bluuebunny/crossref_metadata_2025 huggingface dataset:
Identification of a Novel Transcription Factor Prognostic Index for Breast Cancer
Authors: Liu Junhao , Liu Zexuan , Zhou Yangying , Zeng Manting , Pan Sanshui , Liu Huan , Liu Qiong , Zhu Hong
Published: June 2021

Transcription factors (TFs) are the mainstay of cancer and have a widely reported influence on the initiation, progression, invasion, metastasis, and therapy resistance of cancer. However, the prognostic values of TFs in breast cancer (BC) remained unknown. In this study, comprehensive bioinformatics analysis was conducted with data from The Cancer Genome Atlas (TCGA) and Gene Expression Omnibus (GEO) database. We constructed the co-expression network of all TFs and linked it to clinicopathological data. Differentially expressed TFs were obtained from BC RNA-seq data in TCGA database. The prognostic TFs used to construct the risk model for progression free interval (PFI) were identified by Cox regression analyses, and the PFI was analyzed by the Kaplan-Meier method. A receiver operating characteristic (ROC) curve and clinical variables stratification analysis were used to detect the accuracy of the prognostic model. Additionally, we performed functional enrichment analysis by analyzing the differential expressed gene between high-risk and low-risk group. A total of nine co-expression modules were identified. The prognostic index based on 4 TFs (NR3C2, ZNF652, EGR3, and ARNT2) indicated that the PFI was significantly shorter in the high-risk group than their low-risk counterpart (p < 0.001). The ROC curve for PFI exhibited acceptable predictive accuracy, with an area under the curve value of 0.705 and 0.730. In the stratification analyses, the risk score index is an independent prognostic variable for PFI. Functional enrichment analyses showed that high-risk group was positively correlated with mTORC1 signaling pathway. In conclusion, the TF-related signature for PFI constructed in this study can independently predict the prognosis of BC patients and provide a deeper understanding of the potential biological mechanism of TFs in BC.
Therapeutic Response of Soft Tissue Sarcoma With Novel SS18-POU5F1 Fusion: A Case Report
Authors: Liu Zengjun , Yuan Hongtu , Han Mingyong
Published: June 2021

A novel SS18-POU5F1 fusion gene was recently reported in soft tissue sarcoma occurring in three adolescent and young adult patients. Herein, we firstly reported the treatment response of SS18-POU5F1 sarcoma to immune checkpoint inhibitor, angiogenesis inhibitor, chemotherapy and radiotherapy. Our patient demonstrated no response to various systemic therapies including immune checkpoint inhibitor, angiogenesis inhibitor and chemotherapy. However, we noted that the SS18-POU5F1 sarcoma had a quick, robust but transient clinical response to radiotherapy. Further studies are needed to elucidate the mechanism underlying the different tumor response to radiotherapy and systemic therapy in this kind of tumor.
Genetic Variants in COX2 and ALOX Genes and Breast Cancer Risk in White and Black Women
Authors: Mongiovi Jennifer M. , Hong Chi-Chen , Zirpoli Gary R. , Khoury Thaer , Omilian Angela R. , Qin Bo , Bandera Elisa V. , Yao Song , Ambrosone Christine B. , Gong Zhihong
Published: June 2021

