bluuebunny/crossref_metadata_2025 huggingface dataset:
Association Between CST3 Gene Polymorphisms and Large-Artery Atherosclerotic Stroke
Authors: Ding Yarong , Xu Zhe , Pan Yuesong , Meng Xia , Xiang Xianglong , Li Hao , Liu Liping , Wang Yongjun
Published: October 2021

Objective: Cystatin C, a marker of atherosclerosis, is encoded by CST3. We aimed to evaluate whether two single-nucleotide polymorphisms (SNPs) of CST3 are correlated with large-artery atherosclerotic stroke (LAAS) and prognosis.

Methods: This subgroup analysis of the Third China National Stroke Registry (CNSR-III) enrolled acute ischemic stroke (AIS) patients within 7 days from August 2015 to March 2018 in China. rs13038305 and rs911119 of CST3 were selected based on the strong association with cystatin C concentration.

Results: Two loci of CST3 (rs13038305 and rs911119) were analyzed in 3,833 ischemic stroke patients. Carriers of T allele in rs13038305 and C allele in rs911119 tend to have lower serum cystatin C levels (p < 0.05). Compared with C/C as a reference in rs13038305, odds ratio (OR) of T/T was 0.486, 95% CI 0.237–0.994, p = 0.048. Per C allele of rs13038305 also showed an increased level of low-density lipoprotein cholesterol (LDL-C), β (95% CI) was 1.335 (1.008–1.250), p = 0.044. No correlation was found between the selected SNPs and stroke prognosis (functional outcome, recurrence, and mortality).

Conclusions: Carriers of the T allele in rs13038305 tend to have a lower proportion of LAAS. rs13038305 and rs911119 polymorphisms were likely to affect cystatin C concentration independently of kidney function.
Cerebral Large Vessel Occlusion Caused by Fat Embolism—A Case Series and Review of the Literature
Authors: Ooi Suyi , Raviskanthan Subahari , Campbell Bruce C. V. , Hutton Elspeth J. , Mitchell Peter J. , Cloud Geoffrey C.
Published: October 2021

The diagnosis of fat embolism syndrome typically involves neurological, respiratory and dermatological manifestations of microvascular occlusion 24–72 h after a precipitating event. However, fat embolism causing cerebral large vessel occlusion strokes and their sequelae have rarely been reported in the literature. This case series reports three patients with fat emboli post operatively causing cerebral large vessel occlusions, as well as a review of the literature to identify differences in clinical presentations and outcomes in stroke secondary to fat emboli causing large vessel occlusions compared to those with fat embolism syndrome.
Geographical and Ecological Differences in Pepper Cultivation and Consumption in China
Authors: Zou Ziying , Zou Xuexiao
Published: October 2021

Peppers (Capsicum spp.) are used as food items, and particularly condiments, across most of the world. Accordingly, these vegetables occupy the largest annual stable planting area (>21,000 km2) in China. However, pepper growth, cultivation systems, yield formation, and cultivar traits vary among different environments. China is characteristic for its widely diverse terrains and high ecological heterogeneity, which determine its unique pepper consumption habits and cultivation patterns. The present study provides a comprehensive overview and analysis of the geographical and ecological characteristics of Chinese pepper consumption habits and cultivation systems, and the influence of climatic and human factors on the national pepper planting industry. For this, we analyzed detailed geospatial datasets and reviewed relevant policy papers and academic literature. Based on those findings, we then proposed sustainable management strategies for China's pepper industry; we offered suggestions for aligning the continued development of pepper cultivation with the national objective of achieving an ecological civilization and the nutritional requirements of an increasingly affluent and diverse population.
Study of Diffusion Weighted Imaging Derived Diffusion Parameters as Biomarkers for the Microenvironment in Gliomas
Authors: Bai Yan , Liu Taiyuan , Chen Lijuan , Gao Haiyan , Wei Wei , Zhang Ge , Wang Lifu , Kong Lingfei , Liu Siyun , Liu Huan , Roberts Neil , Wang Meiyun
Published: October 2021

Objectives

To explore the efficacy of diffusion weighted imaging (DWI)-derived metrics under different models as surrogate indicators for molecular biomarkers and tumor microenvironment in gliomas.

Methods

A retrospective study was performed for 41 patients with gliomas. The standard apparent diffusion coefficient (ADCst) and ADC under ultra-high b values (ADCuh) (b values: 2500 to 5000 s/mm2) were calculated based on monoexponential model. The fraction of fast diffusion (f), pseudo ADC (ADCfast) and true ADC (ADCslow) were calculated by bi-exponential model (b values: 0 to 2000 s/mm2). The apparent diffusional kurtosis (Kapp) was derived from the simplified diffusion kurtosis imaging (DKI) model (b values: 200 to 3000 s/mm2). Potential correlations between DWI parameters and immunohistological indices (i.e. Aquaporin (AQP)1, AQP4, AQP9 and Ki-67) were investigated and DWI parameters were compared between high- and low-grade gliomas, and between tumor center and peritumor. Receiver operator characteristic (ROC) curve and area under the curve (AUC) were calculated to determine the performance of independent or combined DWI parameters in grading gliomas.

