bluuebunny/crossref_metadata_2025 huggingface dataset:
Diabetes Attenuates the Contribution of Endogenous Nitric Oxide but Not Nitroxyl to Endothelium Dependent Relaxation of Rat Carotid Arteries
Authors: Li Jasmin Chendi , Velagic Anida , Qin Cheng Xue , Li Mandy , Leo Chen Huei , Kemp-Harper Barbara K. , Ritchie Rebecca H. , Woodman Owen L.
Published: January 2021

Introduction:

Endothelial dysfunction is a major risk factor for several of the vascular complications of diabetes, including ischemic stroke. Nitroxyl (HNO), the one electron reduced and protonated form of nitric oxide (NO•), is resistant to scavenging by superoxide, but the role of HNO in diabetes mellitus associated endothelial dysfunction in the carotid artery remains unknown.

Aim: To assess how diabetes affects the role of endogenous NO• and HNO in endothelium-dependent relaxation in rat isolated carotid arteries.

Methods: Male Sprague Dawley rats were fed a high-fat-diet (HFD) for 2 weeks prior to administration of low dose streptozotocin (STZ; 35 mg/kg i. p./day) for 2 days. The HFD was continued for a further 12 weeks. Sham rats were fed standard chow and administered with citrate vehicle. After 14 weeks total, rats were anesthetized and carotid arteries collected to assess responses to the endothelium-dependent vasodilator, acetylcholine (ACh) by myography. The combination of calcium-activated potassium channel blockers, TRAM-34 (1 μmol/L) and apamin (1 μmol/L) was used to assess the contribution of endothelium-dependent hyperpolarization to relaxation. The corresponding contribution of NOS-derived nitrogen oxide species to relaxation was assessed using the combination of the NO• synthase inhibitor, L-NAME (200 μmol/L) and the soluble guanylate cyclase inhibitor ODQ (10 μmol/L). Lastly, L-cysteine (3 mmol/L), a selective HNO scavenger, and hydroxocobalamin (HXC; 100 μmol/L), a NO• scavenger, were used to distinguish between NO• and HNO-mediated relaxation.

Results: At study end, diabetic rats exhibited significantly retarded body weight gain and elevated blood glucose levels compared to sham rats. The sensitivity and the maximal relaxation response to ACh was significantly impaired in carotid arteries from diabetic rats, indicating endothelial dysfunction. The vasorelaxation evoked by ACh was abolished by L-NAME plus ODQ, but not affected by the apamin plus TRAM-34 combination, indicating that NOS-derived nitrogen oxide species are the predominant endothelium-derived vasodilators in sham and diabetic rat carotid arteries. The maximum relaxation to ACh was significantly decreased by L-cysteine in both sham and diabetic rats, whereas HXC attenuated ACh-induced relaxation only in sham rats, suggesting that diabetes impaired the contribution of NO•, whereas HNO-mediated vasorelaxation remained intact.

Conclusion: Both NO• and HNO contribute to endothelium-dependent relaxation in carotid arteries. In diabetes, NO•-mediated relaxation is impaired, whereas HNO-mediated relaxation was preserved. The potential for preserved HNO activity under pathological conditions that are associated with oxidative stress indicates that HNO donors may represent a viable therapeutic approach to the treatment of vascular dysfunction.
The G Protein Biased Small Molecule Apelin Agonist CMF-019 is Disease Modifying in Endothelial Cell Apoptosis In Vitro and Induces Vasodilatation Without Desensitisation In Vivo
Authors: Read Cai , Nyimanu Duuamene , Yang Peiran , Kuc Rhoda E. , Williams Thomas L. , Fitzpatrick Christopher M. , Foster Richard , Glen Robert C. , Maguire Janet J. , Davenport Anthony P.
Published: January 2021

Signaling through the apelin receptor is beneficial for a number of diseases including pulmonary arterial hypertension. The endogenous small peptides, apelin and elabela/toddler, are downregulated in pulmonary arterial hypertension but are not suitable for exogenous administration owing to a lack of bioavailability, proteolytic instability and susceptibility to renal clearance. CMF-019, a small molecule apelin agonist that displays strong bias towards G protein signaling over β-arrestin (∼400 fold), may be more suitable. This study demonstrates that in addition to being a positive inotrope, CMF-019 caused dose-dependent vasodilatation in vivo (50 nmol 4.16 ± 1.18 mmHg, **p < 0.01; 500 nmol 6.62 ± 1.85 mmHg, **p < 0.01), without receptor desensitization. Furthermore, CMF-019 rescues human pulmonary artery endothelial cells from apoptosis induced by tumor necrosis factor α and cycloheximide (5.66 ± 0.97%, **p < 0.01) by approximately 50% of that observable with rhVEGF (11.59 ± 1.85%, **p < 0.01), suggesting it has disease-modifying potential in vitro. CMF-019 displays remarkable bias at the apelin receptor for a small molecule and importantly recapitulates all aspects of the cardiovascular responses to the endogenous ligand, [Pyr1]apelin-13, in vivo. Additionally, it is able to protect human pulmonary artery endothelial cells from apoptosis, suggesting that the beneficial effects observed with apelin agonists extend beyond hemodynamic alleviation and address disease etiology itself. These findings support CMF-019 as a G protein biased small molecule apelin agonist in vitro and in vivo that could form the basis for the design of novel therapeutic agents in chronic diseases, such as, pulmonary arterial hypertension.
The “C3aR Antagonist” SB290157 is a Partial C5aR2 Agonist
Authors: Li Xaria X. , Kumar Vinod , Clark Richard J. , Lee John D. , Woodruff Trent M.
Published: January 2021

