorylation. Significantly changed phosphoproteins were enriched mainly in categories related to response to abscisic acid, regulation of stomatal movement, plant–pathogen interaction, MAPK signaling pathway, purine metabolism, photosynthesis-antenna proteins, and flavonoid biosynthesis. A total of 28 proteins were regulated at both protein and phosphorylation levels during SAR. RT-qPCR analysis revealed that changes in phosphorylation levels of proteins during SAR did not result from changes in transcript abundance. This study provides comprehensive details of key phosphoproteins associated with SAR, which will facilitate further research on the molecular mechanisms of SAR.
Nucleoredoxin Gene TaNRX1 Positively Regulates Drought Tolerance in Transgenic Wheat (Triticum aestivum L.)
Authors: Zhang Yunrui , Zhou Jianfei , Wei Fan , Song Tianqi , Yu Yang , Yu Ming , Fan Qiru , Yang Yanning , Xue Gang , Zhang Xiaoke
Published: November 2021

Drought is the main abiotic stress factor limiting the growth and yield of wheat (Triticum aestivum L.). Therefore, improving wheat tolerance to drought stress is essential for maintaining yield. Previous studies have reported on the important role of TaNRX1 in conferring drought stress tolerance. Therefore, to elucidate the regulation mechanism by which TaNRX1 confers drought resistance in wheat, we generated TaNRX1 overexpression (OE) and RNA interference (RNAi) wheat lines. The results showed that the tolerance of the OE lines to drought stress were significantly enhanced. The survival rate, leaf chlorophyll, proline, soluble sugar content, and activities of the antioxidant enzymes (catalase, superoxide dismutase, and peroxidase) of the OE lines were higher than those of the wild type (WT); however, the relative electrical conductivity and malondialdehyde, hydrogen peroxide, and superoxide anion levels of the OE lines were lower than those of the WT; the RNAi lines showed the opposite results. RNA-seq results showed that the common differentially expressed genes of TaNRX1 OE and RNAi lines, before and after drought stress, were mainly distributed in the plant–pathogen interaction, plant hormone signal transduction, phenylpropane biosynthesis, starch and sucrose metabolism, and carbon metabolism pathways and were related to the transcription factors, including WRKY, MYB, and bHLH families. This study suggests that TaNRX1 positively regulates drought stress tolerance in wheat.
Genetic Transformation of Sugarcane, Current Status and Future Prospects
Authors: Budeguer Florencia , Enrique Ramón , Perera María Francisca , Racedo Josefina , Castagnaro Atilio Pedro , Noguera Aldo Sergio , Welin Bjorn
Published: November 2021

Sugarcane (Saccharumspp.) is a tropical and sub-tropical, vegetative-propagated crop that contributes to approximately 80% of the sugar and 40% of the world’s biofuel production. Modern sugarcane cultivars are highly polyploid and aneuploid hybrids with extremely large genomes (>10 Gigabases), that have originated from artificial crosses between the two species,Saccharum officinarumandS.spontaneum. The genetic complexity and low fertility of sugarcane under natural growing conditions make traditional breeding improvement extremely laborious, costly and time-consuming. This, together with its vegetative propagation, which allows for stable transfer and multiplication of transgenes, make sugarcane a good candidate for crop improvement through genetic engineering. Genetic transformation has the potential to improve economically important properties in sugarcane as well as diversify sugarcane beyond traditional applications, such as sucrose production. Traits such as herbicide, disease and insect resistance, improved tolerance to cold, salt and drought and accumulation of sugar and biomass have been some of the areas of interest as far as the application of transgenic sugarcane is concerned. Although there have been much interest in developing transgenic sugarcane there are only three officially approved varieties for commercialization, all of them expressing insect-resistance and recently released in Brazil. Since the early 1990’s, different genetic transformation systems have been successfully developed in sugarcane, including electroporation,Agrobacterium tumefaciensand biobalistics. However, genetic transformation of sugarcane is a very laborious process, which relies heavily on intensive and sophisticated tissue culture and plant generation procedures that must be optimized for each new genotype to be transformed. Therefore, it remains a great technical challenge to develop an efficient transformation protocol for any sugarcane variety that has not been previously transformed. Additionally, once a transgenic event is obtained, molecular studies required for a commercial release by regulatory authorities, which include transgene insertion site, number of transgenes and gene expression levels, are all hindered by the genomic complexity and the lack of a complete sequenced reference genome for this crop. The objective of this review is to summarize current techniques and state of the art in sugarcane transformation and provide information on existing and future sugarcane improvement by genetic engineering.
Perceiving Positive Facial Expression Can Relieve Depressive Moods: The Effect of Emotional Contagion on Mood in People With Subthreshold Depression
Authors: Yamashita Yuko , Yamamoto Tetsuya
Published: November 2021