Results

The ADCslow and ADCuh at tumor center showed a stronger correlation with Ki-67 than other DWI metrics. The ADCst, ADCslow and ADCuh at tumor center presented correlations with AQP1 and AQP4 while AQP9 did not correlate with any DWI metric. Kapp showed a correlation with Ki-67 while no significant correlation with AQPs. ADCst (p < 0.001) and ADCslow (p = 0.001) were significantly lower while the ADCuh (p = 0.006) and Kapp (p = 0.005) were significantly higher in the high-grade than in the low-grade gliomas. ADCst, f, ADCfast, ADCslow, ADCuh, Kapp at the tumor center had significant differences with those in peritumor when the gliomas grade became high (p < 0.05). Involving ADCuh and Kapp simultaneously into an independent ADCst model (AUC = 0.833) could further improve the grading performance (ADCst+ADCuh+Kapp: AUC = 0.923).

Conclusion

Different DWI metrics fitted within different b-value ranges (low to ultra-high b values) have different efficacies as a surrogate indicator for molecular expression or microstructural complexity in gliomas. Further studies are needed to better explain the biological meanings of these DWI parameters in gliomas.
Knockdown of PPARδ Induces VEGFA-Mediated Angiogenesis via Interaction With ERO1A in Human Colorectal Cancer
Authors: Luo Wenjun , He Diao , Zhang Jianhao , Ma Zida , Chen Keling , lv Zhaoying , Fan Chuanwen , Yang Lie , Li Yuan , Zhou Zongguang
Published: October 2021

Angiogenesis is an important mechanism underlying the development and metastasis of colorectal cancer (CRC) and has emerged as a therapeutic target for metastatic CRC (mCRC). Our recent studies found that Peroxisome proliferator-activated receptor β/δ/D (PPARδ) regulates vascular endothelial growth factor A(VEGFA) secretion and the sensitivity to bevacizumab in CRC. However, its exact effect and underlying mechanisms remain unidentified. In this study, we showed that PPARδ expression was inversely associated with the microvascular density in human CRC tissues. Knockdown of PPARδ enhanced VEGFA expression in HCT116 cells and HUVEC angiogenesis in vitro; these phenomena were replicated in the experimental in vivo studies. By tandem mass tag (TMT)-labeling proteomics and chromatin immunoprecipitation sequencing (ChIP-seq) analyses, endoplasmic reticulum oxidoreductase 1 alpha (ERO1A) was screened and predicted as a target gene of PPARδ. This was verified by exploring the effect of coregulation of PPARδ and ERO1A on the VEGFA expression in HCT116 cells. The results revealed that PPARδ induced VEGFA by interacting with ERO1A. In conclusion, our results suggest that knockdown of PPARδ can promote CRC angiogenesis by upregulating VEGFA through ERO1A. This pathway may be a potential target for mCRC treatment.
Peritumoral Brain Edema in Metastases May Be Related to Glymphatic Dysfunction
Authors: Toh Cheng Hong , Siow Tiing Yee , Castillo Mauricio
Published: October 2021

Objectives

The proliferation of microvessels with increased permeability is thought to be the cause of peritumoral brain edema (PTBE) in metastases. The contribution of the glymphatic system to the formation of PTBE in brain metastases remains unexplored. We aimed to investigate if the PTBE volume of brain metastases is related to glymphatic dysfunction.

Materials and Methods

A total of 56 patients with brain metastases who had preoperative dynamic susceptibility contrast-enhanced perfusion-weighted imaging for calculation of tumor cerebral blood volume (CBV) and diffusion tensor imaging for calculations of tumor apparent diffusion coefficient (ADC), tumor fractional anisotropy (FA), and analysis along perivascular space (ALPS) index were analyzed. The volumes of PTBE, whole tumor, enhancing tumor, and necrotic and hemorrhagic portions were manually measured. Additional information collected for each patient included age, sex, primary cancer, metastasis location and number, and the presence of concurrent infratentorial tumors. Linear regression analyses were performed to identify factors associated with PTBE volume.

Results

Among 56 patients, 45 had solitary metastasis, 24 had right cerebral metastasis, 21 had left cerebral metastasis, 11 had bilateral cerebral metastases, and 11 had concurrent infratentorial metastases. On univariable linear regression analysis, PTBE volume correlated with whole tumor volume (β = -0.348, P = 0.009), hemorrhagic portion volume (β = -0.327, P = 0.014), tumor ADC (β = 0.530, P <.001), and ALPS index (β = -0.750, P <.001). The associations of PTBE volume with age, sex, tumor location, number of tumors, concurrent infratentorial tumor, enhancing tumor volume, necrotic portion volume, tumor FA, and tumor CBV were not significant. On multivariable linear regression analysis, tumor ADC (β = 0.303; P = 0.004) and ALPS index (β = -0.624; P < 0.001) were the two independent factors associated with PTBE volume.

Conclusion

Metastases with higher tumor ADC and lower ALPS index were associated with larger peritumoral brain edema volumes. The higher tumor ADC may be related to increased periarterial water influx into the tumor interstitium, while the lower ALPS index may indicate insufficient fluid clearance. The changes in both tumor ADC and ALPS index may imply glymphatic dysfunction, which is, at least, partially responsible for peritumoral brain edema formation.
Palbociclib Induces Senescence in Melanoma and Breast Cancer Cells and Leads to Additive Growth Arrest in Combination With Irradiation
Authors: Jost Tina , Heinzerling Lucie , Fietkau Rainer , Hecht Markus , Distel Luitpold V.
Published: October 2021

Introduction

Several kinase inhibitors (KI) bear the potential to act as radiosensitizers. Little is known of the radiosensitizing effects of a wide range of other KI like palbociclib, which is approved in ER+/HER2- metastatic breast cancer.