Innate immune complement activation generates the C3 and C5 protein cleavage products C3a and C5a, defined classically as anaphylatoxins. C3a activates C3aR, while C5a activates two receptors (C5aR1 and C5aR2) to exert their immunomodulatory activities. The non-peptide compound, SB290157, was originally reported in 2001 as the first C3aR antagonist. In 2005, the first report on the non-selective nature of SB290157 was published, where the compound exerted clear agonistic, not antagonistic, activity in variety of cells. Other studies also documented the non-selective activities of this drug in vivo. These findings severely hamper data interpretation regarding C3aR when using this compound. Unfortunately, given the dearth of C3aR inhibitors, SB290157 still remains widely used to explore C3aR biology (>70 publications to date). Given these issues, in the present study we aimed to further explore SB290157's pharmacological selectivity by screening the drug against three human anaphylatoxin receptors, C3aR, C5aR1 and C5aR2, using cell models. We identified that SB290157 exerts partial agonist activity at C5aR2 by mediatingβ-arrestin recruitment at higher compound doses. This translated to a functional outcome in both human and mouse primary macrophages, where SB290157 significantly dampened C5a-induced ERK signaling. We also confirmed that SB290157 acts as a potent agonist at human C3aR in transfected cells, but as an antagonist in primary human macrophages. Our results therefore provide even more caution against using SB290157 as a research tool to explore C3aR function. Given the reported immunomodulatory and anti-inflammatory activities of C5aR2 agonism, any function observed with SB290157 could be due to these off-target activities.
Nanoparticle-Mediated Delivery of Emodin via Colonic Irrigation Attenuates Renal Injury in 5/6 Nephrectomized Rats
Authors: Lu Zhaoyu , Ji Chunlan , Luo Xuewen , Lan Yong , Han Lijuan , Chen Yang , Liu Xusheng , Lin Qinzhan , Lu Fuhua , Wu Xiuqing , Guo Rui , Zou Chuan
Published: January 2021

Our previous study showed that emodin enema modulates gut microbiota and delays CKD progression. However, the poor solubility, limited colonic irrigation retention time, and inadequate colon adhesion of emodin hinder its clinical application. Based on the deficiencies of emodin, we prepared monomethoxy-poly (ethylene glycol)-poly (lactic acid)-chitosan-2-mercaptobenzimidazole nanoparticles with incorporated emodin (emodin-NP) and studied their efficacy in delaying CKD progression. 5/6 nephrectomized Male Sprague Dawley rats were administered via colonic irrigation with emodin-NP every two days for eight weeks. We found that treatment with emodin-NP improved the kidney function of the rats and limited the expansion of tubulointerstitial fibrosis. Treatment with emodin-NP once every two days is comparable to emodin treatment once a day. Furthermore, emodin-NP via colonic irrigation remarkably reduced IL-1β, IL-6, and LPS levels in serum, improved intestinal barrier functions, and downregulated the key proteins (TLR4, MyD88, and NF-κB) expression in intestinal TLR4 signaling pathway. 16S rDNA analyses showed that emodin-NP can regulate microbiota disturbance in CKD. Taken together, these results suggest that emodin-NP alleviates kidney dysfunction and tubulointerstitial fibrosis by mediation through the modification of gut microbiota disorders. Emodin-NP may be a new method to treat CKD.
4-Hydroxyisoleucine Alleviates Macrophage-Related Chronic Inflammation and Metabolic Syndrome in Mice Fed a High-Fat Diet
Authors: Yang Jiali , Ran Yunhui , Yang Yonghui , Song Shuyi , Wu Yahong , Qi Yuanming , Gao Yanfeng , Li Guodong
Published: January 2021

In obesity, macrophages and other immune cells accumulate in organs affected by insulin, leading to chronic inflammation and insulin resistance. 4-Hydroxyisoleucine (4-HIL) is a non-protein amino acid found in fenugreek seeds. 4-HIL enhances insulin sensitivity, but its mechanism is still unclear. In this study, 4-HIL intervention reduced weight gain, liver steatosis, and dyslipidemia; moreover, it increased systemic insulin sensitivity and improved insulin resistance in mice. Importantly, after administration, the accumulation of M1 like CD11c+ macrophages and inflammation in the liver and adipose tissue were reduced in the mice. 4-HIL also reduced the proportion of CD11c+ macrophages among bone marrow-derived macrophages, which were induced in vitro. These observations demonstrate a new role of 4-HIL in insulin resistance in hepatocytes and adipocytes. 4-HIL inhibits obesity-related insulin resistance by reducing inflammation and regulating the state of M1/M2 macrophages.
Short Chain (≤C4) Esterification Increases Bioavailability of Rosmarinic Acid and Its Potency to Inhibit Vascular Smooth Muscle Cell Proliferation
Authors: Blažević Tina , Reznicek Gottfried , Ding Limin , Yang Gangqiang , Haiss Patricia , Heiss Elke H. , Dirsch Verena M. , Liu Rongxia
Published: January 2021