Emotional contagion is a phenomenon by which an individual’s emotions directly trigger similar emotions in others. We explored the possibility that perceiving others’ emotional facial expressions affect mood in people with subthreshold depression (sD). Around 49 participants were divided into the following four groups: participants with no depression (ND) presented with happy faces; ND participants presented with sad faces; sD participants presented with happy faces; and sD participants presented with sad faces. Participants were asked to answer an inventory about their emotional states before and after viewing the emotional faces to investigate the influence of emotional contagion on their mood. Regardless of depressive tendency, the groups presented with happy faces exhibited a slight increase in the happy mood score and a decrease in the sad mood score. The groups presented with sad faces exhibited an increased sad mood score and a decreased happy mood score. These results demonstrate that emotional contagion affects the mood in people with sD, as well as in individuals with ND. These results indicate that emotional contagion could relieve depressive moods in people with sD. It demonstrates the importance of the emotional facial expressions of those around people with sD such as family and friends from the viewpoint of emotional contagion.
Spanish Version of the Teachers’ Sense of Efficacy Scale: An Adaptation and Validation Study
Authors: Salas-Rodríguez Fátima , Lara Sonia , Martínez Martín
Published: November 2021

The Teachers’ Sense of Efficacy Scale (TSES) has been the most widely used instrument to assess teacher efficacy beliefs. However, no study has been carried out concerning the TSES psychometric properties with teachers in Mexico, the country with the highest number of Spanish-speakers worldwide. The purpose of the present study is to examine the reliability, internal and external validity evidence of the TSES (short form) adapted into Spanish with a sample of 190 primary and secondary Mexican teachers from 25 private schools. Results of construct analysis confirm the three-factor-correlated structure of the original scale. Criterion validity evidence was established between self-efficacy and job satisfaction. Differences in self-efficacy were related to teachers’ gender, years of experience and grade level taught. Some limitations are discussed, and future research directions are recommended.
Mindfulness-Based Stress Reduction Increases Mental Wellbeing and Emotion Regulation During the First Wave of the COVID-19 Pandemic: A Synchronous Online Intervention Study
Authors: Sanilevici Maya , Reuveni Omer , Lev-Ari Shahar , Golland Yulia , Levit-Binnun Nava
Published: November 2021

The COVID-19 pandemic imposed extreme living conditions of social distancing, which triggered negative mental health problems and created challenges in seeking mental health support. Mindfulness-based interventions (MBIs) have been found to enhance wellbeing and mental health by reducing stress and anxiety and improving emotion regulation. Preliminary evidence suggests that online, synchronous MBIs may produce beneficial effects similar to face-to-face programs. However, the effectiveness of such online-MBIs to support mental health in highly stressful times, such as a global pandemic, requires further study. To this end, we investigated the effect of an online 8-week Mindfulness-Based Stress Reduction (MBSR) program on aspects of mental health during the first wave of the COVID-19 pandemic. Participants (N=92) who expressed interest in discounted online-MBSR programs were recruited for the study. The division into experimental and control groups was based on actual enrollment to the courses. Those who enrolled in a program were assigned to the experimental condition and those who decided not to enroll served as controls. Participants were assessed pre-intervention, post-intervention, and 1-month post-intervention for levels of mindfulness, perceived stress, anxiety, emotion regulation, and intolerance of uncertainty. Differences between the groups were tested using the general linear mixed effects model (GLMM) and Individual Growth Curve Models (IGCM) in intent to treat analysis. The findings indicated that, relative to the control group, MBSR improved mindfulness abilities (p <0.001), decreased anxiety (p <0.001), and stress (p <0.001) and increased emotion regulation (p <0.001). These effects were found to persist 1 month after the end of the program, despite the increased governmental public-health restrictions due to COVID-19 at that time. The ability to tolerate uncertainty, a central characteristic of the pandemic, was not found to be affected by the program. A mediation analysis revealed that the effect of the intervention on mental health improvement was partially mediated by the improvement in emotion regulation. Overall, the findings provide positive evidence for the feasibility of an online-MBSR program to support the mental health of individuals from the general population through the mediation of emotion regulation in challenging times, such as a global pandemic.
Measuring Emotional Awareness in Patients With Schizophrenia and Schizoaffective Disorders
Authors: Maaßen Eva , Büttner Marielle , Bröcker Anna-Lena , Stuke Frauke , Bayer Samuel , Hadzibegovic Jasmina , Just Sandra Anna , Bertram Gianna , Rau Richard , von Haebler Dorothea , Lempa Günter , Montag Christiane
Published: November 2021