Method

In our study, we used healthy donor fibroblasts and breast cancer and skin cancer cells to investigate the influence of a concomitant KI + radiation therapy. Cell death and cell cycle distribution were studied by flow cytometry after Annexin-V/7-AAD and Hoechst staining. Cellular growth arrest was studied in colony-forming assays. Furthermore, we used C12-FDG staining (senescence) and mRNA expression analysis (qPCR) to clarify cellular mechanisms.

Results

The CDK4/6 inhibitor palbociclib induced a cell cycle arrest in the G0/G1 phase. Cellular toxicity (cell death) was only slightly increased by palbociclib and not enhanced by additional radiotherapy. As the main outcome of the colony formation assays, we found that cellular growth arrest was induced by palbociclib and improved by radiotherapy in an additive manner. Noticeably, palbociclib treatment clearly induced senescence not only in breast cancer and partly in melanoma cells, but also in healthy fibroblasts. According to these findings, the downregulation of senescence-related FOXM1 might be an involved mechanism of the senescence-induction potential of palbociclib.

Conclusion

The effect on cellular growth arrest of palbociclib and radiotherapy is additive. Palbociclib induces permanent G0/G1 cell cycle arrest by inducing senescence in fibroblasts, breast cancer, and melanoma cells. Direct cell death induction is only a minor secondary mechanism of action. Concomitant KI and radiotherapy is a strategy worth studying in clinical trials.
New Prognostic Biomarkers and Drug Targets for Skin Cutaneous Melanoma via Comprehensive Bioinformatic Analysis and Validation
Authors: Zhou Sitong , Han Yuanyuan , Li Jiehua , Pi Xiaobing , Lyu Jin , Xiang Shijian , Zhou Xinzhu , Chen Xiaodong , Wang Zhengguang , Yang Ronghua
Published: October 2021

Skin cutaneous melanoma (SKCM) is the most aggressive and fatal type of skin cancer. Its highly heterogeneous features make personalized treatments difficult, so there is an urgent need to identify markers for early diagnosis and therapy. Detailed profiles are useful for assessing malignancy potential and treatment in various cancers. In this study, we constructed a co-expression module using expression data for cutaneous melanoma. A weighted gene co-expression network analysis was used to discover a co-expression gene module for the pathogenesis of this disease, followed by a comprehensive bioinformatics analysis of selected hub genes. A connectivity map (CMap) was used to predict drugs for the treatment of SKCM based on hub genes, and immunohistochemical (IHC) staining was performed to validate the protein levels. After discovering a co-expression gene module for the pathogenesis of this disease, we combined GWAS validation and DEG analysis to identify 10 hub genes in the most relevant module. Survival curves indicated that eight hub genes were significantly and negatively associated with overall survival. A total of eight hub genes were positively correlated with SKCM tumor purity, and 10 hub genes were negatively correlated with the infiltration level of CD4+ T cells and B cells. Methylation levels of seven hub genes in stage 2 SKCM were significantly lower than those in stage 3. We also analyzed the isomer expression levels of 10 hub genes to explore the therapeutic target value of 10 hub genes in terms of alternative splicing (AS). All 10 hub genes had mutations in skin tissue. Furthermore, CMap analysis identified cefamandole, ursolic acid, podophyllotoxin, and Gly-His-Lys as four targeted therapy drugs that may be effective treatments for SKCM. Finally, IHC staining results showed that all 10 molecules were highly expressed in melanoma specimens compared to normal samples. These findings provide new insights into SKCM pathogenesis based on multi-omics profiles of key prognostic biomarkers and drug targets. GPR143 and SLC45A2 may serve as drug targets for immunotherapy and prognostic biomarkers for SKCM. This study identified four drugs with significant potential in treating SKCM patients.
Conbercept for Treatment of Neovascular Age-Related Macular Degeneration and Visual Impairment due to Diabetic Macular Edema or Pathologic Myopia Choroidal Neovascularization: A Systematic Review and Meta-Analysis
Authors: Zhou Pengxiang , Zheng Siqian , Wang Ente , Men Peng , Zhai Suodi
Published: October 2021

Background: Conbercept is a new anti-vascular endothelial growth factor (VEGF) drug. Here, we systematically conducted the efficacy, safety, compliance, and pharmacoeconomic evaluation of intravitreal conbercept (IVC) compared with other treatments in patients with neovascular age-related macular degeneration (nAMD), diabetic macular edema (DME), or pathologic myopia choroidal neovascularization (pmCNV).

Methods: Databases of PubMed, Embase, Cochrane Library, ClinicalTrials.gov, SinoMed, China National Knowledge Infrastructure, and WanFang Data were systematically searched from the inception to July 27, 2021. Randomized clinical trials and pharmacoeconomic studies comparing IVC with control groups in adults with nAMD, DME, or pmCNV were reviewed and selected. Meta-analyses were performed using the fixed-effects model when pooled data were homogeneous. Heterogeneous data were analyzed using the random-effects model. Primary outcomes included visual improvement rate, mean change in visual acuity or best corrected visual acuity, and pharmacoeconomic outcomes. Additional outcomes were the mean change in fundus examination values, adverse events (AEs), quality-of-life measures, and number of injections.