Rosmarinic acid is a natural phenolic acid and active compound found in many culinary plants, such as rosemary, mint, basil and perilla. Aiming to improve the pharmacokinetic profile of rosmarinic acid and its activity on vascular smooth muscle cell proliferation, we generated a series of rosmarinic acid esters with increasing alkyl chain length ranging from C1 to C12. UHPLC-MS/MS analysis of rat blood samples revealed the highest increase in bioavailability of rosmarinic acid, up to 10.52%, after oral administration of its butyl ester, compared to only 1.57% after rosmarinic acid had been administered in its original form. When added to vascular smooth muscle cells in vitro, all rosmarinic acid esters were taken up, remained esterified and inhibited vascular smooth muscle cell proliferation with IC50 values declining as the length of alkyl chains increased up to C4, with an IC50 of 2.84 µM for rosmarinic acid butyl ester, as evident in a resazurin assay. Vascular smooth muscle cells were arrested in the G0/G1 phase of the cell cycle and the retinoblastoma protein phosphorylation was blocked. Esterification with longer alkyl chains did not improve absorption and resulted in cytotoxicity in in vitro settings. In this study, we proved that esterification with proper length of alkyl chains (C1–C4) is a promising way to improve in vivo bioavailability of rosmarinic acid in rats and in vitro biological activity in rat vascular smooth muscle cells.
Intracolonic Mustard Oil Induces Visceral Pain in Mice by TRPA1-Dependent and -Independent Mechanisms: Role of Tissue Injury and P2X Receptors
Authors: Gonzalez-Cano Rafael , Montilla-García Ángeles , Perazzoli Gloria , Torres Jesús M. , Cañizares Francisco J. , Fernández-Segura Eduardo , Costigan Michael , Baeyens José M. , Cobos Enrique J.
Published: January 2021

Both TRPA1 and purinergic P2X receptors have been proposed as potential targets for the treatment of visceral pain. We found that the intracolonic administration of a low dose mustard oil (0.5%), a well-known TRPA1 agonist, produced nociceptive responses and abdominal wall referred mechanical hyperalgesia, without inducing apparent tissue damage. Both nociceptive responses and referred hyperalgesia were abolished by the ablation of TRPV1-expressing neurons (and the consequent ablation of TRPA1+ nociceptors) by resiniferatoxin (RTX) treatment, and by the TRPA1 antagonist AP18. However, a higher dose of mustard oil (2.5%) damaged the colonic epithelium and induced pERK activation in the spinal cord, and these processes were clearly independent of TRPV1-expressing neurons ablated by RTX. This higher dose of mustard oil induced nociceptive responses and referred mechanical hyperalgesia which were insensitive or only slightly sensitive to resiniferatoxin or AP18, but were markedly reduced by the P2X antagonist TNP-ATP, which is known to inhibit nociceptive actions induced by ATP released from injured tissues. In conclusion, whereas a low dose of intracolonic mustard oil induces visceral pain in a manner fully dependent on TRPA1 actions, when a high dose of this chemical irritant is used, visceral pain becomes mostly independent of TRPA1 activation but clearly enhanced by ATP purportedly released by the damaged colonic epithelium. Therefore, TRPA1 inhibition is not sufficient to substantially decrease visceral pain during tissue injury, whereas purinergic antagonism appears to be a more effective strategy.
Mitochondrial Enzymes of the Urea Cycle Cluster at the Inner Mitochondrial Membrane
Authors: Haskins Nantaporn , Bhuvanendran Shivaprasad , Anselmi Claudio , Gams Anna , Kanholm Tomas , Kocher Kristen M. , LoTempio Jonathan , Krohmaly Kylie I. , Sohai Danielle , Stearrett Nathaniel , Bonner Erin , Tuchman Mendel , Morizono Hiroki , Jaiswal Jyoti K. , Caldovic Ljubica
Published: January 2021

Mitochondrial enzymes involved in energy transformation are organized into multiprotein complexes that channel the reaction intermediates for efficient ATP production. Three of the mammalian urea cycle enzymes: N-acetylglutamate synthase (NAGS), carbamylphosphate synthetase 1 (CPS1), and ornithine transcarbamylase (OTC) reside in the mitochondria. Urea cycle is required to convert ammonia into urea and protect the brain from ammonia toxicity. Urea cycle intermediates are tightly channeled in and out of mitochondria, indicating that efficient activity of these enzymes relies upon their coordinated interaction with each other, perhaps in a cluster. This view is supported by mutations in surface residues of the urea cycle proteins that impair ureagenesis in the patients, but do not affect protein stability or catalytic activity. We find the NAGS, CPS1, and OTC proteins in liver mitochondria can associate with the inner mitochondrial membrane (IMM) and can be co-immunoprecipitated. Our in-silico analysis of vertebrate NAGS proteins, the least abundant of the urea cycle enzymes, identified a protein-protein interaction region present only in the mammalian NAGS protein—“variable segment,” which mediates the interaction of NAGS with CPS1. Use of super resolution microscopy showed that NAGS, CPS1 and OTC are organized into clusters in the hepatocyte mitochondria. These results indicate that mitochondrial urea cycle proteins cluster, instead of functioning either independently or in a rigid multienzyme complex.
Long Non-coding RNA MIAT Knockdown Prevents the Formation of Intracranial Aneurysm by Downregulating ENC1 via MYC
Authors: Li Xinguo , Zhao Hang , Liu Jihui , Tong Jing
Published: January 2021

