bluuebunny/crossref_metadata_2025 huggingface dataset:
Testing Whether Pre-Pod-Fill Symbiotic Nitrogen Fixation in Soybean Is Subject to Drift or Selection Over 100 Years of Soybean Breeding
Authors: Thilakarathna Malinda S. , Torkamaneh Davoud , Bruce Robert W. , Rajcan Istvan , Chu Godfrey , Grainger Christopher M. , Szczyglowski Krzysztof , Hill Brett , Raizada Manish N.
Published: September 2021

Soybean [Glycine max (L.) Merr.] is the world's leading legume crop and the largest oilseed crop. It forms a symbiotic relationship with rhizobia bacteria residing in root nodules that provide fixed nitrogen to host plants through symbiotic nitrogen fixation (SNF). In soybean, it has been widely reported that the highest SNF occurs at the pod-filling stage, associated with the peak demand for nitrogen. However, the majority of seed nitrogen is derived from remobilizing root/shoot nitrogen, representing cumulative SNF from the seedling stage to the pre-pod-fill stage. Therefore, the question arises as to whether there has also been selection for improved SNF at these earlier stages, or whether pre-pod-fill SNF traits have drifted. To test this hypothesis, in this study, pre-pod SNF-related traits were evaluated in soybean cultivars that span 100 years of breeding selection in the Canadian Province of Ontario. Specifically, we evaluated SNF traits in 19 pedigree-related historical cultivars and 25 modern cultivars derived from the University of Guelph soybean breeding program. Field trials were conducted at Woodstock, Ontario, Canada in 2016 and 2017, and various SNF-related traits were measured at pre-pod-fill stages (R1-R3), including nitrogen fixation capacity. Considerable variation was observed among Canadian soybean cultivars released over the past 100 years for pre-pod-fill nitrogen fixation. The modern soybean cultivars had similar or moderately higher pre-pod-fill SNF compared to the historical lines in terms of the percentage of nitrogen derived from the atmosphere (%Ndfa) and total shoot fixed nitrogen. These findings suggest that, despite no direct selection by breeders, pre-pod-fill nitrogen fixation, and associated SNF traits have been maintained and possibly improved in modern soybean breeding. However, the low level of pre-pod-fill SNF in some modern cultivars, and generally wide variation observed in SNF between them, suggest some level of genetic drift for this trait in some pedigrees. Specific historical and modern soybean cultivars were identified as potential parents to enable targeted breeding for improved pre-pod-fill SNF. This retrospective study sheds light on our understanding of the impact of decades of recent selective breeding on pre-pod-fill nitrogen fixation traits in soybean in a temperate environment.
Low Molar Mass Dextran: One-Step Synthesis With Dextransucrase by Site-Directed Mutagenesis and its Potential of Iron-Loading
Authors: Wang Tingting , Jiang Zhiming , Wang Yiya , Wu Hao , Fang Yan , Dong Weiliang , Wu Bin , Ma Jiangfeng , Jiang Min
Published: September 2021

Iron dextran is a common anti-anemia drug, and it requires low molar mass dextran as substrate. In this work, we selected 11 amino acid residues in domain A/B of DSR-MΔ2 within a 5-angstrom distance from sucrose for site-directed mutagenesis by molecular docking. Mutation of Q634 did not affect the enzyme catalytic activity, but showed an obvious impact on the ratio of low molecular weight dextran (L-dextran, 3,000–5,000 Da) and relatively higher molecular weight dextran (H-dextran, around 10,000 Da). L-dextran was the main product synthesized by DSR-MΔ2 Q634A, and its average molecular weight was 3,951 Da with a polydispersity index <1.3. The structural characterization of this homopolysaccharide revealed that it was a dextran, with 86.0% α(1→6) and 14.0% α(1→4) glycosidic linkages. Moreover, L-dextran was oxidized with NaOH and chelated with ferric trichloride, and an OL-dextran-iron complex was synthesized with a high iron-loading potential of 33.5% (w/w). Altogether, mutation of amino acids near the sucrose binding site of dextransucrase can affect the chain elongation process, making it possible to modulate dextran size.
Critical Considerations for the Design of Multi-Organ Microphysiological Systems (MPS)
Authors: Malik Mridu , Yang Yang , Fathi Parinaz , Mahler Gretchen J. , Esch Mandy B.
Published: September 2021

Identification and approval of new drugs for use in patients requires extensive preclinical studies and clinical trials. Preclinical studies rely on in vitro experiments and animal models of human diseases. The transferability of drug toxicity and efficacy estimates to humans from animal models is being called into question. Subsequent clinical studies often reveal lower than expected efficacy and higher drug toxicity in humans than that seen in animal models. Microphysiological systems (MPS), sometimes called organ or human-on-chip models, present a potential alternative to animal-based models used for drug toxicity screening. This review discusses multi-organ MPS that can be used to model diseases and test the efficacy and safety of drug candidates. The translation of an in vivo environment to an in vitro system requires physiologically relevant organ scaling, vascular dimensions, and appropriate flow rates. Even small changes in those parameters can alter the outcome of experiments conducted with MPS. With many MPS devices being developed, we have outlined some established standards for designing MPS devices and described techniques to validate the devices. A physiologically realistic mimic of the human body can help determine the dose response and toxicity effects of a new drug candidate with higher predictive power.
Antioxidant Effects of Caffeic Acid Lead to Protection of Drosophila Intestinal Stem Cell Aging
Authors: Sheng Xiao , Zhu Yuedan , Zhou Juanyu , Yan La , Du Gang , Liu Zhiming , Chen Haiyang
Published: September 2021