COX and ALOX genes are involved in inflammatory processes and that may be related to breast cancer risk differentially between White and Black women. We evaluated distributions of genetic variants involved in COX2 and ALOX-related pathways and examined their associations with breast cancer risk among 1,275 White and 1,299 Black cases and controls who participated in the Women’s Circle of Health Study. Odds ratios (ORs) and 95% confidence intervals (CIs) were estimated using multivariable-adjusted logistic regression models. Our results showed differential associations of certain genetic variants with breast cancer according to menopausal and ER status in either White or Black women. In White women, an increased risk of breast cancer was observed for COX2-rs689470 (OR: 2.02, P = 0.01) in the dominant model, and was strongest among postmenopausal women (OR: 2.72, P = 0.02) and for estrogen receptor positive (ER+) breast cancers (OR: 2.60, P = 0.001). A reduced risk was observed for ALOX5-rs7099874 (OR: 0.75, P = 0.01) in the dominant model, and was stronger among postmenopausal women (OR: 0.68, P = 0.03) and for ER+ cancer (OR: 0.66, P = 0.001). Four SNPs (rs3840880, rs1126667, rs434473, rs1042357) in the ALOX12 gene were found in high LD (r2 >0.98) in White women and were similarly associated with reduced risk of breast cancer, with a stronger association among postmenopausal women and for ER− cancer. Among Black women, increased risk was observed for ALOX5-rs1369214 (OR: 1.44, P = 0.003) in the recessive model and was stronger among premenopausal women (OR: 1.57, P = 0.03) and for ER+ cancer (OR: 1.53, P = 0.003). Our study suggests that genetic variants of COX2 and ALOX genes are associated with breast cancer, and that these associations and genotype distributions differ in subgroups defined by menopausal and ER status between White and Black women. Findings may provide insights into the etiology of breast cancer and areas for further research into reasons for breast cancer differences between races.
Prognostic Value of Pretreatment Overweight/Obesity and Adipose Tissue Distribution in Resectable Gastric Cancer: A Retrospective Cohort Study
Authors: Gu Lihu , Zhang Yangfan , Hong Jiaze , Xu Binbin , Yang Liuqiong , Yan Kun , Zhang Jingfeng , Chen Ping , Zheng Jianjun , Lin Jie
Published: June 2021

Background

This is a study aimed at exploring the relationship between pretreatment overweight/obesity, adipose tissue distribution, and long-term prognosis of gastric cancer.

Methods

A total of 607 gastric cancer patients were involved in the retrospective cohort study. Overweight/obese patients were defined as body mass index (BMI) greater than 25 kg/m2, and adipose tissue distribution parameters, including visceral adipose tissue (VAT), subcutaneous adipose tissue (SAT), and VAT/SAT ratio were measured at the level of the third lumbar vertebra using computerized tomography images within 15 days before the surgery. Multiple Cox regression models were applied to evaluate the association between overweight/obesity and disease-specific survival (DSS) of gastric cancer, and covariates including age, gender, T stage, N stage, and chemotherapy were adjusted. Furthermore, multiple Cox regression models were performed to evaluate the association between adipose tissue distribution parameters and DSS of gastric cancer; except for covariates mentioned above, overweight/obesity was adjusted additionally.

Results

Overweight/obesity was a predictive factor (HR = 0.61, 95% CI: 0.37–0.99) for the prognosis of gastric cancer. After additionally adjusting for overweight/obesity, high SAT percentage was an independent protective factor (HR = 0.59, 95% CI: 0.36–0.96), while high VAT percentage (HR = 1.68, 95% CI: 1.06–2.68) and high VAT/SAT ratio (HR = 1.99, 95% CI: 1.19–3.34) were independent risk factors for DSS of gastric cancer. Compared with other patients (overweight/obesity with low VAT/SAT ratio group, non-overweight/obesity or high VAT/SAT ratio group), patients in the non-overweight/obesity with high VAT/SAT ratio group had a worse prognosis (HR = 1.89, 95% CI: 1.28–2.77).

Conclusion

These results suggest that overweight/obesity is a predictive factor for the prognosis of gastric cancer. The VAT/SAT ratio could be used as a promising prognostic factor for gastric cancer. Therefore, in preoperative evaluation of gastric cancer patients, attention should be paid not only to BMI but also to adipose tissue distribution.
Expression of Glycolysis-Related Proteins in Cancer of Unknown Primary Origin
Authors: Bonatelli Murilo , Fornari Isabella Fernandes , Bernécule Priscila Neves , Pinheiro Lara Esquiapatti , Costa Ricardo Filipe Alves , Longatto-Filho Adhemar , Junior João Neif Antonio , Silva Eduardo Caetano Albino , Cárcano Flávio Mavignier , Pinheiro Céline
Published: June 2021

Introduction

Cancer of unknown primary origin (CUP) is defined as metastatic cancer without identification of the primary site. Considering that only 15–20% of patients with CUP show a favorable outcome, identifying biomarkers may help improve the clinical management of patients who do not respond well to conventional therapies. In this context, the study of the metabolic profile of CUP may pave the way to establish new biomarkers and/or therapeutic targets; therefore, this study aimed to characterize the expression of metabolism-related proteins in CUP.

Materials and Methods

The expression of monocarboxylate transporters MCT1, MCT2 and MCT4, their chaperone CD147, the glucose transporter GLUT1 and the pH regulator CAIX was evaluated by immunohistochemistry in a series of 118 CUP patients, and the results were associated with the available clinicopathological information.