Intracranial aneurysm (IA) is vascular enlargement occurred on the wall of cerebral vessels and can result in fatal subarachnoid hemorrhage when ruptured. Recent studies have supported the important role of long non-coding RNAs (lncRNAs) in IA treatment. This study identified functional significance of lncRNA myocardial infarction associated transcript (MIAT) in IA. Myocardial infarction associated transcript and ectodermal-neural cortex 1 (ENC1) expression was detected by reverse transcription quantitative polymerase chain reaction. Cell counting kit 8 assay flow cytometry were conducted to detect cell viability and apoptosis of endothelial cells in IA. The interaction among MIAT, ENC1, and myelocytomatosis oncogene (MYC) was analyzed by RNA pull down, RNA immunoprecipitation assay, chromatin immunoprecipitation assay, and dual luciferase reporter assay. Intracranial aneurysm was induced by ligating the left carotid artery and the bilateral posterior branch of the renal artery in rats for studying the role of MIAT and ENC1 in vivo. Myocardial infarction associated transcript and ENC1 were upregulated in IA. Endothelial cells in IA presented a decreased cell viability and an increased apoptotic rate. Myocardial infarction associated transcript could regulate the expression of ENC1, and MYC could bind to the promoter region of ENC1. High expression of MIAT increased endothelial cell apoptosis and vascular endothelial injury, while MIAT knockdown was identified to reduce the risk of IA both in vitro and in vivo through regulating ENC1. To sum up, MIAT silencing is preventive for IA occurrence by decreasing the MYC-mediated ENC1 expression, which represents a novel therapeutic target for IA.
Neuromuscular Adaptations and Enhancement of Physical Performance in Female Basketball Players After 8 Weeks of Plyometric Training
Authors: Cherni Yosser , Hammami Mehrez , Jelid Mohamed Chedly , Aloui Ghaith , Suzuki Katsuhiko , Shephard Roy J. , Chelly Mohamed Souhaiel
Published: January 2021

The aim of this study was to examine the effects of an 8-week in-season plyometric training (PT) program on the physical performance and neuromuscular adaptations of female basketball players. Twenty-seven elite female basketball players (aged 21.0 ± 2.6 years) were assigned between an experimental group (n= 15) who substituted a part of their usual training with biweekly PT, and a control group (n= 12) who maintained their standard basketball training. Analyses of variance and co-variance assessed changes in 10, 20, and 30 m sprint times, ability to change direction (T-test) and jumping ability [squat jump (SJ) and countermovement jump (CMJ)] with electromyographic assessment of the vastus lateralis, vastus medialis, and rectus femoris muscles during jumping and meassurement of the isokinetic strength of the knee muscles. After 8 weeks of the plyometric program the experimental group enhanced change of direction performance (Δ = −3.90%,d= 0.67) and showed a greater thigh cross sectional area (Δ = 9.89%,d= 0.95) relative to controls. Neural adaptations included significant improvements of EMG parameters for the vastus medialis muscle during Squat Jumping (Δ = 109.3%,d= 0.59). However, trends to improvements of sprinting times and jumping performances did not reach statistical significance. In addition, there were no gains in the peak torque and the average power of the quadriceps and hamstring muscles at either slow or moderate test speeds. We conclude that 8-weeks of PT (72–126 jumps) was insufficient to improve many of the variables associated with basketball performance in our subject-group. Further studies of female basketball players, extending the program period and increasing the intensity and speed of jumps are recommended in the search for more significant results.
Calcium Signaling in T Cells Is Induced by Binding to Nickel-Chelating Lipids in Supported Lipid Bilayers
Authors: Dam Tommy , Junghans Victoria , Humphrey Jane , Chouliara Manto , Jönsson Peter
Published: January 2021

Supported lipid bilayers (SLBs) are one of the most common cell-membrane model systems to study cell-cell interactions. Nickel-chelating lipids are frequently used to functionalize the SLB with polyhistidine-tagged ligands. We show here that these lipids by themselves can induce calcium signaling in T cells, also when having protein ligands on the SLB. This is important to avoid “false” signaling events in cell studies with SLBs, but also to better understand the molecular mechanisms involved in T-cell signaling. Jurkat T cells transfected with the non-signaling molecule rat CD48 were found to bind to ligand-free SLBs containing ≥2 wt% nickel-chelating lipids upon which calcium signaling was induced. This signaling fraction steadily increased from 24 to 60% when increasing the amount of nickel-chelating lipids from 2 to 10 wt%. Both the signaling fraction and signaling time did not change significantly compared to ligand-free SLBs when adding the CD48-ligand rat CD2 to the SLB. Blocking the SLB with bovine serum albumin reduced the signaling fraction to 11%, while preserving CD2 binding and the exclusion of the phosphatase CD45 from the cell-SLB contacts. Thus, CD45 exclusion alone was not sufficient to result in calcium signaling. In addition, more cells signaled on ligand-free SLBs with copper-chelating lipids instead of nickel-chelating lipids and the signaling was found to be predominantly via T-cell receptor (TCR) triggering. Hence, it is possible that the nickel-chelating lipids act as ligands to the cell’s TCRs, an interaction that needs to be blocked to avoid unwanted cell activation.
The Experimental TASK-1 Potassium Channel Inhibitor A293 Can Be Employed for Rhythm Control of Persistent Atrial Fibrillation in a Translational Large Animal Model
Authors: Wiedmann Felix , Beyersdorf Christoph , Zhou Xiao-Bo , Kraft Manuel , Foerster Kathrin I. , El-Battrawy Ibrahim , Lang Siegfried , Borggrefe Martin , Haefeli Walter E. , Frey Norbert , Schmidt Constanze
Published: January 2021

Background

Upregulation of the two-pore-domain potassium channel TASK-1 (hK2P3.1) was recently described in patients suffering from atrial fibrillation (AF) and resulted in shortening of the atrial action potential. In the human heart, TASK-1 channels facilitate repolarization and are specifically expressed in the atria. In the present study, we tested the antiarrhythmic effects of the experimental ion channel inhibitor A293 that is highly affine for TASK-1 in a porcine large animal model of persistent AF.