The dysfunction or exhaustion of adult stem cells during aging is closely linked to tissue aging and age-related diseases. Circumventing this aging-related exhaustion of adult stem cells could significantly alleviate the functional decline of organs. Therefore, identifying small molecular compounds that could prevent the age-related decline of stem cell function is a primary goal in anti-aging research. Caffeic acid (CA), a phenolic compound synthesized in plants, offers substantial health benefits for multiple age-related diseases and aging. However, the effects of CA on adult stem cells remain largely unknown. Using the Drosophila midgut as a model, this study showed that oral administration with CA significantly delayed age-associated Drosophila gut dysplasia caused by the dysregulation of intestinal stem cells (ISCs) upon aging. Moreover, administering CA retarded the decline of intestinal functions in aged Drosophila and prevented hyperproliferation of age-associated ISC by suppressing oxidative stress-associated JNK signaling. On the other hand, CA supplementation significantly ameliorated the gut hyperplasia defect and reduced environmentally induced mortality, revealing the positive effects of CA on tolerance to stress responses. Taken together, our findings report a crucial role of CA in delaying age-related changes in ISCs of Drosophila.
The Language of Gángan, A Yorùbá Talking Drum
Authors: Akinbo Samuel Kayode
Published: September 2021

It is widely known that Yorùbá drummers communicate through their native drums. This paper investigates the grammar of gángan, which belongs to a family of Yoruba drums called dùndún. The results of this study show that Yorùbá drummers represent the phonetic realisation of lexical and grammatical tones of their language with the drum. Statistically, the speech tones and the acoustic correlate of the corresponding drum representations have a significant positive relationship. In both spoken and drum communication, vowel (V) and consonant-vowel (CV) prosodic units have different statuses. To conclude, Yorùbá drummers communicate via the gángan drum by transposing certain phonemic features and maybe phonological conditions of their language to musical forms.
Histone Methylation Related Therapeutic Challenge in Cardiovascular Diseases
Authors: Yang Yang , Luan Ying , Yuan Rui-Xia , Luan Yi
Published: September 2021

The epidemic of cardiovascular diseases (CVDs) is predicted to spread rapidly in advanced countries accompanied by the high prevalence of risk factors. In terms of pathogenesis, the pathophysiology of CVDs is featured by multiple disorders, including vascular inflammation accompanied by simultaneously perturbed pathways, such as cell death and acute/chronic inflammatory reactions. Epigenetic alteration is involved in the regulation of genome stabilization and cellular homeostasis. The association between CVD progression and histone modifications is widely known. Among the histone modifications, histone methylation is a reversible process involved in the development and homeostasis of the cardiovascular system. Abnormal methylation can promote CVD progression. This review discusses histone methylation and the enzymes involved in the cardiovascular system and determine the effects of histone methyltransferases and demethylases on the pathogenesis of CVDs. We will further demonstrate key proteins mediated by histone methylation in blood vessels and review histone methylation-mediated cardiomyocytes and cellular functions and pathways in CVDs. Finally, we will summarize the role of inhibitors of histone methylation and demethylation in CVDs and analyze their therapeutic potential, based on previous studies.
Halogen Enrichment of Siberian Traps Magmas During Interaction With Evaporites
Authors: Sibik Svetlana , Edmonds Marie , Villemant Benoit , Svensen Henrik H. , Polozov Alexander G. , Planke Sverre
Published: September 2021

Volatile emissions to the atmosphere associated with the Siberian Traps eruptions at the Permian-Triassic boundary were sourced from the outgassing of primary magmas and the sedimentary host rocks into which they were intruded. Halogens in volcanic gases may have played an important role in environmental degradation and in stratospheric ozone destruction. Here we investigate how halogens behave during the interaction between salts and basalt magma emplaced as sills and erupted as lava. We present whole-rock, trace, and halogen concentrations for a suite of samples from three locations in the Siberian Traps Large Igneous Province, including basalt lavas erupted, and dolerites intruded into both organic-bearing shales and evaporites. Dolerites are enriched in Cl, Br, and I; their enrichment in Cl is similar to MORB and OIB that have been inferred to have assimilated seawater. The dolerites exhibit halogen compositional systematics, which extend towards both evaporites and crustal brines. Furthermore, all analyzed samples show enrichment in Rb/Nb; with the dolerites also showing enrichment in Cl/K similar to MORB and OIB that have been inferred to have assimilated seawater. We infer that samples from all three locations have assimilated fluids derived from evaporites, which are components of crustal sedimentary rocks. We show that up to 89% of the chlorine in the dolerites may have been assimilated as a consequence of the contact metamorphism of evaporites. We show, by thermal modeling, that halogen transfer may occur via assimilation of a brine phase derived from heating evaporites. Halogen assimilation from subcropping evaporites may be pervasive in the Siberian Traps Large Igneous Province and is expected to have enhanced emissions of Cl and Br into the atmosphere from both intrusive and extrusive magmatism.
Introducing Databases in Context Through Customizable Visualizations
Authors: Dietrich Suzanne W. , Goelman Don , Broatch Jennifer , Crook Sharon , Ball Becky , Kobojek Kimberly , Ortiz Jennifer
Published: September 2021