Results

The metabolism-related proteins MCT1, MCT4, CD147, GLUT1 and CAIX were expressed in a critical portion of the CUP (approximately 20 to 70%). MCT1 and CD147 were both more frequently expressed in cases with lymph nodes as metastasis dominant sites (p = 0.001) as well as in samples from lymph nodes (p <0.001 and p = 0.002, respectively), while MCT1 expression was more frequently expressed in squamous cell carcinomas (p = 0.045). A higher overall survival was observed in patients with tumors positive for GLUT1 and CAIX expression (p = 0.011 and p = 0.041, respectively), but none of the proteins was an independent prognostic factor for overall survival in multivariable analysis.

Conclusion

The results suggest that a portion of CUPs present a hyperglycolytic phenotype, which is associated with higher overall survival.
SPNS2 Downregulation Induces EMT and Promotes Colorectal Cancer Metastasis via Activating AKT Signaling Pathway
Authors: Lv Lei , Yi Qiyi , Yan Ying , Chao Fengmei , Li Ming
Published: June 2021

Spinster homologue 2 (SPNS2), a transporter of S1P (sphingosine-1-phosphate), has been reported to mediate immune response, vascular development, and pathologic processes of diseases such as cancer via S1P signaling pathways. However, its biological functions and expression profile in colorectal cancer (CRC) is elusive. In this study, we disclosed that SPNS2 expression, which was regulated by copy number variation and DNA methylation of its promoter, was dramatically upregulated in colon adenoma and CRC compared to normal tissues. However, its expression was lower in CRC than in colon adenoma, and low expression of SPN2 correlated with advanced T/M/N stage and poor prognosis in CRC. Ectopic expression of SPNS2 inhibited cell proliferation, migration, epithelial–mesenchymal transition (EMT), invasion, and metastasis in CRC cell lines, while silencing SPNS2 had the opposite effects. Meanwhile, measuring the intracellular and extracellular level of S1P after overexpression of SPNS2 pinpointed a S1P-independent model of SPNS2. Mechanically, SPNS2 led to PTEN upregulation and inactivation of Akt. Moreover, AKT inhibitor (MK2206) abrogated SPNS2 knockdown-induced promoting effects on the migration and invasion, while AKT activator (SC79) reversed the repression of migration and invasion by SPNS2 overexpression in CRC cells, confirming the pivotal role of AKT for SPNS2’s function. Collectively, our study demonstrated the suppressor role of SPNS2 during CRC metastasis, providing new insights into the pathology and molecular mechanisms of CRC progression.
An Original Ferroptosis-Related Gene Signature Effectively Predicts the Prognosis and Clinical Status for Colorectal Cancer Patients
Authors: Shao Yanfei , Jia Hongtao , Huang Ling , Li Shuchun , Wang Chenxing , Aikemu Batuer , Yang Guang , Hong Hiju , Yang Xiao , Zhang Sen , Sun Jing , Zheng Minhua
Published: June 2021

Background

Colorectal cancer (CRC) is one of the most common malignant tumors in the world. Ferroptosis is a newly defined form of cell death, distinguished by different morphology, biochemistry, and genetics, and involved in CRC progression and treatment. This study aims to establish a predictive model to elucidate the relationship between ferroptosis and prognosis of CRC patients, to explore the potential value of ferroptosis in therapeutic options.

Methods

The ferroptosis-related genes were obtained from the GeneCards and FerrDb websites. The limma R package was used to screen the differential ferroptosis-related genes (DEGs) in CRC from The Cancer Genome Atlas (TCGA) dataset. The least absolute shrinkage and selection operator (LASSO) and multivariate Cox regressions were to establish the 10-gene prognostic signature. The survival and receiver operating characteristic (ROC) curves were illustrated to evaluate the predictive effect of the signature. Besides, independent prognostic factors, downstream functional enrichment, drug sensitivity, somatic mutation status, and immune feature were analyzed. Moreover, all these conclusions were verified by using multiple datasets in International Cancer Genome Consortium (ICGC) and Gene Expression Omnibus (GEO).