Methods

Persistent AF was induced in German landrace pigs by right atrial burst stimulation via implanted pacemakers using a biofeedback algorithm over 14 days. Electrophysiological and echocardiographic investigations were performed before and after the pharmacological treatment period. A293 was intravenously administered once per day. After a treatment period of 14 days, atrial cardiomyocytes were isolated for patch clamp measurements of currents and atrial action potentials. Hemodynamic consequences of TASK-1 inhibition were measured upon acute A293 treatment.

Results

In animals with persistent AF, the A293 treatment significantly reduced the AF burden (6.5% vs. 95%; P < 0.001). Intracardiac electrophysiological investigations showed that the atrial effective refractory period was prolonged in A293 treated study animals, whereas, the QRS width, QT interval, and ventricular effective refractory periods remained unchanged. A293 treatment reduced the upregulation of the TASK-1 current as well as the shortening of the action potential duration caused by AF. No central nervous side effects were observed. A mild but significant increase in pulmonary artery pressure was observed upon acute TASK-1 inhibition.

Conclusion

Pharmacological inhibition of atrial TASK-1 currents exerts in vivo antiarrhythmic effects that can be employed for rhythm control in a porcine model of persistent AF. Care has to be taken as TASK-1 inhibition may increase pulmonary artery pressure levels.
Multi-Parental Populations Suitable for Identifying Sources of Resistance to Powdery Mildew in Winter Wheat
Authors: Nordestgaard Nana Vagndorf , Thach Tine , Sarup Pernille , Rodriguez-Algaba Julian , Andersen Jeppe Reitan , Hovmøller Mogens Støvring , Jahoor Ahmed , Jørgensen Lise Nistrup , Orabi Jihad
Published: January 2021

Wheat (Triticum aestivum L.) is one of the world’s staple food crops and one of the most devastating foliar diseases attacking wheat is powdery mildew (PM). In Denmark only a few specific fungicides are available for controlling PM and the use of resistant cultivars is often recommended. In this study, two Chinese wheat landraces and two synthetic hexaploid wheat lines were used as donors for creating four multi-parental populations with a total of 717 individual lines to identify new PM resistance genetic variants. These lines and the nine parental lines (including the elite cultivars used to create the populations) were genotyped using a 20 K Illumina SNP chip, which resulted in 8,902 segregating single nucleotide polymorphisms for assessment of the population structure and whole genome association study. The largest genetic difference among the lines was between the donors and the elite cultivars, the second largest genetic difference was between the different donors; a difference that was also reflected in differences between the four multi-parental populations. The 726 lines were phenotyped for PM resistance in 2017 and 2018. A high PM disease pressure was observed in both seasons, with severities ranging from 0 to >50%. Whole genome association studies for genetic variation in PM resistance in the populations revealed significant markers mapped to either chromosome 2A, B, or D in each of the four populations. However, linkage disequilibrium between these putative quantitative trait loci (QTL) were all above 0.80, probably representing a single QTL. A combined analysis of all the populations confirmed this result and the most associated marker explained 42% of the variation in PM resistance. This study gives both knowledge about the resistance as well as molecular tools and plant material that can be utilised in marker-assisted selection. Additionally, the four populations produced in this study are highly suitable for association studies of other traits than PM resistance.
Enhancement of Tobacco (Nicotiana tabacum L.) Seed Lipid Content for Biodiesel Production by CRISPR-Cas9-Mediated Knockout of NtAn1
Authors: Tian Yinshuai , Liu Xinanbei , Fan Caixin , Li Tingting , Qin Huan , Li Xiao , Chen Kai , Zheng Yunpu , Chen Fang , Xu Ying
Published: January 2021

Tobacco (Nicotiana tabacum L.) seed lipid is a promising non-edible feedstock for biodiesel production. In order to meet the increasing demand, achieving high seed lipid content is one of the major goals in tobacco seed production. The TT8 gene and its homologs negatively regulate seed lipid accumulation in Arabidopsis and Brassica species. We speculated that manipulating the homolog genes of TT8 in tobacco could enhance the accumulation of seed lipid. In this present study, we found that the TT8 homolog genes in tobacco, NtAn1a and NtAn1b, were highly expressed in developing seed. Targeted mutagenesis of NtAn1 genes was created by the CRISPR-Cas9-based gene editing technology. Due to the defect of proanthocyanidin (PA) biosynthesis, mutant seeds showed the phenotype of a yellow seed coat. Seed lipid accumulation was enhanced by about 18 and 15% in two targeted mutant lines. Protein content was also significantly increased in mutant seeds. In addition, the seed yield-related traits were not affected by the targeted mutagenesis of NtAn1 genes. Thus, the overall lipid productivity of the NtAn1 knockout mutants was dramatically enhanced. The results in this present paper indicated that tobacco NtAn1 genes regulate both PAs and lipid accumulation in the process of seed development and that targeted mutagenesis of NtAn1 genes could generate a yellow-seeded tobacco variety with high lipid and protein content. Furthermore, the present results revealed that the CRISPR-Cas9 system could be employed in tobacco seed de novo domestication for biodiesel feedstock production.
Emotional Intelligence Mitigates the Effects of Customer Incivility on Surface Acting and Exhaustion in Service Occupations: A Moderated Mediation Model
Authors: Szczygiel Dorota Daniela , Bazińska Róz·a
Published: January 2021

