bluuebunny/crossref_metadata_2025 huggingface dataset:
Transcriptomic and genetic approaches reveal that low-light-induced disease susceptibility is related to cellular oxidative stress in tomato
Authors: Luo Qian , Wang Jiao , Wang Ping , Liang Xiao , Li Jianxin , Wu Changqi , Fang Hanmo , Ding Shuting , Shao Shujun , Shi Kai
Published: August 2023

The impact of low light intensities on plant disease outbreaks represents a major challenge for global crop security, as it frequently results in significant yield losses. However, the underlying mechanisms of the effect of low light on plant defense are still poorly understood. Here, using an RNA-seq approach, we found that the susceptibility of tomato to Pseudomonas syringae pv. tomato DC3000 (Pst DC3000) under low light was associated with the oxidation–reduction process. Low light conditions exacerbated Pst DC3000-induced reactive oxygen species (ROS) accumulation and protein oxidation. Analysis of gene expression and enzyme activity of ascorbate peroxidase 2 (APX2) and other antioxidant enzymes revealed that these defense responses were significantly induced by Pst DC3000 inoculation under normal light, whereas these genes and their associated enzyme activities were not responsive to pathogen inoculation under low light. Additionally, the reduced ascorbate to dehydroascorbate (AsA/DHA) ratio was lower under low light compared with normal light conditions upon Pst DC3000 inoculation. Furthermore, the apx2 mutants generated by a CRISPR-Cas9 gene-editing approach were more susceptible to Pst DC3000 under low light conditions. Notably, this increased susceptibility could be significantly reduced by exogenous AsA treatment. Collectively, our findings suggest that low-light-induced disease susceptibility is associated with increased cellular oxidative stress in tomato plants. This study sheds light on the intricate relationship between light conditions, oxidative stress, and plant defense responses, and may pave the way for improved crop protection strategies in low light environments.
CircEXOC5 Aggravates Sepsis-Induced Acute Lung Injury by Promoting Ferroptosis Through the IGF2BP2/ATF3 Axis
Authors: Wang Wei , Xu Rongli , He Ping , Xiong Yuqing , Zhao Haomiao , Fu Xuewei , Lin Jie , Ye Lijiao
Published: August 2023

Background

Patients with sepsis resulting in acute lung injury (ALI) usually have increased mortality. Ferroptosis is a vital regulator in sepsis-induced ALI. Exploring the association of ferroptosis and sepsis-induced ALI is crucial for the management of sepsis-induced ALI.

Methods

Whole blood was collected from sepsis patients. Mice were treated with cecal ligation and puncture (CLP) to model sepsis. Primary murine pulmonary microvascular endothelial cells were treated with lipopolysaccharide as a cell model. Ferroptosis was evaluated by analyzing levels of iron, malonaldehyde, glutathione, nonheme iron, ferroportin, ferritin, and GPX4. Hematoxylin and eosin and Masson's trichrome staining were applied to examine lung injury and collagen deposition. Cell apoptosis was analyzed by caspase-3 activity and TUNEL assays. Gene regulatory relationship was verified using RNA pull-down and immunoprecipitation assays.

Results

CircEXOC5 was highly expressed in sepsis patients and CLP-treated mice, in which knockdown alleviated CLP-induced pulmonary inflammation and injury, and ferroptosis. CircEXOC5 recruited IGF2BP2 to degrade ATF3 mRNA. The demethylase ALKBH5 was responsible for circEXOC5 upregulation through demethylation. CircEXOC5 silencing significantly improved sepsis-induced ALI and survival rate of mice by downregulating ATF3.

Conclusions

ALKBH5-mediated upregulation of circEXOC5 exacerbates sepsis-induced ALI by facilitating ferroptosis through IGF2BP2 recruitment to degrade ATF3 mRNA.
Promoting Diversity and Inclusion in Professional Associations: Experiences from Security Studies
Authors: Rublee Maria Rost , Duncombe Constance , Karavas George , Barma Naazneen H , Idika-Kalu Cecilia , Sotomayor Arturo C , Kalil Mariana , Kang Hye Yun
Published: August 2023

The International Security Studies Section (ISSS) of the International Studies Association aims to promote the study of global, international, regional, and national security—broadly conceived. Over the past decade, ISSS has also sought to improve diversity and inclusion for its membership, culminating in its Taskforce on Diversity in Security Studies. In this forum, taskforce organizers, researchers, and participants examine the ways in which ISSS has collected data and then acted to improve both experiences and outcomes for historically excluded scholars, using an intersectional approach but with a specific focus on race. By critically reflecting on the role of professional associations in combatting racism in academia, using the case study of ISSS, the forum has two aims. First, we hope that by sharing ISSS experiences and processes, we may encourage other professional associations to self-reflect on how they may contribute to racial injustice, as well as how they can reveal and counteract racial oppression. Second, rather than solely focusing on goals and outcomes, the forum also gives voice to personal perspectives of researchers and participants to highlight how it is people who ultimately make up the heart of efforts to challenge racism and discrimination.
Fitness landscape analysis for assisted seismic history matching problems
Authors: Mitchell Paul , Chassagne Romain
Published: August 2023