Results: Among 3,591 screened articles, 22 original studies with 1,910 eyes of patients were finally included. For nAMD and DME, IVC was significantly associated with better visual acuity or best corrected visual acuity improvement and fundus quantitative measures than placebo, laser photocoagulation (LP), or intravitreal triamcinolone acetonide (IVT). However, IVC showed non-inferior efficacy to intravitreal ranibizumab (IVR) according to low quality of evidence, and there was lack of trials comparing the priority of IVC to other anti-VEGF regimens. No definitive increased risk of ocular or non-ocular AEs were observed in the study groups. All patients with AEs recovered after symptomatic treatments, and no severe AEs occurred. Patients treated with IVC might have higher quality-of-life scores than those in IVR in nAMD or LP in DME. Additionally, IVC showed cost–utility advantages in nAMD and cost-effectiveness advantages than IVR in pmCNV in China.

Conclusion: IVC is well-tolerated and effective for improving vision acuity and quantitative measures in fundus condition in patients with nAMD and DME compared with LP, IVT, and placebo, but gains comparable efficacy to IVR. However, well-designed, large-sample, and long-term evaluation of IVC shall be conducted in additional studies worldwide.
Predicting the Outcome of Voriconazole Individualized Medication Using Integrated Pharmacokinetic/Pharmacodynamic Model
Authors: Yang Ping , Liu Wei , Zheng Jiajia , Zhang Yuanyuan , Yang Li , He Na , Zhai Suodi
Published: October 2021

Therapeutic drug monitoring is considered to be an effective tool for the individualized use of voriconazole. However, drug concentration measurement alone doesn’t take into account the susceptibility of the infecting microorganisms to the drug. Linking pharmacodynamic data with the pharmacokinetic profile of individuals is expected to be an effective method to predict the probability of a certain therapeutic outcome. The objective of this study was to individualize voriconazole regimens by integrating individual pharmacokinetic parameters and pathogen susceptibility data through Monte Carlo simulations The individual pharmacokinetic parameters of 35 hospitalized patients who received voriconazole were calculated based on a validated population pharmacokinetic model. The area under the concentration-time curve for free drug/minimal inhibitory concentration (fAUCss/MIC) > 25 was selected as the pharmacokinetic/pharmacodynamic (PK/PD) parameter predicting the efficacy of voriconazole. The cumulative fraction of response (CFR) of the target value was assessed. To verify this conclusion, a logistic regression analysis was used to explore the relationship between actual clinical efficiency and the CFR value. For the 35 patients, the area under the free drug concentration-time curve (fAUCss) was calculated to be 34.90 ± 21.67 mgh/L. According to the dualistic logistic regression analysis, the minimal inhibitory concentration (MIC) value of different kinds of fungi had a great influence on the effectiveness of clinical treatment. It also showed that the actual clinical efficacy and the CFR value of fAUCss/MIC had a high degree of consistency. The results suggest that it is feasible to individualize voriconazole dosing and predict clinical outcomes through the integration of data on pharmacokinetics and antifungal susceptibility.
Estimating Precipitating Energy Flux, Average Energy, and Hall Auroral Conductance From THEMIS All-Sky-Imagers With Focus on Mesoscales
Authors: Gabrielse Christine , Nishimura Toshi , Chen Margaret , Hecht James H. , Kaeppler Stephen R. , Gillies D. Megan , Reimer Ashton S. , Lyons Larry R. , Deng Yue , Donovan Eric , Evans J. Scott
Published: October 2021

Recent attention has been given to mesoscale phenomena across geospace (∼10 s km to 500 km in the ionosphere or ∼0.5 RE to several RE in the magnetosphere), as their contributions to the system global response are important yet remain uncharacterized mostly due to limitations in data resolution and coverage as well as in computational power. As data and models improve, it becomes increasingly valuable to advance understanding of the role of mesoscale phenomena contributions—specifically, in magnetosphere-ionosphere coupling. This paper describes a new method that utilizes the 2D array of Time History of Events and Macroscale Interactions during Substorms (THEMIS) white-light all-sky-imagers (ASI), in conjunction with meridian scanning photometers, to estimate the auroral scale sizes of intense precipitating energy fluxes and the associated Hall conductances. As an example of the technique, we investigated the role of precipitated energy flux and average energy on mesoscales as contrasted to large-scales for two back-to-back substorms, finding that mesoscale aurora contributes up to ∼80% (∼60%) of the total energy flux immediately after onset during the early expansion phase of the first (second) substorm, and continues to contribute ∼30–55% throughout the remainder of the substorm. The average energy estimated from the ASI mosaic field of view also peaked during the initial expansion phase. Using the measured energy flux and tables produced from the Boltzmann Three Constituent (B3C) auroral transport code (Strickland et al., 1976; 1993), we also estimated the 2D Hall conductance and compared it to Poker Flat Incoherent Scatter Radar conductance values, finding good agreement for both discrete and diffuse aurora.
Fine Tuning of Phosphorothioate Inclusion in 2′-O-Methyl Oligonucleotides Contributes to Specific Cell Targeting for Splice-Switching Modulation
Authors: Aoki Yoshitsugu , Rocha Cristina S. J. , Lehto Taavi , Miyatake Shouta , Johansson Henrik , Hashimoto Yasumasa , Nordin Joel Z. , Mager Imre , Aoki Misako , Graham McClorey , Sathyaprakash Chaitra , Roberts Thomas C. , Wood Matthew J. A. , Behlke Mark A. , Andaloussi Samir El
Published: October 2021