This study contributes to the constantly accumulating evidence on the effects of customer incivility (CI) on service employee exhaustion. Previous research has demonstrated that surface acting (SA) acts as a mediating variable in the relationship between CI and exhaustion. This study extended prior findings in two ways. The results of Study 1 (315 retail sales employees, 62.2% female) demonstrated that SA mediates the positive relationship between CI and exhaustion while controlling for employees’ trait positive and negative affectivity (NA). The results of Study 2 (292 customer service representatives, 51% female) supported a moderated mediation model demonstrating that trait emotional intelligence (EI) buffers the direct and indirect (through SA) effects of CI on exhaustion. Specifically, it was found that employees exposed to many uncivil customer behaviors but high in trait EI reported using less SA and, thus, experienced fewer exhaustion symptoms than their low in trait EI counterparts. These results highlight EI as an important personal resource that mitigates the adverse effects of CI on service employees’ exhaustion, and suggest that organizations should consider implementing EI training programmes for their frontline service employees.
Supporting Mathematical Argumentation and Proof Skills: Comparing the Effectiveness of a Sequential and a Concurrent Instructional Approach to Support Resource-Based Cognitive Skills
Authors: Sommerhoff Daniel , Kollar Ingo , Ufer Stefan
Published: January 2021

An increasing number of learning goals refer to the acquisition of cognitive skills that can be described as ‘resource-based,’ as they require the availability, coordination, and integration of multiple underlying resources such as skills and knowledge facets. However, research on the support of cognitive skills rarely takes this resource-based nature explicitly into account. This is mirrored in prior research on mathematical argumentation and proof skills: Although repeatedly highlighted as resource-based, for example relying on mathematical topic knowledge, methodological knowledge, mathematical strategic knowledge, and problem-solving skills, little evidence exists on how to support mathematical argumentation and proof skills based on its resources. To address this gap, a quasi-experimental intervention study with undergraduate mathematics students examined the effectiveness of different approaches to support both mathematical argumentation and proof skills and four of its resources. Based on the part-/whole-task debate from instructional design, two approaches were implemented during students’ work on proof construction tasks: (i) asequential approachfocusing and supporting each resource of mathematical argumentation and proof skills sequentially after each other and (ii) aconcurrent approachfocusing and supporting multiple resources concurrently. Empirical analyses show pronounced effects of both approaches regarding the resources underlying mathematical argumentation and proof skills. However, the effects of both approaches are mostly comparable, and only mathematical strategic knowledge benefits significantly more from the concurrent approach. Regarding mathematical argumentation and proof skills, short-term effects of both approaches are at best mixed and show differing effects based on prior attainment, possibly indicating an expertise reversal effect of the relatively short intervention. Data suggests that students with low prior attainment benefited most from the intervention, specifically from the concurrent approach. A supplementary qualitative analysis showcases how supporting multiple resources concurrently alongside mathematical argumentation and proof skills can lead to a synergistic integration of these during proof construction and can be beneficial yet demanding for students. Although results require further empirical underpinning, both approaches appear promising to support the resources underlying mathematical argumentation and proof skills and likely also show positive long-term effects on mathematical argumentation and proof skills, especially for initially weaker students.
Attraction Effects for Verbal Gender and Number Are Similar but Not Identical: Self-Paced Reading Evidence From Modern Standard Arabic
Authors: Tucker Matthew A. , Idrissi Ali , Almeida Diogo
Published: January 2021

Previous work on the comprehension of agreement has shown that incorrectly inflected verbs do not trigger responses typically seen with fully ungrammatical verbs when the preceding sentential context furnishes a possibly matching distractor noun (i.e., agreement attraction). We report eight studies, three being direct replications, designed to assess the degree of similarity of these errors in the comprehension of subject-verb agreement along the dimensions of grammatical gender and number in Modern Standard Arabic. A meta-analysis of the results demonstrate the presence of agreement attraction effects in reading comprehension for gender and number on verbs. Moreover, the meta-analysis demonstrates that these two features do not behave identically: gender effects are larger and occur later relative to number attraction effects. These results challenge models of agreement that predict agreement features to be equipotent and show that real-time models of agreement require modifications in the form of cue-weighting in order to account for these differential results.
Sports and Functional Training Improve a Subset of Obesity-Related Health Parameters in Adolescents: A Randomized Controlled Trial
Authors: Branco Braulio Henrique Magnani , Mariano Isabela Ramos , de Oliveira Leonardo Pestillo , Bertolini Sônia Maria Marques Gomes , de Oliveira Fabiano Mendes , Araújo Cynthia Gobbi Alves , Adamo Kristi
Published: January 2021