Despite over 20 years of research, assisted seismic history matching (ASHM) remains a challenging problem for the energy industry. ASHM is an optimisation problem to find the best subsurface reservoir model for robust predictions of field performance. The results are typically assessed by a decreasing misfit between simulated and observed data, but the optimised models are often inaccurate, uncertain, and non-unique. In this paper, we take a fresh look at ASHM and view it from the perspective of the fitness landscape, or search space. We propose that characterising the fitness landscape will lead to a deeper understanding of the problem, greater confidence in the optimised models, and a better appreciation of the uncertainties. Fitness landscape analysis (FLA) is established in other fields, but has mostly been applied to combinatorial problems or continuous problems with analytical solutions. In contrast, ASHM is a real-world, ill-posed, inverse problem, which is computationally expensive and contains data errors and model uncertainties. We introduce a new method for FLA that provides intuitive information on the setup of the problem. It uses multidimensional clustering and visualisation to explore the structure of the landscape and detects the presence and relative magnitude of data errors, which are typical of real data. It is applied to a synthetic, full-field, reservoir model and the results are compared with another more-established method. We found that the fitness landscapes of ASHM problems are low-lying plateaus with many minima, which makes it difficult to solve ASHM problems for real-world datasets.
Porosity prediction from prestack seismic data via deep learning: incorporating a low-frequency porosity model
Authors: Liu Jingyu , Zhao Luanxiao , Xu Minghui , Zhao Xiangyuan , You Yuchun , Geng Jianhua
Published: August 2023

Porosity prediction from seismic data is of considerable importance in reservoir quality assessment, geological model building, and flow unit delineation. Deep learning approaches have demonstrated great potential in reservoir characterization due to their strong feature extraction and nonlinear relationship mapping abilities. However, the reliability of porosity prediction is often compromised by the lack of low-frequency information in bandlimited seismic data. To address this issue, we propose incorporating a low-frequency porosity model based on geostatistical methodology, into the supervised convolutional neural network to predict porosity from prestack seismic angle gather and seismic inversion results. Our study demonstrates that the inclusion of the low-frequency porosity model significantly improves the reliability of porosity predictions in a heterogeneous carbonate reservoir. The low-frequency information can be compensated to enhance the network's capabilities of capturing the background porosity trend. Additionally, the blind well tests validate that considering the low-frequency constraint leads to stronger model prediction and generalization abilities, with the root mean square error of the two blind wells reduced by up to 34%. The incorporation of the low-frequency reservoir model in network training also remarkably enhances the geological continuity of seismic porosity prediction, providing more geologically reasonable results for reservoir characterization.
Comparison of neoadjuvant and adjuvant chemotherapy for upper tract urothelial carcinoma in real-world practice: a multicenter retrospective study
Authors: Takahashi Kazuhiro , Urabe Fumihiko , Suhara Yushi , Nakano Juria , Yoshihara Kentaro , Goto Yuma , Sadakane Ibuki , Koike Yuhei , Yata Yuji , Suzuki Hirotaka , Kurawaki Shiro , Miyajima Keiichiro , Iwatani Kosuke , Imai Yu , Sakanaka Keigo , Nakazono Minoru , Kurauchi Takashi , Kayano Sotaro , Onuma Hajime , Aikawa Koichi , Yanagisawa Takafumi , Tashiro Kojiro , Tsuzuki Shunsuke , Koike Yusuke , Furuta Akira , Miki Jun , Kimura Takahiro
Published: August 2023

Background

Multiple studies have demonstrated the effectiveness of neoadjuvant chemotherapy and adjuvant chemotherapy in patients with upper tract urothelial carcinoma compared with surgery alone. However, no clinical trial has established the superiority of neoadjuvant chemotherapy or adjuvant chemotherapy in terms of perioperative outcomes.

Methods

We conducted a retrospective analysis encompassing 164 upper tract urothelial carcinoma patients who underwent radical nephroureterectomy and received perioperative chemotherapy. Of these patients, 65 (39.6%) and 99 (60.4%) received neoadjuvant chemotherapy and adjuvant chemotherapy, respectively. Recurrence-free survival and cancer-specific survival were computed using the Kaplan–Meier method. Additionally, we conducted Cox regression analyses to evaluate the risk factors for recurrence-free survival and cancer-specific survival.

Results

Pathological downstaging was seen in 37% of the neoadjuvant chemotherapy group. However, no pathological complete response was observed in this cohort. The Kaplan–Meier curves demonstrated significantly lower recurrence-free survival and cancer-specific survival in patients who received adjuvant chemotherapy. Multivariate Cox regression analysis revealed patients treated with adjuvant chemotherapy exhibited a marked association with inferior recurrence-free survival and cancer-specific survival.

Conclusion

Our study has suggested that neoadjuvant chemotherapy would be more effective in high-risk upper tract urothelial carcinoma patients compared with adjuvant chemotherapy.
Rights claims of citizen children of foreign national parents in South Africa, the UK, and the European Court of Human Rights: hierarchies of ‘illegality’ and deservingness
Authors: Sloth-Nielsen Julia , Collinson Jonathan , Spalding Amanda
Published: August 2023