The goal of the Databases for Many Majors project is to engage a broad audience in understanding fundamental database concepts using visualizations with color and visual cues to present these topics to students across many disciplines. There are three visualizations: introducing relational databases, querying, and design. A unique feature of these learning tools is the ability for instructors in diverse disciplines to customize the content of the visualization’s example data, supporting text, and formative assessment questions to promote relevance to their students. This paper presents a study on the impact of the customized introduction to relational databases visualization on both conceptual learning and attitudes towards databases. The assessment was performed in three different courses across two universities. The evaluation shows that learning outcomes are met with any visualization, which appears to be counter to expectations. However, students using a visualization customized to the course context had more positive attitudes and beliefs towards the usefulness of databases than the control group.
Classifying Students With School Refusal Behavior and Their Relationship to Learning Strategies
Authors: Giménez-Miralles Mariola , Gonzálvez Carolina , Sanmartín Ricardo , Vicent María , Aparicio-Flores María del Pilar , García-Fernández José Manuel
Published: September 2021

Students with School Refusal Behaviour (SRB) are a diverse group, often associated with negative academic repercussions (e.g., low academic performance, learning difficulties or academic demotivation). The aims of this research were: 1) to identify school refusal behaviour profiles based on low and high scores on the four functional conditions assessed by the School Refusal Assessment Scale-Revised (SRAS-R) and 2) to examine the relationship between SRB profiles and learning strategies. The SRAS-R and the Inventory of Learning and Study Strategies-High School version were administered to 1,261 students aged to 14 to 18 (M = 16.51; SD = 1.84). Four SRB profiles were obtained: SRB by positive reinforcement, Low SRB, SRB by negative reinforcement and Mixed SRB. School refusers belonging to the Mixed SRB and SRB by negative reinforcement profiles are characterised by low scores on learning strategies, except for the Anxiety dimension. The practical implications of these findings suggest that implementing study techniques and learning strategies programmes, in addition to courses on anxiety management and self-care will help students improve their learning paths and reduce anxiety-based school refusal.
Hierarchical Power Allocation Control for Star-Connected Hybrid Energy Storage System Using Cascaded Multilevel Converters
Authors: Lu Yiyan , Liu Zhao , Lyu Jianguo , Wei Xing
Published: September 2021

Hybrid energy storage system (HESS) using cascaded multilevel converters (CMC) has received increasing attention due to its merits on smoothing power fluctuations for renewable energy systems (RESs). However, CMC-based HESS still faces tough challenges due to asymmetrical ac power distribution. In this paper, hierarchical power allocation control strategy is utilized in CMC-based star-connected HESS to coordinate power between batteries and supercapacitors (SCs). Using the proposed power allocation mechanism, energy management strategy (EMS) with two operation modes can be achieved, which includes SC voltage regulation mode and power compensation mode. In SC voltage regulation mode, SC voltages are regulated to achieve long-term stable operation. Power compensation mode aims to allocate the active power fluctuation and employs SCs to mitigate it. Meanwhile, the principle of the hierarchical power allocation strategy is analyzed to facilitate the accurate control and flexible switching of different operation modes. A series of simulation and experiment tests are executed to demonstrate the performance of the proposed control strategy.
iCDI-W2vCom: Identifying the Ion Channel–Drug Interaction in Cellular Networking Based on word2vec and node2vec
Authors: Zheng Jie , Xiao Xuan , Qiu Wang-Ren
Published: September 2021

Ion channels are the second largest drug target family. Ion channel dysfunction may lead to a number of diseases such as Alzheimer’s disease, epilepsy, cephalagra, and type II diabetes. In the research work for predicting ion channel–drug, computational approaches are effective and efficient compared with the costly, labor-intensive, and time-consuming experimental methods. Most of the existing methods can only be used to deal with the ion channels of knowing 3D structures; however, the 3D structures of most ion channels are still unknown. Many predictors based on protein sequence were developed to address the challenge, while most of their results need to be improved, or predicting web servers are missing. In this paper, a sequence-based classifier, called “iCDI-W2vCom,” was developed to identify the interactions between ion channels and drugs. In the predictor, the drug compound was formulated by SMILES-word2vec, FP2-word2vec, SMILES-node2vec, and ECFPs via a 1184D vector, ion channel was represented by the word2vec via a 64D vector, and the prediction engine was operated by the LightGBM classifier. The accuracy and AUC achieved by iCDI-W2vCom via the fivefold cross validation were 91.95% and 0.9703, which outperformed other existing predictors in this area. A user-friendly web server for iCDI-W2vCom was established at http://www.jci-bioinfo.cn/icdiw2v. The proposed method may also be a potential method for predicting target–drug interaction.
Rituximab and Abatacept Are Effective in Differential Treatment of Interstitial Lymphocytic Lung Disease in Children With Primary Immunodeficiencies
Authors: Rodina Yulia , Deripapa E. , Shvets O. , Mukhina A. , Roppelt A. , Yuhacheva D. , Laberko A. , Burlakov V. , Abramov D. , Tereshchenko G. , Novichkova G. , Shcherbina Anna
Published: September 2021

Background

Interstitial lymphocytic lung disease (ILLD), a recently recognized complication of primary immunodeficiencies (PID), is caused by immune dysregulation, abnormal bronchus-associated lymphoid tissue (BALT) hyperplasia, with subsequent progressive loss of pulmonary function. Various modes of standard immunosuppressive therapy for ILLD have been shown as only partially effective.

Objectives

To retrospectively evaluate the safety and efficacy of abatacept or rituximab in treatment of ILLD in children with PID.