Splice-switching antisense oligonucleotide- (SSO-) mediated correction of framedisrupting mutation-containing premessenger RNA (mRNA) transcripts using exon skipping is a highly promising treatment method for muscular diseases such as Duchenne muscular dystrophy (DMD). Phosphorothioate (PS) chemistry, a commonly used oligonucleotide modification, has been shown to increase the stability of and improve the pharmacokinetics of SSOs. However, the effect of PS inclusion in 2′-O-methyl SSOs (2OMe) on cellular uptake and splice switching is less well-understood. At present, we demonstrate that the modification of PS facilitates the uptake of 2OMe in H2k-mdx myoblasts. Furthermore, we found a dependency of SSO nuclear accumulation and high splice-switching activity on PS inclusion in 2OMe (2OMePS), as tested in various reporter cell lines carrying pLuc/705. Increased exon-inclusion activity was observed in muscle, neuronal, liver, and bone cell lineages via both the gymnotic uptake and lipofection of 2OMePS. Using the photoactivatable ribonucleoside-enhanced crosslinking and a subsequent proteomic approach, we identified several 2OMePS-binding proteins, which are likely to play a role in the trafficking of 2OMePS to the nucleus. Ablation of one of them, Ncl by small-interfering RNA (siRNA) enhanced 2OMePS uptake in C2C12 myoblasts and upregulated luciferase RNA splicing in the HeLa Luc/705 reporter cell line. Overall, we demonstrate that PS inclusion increases nuclear delivery and splice switching in muscle, neuronal, liver, and bone cell lineages and that the modulation of 2OMePS-binding partners may improve SSO delivery.
Alternate Partial Root-Zone Drip Nitrogen Fertigation Reduces Residual Nitrate Loss While Improving the Water Use but Not Nitrogen Use Efficiency
Authors: Liu Rui , Zhu Peng-Fei , Wang Yao-Sheng , Chen Zhen , Zhu Ji-Rong , Shu Liang-Zuo , Zhang Wen-Ju
Published: October 2021

The efficient utilization of irrigation water and nitrogen is of great importance for sustainable agricultural production. Alternate partial root-zone drip irrigation (APRD) is an innovative water-saving drip irrigation technology. However, the coupling effects of water and nitrogen (N) supply under APRD on crop growth, water and N use efficiency, as well as the utilization and fate of residual nitrates accumulated in the soil profile are not clear. A simulated soil column experiment where 30–40 cm soil layer was 15NO3-labeled as residual nitrate was conducted to investigate the coupling effects of different water [sufficient irrigation (W1), two-thirds of the W1(W2)] and N [high level (N1), 50% of N1 (N2)] supplies under different irrigation modes [conventional irrigation (C), APRD (A)] on tomato growth, irrigation water (IWUE) and N use efficiencies (NUE), and the fate of residual N. The results showed that, compared with CW1N1, AW1N1 promoted root growth and nitrogen absorption, and increased tomato yield, while the N absorption and yield did not vary significantly in AW2N1. The N absorption in AW2N2 decreased by 16.1%, while the tomato yield decreased by only 8.8% compared with CW1N1. The highest IWUE appeared in AW2N1, whereas the highest NUE was observed in AW2N2, with no significant difference in NUE between AW2N1 and CW1N1 at the same N supply level. The 15N accumulation peak layer was almost the same as the originally labeled layer under APRD, whereas it moved 10–20 cm downwards under CW1N1. The amount of 15N accumulated in the 0-40 cm layer increased with the decreasing irrigation water and nitrogen supply, with an increase of 82.9–141.1% in APRD compared with that in CW1N1. The utilization of the 15N labeled soil profile by the tomato plants increased by 9–20.5%, whereas the loss rate of 15N from the plant-soil column system decreased by 21.3–50.1% in APRD compared with the CW1N1 treatment. Thus, APRD has great potential in saving irrigation water, facilitating water use while reducing the loss of residual nitrate accumulated in the soil profile, but has no significant effect on the NUE absorbed.
Transcriptome Analysis of Zygophyllum xanthoxylum Adaptation Strategies to Phosphate Stress
Authors: Hu Xiaowei , Zhang Lijing , Niu Decao , Nan Shuzhen , Wu Shujuan , Gao Hongjuan , Fu Hua
Published: October 2021