This article examines the South African High Court judgement in TR & others v Minister of Home Affairs & others, which is the first time that a South African court has addressed the constitutional rights of children in the immigration context. In this case, constitutional rights claims were made by South African citizen children because South African immigration law deemed a foreign national parent to be an ‘illegal alien’, subject to expulsion, as soon their spousal relationship with a South African citizen had broken down. The law allowed no other outcome, other than expulsion, regardless of the impact on the affected children. We argue, therefore, that although the High Court deployed the language of children’s dignity and best interests, TR is not really a decision about children at all. Instead, it is a judgement about whether the parents’ deserved the status of ‘illegality’, and its consequences, which had been imposed by South African immigration law. This focus on the deservingness of the parents, rather than the best interests of the children, can be found in other jurisdictions and this article explores how the law deals with similar circumstances in the UK and the European Court of Human Rights. This article concludes by arguing that Article 3 CRC requires that ‘the sins and traumas of fathers and mothers should not be visited on their children’ and that this should be foundational to the best interests of the child provision in the South African constitution in the immigration context.
Associations with Prehospital Antibiotic Receipt among Combat Casualties with Open Wounds: A Department of Defense Trauma Registry Study
Authors: Karp Marissa C , April Michael D , Newberry Ryan K , Schauer Steven G
Published: August 2023

Introduction

Current Tactical Combat Casualty Care (TCCC) guidelines recommend antibiotic administration for all open wounds to prevent infection. We identified associations between demographics, procedures, and medicines with the receipt of prehospital antibiotics among combat casualties.

Materials and Methods

We used a series of emergency department procedure codes to identify adult subjects within the Department of Defense Trauma Registry from January 2007 to August 2016 who sustained open wounds. We compared demographics, procedures, and medicines administered among casualties receiving prehospital wound prophylaxis versus casualties not receiving antibiotic prophylaxis. We controlled for confounders with multivariable logistical regression.

Results

We identified 18,366 encounters meeting inclusion criteria. Antibiotic recipients (n = 2384) were comparable to nonrecipients (n = 15,982) with regard to age and sex. Antibiotic recipients were more likely to sustain injuries from firearms and undergo all procedures examined related to hemorrhage control, airway management, pneumothorax treatment, and volume replacement except for intraosseous access. Antibiotic recipients were less likely to sustain injuries from explosives. Antibiotic recipients had a modestly higher survival than nonrecipients (97.4% versus 96.0%). Associations with prehospital antibiotic receipt in multivariable logistic regression included non-North Atlantic Treaty Organization military force affiliation (odds ratio (OR) 4.65, 95% CI, 1.0-20.8), tachycardia (OR 3.4, 95% CI, 1.1-10.5), intubation (OR 2.0, 95% CI, 1.1-3.8), and administration of tranexamic acid (OR 5.6, 95% CI, 1.2-26.5).

Conclusions

The proportion of combat casualties with open wounds receiving prehospital antibiotics was low despite published recommendations for early antibiotics in patients with open wounds. These findings highlight the ongoing need for additional educational and quality assurance initiatives to continue improving adherence to TCCC guidelines with regard to prehospital antibiotic administration. Future studies are necessary to determine reasons for suboptimal TCCC guideline compliance.
Antidepressants and survival in glioma—A registry-based retrospective cohort study
Authors: Edström Sonja , Hellquist Barbro Numan , Sandström Maria , Sadanandan Sajna Anand , Björkblom Benny , Melin Beatrice , Sjöberg Rickard L
Published: August 2023

Background

Depression and treatment with antidepressant medication is common in patients with malignant glioma. However, the extent to which antidepressants may affect the disease is not fully understood. Therefore, the purpose of the present study was to investigate possible associations between treatment with antidepressant medication and survival in glioma patients.

Methods

We performed a registry-based cohort study including 1231 patients with malignant glioma (WHO grades 2, 3, and 4) having undergone surgery, and 6400 matched controls without glioma. All data were extracted from the RISK North database, which contains information from multiple national population-based registries in Sweden.

Results

Treatment with antidepressants is more common in patients with malignant glioma (27%), compared to controls (16%), P < .001. Treatment with antidepressants after surgery for glioma was significantly associated with poorer survival. These effects were observed both for selective serotonin reuptake inhibitors (SSRIs) and non-SSRIs. In grade 4 glioma, SSRI treatment was associated with a hazard ratio (HR) of 3.32 (95% CI 2.69–4.10, P < .001), and non-SSRI treatment a HR of 3.54 (95% CI 2.52–4.99, P < .001), compared to glioma patients without antidepressants. In grade 2-3 glioma, the HR for SSRI treatment was 3.26 (95% CI 2.19–4.85, P < .001), and for non-SSRI treatment was 7.71 (95% CI 4.22–14.12, P < .001).

Conclusions

Our results demonstrate a negative association between antidepressant medication and survival in glioma. Further research will be needed to clarify causation.
Prevalence of Underreported Nicotine Exposure Among US Nonsmoking Adults: A Comparison of Self-Reported Exposure and Serum Cotinine Levels From NHANES 2013–2020
Authors: Wang Ruixuan , Hall Jaclyn M , Salloum Ramzi G , Kates Frederick , Cogle Christopher R , Bruijnzeel Adriaan W , Hong Young-Rock , LeLaurin Jennifer H
Published: August 2023

Introduction

Secondhand smoke (SHS) poses a significant health risk. However, individuals who do not smoke may be unaware of their exposure, thereby failing to take protective actions promptly.