Methods

29 children (median age 11 years) with various forms of PID received one of the two therapy regimens predominantly based on the lesions’ immunohistopathology: children with prevalent B-cell lung infiltration received rituximab (n = 16), and those with predominantly T-cell infiltration received abatacept (n = 17). Clinical and radiological symptoms were assessed using a severity scale developed for the study.

Results

The targeted therapy with abatacept (A) or rituximab (R) enabled long-term control of clinical (A 3.4 ± 1.3 vs. 0.6 ± 0.1; R 2.8 ± 1 vs. 0.7 ± 0.05, p < 0.01) and radiological (A 18.4 ± 3.1 vs. 6.0 ± 2.0; R 30 ± 7.1 vs. 10 ± 1.7, p < 0.01) symptoms of ILLD in both groups and significantly improved patients’ quality of life, as measured by the total scale (TS) score of 57 ± 2.1 in treatment recipients vs. 31.2 ± 1.9 before therapy (p < 0.01).

Conclusions

ILLD histopathology should be considered when selecting treatment. Abatacept and rituximab are effective and safe in differential treatment of ILLD in children.
The Effects of Hypoxia and Anthropogenic Disturbance on the Distribution, Abundance and Recruitment of the Sea Cucumber Holothuria leucospilota at the Mouth of a Subtropical Bay, China
Authors: Yu Zonghe , Zhang Yingqiu , Zhou Lei , Sun Hongyan
Published: September 2021

Despite the commercial importance of the sea cucumberHolothuria leucospilotaincreasing in recent years, little is known of its spatial distribution and ecology in the South China Sea. We investigate the distribution, abundance, and recruitment ofH. leucospilotafrom 2017 to 2020 at two sites (S1 and S2) in Daya Bay, a typical subtropical bay which is strongly influenced by human activities in the South China Sea. We report hypoxia to driveH. leucospilotafrom deeper into shallower waters with higher DO concentrations at the mouth of Dapeng Cove in Daya Bay (S1), particularly during summer. Population size at S1 decreased by 90% from 2017 levels, before this area was opened to the public in 2018; recruitment was not observed by August (summer) of 2020. In contrast, in summers of 2017 and 2020,H. leucospilotaabundance at S2, a protected open-water area, increased by 84%, and the proportion of small-sized (recently recruited) sea cucumber in the population increased by 20%. Severe summer hypoxia at S1 could negatively influenceH. leucospilotaspawning and larval settlement, which combined with depletion of broodstock because of fishing pressure and/or hypoxia-induced mortality, could inhibit recruitment. In contrast, higher DO concentrations and abundant broodstock during summer (the breeding season) favoured recruitment ofH. leucospilotaat S2. Overall, hypoxia and anthropogenic disturbance impede recovery ofH. leucospilotaat S1, while at the protected S2, larvae may be released to settle in nearby areas. It is imperative to develop a better understanding of the biology, ecology and conservation of tropical sea cucumbers in China.
Association Between Oxygen Partial Pressure Trajectories and Short-Term Outcomes in Patients With Hemorrhagic Brain Injury
Authors: Cai Guolong , Ru Weizhe , Xu Qianghong , Wu Jiong , Gong Shijin , Yan Jing , Shen Yanfei
Published: September 2021

Objectives: Arterial hyperoxia is reportedly a risk factor for poor outcomes in patients with hemorrhagic brain injury (HBI). However, most previous studies have only evaluated the effects of hyperoxia using static oxygen partial pressure (PaO2) values. This study aimed to investigate the association between overall dynamic oxygenation status and HBI outcomes, using longitudinal PaO2 data.

Methods: Data were extracted from the Medical Information Mart for Intensive Care III database. Longitudinal PaO2 data obtained within 72 h of admission to an intensive care unit were analyzed, using a group-based trajectory approach. In-hospital mortality was used as the primary outcomes. Multivariable logistic models were used to explore the association between PaO2 trajectory and outcomes.

Results: Data of 2,028 patients with HBI were analyzed. Three PaO2 trajectory types were identified: Traj-1 (mild hyperoxia), Traj-2 (transient severe hyperoxia), and Traj-3 (persistent severe hyperoxia). The initial and maximum PaO2 of patients with Traj-2 and Traj-3 were similar and significantly higher than those of patients with Traj-1. However, PaO2 in patients with Traj-2 decreased more rapidly than in patients with Traj-3. The crude in-hospital mortality was the lowest for patients with Traj-1 and highest for patients with Traj-3 (365/1,303, 209/640, and 43/85 for Traj-1, Traj-2, and Traj-3, respectively; p < 0.001), and the mean Glasgow Coma Scale score at discharge (GCSdis) was highest for patients with Traj-1 and lowest in patients with Traj-3 (13 [7–15], 11 [6–15], and 7 [3–14] for Traj-1, Traj-2, and Traj-3, respectively; p < 0.001). The multivariable model revealed that the risk of death was higher in patients with Traj-3 than in patients with Traj-1 (odds ratio [OR]: 3.3, 95% confidence interval [CI]: 1.9–5.8) but similar for patients with Traj-1 and Traj-2. Similarly, the logistic analysis indicated the worst neurological outcomes in patients with Traj-3 (OR: 3.6, 95% CI: 2.0–6.4, relative to Traj-1), but similar neurological outcomes for patients in Traj-1 and Traj-2.