The ability to mentalize (i.e., to form representations of mental states and processes of oneself and others) is often impaired in people with schizophrenia spectrum disorders. Emotional awareness (EA) represents one aspect of affective mentalizing and can be assessed with the Levels of Emotional Awareness Scale (LEAS), but findings regarding individuals with schizophrenia spectrum disorders are inconsistent. The present study aimed at examining the usability and convergent validity of the LEAS in a sample of N = 130 stabilized outpatients with schizophrenia or schizoaffective disorders. An adequacy rating was added to the conventional LEAS rating to account for distortions of content due to, for example, delusional thinking. Scores of the patient group were compared with those of a matched healthy control sample. Correlation with symptom clusters, a self-report measure of EA, a measure of synthetic metacognition (MAS-A-G), and an expert rating capturing EA from the psychodynamic perspective of psychic structure (OPD-LSIA) were examined. Regarding self-related emotional awareness, patients did not score lower than controls neither in terms of conventional LEAS nor in terms of adequacy. Regarding other-related emotional awareness, however, patients showed a reduced level of adequacy compared to controls whereas no such difference was found for conventional LEAS scores. Higher conventional LEAS scores were associated with fewer negative symptoms, and higher structural integration of self-perceptions measured by the OPD-LSIA. Higher adequacy of responses correlated with fewer symptoms of disorganization as well as excitement, higher scores of self-reflection on the MAS-A-G as well as self- and object-perception and internal and external communication as measured by the subscales of the OPD-LSIA. Findings suggest that the LEAS might not be sensitive enough to detect differences between mildly symptomatic patients with schizophrenia or schizoaffective disorders and healthy controls. However, LEAS ratings are still suitable to track intraindividual changes in EA over time. Observing the adequacy of patients’ responses when using the LEAS may be a promising way to increase diagnostical utility and to identify patterns of formal and content-related alterations of mentalizing in this patient group. Methodological indications for future studies are discussed.
Visuospatial but Not Verbal Working Memory Deficits in Adult Patients With Neurofibromatosis Type 1
Authors: Tang Hanlu , Wu Qiong , Li Shiwei , Fang Yehong , Yang Zhijun , Wang Bo , Wang Xingchao , Liu Pinan
Published: November 2021

Background: Cognitive dysfunction is one of the main symptoms of neurofibromatosis type 1 (NF1). As an important cognitive function, working memory (WM) has rarely been systematically analyzed in NF1 by isolating the particular domain of WM, and existing data involving WM in adult patients with NF1 are insufficient. This study aimed to investigate the characteristics of different types of WM in NF1 from the perspective of the adult population.

Method: We comprehensively analyzed WM in both verbal and visuospatial WM domains by using the N-back task (including the verbal N-back task and the visuospatial N-back task) in 31 adults with NF1 and 34 healthy controls matched for age, gender, education levels, and general cognitive status. The accuracy and reaction times (RTs) in the N-back task were entered into mixed-design ANOVA.

Results: Compared with healthy controls, adults with NF1 presented significantly lower mean accuracy and longer RTs in the visuospatial N-back task. However, no significant difference was found between the NF1 group and healthy controls in the verbal N-back task.

Conclusions: The present study suggested that adults with NF1 might have deficits in visuospatial WM. We did not find evidence for verbal WM deficits in adult patients with NF1. Our findings supplement and refine the existing data on WM in the context of NF1.
Empathy and Its Relationship With Social Functioning in Individuals at Ultra-High Risk for Psychosis
Authors: Kuis Daan Jan , van de Giessen Tara , de Jong Steven , Sportel Bouwina Esther , Boonstra Nynke , van Donkersgoed Rozanne , Lysaker Paul H. , Hasson-Ohayon Ilanit , Pijnenborg Gerdina Hendrika Maria
Published: November 2021

Introduction: Social functioning is often impaired in the ultra-high-risk (UHR) phase of psychosis. There is some evidence that empathy is also impaired in this phase and that these impairments may underlie difficulties in social functioning. The main aim of this study was to investigate whether cognitive and affective empathy are lower in people in the UHR phase of psychosis in comparison to healthy controls, and whether possible impairments have the same magnitude as in people with schizophrenia. A second aim was to examine whether there is a relationship between empathy and social functioning in individuals in the UHR phase.

Method: Forty-three individuals at UHR for psychosis, 92 people with a schizophrenia spectrum disorder, and 49 persons without a psychiatric disorder completed the Interpersonal Reactivity Index (IRI), Questionnaire of Cognitive and Affective Empathy (QCAE), and Faux Pas as instruments to measure empathy. The Time Use survey was used to measure social functioning. MAN(C)OVA was used to analyse differences between groups on empathy and social functioning, and correlations were calculated between empathy measures and social functioning for each group.

Results: The UHR group presented significantly lower levels of self-reported cognitive empathy than the healthy controls, but not compared to patients with SSD, while performance-based cognitive empathy was unimpaired in the UHR group. On the affective measures, we found that people with UHR and patients with SSD had significantly higher levels of self-reported distress in interpersonal settings compared to healthy controls. In the UHR group, perspective-taking was negatively associated with time spent on structured social activities. In the SSD group, we found that structured social activities were positively associated with perspective-taking and negatively associated with personal distress in interactions with others. Lastly, in people without mental illness, social activities were positively associated with performance-based perspective-taking.

Conclusion: Impairments in subjective cognitive empathy appear to be present in the UHR phase, suggesting that difficulties in interpreting the thoughts and feelings of others precede the onset of psychotic disorders. This can inform future interventions in the UHR phase.