Aims and Methods

We assessed the prevalence of underreported nicotine exposure in a nationally representative sample of US nonsmoking adults using data from the US National Health and Examination Survey. Individuals with underreported nicotine exposure were defined as those who reported no exposure to all tobacco products (traditional tobacco, nicotine replacements, and e-cigarettes) or SHS, yet had detectable levels of serum cotinine (>0.015 ng/mL). We fitted logistic regression models to determine sociodemographic and chronic condition factors associated with underreported nicotine exposure.

Results

Our analysis included 13 503 adults aged 18 years and older. Between 2013 and 2020, the prevalence of self-reported SHS exposure, serum cotinine-assessed nicotine exposure, and underreported nicotine exposure among US nonsmokers were 22.0%, 51.2%, and 34.6%, respectively. Remarkably, 67.6% with detectable serum cotinine reported no SHS exposure. Males, non-Hispanic blacks, individuals of other races (including Asian Americans, Native Americans, and Pacific Islanders), and those without cardiovascular diseases were more likely to underreport nicotine exposure than their counterparts. The median serum cotinine value was higher in respondents who reported SHS exposure (0.107 ng/mL) than in those who reported no exposure (0.035 ng/mL). We estimate that approximately 56 million US residents had underreported nicotine exposure.

Conclusions

Over a third of US nonsmokers underreport their nicotine exposure, underlining the urgent need for comprehensive public awareness campaigns and interventions. Further research into sociodemographic determinants influencing this underreporting is needed.

Implications

Understanding the extent of underreported nicotine exposure is crucial for developing effective public health strategies and interventions. It is imperative to bolster public consciousness about the risks associated with SHS. Additionally, surveillance tools should also incorporate measures of exposure to outdoor SHS and e-cigarette vapor to enhance the quality of data monitoring. Findings from this study can guide tobacco control initiatives and inform smoke-free air legislation.
A meta-analysis and systematic review of randomized clinical trials on the effect of coffee consumption on heart rate
Authors: Han Shufen , Qiu Yue , Zhang Gus Q , Lian Fuzhi , Zhang Weiguo
Published: August 2023

Context

Resting heart rate (HR) is increasingly recognized as an indicator of disease and overall morbidity and mortality. Whether chronic coffee consumption affects resting HR is an important consideration for individual consumers as well as from a public health perspective.

Objective

A meta-analysis of randomized controlled trials (RCTs) was conducted to examine the effectiveness of coffee consumption on resting HR.

Data Sources

Original RCTs assessing the effect of coffee consumption on resting HR and published prior to March 2023 were identified by searching online databases, including PubMed, Web of Science, and Cochrane Library databases.

Data Extraction and Analysis

Data searches and extraction and risk-of-bias assessments were performed according to the Cochrane guidelines, and the PRISMA (Preferred Reporting Items for Systematic Reviews and Meta-Analyses) guidelines for systematic reviews were followed. Data on study characteristics, type, and amount of coffee and net change and measurement resting HR were extracted. A random-effects or a fixed-effects model was used to estimate the pooled effect sizes. Homogeneity was determined with the Cochran Q test, and publication bias was assessed through Begg’s test, Egger’s test, and funnel plots.

Results

A total of 6 RCTs with 11 intervention trials or arms involving 485 individuals were included. The participants were generally healthy, although some had hypertension, hypercholesterolemia, or were overweight. The trial duration ranged from 2 weeks to 24 weeks. The overall pooled analysis showed that coffee consumption resulted in a negligible increase in resting HR of 0.40 beats per minute (95% CI: −0.78 to 1.57; P = 0.506), which was statistically insignificant. Subgroup analysis of all specified categories was consistent with the overall analysis. No heterogeneity was observed among included trials (I2 = 0.0%, P = 0.756).

Conclusion

The results of the present meta-analysis study demonstrate that daily coffee consumption of 3 to 6 cups for a period of 2 to 24 weeks has no statistically significant effect on resting HR.
Adjuvant Systemic Therapies for Resected Stages III and IV Melanoma: A Multi-Center Retrospective Clinical Study
Authors: Rigo Rodrigo , Ding Philip Q , Batuyong Eugene , Cheung Winson Y , Walker John , Monzon Jose G , Cheng Tina
Published: August 2023

Background

Adjuvant therapies have been approved for resected melanoma based on improved recurrence-free survival. We present early findings from a real-world study on adjuvant treatments for melanoma.

Methods

A comprehensive chart review was conducted for patients receiving adjuvant systemic therapy for resected high-risk stages III and IV melanoma. Statistical analysis was performed to assess recurrence-free survival and subgroup differences.

Results

A total of 149 patients (median age = 58.0 years, 61.1% men, 49.7% with BRAF V600E/K genotypes) were included, with 94.6% having resected stage III melanoma. Anti-PD-1 immunotherapy was received by 86.5% of patients, while 13.4% received BRAF-targeted therapy. At a median follow-up of 22.4 months, the recurrence rate was 31.5%, with 1-year and 2-year recurrence-free survival rates of 79% and 62%, respectively. Similar recurrence rates were observed between anti-PD-1 immunotherapy and BRAF-targeted therapy. Long-term toxicity affected 27.4% of patients, with endocrinopathies and late-emergent immune-related adverse events being common.