Soil phosphate (Pi) deficiency is a global issue and a major constraint on plant growth. Plants typically acclimatize to low Pi by enhancing their P utilization and/or P acquisition efficiencies; however, different species have variable preferred strategies. RNA sequencing analysis was performed on the shoots and roots of Zygophyllum xanthoxylum, under 1 day and 10 days of Pi stress, to investigate their adaptation strategies to P deprivation. A total of 364,614 unigenes and 9,270 differentially expressed genes (DEGs) were obtained via transcriptome sequencing. An analysis of the DEGs revealed that under the 10D treatment, anthocyanin synthesis genes were upregulated under Pi stress, whereas gibberellin, ethylene, and cytokinins synthesis genes were upregulated, and abscisic acid synthesis genes were downregulated. Genes related to organic acid synthesis, encoding for purple acid phosphatases (APase) and nucleases (RNase) were upregulated under the 1D and 10D treatments, respectively. Furthermore, genes associated with Pi transport were induced by Pi stress. Zygophyllum xanthoxylum has special P adaptation strategies, the variation trends of genes involved in external P mobilization and acquisition, which were different from that of most other species; however, the expression levels of organophosphorus mobilization related genes, such as APases and RNases, were significantly increased. Meanwhile, PHT2s and TPTs, which distributed Pi to effective sites (e.g., chloroplast), played critical roles in the maintenance of photosynthesis. We speculated that these were economic and energy saving strategies, and there are critical adaptive mechanisms that Z. xanthoxylum employs to cope with deficits in Pi.
Characterization of the Brassica napus Flavonol Synthase Gene Family Reveals Bifunctional Flavonol Synthases
Authors: Schilbert Hanna Marie , Schöne Maximilian , Baier Thomas , Busche Mareike , Viehöver Prisca , Weisshaar Bernd , Holtgräwe Daniela
Published: October 2021

Flavonol synthase (FLS) is a key enzyme for the formation of flavonols, which are a subclass of the flavonoids. FLS catalyzes the conversion of dihydroflavonols to flavonols. The enzyme belongs to the 2-oxoglutarate-dependent dioxygenases (2-ODD) superfamily. We characterized the FLS gene family of Brassica napus that covers 13 genes, based on the genome sequence of the B. napus cultivar Express 617. The goal was to unravel which BnaFLS genes are relevant for seed flavonol accumulation in the amphidiploid species B. napus. Two BnaFLS1 homeologs were identified and shown to encode bifunctional enzymes. Both exhibit FLS activity as well as flavanone 3-hydroxylase (F3H) activity, which was demonstrated in vivo and in planta. BnaFLS1-1 and -2 are capable of converting flavanones into dihydroflavonols and further into flavonols. Analysis of spatio-temporal transcription patterns revealed similar expression profiles of BnaFLS1 genes. Both are mainly expressed in reproductive organs and co-expressed with the genes encoding early steps of flavonoid biosynthesis. Our results provide novel insights into flavonol biosynthesis in B. napus and contribute information for breeding targets with the aim to modify the flavonol content in rapeseed.
Cation/Ca2+ Exchanger 1 (MdCCX1), a Plasma Membrane-Localized Na+ Transporter, Enhances Plant Salt Tolerance by Inhibiting Excessive Accumulation of Na+ and Reactive Oxygen Species
Authors: Yang Jie , Li Weihan , Guo Xin , Chen Peihong , Cheng Yunpeng , Mao Ke , Ma Fengwang
Published: October 2021

High salinity causes severe damage to plant growth and significantly reduces crop yields. The CCX family proteins can facilitate the transport of multiple ions to prevent toxicity. CCX proteins play an important role in regulating plant salt tolerance, but no detailed studies on CCX proteins in apples have been reported. Here, the CCX family gene MdCCX1 was cloned from apple (Malus domestica). It is constitutively expressed in various apple tissues and is significantly induced by salt stress. As a plasma membrane-localized protein, MdCCX1-overexpression could complement the Na+-sensitive phenotype of yeast mutants and reduce the Na+ content in yeast cells under NaCl treatment, suggesting that MdCCX1 could be a plasma membrane-localized Na+ transporter. To identify the function of MdCCX1 in salt response, we transformed this gene into Arabidopsis, apple calli, and apple plants. Overexpression of MdCCX1 significantly improved the salt tolerance of these transgenic materials. The significantly reduced Na+ content under NaCl treatment indicated that MdCCX1 overexpression could enhance plant salt tolerance by inhibiting the excessive accumulation of Na+. Besides, MdCCX1 overexpression could also enhance plant salt tolerance by promoting ROS scavenging. These findings provide new insight and rich resources for future studies of CCX proteins in plant species.
Importance of Voting at the Municipal Level: The Seniors’ Voices
Authors: Vallette Salomé
Published: October 2021

While municipal elections in Quebec are characterized by low voter turnout, it appears that people over 65 years old are the ones who vote in higher numbers. In fact, this is the case for both federal and provincial elections. However, the lack of individual data on municipal elections does not yet allow us to say that seniors vote more than younger people. This finding invites political scientists to look at the electoral behaviour of individual voters and the importance attached to the act of voting at this level of government. In addition, the majority of studies on elections focus on the behaviours of voters living in large cities such as Montreal or Quebec City. In Quebec, the few studies that have looked at medium size municipality voting behaviour have mainly studied the cities of Quebec City, but not Montreal. Based on 19 interviews conducted with people aged between 65 and 84 and living in one medium size cities, Saint-Jean-sur-Richelieu, our research illustrates the importance of the exercise of a duty, the access to political information, the proximity of electoral behaviour and the influential role of seniors. According to participants, it is easier to talk to municipal candidates and get to know the person who will become their official representative, compared to the provincial and federal levels where it is more difficult to talk to candidates. Also, their knowledge of the municipal political system is better than when they were younger. While voting is similarly important at each level of government, participants felt that voting at the municipal level is directly relevant to them because of the municipal services but also by the influence they can have on their councillor.
Contribution of Entrepreneurship to the Social Integration of People Intellectual Disabilities: A Case Study Based on the Analysis of Social Networks
Authors: Barba-Sánchez Virginia , Salinero Yolanda , Jiménez-Estevez Pedro , Galindo Esteban
Published: October 2021