Conclusion: Persistent, but not transient severe arterial hyperoxia, was associated with poor outcome in patients with HBI.
Metabolomic Characterization Reveals ILF2 and ILF3 Affected Metabolic Adaptions in Esophageal Squamous Cell Carcinoma
Authors: Zang Bin , Wang Wen , Wang Yiqian , Li Pengfei , Xia Tian , Liu Xiaolong , Chen Di , Piao Hai-long , Qi Huan , Ma Yegang
Published: September 2021

Esophageal cancer (EC) is a common malignant disease in eastern countries. However, a study of the metabolomic characteristics associated with other biological factors in esophageal squamous cell carcinoma (ESCC) is limited. Interleukin enhancer binding factor 2 (ILF2) and ILF3, double-stranded RNA-binding proteins, have been reported to contribute to the occurrence and development of various types of malignancy. Nevertheless, the underlying functions of ILF2 and ILF3 in ESCC metabolic reprogramming have never been reported. This study aimed to contribute to the metabolic characterization of ESCC and to investigate the metabolomic alterations associated with ILF2 and ILF3 in ESCC tissues. Here, we identified 112 differential metabolites, which were mainly enriched in phosphatidylcholine biosynthesis, fatty acid metabolism, and amino acid metabolism pathways, based on liquid chromatography–mass spectrometry and capillary electrophoresis–mass spectrometry approaches using ESCC tissues and paired para-cancer tissues from twenty-eight ESCC patients. In addition, ILF2 and ILF3 expression were significantly elevated in EC tissues compared to the histologically normal samples, and closely associated with PI3K/AKT and MAPK signaling pathways in ESCC. Moreover, in ESCC tissues with a high ILF2 expression, several short-chain acyl-carnitines (C3:0, C4:0, and C5:0) related to the BCAA metabolic pathway and long-chain acyl-carnitines (C14:0, C16:0, C16:0-OH, and C18:0) involved in the oxidation of fatty acids were obviously upregulated. Additionally, a series of intermediate metabolites involved in the glycolysis pathway, including G6P/F6P, F1,6BP, DHAP, G3P, and 2,3BPG, were remarkably downregulated in highly ILF3-expressed ESCC tissues compared with the corresponding para-cancer tissues. Overall, these findings may provide evidence for the roles of ILF2 and ILF3 during the process of ESCC metabolic alterations, and new insights into the development of early diagnosis and treatment for ESCC. Further investigation is needed to clarify the underlying mechanism of ILF2 and ILF3 on acyl-carnitines and the glycolysis pathway, respectively.
LncRNA KASRT Serves as a Potential Treatment Target by Regulating SRSF1-Related KLF6 Alternative Splicing and the P21/CCND1 Pathway in Osteosarcoma: An In Vitro and In Vivo Study
Authors: Chen Kai , Li Cheng , Huang Shuai , Chen Yu , Zhu Xiaodong
Published: September 2021

Purpose

Long non-coding RNA KLF6 alternative splicing regulating transcript (lnc-KASRT) locates within the intronic region of SRSF1, possessing the potential to regulate KLF6 alternative splicing to promote carcinogenicity. Then, the current in vitro and in vivo study aimed to investigate the effect of lnc-KASRT on regulating tumor malignant behaviors, and the implication of its interaction with KLF6 alternative splicing in osteosarcoma.

Methods

Lnc-KASRT overexpression or knockdown plasmid was transfected into U-2OS and Saos-2 cells. Then, KLF6-SV1 knockdown plasmid with or without lnc-KASRT overexpression plasmid was transfected into these cells for compensative experiments. In vivo, lnc-KASRT overexpression or knockdown Saos-2 cells were injected in mice for tumor xenograft construction.

Results

Lnc-KASRT expression was increased in most osteosarcoma cell lines compared to control cell line. Lnc-KASRT overexpression promoted cell viability, mobility, and anti-apoptotic marker expression, while reducing apoptosis rate and pro-apoptotic marker expression; meanwhile, it regulated SRSF1, KLF6 alternative splicing (increased KLF6-splice variant 1 (KLF6-SV1), decreased KLF6-wild type (KLF6-WT)), and followed P21/CCND1 pathway in U-2OS/Saos-2 cells. The lnc-KASRT knockdown exhibited opposite trends. Subsequent compensative experiments disclosed that KLF6-SV1 knockdown attenuated most of the tumor-promoting effects of lnc-KASRT overexpression in U-2OS/Saos-2 cells. In vivo experiments further validated that lnc-KASRT enhanced tumor growth and reduced tumor apoptosis; meanwhile, it also increased tumor KLF6-SV1, MMP-1, and MMP-9 expressions but decreased tumor SRSF1 and KLF6-WT expressions in xenograft mice.

Conclusion

Lnc-KASRT serves as a potential treatment target via regulating SRSF1-related KLF6 alternative splicing and following P21/CCND1 pathway in osteosarcoma.
Prevalence of Delta-Like Protein 3 in a Consecutive Series of Surgically Resected Lung Neuroendocrine Neoplasms
Authors: Alì Greta , Di Stefano Iosè , Poma Anello Marcello , Ricci Stefano , Proietti Agnese , Davini Federico , Lucchi Marco , Melfi Franca , Fontanini Gabriella
Published: September 2021