Conclusions

Real-world adjuvant systemic therapy aligns with clinical trial practice. Recurrence rates remain high despite treatment, and long-term toxicities, including endocrinopathies and chronic inflammatory conditions, are not uncommon.
Arabidopsis thaliana Subclass I ACTIN DEPOLYMERIZING FACTORs Regulate Nuclear Organization and Gene Expression
Authors: Matsumoto Tomoko , Higaki Takumi , Takatsuka Hirotomo , Kutsuna Natsumaro , Ogata Yoshiyuki , Hasezawa Seiichiro , Umeda Masaaki , Inada Noriko
Published: August 2023

ACTIN DEPOLYMERIZING FACTOR (ADF) is a conserved protein that regulates the organization and dynamics of actin microfilaments. Eleven ADFs in the Arabidopsis thaliana genome are grouped into four subclasses, and subclass I ADFs, ADF1–4, are all expressed throughout the plant. Previously, we showed that subclass I ADFs function in the regulation of the response against powdery mildew fungus as well as in the regulation of cell size and endoreplication. Here, we report a new role of subclass I ADFs in the regulation of nuclear organization and gene expression. Through microscopic observation of epidermal cells in mature leaves, we found that the size of chromocenters in both adf4 and transgenic lines where expression of subclass I ADFs is downregulated (ADF1-4Ri) was reduced compared with that of wild-type Col-0. Arabidopsis thaliana possesses eight ACTIN (ACT) genes, among which ACT2, −7 and −8 are expressed in vegetative organs. The chromocenter size in act7, but not in the act2/8 double mutant, was enlarged compared with that in Col-0. Microarray analysis revealed that 1,818 genes were differentially expressed in adf4 and ADF1-4Ri. In particular, expression of 22 nucleotide-binding leucine-rich repeat genes, which are involved in effector-triggered plant immunity, was reduced in adf4 and ADF1-4Ri. qRT-PCR confirmed the altered expressions shown with microarray analysis. Overall, these results suggest that ADF regulates various aspects of plant physiology through its role in regulation of nuclear organization and gene expression. The mechanism how ADF and ACT regulate nuclear organization and gene expression is discussed.
Whole-genome sequencing of diverse wheat accessions uncovers genetic changes during modern breeding in China and the United States
Authors: Niu Jianqing , Ma Shengwei , Zheng Shusong , Zhang Chi , Lu Yaru , Si Yaoqi , Tian Shuiquan , Shi Xiaoli , Liu Xiaolin , Naeem Muhammad Kashif , Sun Hua , Hu Yafei , Wu Huilan , Cui Yan , Chen Chunlin , Long Wenbo , Zhang Yue , Gu Mengjun , Cui Man , Lu Qiao , Zhou Wenjuan , Peng Junhua , Akhunov Eduard , He Fei , Zhao Shancen , Ling Hong-Qing
Published: August 2023

Breeding has dramatically changed the plant architecture of wheat (Triticum aestivum), resulting in the development of high-yielding varieties adapted to modern farming systems. However, how wheat breeding shaped the genomic architecture of this crop remains poorly understood. Here, we performed a comprehensive comparative analysis of a whole-genome resequencing panel of 355 common wheat accessions (representing diverse landraces and modern cultivars from China and the United States) at the phenotypic and genomic levels. The genetic diversity of modern wheat cultivars was clearly reduced compared to landraces. Consistent with these genetic changes, most phenotypes of cultivars from China and the United States were significantly altered. Of the 21 agronomic traits investigated, 8 showed convergent changes between the 2 countries. Moreover, of the 207 loci associated with these 21 traits, more than half overlapped with genomic regions that showed evidence of selection. The distribution of selected loci between the Chinese and American cultivars suggests that breeding for increased productivity in these 2 regions was accomplished by pyramiding both shared and region-specific variants. This work provides a framework to understand the genetic architecture of the adaptation of wheat to diverse agricultural production environments, as well as guidelines for optimizing breeding strategies to design better wheat varieties.
Flowering repressor CmSVP recruits the TOPLESS corepressor to control flowering in chrysanthemum
Authors: Zhang Zixin , Hu Qian , Gao Zheng , Zhu Yuqing , Yin Mengru , Shang Erlei , Liu Gaofeng , Liu Weixin , Hu RongQian , Cheng Hua , Chong Xinran , Guan Zhiyong , Fang Weimin , Chen Sumei , Sun Bo , He Yuehui , Chen Fadi , Jiang Jiafu
Published: August 2023

Plant flowering time is induced by environmental and endogenous signals perceived by the plant. The MCM1-AGAMOUSDEFICIENS-Serum Response Factor-box (MADS-box) protein SHORT VEGETATIVE PHASE (SVP) is a pivotal repressor that negatively regulates the floral transition during the vegetative phase; however, the transcriptional regulatory mechanism remains poorly understood. Here, we report that CmSVP, a chrysanthemum (Chrysanthemum morifolium Ramat.) homolog of SVP, can repress the expression of a key flowering gene, a chrysanthemum FLOWERING LOCUS T-like gene (CmFTL3), by binding its promoter CArG element to delay flowering in the ambient temperature pathway in chrysanthemum. Protein–protein interaction assays identified an interaction between CmSVP and CmTPL1-2, a chrysanthemum homologue of TOPLESS (TPL) that plays critical roles as transcriptional corepressor in many aspects of plant life. Genetic analyses revealed the CmSVP-CmTPL1-2 transcriptional complex is a prerequisite for CmSVP to act as a floral repressor. Furthermore, overexpression of CmSVP rescued the phenotype of the svp-31 mutant in Arabidopsis (Arabidopsis thaliana), overexpression of AtSVP or CmSVP in the Arabidopsis dominant-negative mutation tpl-1 led to ineffective late flowering, and AtSVP interacted with AtTPL, confirming the conserved function of SVP in chrysanthemum and Arabidopsis. We have validated a conserved machinery wherein SVP partially relies on TPL to inhibit flowering via a thermosensory pathway.
Chloroplast-targeted late embryogenesis abundant 1 increases alfalfa tolerance to drought and aluminum
Authors: Lv Aimin , Su Liantai , Fan Nana , Wen Wuwu , Wang Zheng , Zhou Peng , An Yuan
Published: August 2023