In an environment characterized by high unemployment rates among people with disabilities, the objective of the present work is to analyze entrepreneurship as a labor option which fully inserts people with intellectual disabilities (PwID) into their societies. In order to carry out this research, a case study methodology based on social network analysis has been adopted, given the nature of the variables analyzed. The results indicate that the fact of having managed to start up the company has been an important source of self-confidence and inspiration, as well as increasing and intensifying the social networks of PwID involved in the entrepreneurial project.
The Mindfulness Map: A Practical Classification Framework of Mindfulness Practices, Associated Intentions, and Experiential Understandings
Authors: Levit-Binnun Nava , Arbel Keren , Dorjee Dusana
Published: October 2021

When considering the numerous mindfulness-based and mindfulness-informed programs that have flourished in the past decades it is not always clear that they all refer to the same “mindfulness. ” To facilitate more clarity and precision in describing, researching and teaching mindfulness in the secular settings, we propose a classification framework of mindfulness practices, intentions behind them and the experiential understandings the practices may aim to develop. Accordingly, the proposed framework, called the Mindfulness Map, has two axes. The first axis outlines mindfulness practices (and associated instructions) classified into four groups (MGs), e.g. the MG1 focuses on cultivating attention to the present moment somatic and sensory experience while the MG4 focuses on cultivating the ability to recognize and deconstruct perceptual, cognitive and emotional experiences and biases. The second axis outlines possible intentions (INTs) to cultivate particular experiential understanding (EU) via teaching and practicing the MGs, e.g., the INT1 designates the intention to gain EU of how our relationship to experience contributes to wellbeing, the INT2 refers to the intention to gain EU of the changing nature of body, mind and external phenomenon. We suggest that the same MG can lead to different EUs outcomes based on the specific INTs applied in their teaching or practice. The range of INTs and EUs included here is not exhaustive, there are further types the Map could be expanded toward. Aside from encouraging more fine-grained distinctions of mindfulness practices, the proposed Map aims to open discussions about interactions between MGs, INTs, EUs and practice outcomes. The Map may facilitate more nuanced and precise approaches to researching the range of outcomes cultivated by mindfulness practices, help bridge contradictory findings, and catalyze further debate and research into ethical aspects of mindfulness. The Map also highlights the need for further teaching development and research on longer-term trajectories of mindfulness practice. While the proposed Mindfulness Map organises the mindfulness practice territory along two axes, it is aimed as a starting point for further discussion and can be further revised and/or expanded by other axes.
Baby’s Online Live Database: An Open Platform for Developmental Science
Authors: Kato Masaharu , Doi Hirokazu , Meng Xianwei , Murakami Taro , Kajikawa Sachiyo , Otani Takashi , Itakura Shoji
Published: October 2021

Efficient data collection in developmental studies is facing challenges due to the decreased birth rates in many regions, reproducibility problems in psychology research, and the COVID-19 pandemic. Here, we propose a novel platform for online developmental science research, the Baby’s Online Live Database (BOLD), which extends the scope of the accessible participant pool, simplifies its management, and enables participant recruitment for longitudinal studies. Through BOLD, researchers can conduct online recruitment of participants preregistered to BOLD simply by specifying their attributes, such as gender and age, and direct the participants to dedicated webpages for each study. Moreover, BOLD handles participant recruitment and reward payment, thereby freeing researchers from the labor of participant management. BOLD also allows researchers the opportunity to access data that were collected from participants in previous research studies. This enables researchers to carry out longitudinal analyses at a relatively low cost. To make BOLD widely accessible, a consortium was formed within the Japan Society of Baby Science, where members from diverse research groups discussed the blueprint of this system. Once in full-scaled operation, BOLD is expected to serve as a platform for various types of online studies and facilitate international collaboration among developmental scientists in the near future.
Designing Virtual, Moderated Studies of Early Childhood Development
Authors: Gijbels Liesbeth , Cai Ruofan , Donnelly Patrick M. , Kuhl Patricia K.
Published: October 2021

With increased public access to the Internet and digital tools, web-based research has gained prevalence over the past decades. However, digital adaptations for developmental research involving children have received relatively little attention. In 2020, as the COVID-19 pandemic led to reduced social contact, causing many developmental university research laboratories to close, the scientific community began to investigate online research methods that would allow continued work. Limited resources and documentation of factors that are essential for developmental research (e.g., caregiver involvement, informed assent, controlling environmental distractions at home for children) make the transition from in-person to online research especially difficult for developmental scientists. Recognizing this, we aim to contribute to the field by describing three separate moderated virtual behavioral assessments in children ranging from 4 to 13years of age that were highly successful. The three studies encompass speech production, speech perception, and reading fluency. However varied the domains we chose, the different age groups targeted by each study and different methodological approaches, the success of our virtual adaptations shared certain commonalities with regard to how to achieve informed consent, how to plan parental involvement, how to design studies that attract and hold children’s attention and valid data collection procedures. Our combined work suggests principles for future facilitation of online developmental work. Considerations derived from these studies can serve as documented points of departure that inform and encourage additional virtual adaptations in this field.
Reduced Plasma Levels of α-Klotho and Their Correlation With Klotho Polymorphisms in Elderly Patients With Major Depressive Disorders
Authors: Gao Xiang , Sun Zuoli , Ma Guangwei , Li Yuhong , Liu Min , Zhang Guofu , Xu Hong , Gao Yane , Zhou Jixuan , Deng Qi , Li Rena
Published: October 2021

Background: Recent literature suggests that α-Klotho, a widely recognized anti-aging protein, is involved in longevity as well as in many diseases, including Alzheimer's disease, and depression. Although the Klotho gene encodes α-Klotho, a single transmembrane protein with intracellular and extracellular domains, the relationship between Klotho gene polymorphism and circulating α-Klotho levels in patients with major depressive disorder (MDD) is not clear.