To investigate the effects of two different modes of physical activity on body composition, physical fitness, cardiometabolic risk, and psychological responses in female adolescents participating in a multi-disciplinary program. The 12-week randomized intervention included 25-adolescents with overweight divided into two groups: sports practice-SPG and functional training-FTG. The SPG intervention was divided into three sports: basketball, handball, and futsal. SPG participants performed one sport 3-times/week, over the course of 1 month. The FTG performed concurrent exercises 3-times/week. This study was registered in Clinical Trials Registry Platform under number: RBR-45ywtg and registered in Local Ethics Committee number: 2,505.200/2018. The intensity of physical exercises-PE was matched between groups by the rating of perceived exertion. The primary outcome was body composition, and secondary outcomes were physical fitness, cardiometabolic risk, and psychological responses. There was a significant time-effect for body mass, body mass index, and low-density lipoprotein (LDL-c), all being reduced. There were increases over time for musculoskeletal mass, aerobic fitness, and high-density lipoprotein (HDL-c) (p < 0.05). There was a group time interaction with body fat percentage being lower post-intervention in the SPG (p < 0.05). No significant differences were observed for the other variables. Both physical activity models were effective in improving a subset of obesity-related health parameters. The findings should be extended by further investigation using more sophisticated measures of energy expenditure.

Clinical Trial Registration:https://ensaiosclinicos.gov.br/, identifier: RBR-45ywtg.
Not All Forms of Independence Are Created Equal: Only Being Independent the “Right Way” Is Associated With Self-Esteem and Life Satisfaction
Authors: Moza Daniela , Lawrie Smaranda Ioana , Maricuțoiu Laurențiu P. , Gavreliuc Alin , Kim Heejung S.
Published: January 2021

Past research has found a strong and positive association between the independent self-construal and life satisfaction, mediated through self-esteem, in both individualistic and collectivistic cultures. In Study 1, we collected data from four countries (the United States, Japan, Romania, and Hungary; N = 736) and replicated these findings in cultures which have received little attention in past research. In Study 2, we treated independence as a multifaceted construct and further examined its relationship with self-esteem and life satisfaction using samples from the United States and Romania (N = 370). Different ways of being independent are associated with self-esteem and life satisfaction in the two cultures, suggesting that it is not independence as a global concept that predicts self-esteem and life satisfaction, but rather, feeling independent in culturally appropriate ways is a signal that one’s way of being fits in and is valued in one’s context.
How Social Power Affects the Processing of Angry Expressions: Evidence From Behavioral and Electrophysiological Data
Authors: Zhang Entao , Ma Xueling , Tao Ruiwen , Suo Tao , Gu Huang , Li Yongxin
Published: January 2021

With the help of event-related potentials (ERPs), the present study used an oddball paradigm to investigate how both individual and target power modulate neural responses to angry expressions. Specifically, participants were assigned into a high-power or low-power condition. Then, they were asked to detect a deviant angry expression from a high-power or low-power target among a series of neutral expressions, while behavioral responses and electroencephalogram (EEG) were recorded. The behavioral results showed that high-power individuals responded faster to detect angry expressions than low-power individuals. The ERP analysis showed that high-power individuals showed larger P3 amplitudes in response to angry expressions than low-power individuals did. Target power increased the amplitudes of the P1, VPP, N3, and P3 in response to angry expressions did, but decreased the amplitudes of the N1 and N170 in response to angry expressions. The present study extended previous studies by showing that having more power could enhance individuals’ neural responses to angry expressions in the late-stage processes, and individuals could show stronger neural responses to angry expressions from high-power persons in both the early‐ and late-stage processes.
Feasibility and Effectiveness of a New Short-Term Psychotherapy Concept for Adolescents With Emotional Dysregulation
Authors: Dixius Andrea , Möhler Eva
Published: January 2021

Background:The ‘Stress-Trauma-Symptoms-Regulation-Treatment’ (START) is an innovative manualized short-term treatment program for stabilization and stress resilience in emotionally dysregulated adolescents, based on an approach of stress and management and emotional regulation. The current pilot trial aims to assess the feasibility and effectiveness of the START intervention program for improvement of emotion regulation.

Methods:Sixty-six adolescents between the age of 13–18 years admitted to a psychiatric unit for acute emotional or behavioral dysregulation took part in the START program for 5 weeks in an open group setting with two sessions per week (70 min/session). Before treatment, we assessed a history of adverse experience with the Child and Adolescent Trauma Screen (CATS) and the Child Posttraumatic Cognitions Inventory (CPTCI). Before and after treatment, the participants completed the FEEL-KJ, a self-report screening instrument of emotional regulation and coping strategies.

Results:A large proportion of this sample had experienced traumatic events based on the CATS (75%) and the CPTCI (82%). The mean FEEL-KJ score significantly decreased after the intervention (d= −0.248,p= 0.037), while no difference was observed with regard to mean level of adaptive emotion regulation strategies (d= 0.202,p= 0.207). A positive effect of the intervention was observed on three components of the adaptive FEEL-KJ scale: accepting(d= 0.289,p= 0.08), forgetting (d= 0.271,p= 0.049) and dealing with anger (d= 0.309,p= 0.034).