Late embryogenesis-abundant (LEA) proteins are important stress-response proteins that participate in protecting plants against abiotic stresses. Here, we investigated LEA group 3 protein MsLEA1, containing the typically disordered and α-helix structure, via overexpression and RNA interference (RNAi) approaches in alfalfa (Medicago sativa L.) under drought and aluminum (Al) stresses. MsLEA1 was highly expressed in leaves and localized in chloroplasts. Overexpressing MsLEA1 increased alfalfa tolerance to drought and Al stresses, but downregulating MsLEA1 decreased the tolerance. We observed a larger stomatal aperture and a lower water use efficiency in MsLEA1 RNAi lines compared with wild-type plants under drought stress. Photosynthetic rate, Rubisco activity, and superoxide dismutase (SOD) activity increased or decreased in MsLEA1-OE or MsLEA1-RNAi lines, respectively, under drought and Al stress. Copper/zinc SOD (Cu/Zn-SOD), iron SOD (Fe-SOD), and Rubisco large subunit proteins (Ms1770) were identified as binding partners of MsLEA1, which protected chloroplast structure and function under drought and Al stress. These results indicate that MsLEA1 recruits and protects its target proteins (SOD and Ms1770) and increases alfalfa tolerance against drought and Al stresses.
Transcription factor DgMYB recruits H3K4me3 methylase to DgPEROXIDASE to enhance chrysanthemum cold tolerance
Authors: Luo Yunchen , Wang Yongyan , Li Xin , Yang Xiaohan , Bai Huiru , Liao Xiaoqin , Luo Xuanling , Zhang Fan , Zhang Lei , Liu Qinglin
Published: August 2023

Cold affects the growth and development of plants. MYB transcription factors and histone H3K4me3 transferase ARABIDOPSIS TRITHORAXs (ATXs) play important regulatory functions in the process of plant resistance to low-temperature stress. In this study, DgMYB expression was responsive to low temperature, and overexpression of DgMYB led to increased tolerance, whereas the dgmyb mutant resulted in decreased tolerance of Chrysanthemum morifolium (Dendranthema grandiflorum var. Jinba) to cold stresses. Interestingly, we found that only peroxidase (POD) activity differed substantially between wild type (WT), overexpression lines, and the mutant line. A DgATX H3K4me3 methylase that interacts with DgMYB was isolated by further experiments. DgATX expression was also responsive to low temperature. Overexpression of DgATX led to increased tolerance, whereas the dgatx mutant resulted in decreased tolerance of chrysanthemum to cold stresses. Moreover, the dgmyb, dgatx, and dgmyb dgatx double mutants all led to reduced H3K4me3 levels at DgPOD, thus reducing DgPOD expression. Together, our results show that DgMYB interacts with DgATX, allowing DgATX to specifically target DgPOD, altering H3K4me3 levels, increasing DgPOD expression, and thereby reducing the accumulation of reactive oxygen species (ROS) in chrysanthemum.
Expert knowledge for global pandemic policy: a chorus of evidence or a clutter of global commissions?
Authors: Stone Diane , Schmider Anneke
Published: August 2023

“Global Commissions of Inquiry” have usually been associated with the multilateral initiatives of governments and international organizations. However, various styles of “global commission” have emerged over time. During the COVID-19 pandemic, global commissions have been a key aspect of the COVID-19 international policy landscape, quickly emerging, in 2020 and 2021, to corral knowledge and evidence. These include “formal” commissions, such as the Independent Panel for Pandemic Preparedness and Response and the Global Commission for Post-Pandemic Policy, and “informal” commissions, including the Reform for Resilience and The Lancet Covid Commissions. This paper considers whether these Commissions have been engines for new ideas and global policy knowledge or whether this “chorus” of COVID Commissions represented a “clutter” of ideas at a time when global policy focus was needed. Global Commissions, in general, deserve greater scholarly attention to their design and the construction of their legitimate authority as hybrid and private commissions enter global policy making alongside official commissions.
MicroRNA-21a-5p-modified macrophage exosomes as natural nanocarriers promote bone regeneration by targeting GATA2
Authors: Luo Xin , Meng Chunxiu , Zhang Yujue , Du Qicui , Hou Caiyao , Qiang Huifen , Liu Kun , Lv Zhaoyong , Li Jun , Liu Fengzhen
Published: August 2023