Methods: A total of 144 MDD patients and 112 age-matched healthy controls were included in this study. The Klotho genetic polymorphisms (rs9536314, rs9527025, and rs9315202) and plasma α-Klotho levels were measured by PCR and ELISA, respectively. The severity of depressive symptoms was estimated using the Hamilton Depression Scale (HAMD).

Results: We found a significantly lower level of plasma α-Klotho in the MDD patients than in controls. Among them, only elderly MDD patients (first episode) showed significantly lower α-Klotho levels than the age-matched controls, while elderly recurrent and young MDD patients showed no difference in plasma α-Klotho levels from age-matched controls. The young MDD group showed a significantly earlier onset age, higher plasma α-Klotho levels, and lower HAMD scores than those in the elderly MDD group. While the plasma α-Klotho levels were higher in rs9315202 T alleles carrier regardless age or sex, the rs9315202 T allele was negatively correlated with disease severity only in the elderly MDD patients.

Conclusion: The results of our study showed that only elderly MDD patients showed a decrease in plasma α-Klotho levels along with an increase in disease severity as well as an association with the number of rs9315202 T alleles, and not young MDD patients compared to age-matched controls. Our data suggest that circulating α-Klotho levels combined with Klotho genetic polymorphisms are important in elderly MDD patients, particularly carriers of the Klotho gene rs9315202 T allele.
Which Social, Economic, and Health Sector Strategies Will Deliver the Greatest Impacts for Youth Mental Health and Suicide Prevention? Protocol for an Advanced, Systems Modelling Approach
Authors: Occhipinti Jo-An , Skinner Adam , Freebairn Louise , Song Yun Ju Christine , Ho Nicholas , Lawson Kenny , Lee Grace Yeeun , Hickie Ian B.
Published: October 2021

Background:Current global challenges are generating extensive social disruption and uncertainty that have the potential to undermine the mental health, wellbeing, and futures of young people. The scale and complexity of challenges call for engagement with systems science-based decision analytic tools that can capture the dynamics and interrelationships between physical, social, economic, and health systems, and support effective national and regional responses. At the outset of the pandemic mental health-related systems models were developed for the Australian context, however, the extent to which findings are generalisable across diverse regions remains unknown. This study aims to explore the context dependency of systems modelling insights.

Methods:This study will employ a comparative case study design, applying participatory system dynamics modelling across eight diverse regions of Australia to answer three primary research questions: (i) Will current regional differences in key youth mental health outcomes be exacerbated in forward projections due to the social and economic impacts of COVID-19?; (ii) What combination of social policies and health system strengthening initiatives will deliver the greatest impacts within each region?; (iii) To what extent are optimal strategic responses consistent across the diverse regions? We provide a detailed technical blueprint as a potential springboard for more timely construction and deployment of systems models in international contexts to facilitate a broader examination of the question of generalisability and inform investments in the mental health and wellbeing of young people in the post COVID-19 recovery.

Discussion:Computer simulation is known as the third pillar of science (after theory and experiment). Simulation allows researchers and decision makers to move beyond what can be manipulated within the scale, time, and ethical limits of the experimental approach. Such learning when achieved collectively, has the potential to enhance regional self-determination, help move beyond incremental adjustments to the status quo, and catalyze transformational change. This research seeks to advance efforts to establish regional decision support infrastructure and empower communities to effectively respond. In addition, this research seeks to move towards an understanding of the extent to which systems modelling insights may be relevant to the global mental health response by encouraging researchers to use, challenge, and advance the existing work for scientific and societal progress.
Characterizing the Heterogeneity of Aging: A Vision for a Staging System for Aging
Authors: Jaul Efraim , Barron Jeremy
Published: October 2021

Introduction: Older adulthood encompasses several decades of change and heterogeneity. Primary care providers need a geriatric comprehensive vision for defining older adult subpopulations.

Methods: Using PubMed and Google searches, we reviewed the literature on epidemiology of age-related physiological changes, age-related diseases and geriatric syndromes, functional state, and emotional and social changes. We divided old age into strata based on chronological age and strata based on functional state, disease burden, and geriatric syndromes.

Results: We describe 4 chronological-age strata beginning at age 60, and 4 functional-age strata based on frailty according to a modified clinical frailty scale. We provide clinical considerations and anticipatory guidance topics for each of the age strata and functional strata.

Conclusion: Chronological age, functional status, chronic disease burden and geriatric syndromes, and life expectancy are all important domains that impact clinical care and appropriate anticipatory guidance for individual older adults. Better knowledge for differentiating subpopulations of older adults may improve clinical care, reduce medical overuse, improve personalized anticipatory guidance, and focus on the impact of functional state on the quality of life.