Conclusion:START demonstrates preliminary evidence for improvement in emotional dysregulation after a 5-weeks course of treatment. Therefore, this short-term intervention can possibly be regarded as a tool to improve emotional stability in children with a high load of trauma-related psychopathology. The results are promising and warrant future studies, specifically randomized controlled trials on the effectiveness of START for strengthening resilience at-risk-populations.
Dietary Glutamic Acid, Obesity, and Depressive Symptoms in Patients With Schizophrenia
Authors: Kumar Pooja , Kraal A. Zarina , Prawdzik Andreas M. , Ringold Allison E. , Ellingrod Vicki
Published: January 2021

Introduction:Schizophrenia is a lifelong condition associated with several comorbid conditions such as physical illnesses like obesity, as well as co-occurring psychiatric symptoms such as depression. Research regarding susceptibility to some of these comorbidities has primary focused on genetic risks or neurotransmitters and very little work has been done to understand environmental factors such as diet. In particular, understanding the role of dietary glutamic acid consumption on co-morbidities in patients with schizophrenia is important, as evidence suggests that glutamic acid consumption may directly influence glutamatergic neurotransmission; a key neurotransmitter related to schizophrenia, its associated co-morbidities, and depression. Therefore, the aim of this study was to examine the potential relationship between dietary glutamic acid and depressive symptomatology in patients with schizophrenia, stratified by obesity status, due to its relationship with inflammation, antipsychotic use, and depressive symptoms.

Methods:Subjects included in this analysis, were part of a parent cross-sectional study in which included three dietary recalls analyzed using protocols outlined as part of the National Health and Nutrition Examination Surveys (NHANES) standardized criteria. Additionally, body mass index (BMI), and Beck Depression Inventory were obtained at this visit. Subjects with a BMI ≥ 30 kg/m2were included in the obesity group, and the relationship between glutamic acid consumption and BDI scores was analyzed after controlling for age, race, sex, antidepressant and antipsychotic use, and animal and vegetable protein intake which provide natural forms of dietary glutamic acid.

Results:A total of 168 participants were included in this study, of which 42.5% were female and 52.9% were White. The mean BMI for the group as a whole was 33.5 ± 8.7 (kg/m2) and the mean BDI was 14.5 ± 10.2 (range 2–50). No differences were found between obesity groups, other than a greater hyperlipidemia, hypertension, and lower waist to hip ratio. Overall, no relationship was found between dietary glutamic acid and BDI scores, However, for non-obese participants, diets higher levels of glutamic acid were associated with greater depression symptomatology (p= 0.021).

Conclusion:These preliminary results indicate a possible correlation between dietary glutamic acid a depressive symptoms in non-obese patients with schizophrenia, although further research is needed to specifically examine this relationship.
Clustering and Healthcare Costs With Multiple Chronic Conditions in a US Study
Authors: Hajat Cother , Siegal Yakir , Adler-Waxman Amalia
Published: January 2021

Objective: To investigate healthcare costs and contributors to costs for multiple chronic conditions (MCCs), common clusters of conditions and their impact on cost and utilization.

Methods: This was a cross-sectional analysis of US financial claims data representative of the US population, including Medicare, Medicaid, and Commercial insurance claims in 2015. Outcome measures included healthcare costs and contributors; ranking of clusters of conditions according to frequency, strength of association and unsupervised (k-means) analysis; the impact of clustering on costs and contributors to costs.

Results: Of 1,878,951 patients, 931,045(49.6%) had MCCs, 56.5% weighted to the US population. Mean age was 53.0 years (SD16.7); 393,121(42.20%) were male. Mean annual healthcare spending was $12,601, ranging from $4,385 (2 conditions) to $33,874 (11 conditions), with spending increasing by 22-fold for inpatient services, 6-fold for outpatient services, 4.5-fold for generic drugs, and 4.2-fold for branded drugs. Cluster ranking using the 3 methodologies yielded similar results: highest ranked clusters included metabolic syndrome (12.2% of US insured patients), age related diseases (7.7%), renal failure (5.6%), respiratory disorders (4.5%), cardiovascular disease(CVD) (4.3%), cancers (4.1–4.3%), mental health-related clusters (1.0–1.5%), and HIV/AIDS (0.2%). Highest spending was in HIV/AIDS clusters ($48,293), mental health-related clusters ($38,952–$40,637), renal disease ($38,551), and CVD ($37,155); with 89.9% of spending on outpatient and inpatient care combined, and 10.1% on medication.

Conclusion and Relevance: Over 57% of insured patients in the US may have MCCs. MCC Clustering is frequent and is associated with healthcare utilization. The findings favor health system redesign toward a multiple condition approach for clusters of chronic conditions, alongside other cost-containment measures for MCCs.
Household Energy Insecurity and COVID-19 Have Independent and Synergistic Health Effects on Vulnerable Populations
Authors: Boateng Godfred O. , Phipps Laura M. , Smith Laura E. , Armah Frederick A.
Published: January 2021

Household energy insecurity (HEINS) is detrimental to the health of the poor and most vulnerable in resource-poor settings. However, this effect amidst the COVID-19 pandemic and the uneven implementation of restrictions can create a synergistic burden of diseases and health risks for the most vulnerable in low- and middle-income countries, exacerbating the health equity gap. Based on existing literature, this paper develops three key arguments: (1) COVID-19 increases the health risks of energy insecurity; (2) HEINS increases the risk of spreading COVID-19; and (3) the co-occurrence of COVID-19 and HEINS will have compounding health effects. These arguments make context-specific interventions, rather than a generic global health approach without recourse to existing vulnerabilities critical in reducing the spread of COVID-19 and mitigating the effects of energy insecurity. Targeted international efforts aimed at financing and supporting resource security, effective testing, contact tracing, and the equitable distribution of vaccines and personal protective equipment have the potential to ameliorate the synergistic effects of HEINS and COVID-19 in resource-poor countries.