Bone immune responses based on macrophages are critical in the osteogenesis of bone abnormalities. In general, M2 macrophage facilitate the promotion of osteogenesis, as well, M1 macrophage play an important role in early bone healing, as confirmed by previous studies. However, it is not clear how M1 macrophage are involved in the bone immune response. MiR-21a-5p is a highly expressed microRNA in M1 macrophage in contrast to M2. Therefore, the current work sought to ascertain the influence of M1 macrophage on bone healing via exosomal miR-21a-5p and the probable mechanism. We discovered that injecting M1 macrophage exosomes overexpressing miR-21a-5p into bone defect locations enhanced bone regeneration in vivo. Furthermore, by directly targeting GATA2, miR-21a-5p accelerated MC3T3-E1 osteogenic differentiation. Our findings showed that exosomal miR-21a-5p from M1 macrophage may be transported to osteoblasts and target GATA2 to enhance bone defect healing.
Adherence to therapy of ixekizumab and secukinumab in psoriatic arthritis patients using first- or second-line IL-17A inhibitor treatment: a Danish population-based cohort study
Authors: Hansen Rebekka L , Jørgensen Tanja S , Egeberg Alexander , Rosenø Nana A L , Skougaard Marie , Stisen Zara R , Dreyer Lene , Kristensen Lars Erik
Published: August 2023

Objectives

To assess the effectiveness and tolerability of first- and second-line interleukin (IL)-17A inhibitor treatment in PsA patients from 2014 to 2021 using data from the Danish Rheumatology Registry (DANBIO) by investigating adherence to therapy.

Method

PsA patients recorded in the DANBIO who received a first- or second-line IL-17A inhibitor treatment were included in this study. All patients included had previously received one or more TNF inhibitor treatment. Baseline characteristics were analysed in subgroups as first-line IL-17A inhibitor treatment and second-line IL-17A inhibitor treatment. Adherence to therapy of first- or second-line IL-17A inhibitor treatments was reported as Kaplan–Meier plots.

Results

A total of 534 patients were included in the study, with 534 first-line switchers (secukinumab: 510, ixekizumab: 24) and 102 second-line switchers (secukinumab: 35, ixekizumab: 67). Baseline characteristics showed a similar HAQ and visual analogue scale (VAS) for pain. VAS global, 28-joint DAS with CRP and the previous number of biologic DMARD treatments were similar, with a greater value for second-line switchers. First-line ixekizumab-treated patients present a younger age, greater percentage of females, a lower disease duration and a lower CRP value. Concomitant MTX use was greater for the first-line secukinumab-treated patients. First- and second-line switchers had a similar adherence to therapy. Second-line secukinumab and second-line ixekizumab switchers showed a similar adherence to treatment.

Conclusion

PsA patients receiving first- or second-line IL-17A inhibitors showed homogeneous baseline characteristics and similar adherence to therapy. Treatment failure of the first IL-17A inhibitor treatment should not preclude a second-line IL-17A inhibitor treatment.
Operator radiation exposure during radioembolisation of the liver: transfemoral versus transradial access using real-time dose monitoring
Authors: Pedersoli Federico , Fang Jieming , Boas Edward , Park John J
Published: August 2023

In this study, operator radiation exposure is compared utilising transradial access (TRA) versus transfemoral access (TFA) during transarterial radioembolisation (TARE) of liver tumors. Patients who underwent Y90 TARE between May 2017 and April 2018 were included. Electronic medical records and interventional data were collected and the following parameters evaluated: technical success, fluoroscopy time, operator radiation exposure and rate of operator radiation exposure per fluoroscopy time. Statistical analysis was performed with the Wilcoxon rank-sum test. A total of 22 patients (12 males, 10 females) underwent 22 procedures. A total of 12 procedures were performed via TFA and 10 via TRA. Technical success was 100% in both groups. Median fluoroscopy time (10 minutes for TRA vs 6.4 minutes for TFA, p = 0.082) was not statistically different. Both operator radiation exposure (49 vs 4.2 μSv, p = 0.00016) and rate of operator exposure (4.9 vs 0.71 μSv per min, p = 0.00021) were significantly higher in the TRA versus TFA groups, respectively.
Gendered Family Violence among Migrants Seeking International Protection: A Life Course Perspective
Authors: Weitzman Abigail , Swindle Jeffrey , Brenes-Camacho Gilbert
Published: August 2023

Although family and migration scholars recognize that intimate partner violence (IPV) can motivate women’s movement between countries, little research considers IPV or other gendered family violence further back in women migrants’ life histories or explores the legacy of gendered family violence in cases where such violence is not the primary push factor. Here, we analyze in-depth interviews conducted among thirty-four Latin American women seeking asylum or international protection from a diversity of threats to comprehensively understand their experiences with childhood and adult family violence prior to migration. Our analysis reveals three key takeaways. First, IPV, incest, abandonment, and other forms of gendered family violence can characterize women’s family dynamics across the life course even when these experiences do not directly prompt migration. Second, amidst pervasive patriarchal norms, family violence has the power to destabilize women’s social circumstances and fracture their ties to family members in ways that indirectly encourage migration. Third, owing to these same gender norms, even when gendered family violence directly prompts migration, women may conceptualize their primary motive as protecting their children rather than themselves. These findings move beyond common conceptualizations of the family violence–migration nexus and highlight the breadth and implications of gendered family violence among migrants seeking protection from a broad spectrum of intra- and extra-familial threats.
Polystyrene microplastic alters the redox state and arsenic metabolization in the freshwater bivalve Limnoperna fortunei
Authors: Nunes Silvana Manske , Josende Marcelo Estrella , Fattorini Daniele , Regoli Francesco , Monserrat José Maria , Ventura-Lima Juliane
Published: August 2023