Delta-like protein 3 (DLL3) is a protein of the Notch pathway, and it is a potential therapeutic target for high-grade lung neuroendocrine tumors (NETs), i.e., small cell lung carcinoma (SCLC) and large cell neuroendocrine carcinoma (LCNEC). However, DLL3 prevalence in lung NETs and its association with clinicopathological characteristics and prognosis remained unclear. We analyzed the immunohistochemical expression of DLL3 and its prognostic role in a consecutive series of 155 surgically resected lung NETs, including typical carcinoid (TC), atypical carcinoid (AC), LCNEC, and SCLC patients. The DLL3 expression was categorized as high (>50% positive tumor cells) or low (<50%). In addition, tumors were categorized by H-score (i.e., percentage of positive cells by staining intensity, ≥150 vs. <150). DLL3 staining was positive in 99/155 (64%) samples, and high DLL3 expression was frequently observed in high-grade tumors. In detail, 46.9% and 75% of SCLC and 48.8% and 53.7% of LCNEC specimens showed a high DLL3 expression by using H-score and percentage of positive tumor cells, respectively. Regarding low-grade NETs, only 4.9% and 12.2% TCs and 19.5% and 24.4% ACs had high DLL3 expression considering H-score and percentage of positive tumor cells, respectively. High DLL3 expression was associated with advanced American Joint Committee on Cancer (AJCC) stage, peripheral location, and chromogranin A expression in high-grade tumors (p < 0.05). In low-grade NETs, high DLL3 expression was associated with female sex, peripheral location, a higher number of mitoses, higher Ki-67 index, presence of necrosis, and pleural infiltration (p < 0.05). No association was observed between high DLL3 expression and overall survival (OS) and disease-free survival (DFS) in high-grade NETs, whereas high DLL3 expression was associated with lower DFS in ACs (p = 0.01). In conclusion, our study demonstrated a high prevalence of DLL3 expression in high-grade lung NET patients and its association with aggressive clinicopathological features. These findings confirm that DLL3 could represent a useful biomarker for target therapy in high-grade tumors. Our results also suggest that the DLL3 expression could identify a subset of AC tumors with more aggressive behavior, thus providing the basis for new therapeutic options in this group of patients.
Pre- and Early Post-treatment With Arthrospira platensis (Spirulina) Extract Impedes Lipopolysaccharide-triggered Neuroinflammation in Microglia
Authors: Piovan Anna , Battaglia Jessica , Filippini Raffaella , Dalla Costa Vanessa , Facci Laura , Argentini Carla , Pagetta Andrea , Giusti Pietro , Zusso Morena
Published: September 2021

Background: Uncontrolled neuroinflammation and microglia activation lead to cellular and tissue damage contributing to neurodegenerative and neurological disorders. Spirulina (Arthrospira platensis (Nordstedt) Gomont, or Spirulina platensis), a blue-green microalga, which belongs to the class of cyanobacteria, has been studied for its numerous health benefits, which include anti-inflammatory properties, among others. Furthermore, in vivo studies have highlighted neuroprotective effects of Spirulina from neuroinflammatory insults in different brain areas. However, the mechanisms underlying the anti-inflammatory effect of the microalga are not completely understood. In this study we examined the effect of pre- and post-treatment with an acetone extract of Spirulina (E1) in an in vitro model of LPS-induced microglia activation.

Methods: The effect of E1 on the release of IL-1β and TNF-α, expression of iNOS, nuclear factor erythroid 2–related factor 2 (Nrf2), and heme oxygenase-1 (HO-1), and the activation of NF-κB was investigated in primary microglia by ELISA, real-time PCR, and immunofluorescence.

Results: Pre- and early post-treatment with non-cytotoxic concentrations of E1 down-regulated the release of IL-1β and TNF-α, and the over-expression of iNOS induced by LPS. E1 also significantly blocked the LPS-induced nuclear translocation of NF-κB p65 subunit, and upregulated gene and protein levels of Nrf2, as well as gene expression of HO-1.

Conclusions: These results indicate that the extract of Spirulina can be useful in the control of microglia activation and neuroinflammatory processes. This evidence can support future in vivo studies to test pre- and post-treatment effects of the acetone extract from Spirulina.
Transoesophageal Ultrasound Assessment of Lung Aeration in Patients With Acute Respiratory Distress Syndrome
Authors: Brault Clément , Zerbib Yoann , Kontar Loay , Maizel Julien , Slama Michel
Published: September 2021

Introduction: The effect of positive end-expiratory pressure (PEEP) depends closely on the potential for lung recruitment. Bedside assessment of lung recruitability is crucial for personalized lung-protective mechanical ventilation in acute respiratory distress syndrome (ARDS) patients.

Methods: We developed a transoesophageal lung ultrasound (TE-LUS) method in which a quantitative (computer-assisted) grayscale determination served as a guide to PEEP-induced lung recruitment. The method is based on the following hypothesis: when the PEEP increases, inflation of the recruited alveoli leads to significant changes in the air/water ratio. Normally ventilated areas are hypoechoic because the ultrasound waves are weakly reflected while poorly aerated areas or non-aerated areas are hyperechoic. We calculated the TE-LUS re-aeration score (RAS) as the ratio of the mean gray scale level at low PEEP to that value at high PEEP for the lower and upper lobes. A RAS > 1 indicated an increase in ventilated area. We used this new method to detect changes in ventilation in patients with a low (<0.5) vs. high (≥0.5) recruitment-to-inflation (R/I) ratio (i.e., the ratio between the recruited lung compliance and the respiratory system compliance at low PEEP).

Results: We included 30 patients with moderate-to-severe ARDS. In patients with a high R/I ratio, the TE-LUS RAS was significantly higher in the lower lobes than in the upper lobes (1.20 [1.12–1.63] vs. 1.05 [0.89–1.38]; p = 0.05). Likewise, the TE-LUS RAS in the lower lobes was significantly higher in the high R/I group than in the low R/I group (1.20 [1.12–1.63] vs. 1.07 [1.00–1.20]; p = 0.04).