Most organisms possess the capacity to metabolize arsenic (As) accumulating compounds to less toxic forms, thus minimizing the adverse effect induced by this metalloid. However, other contaminants may to interfere with As metabolism, contributing to the accumulation of more toxic compounds. Microplastics (MPs) are omnipresent in aquatic environment and may induce toxicological effects (alone or in combination with other contaminants) on living organisms. Therefore, the objective of the present study was to evaluate the effect of the exposure of the freshwater clam Limnoperna fortunei to a combination of MP (4 and 40 μg/L of polystyrene microbeads, 1.05 μm) and As (50 μg/L) for 48 h, evaluating the accumulation and metabolization of As and oxidative stress parameters, such as catalase (CAT), glutathione-S-transferase activities, total antioxidant competence, reduced glutathione (GSH), and lipid damage in the gills and digestive glands. Results revealed that low MP concentration disrupts the redox state of the digestive gland by a decrease in the antioxidant activity (CAT and total antioxidant capacity). GSH levels in the gills of animals exposed to MP (4 μg/L) alone and the combination of MP + As increased, concomitant with an increase in the percentage of toxic compounds, indicating the effect of MP on As metabolism. Although, few studies evaluated the effect of coexposure to MP + As by considering metabolization of metalloid in freshwater bivalve, our results revealed that exposure to MP reduced the metabolization capacity of As, favoring the accumulation of more toxic compounds besides the MP alone, which showed a pro-oxidant effect in L. fortunei.
A systems approach reveals species differences in hepatic stress response capacity
Authors: Russomanno Giusy , Sison-Young Rowena , Livoti Lucia A , Coghlan Hannah , Jenkins Rosalind E , Kunnen Steven J , Fisher Ciarán P , Reddyhoff Dennis , Gardner Iain , Rehman Adeeb H , Fenwick Stephen W , Jones Andrew R , Vermeil De Conchard Guy , Simonin Gilles , Bertheux Helene , Weaver Richard J , Johnson Robert L , Liguori Michael J , Clausznitzer Diana , Stevens James L , Goldring Christopher E , Copple Ian M
Published: August 2023

To minimize the occurrence of unexpected toxicities in early phase preclinical studies of new drugs, it is vital to understand fundamental similarities and differences between preclinical species and humans. Species differences in sensitivity to acetaminophen (APAP) liver injury have been related to differences in the fraction of the drug that is bioactivated to the reactive metabolite N-acetyl-p-benzoquinoneimine (NAPQI). We have used physiologically based pharmacokinetic modeling to identify oral doses of APAP (300 and 1000 mg/kg in mice and rats, respectively) yielding similar hepatic burdens of NAPQI to enable the comparison of temporal liver tissue responses under conditions of equivalent chemical insult. Despite pharmacokinetic and biochemical verification of the equivalent NAPQI insult, serum biomarker and tissue histopathology analyses revealed that mice still exhibited a greater degree of liver injury than rats. Transcriptomic and proteomic analyses highlighted the stronger activation of stress response pathways (including the Nrf2 oxidative stress response and autophagy) in the livers of rats, indicative of a more robust transcriptional adaptation to the equivalent insult. Components of these pathways were also found to be expressed at a higher basal level in the livers of rats compared with both mice and humans. Our findings exemplify a systems approach to understanding differential species sensitivity to hepatotoxicity. Multiomics analysis indicated that rats possess a greater basal and adaptive capacity for hepatic stress responses than mice and humans, with important implications for species selection and human translation in the safety testing of new drug candidates associated with reactive metabolite formation.
Criminal Justice Referrals to Cannabis Use Disorder Treatment among Adolescents and Young Adults following Recreational Cannabis Legalization in the United States
Authors: Mennis Jeremy , Stahler Gerald J. , McKeon Thomas P.
Published: August 2023

Objectives

This study investigates whether the proportion of referrals to cannabis use disorder (CUD) treatment from the criminal justice system declined among adolescents (aged 12–17 years) and young adults (aged 18–24 years) following state recreational (adult use) cannabis legalization in the United States between 2008 and 2019.

Methods

Cannabis use disorder treatment referral data were extracted from the Treatment Episode Dataset—Admissions and used to calculate trends in the number and proportion of criminal justice referrals. Difference-in-differences analysis was used to estimate the effect of recreational legalization on the state-level proportion of criminal justice referrals as a share of all admissions.

Results

Nationwide, the number and proportion of adolescent and young adult criminal justice referrals to CUD treatment declined over the study period. The proportion of young adult criminal justice referrals declined significantly more rapidly after recreational legalization as compared with before (β = −0.045; 95% confidence interval, −0.079 to −0.010; P = 0.01). Among adolescents, the trajectory of decline in the proportion of criminal justice referrals did not change significantly following recreational legalization (β = −0.033; 95% confidence interval, −0.073 to 0.008; P = 0.11)

Conclusions

The decline in the proportion of young adult criminal justice referrals to CUD treatment following recreational legalization is likely due to falling cannabis-related arrests. Although cannabis criminalization may result in court-mandated CUD treatment for some young adults without CUD, the decline in CUD treatment admissions during a period of increasing CUD risk factors associated with recreational legalization represents a key health concern. Promoting screening and other CUD treatment referral sources, such as through primary care, may be warranted.