Conclusion: The increase in PEEP induces a substantial gain in the ventilation detected by TE-LUS of poorly or non-aerated lower lobes (dependent lung regions), especially in patients with a high R/I ratio.
Effect of Apnea-Induced Hypoxia on Cardiovascular Adaptation and Circulating Biomarkers of Oxidative Stress in Elite Breath-Hold Divers
Authors: Solich-Talanda Magdalena , Żebrowska Aleksandra , Mikołajczyk Rafał , Kostorz-Nosal Sabina , Ziora Dariusz , Jastrzębski Dariusz , Siermontowski Piotr
Published: September 2021

Given the previous evidence that breath-hold diving is a cause of physiological stress, this study aimed to determine whether a combination static and dynamic apnea would affect total oxidant status, nitric oxide, heat shock proteins and cardiovascular parameters in elite freedivers. Thirteen finalists of the World and European championships in swimming pool breath-hold diving participated in the study. Whole-body plethysmography and electrocardiography was performed to determine the cardiorespiratory variables at baseline and during the simulation static apnea. An assessment of the heart rate, blood oxygen saturation and biochemical variables was performed before and in response to a combination of a static followed by a dynamic apnea. Static and dynamic breath-holding had a significant effect on oxidative stress, as evidenced by an increase in the total oxidant status/capacity (p< 0.001). The post apnea concentrations of heat shock proteins 27 (HSP27) were significantly elevated (p< 0.03, but total antioxidant status (TAS), HSP90, HSP70, and nitric oxide (NO) changes were not significant. levels under the influence of the static and dynamic breath-hold protocol. A significant positive correlation between HSPs and TAS (r= 0.63;p< 0.05) as well as NO levels was associated with beneficial cardiovascular adaptation. An increase in serum HSP27 levels mediated in nitric oxide levels could explain its important role in improving cardiovascular functions in elite freedivers. Further studies are necessary to explain the exact mechanisms of breath holds training of cardiovascular adaptation responsible for maintaining adequate oxygen supply in elite divers.
Combining Ability and Heterosis for Endosperm Carotenoids and Agronomic Traits in Tropical Maize Lines
Authors: Azmach Girum , Gedil Melaku , Spillane Charles , Menkir Abebe
Published: September 2021

Provitamin A enrichment of staple crops through biofortification breeding is a powerful approach to mitigate the public health problem of vitamin A deficiency in developing countries. Twenty-four genetically diverse yellow and orange endosperm maize inbred lines with differing levels of provitamin A content were used for the analysis of their combining ability. Each inbred line was developed from crosses and backcrosses between temperate and tropical germplasm. The inbred lines were grouped into different sets according to their provitamin A levels and were then intercrossed in a factorial mating scheme to generate 80 different single-cross hybrids. The hybrids were evaluated in field trials across a range of agroecological zones in Nigeria. The effect of hybrids was significant on all the measured provitamin A and non-provitamin A carotenoids and agronomic traits. While the effect of genotype-by-environment (GxE) interaction was significant for almost all traits, it was a non-crossover-type interaction for carotenoid content. Partitioning of the variances associated with the carotenoid and agronomic traits into their respective components revealed the presence of significant positive and negative estimates of general combining ability (GCA) and specific combining ability (SCA) effects for both carotenoid content and agronomic traits. The preponderance of GCA effects indicates the importance of additive gene effects in the inheritance of carotenoid content. We found F1 hybrids displaying high parent heterosis for both provitamin A content and agronomic performance. Our study demonstrates that provitamin A biofortification can be effectively implemented in maize breeding programs without adverse effects on important agronomic traits, including grain yield.
Insights Into the Molecular Evolution of AT-Hook Motif Nuclear Localization Genes in Brassica napus
Authors: Zhang Wei-Meng , Fang Da , Cheng Xiu-Zhu , Cao Jun , Tan Xiao-Li
Published: September 2021

AT-hook motif nuclear localization (AHL) proteins belong to a family of transcription factors, and play important roles in plant growth and development and response to various stresses through protein-DNA and protein-protein interactions. To better understand the Brassica napus AHL gene family, AHL genes in B. napus and related species were analyzed. Using Arabidopsis as a reference, 122 AHL gene family members were first identified in B. napus. According to the phylogenetic tree and gene organization, the BnaAHLs were classified into two clades (Clade-A and Clade-B) and three types (Type-I, Type-II, and Type-III). Gene organization and motif distribution analysis suggested that the AHL gene family is relatively conserved during evolution. These BnaAHLs are unevenly distributed on 38 chromosomes and expanded by whole-genome duplication (WGD) or segmental duplication. And large-scale loss events have also occurred in evolution. All types of BnaAHLs are subject to purification or neutral selection, while some positive selection sites are also identified in Type-II and Type-III groups. At the same time, the purification effect of Type-I members are stronger than that of the others. In addition, RNA-seq data and cis-acting element analysis also suggested that the BnaAHLs play important roles in B. napus growth and development, as well as in response to some abiotic and biotic stresses. Protein-protein interaction analysis identified some important BnaAHL-binding proteins, which also play key roles in plant growth and development. This study is helpful to fully understand the origin and evolution of the AHL gene in B. napus, and lays the foundation for their functional studies.
Can the Biophilia Hypothesis Be Applied to Long-Duration Human Space Flight? A Mini-Review
Authors: Neilson Brittany N. , Craig Curtis M. , Altman George C. , Travis Alexandra T. , Vance Joseph A. , Klein Martina I.
Published: September 2021

The International Space Station (ISS) has around 3–5 crew members on-board at all times, and they normally stay on the ISS for about 5–7months in duration. Since March 2020, 170 long-duration space missions have occurred on the ISS. Thus, long-duration space missions are an integral part of space exploration and will only continue to expand in duration as missions to the Moon and Mars are on the horizon. However, long-duration space missions present several challenges to human crew members. Most of these challenges have been associated with physiological adaptation to microgravity, including motion sickness, muscle atrophy, and cardiovascular deconditioning. While not as well-studied, another major factor to consider when planning long-duration space missions is the psychological impact of the environment on the astronauts. Astronauts living in space will be unable to access natural landscapes and other environments found to have restorative effects on psychological stress and overall well-being. On top of being unable to access these restorative natural environments, astronauts will also be exposed to the stressful, unfamiliar environment of space. The purpose of this mini-review is to first summarize the literature related to stressors associated with space. Next, an overview of the large breadth of literature on the biophilia hypothesis and restorative environments will be provided, as these may serve as relatively simple and cost-effective solutions to mitigate the stress faced during long-duration space missions. Lastly, considerations related to the design of such environments in a space capsule as well as future directions will be presented.
Development and Validation of the Robust - Pandemic Coping Scale (R-PCS)
Authors: Burro Roberto , Vicentini Giada , Rocca Emmanuela , Barnaba Veronica , Hall Rob , Raccanello Daniela
Published: September 2021

The psychological consequences of epidemics/pandemics, such as the COVID-19 pandemic, include an increase in psychopathological symptoms, such as depression, anxiety, and stress, and negative emotions, such as fear. However, relatively little attention has been paid to how people cope with the pandemic. Coping is a multi-component process, helping to diminish the traumatic impact of stressful events in a variety of ways. We studied how university students coped with the first wave of the COVID-19 pandemic, by developing the Robust - Pandemic Coping Scale (R-PCS), a new scale for measuring coping strategies related to epidemics/pandemics. The scale is based on a classification of coping strategies referred to the needs of competence, relatedness, and autonomy. To create a robust scale, such that the item values would be independent of the sample used for developing it, we employed Rasch modeling. We used a sample of 2,987 Italian university students who participated in an online survey including the R-PCS and the Power to Live with Disasters Questionnaire (PLDQ), during March 2020. First, we applied a dual approach combining exploratory and confirmatory factor analyses, which supported the goodness of a 4-factor model (i.e., Despair, Adjustment, Proactivity, and Aversion) for the R-PCS, invariant across gender and age of respondents (younger or as old as 23 years, older than 23 years). We then transformed the raw scores of the R-PCS into interval logit scale scores applying the Rasch model. Second, our findings supported the discriminant validity and the criterion validity of the R-PCS, examining the correlations with the PLDQ. They also confirmed its predictive validity: the R-PCS scores were related to 2-month-later enjoyment and anger, indicating that Adjustment and Proactivity were adaptive while Despair and Aversion were maladaptive. Third, our study revealed gender and age differences: the scores were higher for Despair, Adjustment, and Proactivity for females; for Aversion for males; and for Proactivity for students older than 23 years. The study suffers from limitations related to social desirability, gender imbalance, and self-selection effects in the recruitment.
Impact of Executive Functions and Parental Anxiety on the Development of Social Cognition in Premature Children: A Cross-Sectional Case-Control Protocol
Authors: Eutrope Julien , Novo Alexandre , Barbe Coralie , Loron Gauthier , Rolland Anne-Catherine , Caillies Stéphanie
Published: September 2021

Background: Recent research has identified neuropsychological disorders, specifically executive function disorders, in premature children. Executive functions support goal-oriented mental activity and play a role in the development of social cognition. This underlies the social and emotional behavior of individuals. Parental anxiety is also an important environmental factor that can influence the psycho-emotional development of children.

Objectives: The present protocol aims to compare the development of social cognition in school-age children born prematurely to that of school-age children born full-term, and to determine the impact of executive (dys)function and parental anxiety on such development.

Methods/Design: In this cross-sectional protocol, 28 prematurely born children aged 7-10 years (“preterm”) and 28 full-term born children aged 7-10 years (“control”) will be included. The “preterm” and “control” groups will be matched for sex and age. The neuropsychological evaluation will include that of non-verbal intellectual efficiency (Raven's colored progressive matrices), verbal level (WISC-IV subtests), and executive functions (NEPSY II subtests and the opposite worlds of TEA-CH). The evaluation of social cognition will be conducted via tests of the theory of cognitive and affective mind. Several dimensions of the level of parental anxiety will be collected through the Spielberg Trait Anxiety Inventory Form Y, Beck Depression Inventory, Social Support Questionnaire-6, Parental Stress Index and, specifically for mothers, the Modified Perinatal Post-Traumatic Stress Disorder Questionnaire.

Discussion: The results of this protocol will aid our understanding of the development of social cognition in premature children and to determine the factors that influence such development. This clinical research project, although following a fundamental approach, will have clinical implications because a more precise description of the development of social cognition in this school-age population will make it possible to better determine the cognitive targets of therapeutic actions and to search for predictive indices of the efficacy of practices.

Trial Registration:https://clinicaltrials.gov/ct2/show/NCT03007095, identifier: NCT03007095.