Results

Ten ferroptosis-related gene signature (TFAP2C, SLC39A8, NOS2, HAMP, GDF15, FDFT1, CDKN2A, ALOX12, AKR1C1, ATP6V1G2) was established to predict the prognosis of CRC patients by Lasso cox analysis, demonstrating a good performance on Receiver operating characteristic (ROC) and Kaplan–Meier (K–M) analyses. The CRC patients in the high- or low-risk group showed significantly different fractions of immune cells, such as macrophage cells and CD8+ T cells. Drug sensitivity and somatic mutation status like TP53 were also closely associated with the risk scores.

Conclusions

In this study, we identified a novel ferroptosis-related 10-gene signature, which could effectively predict the prognosis and survival time of CRC patients, and provide meaningful clinical implications for targeted therapy or immunotherapy. Targeting ferroptosis is a good therapeutic option for CRC patients. Further studies are needed to reveal the underlying mechanisms of ferroptosis in CRC.
Germline Compound Heterozygous Variants Identified in the STXBP2 Gene Leading to a Familial Hemophagocytic Lymphohistiocytosis Type 5: A Case Report
Authors: Dantas Vera Maria , Valle Cassandra Teixeira , de Oliveira Roberta Piccin , Bezerra Mylena Taíse Azevedo L. , do Amaral Cleia Teixeira , Brandão Raissa Anielle S. , Cerqueira Maia Jussara M. , Petta Tirzah Braz
Published: June 2021

Familial hemophagocytic lymphohistiocytosis (FHL) is a rare, potentially fatal autosomal-recessive immunodeficiency, and STXBP2 mutations have been associated with FHL type 5 (FHL-5). Here, we report a case of a 2-year-old boy who presented with recurrent fever, hepatosplenomegaly, pancytopenia, hyperferritinemia, and hypofibrinogenemia since 4 months of age. His genetic analysis revealed a compound heterozygosity of the STXBP2 gene with a described pathogenic mutation, c.1247-1G>C (splicing acceptor site), harbored by his father and a likely pathogenic variant of uncertain significance (VUS), c.704G>A (p.Arg235Gln), harbored by his mother. He was diagnosed as compound heterozygous for FHL-5 and was treated with the HLH-2004 protocol. Since treatment, this patient has been in remission, and he is being evaluated for a hematopoietic stem cell transplantation (HSCT).
Prevention of Neural Tube Defects in Europe: A Public Health Failure
Authors: Morris Joan K. , Addor Marie-Claude , Ballardini Elisa , Barisic Ingeborg , Barrachina-Bonet Laia , Braz Paula , Cavero-Carbonell Clara , Den Hond Elly , Garne Ester , Gatt Miriam , Haeusler Martin , Khoshnood Babak , Lelong Nathalie , Kinsner-Ovaskainen Agnieszka , Kiuru-Kuhlefelt Sonja , Klungsoyr Kari , Latos-Bielenska Anna , Limb Elizabeth , O'Mahony Mary T , Perthus Isabelle , Pierini Anna , Rankin Judith , Rissmann Anke , Rouget Florence , Sayers Gerardine , Sipek Antonin , Stevens Sarah , Tucker David , Verellen-Dumoulin Christine , de Walle Hermien E. K. , Wellesley Diana , Wertelecki Wladimir , Bermejo-Sanchez Eva
Published: June 2021

Objective: Thirty years ago it was demonstrated that folic acid taken before pregnancy and in early pregnancy reduced the risk of a neural tube defect (NTD). Despite Public Health Initiatives across Europe recommending that women take 0.4 mg folic acid before becoming pregnant and during the first trimester, the prevalence of NTD pregnancies has not materially decreased in the EU since 1998, in contrast to the dramatic fall observed in the USA. This study aimed to estimate the number of NTD pregnancies that would have been prevented if flour had been fortified with folic acid in Europe from 1998 as it had been in the USA.

Design and Setting: The number of NTD pregnancies from 1998 to 2017 that would have been prevented if folic acid fortification had been implemented in the 28 countries who were members of the European Union in 2019 was predicted was predicted using data on NTD prevalence from 35 EUROCAT congenital anomaly registries and literature searches for population serum folate levels and folic acid supplementation.

Results: From 1998 to 2017 an estimated 95,213 NTD pregnancies occurred amongst 104 million births in the 28 countries in the EU, a prevalence of 0.92 per 1,000 births. The median serum folate level in Europe over this time period was estimated to be 14.1 μg/L. There is a lack of information about women taking folic acid supplements before becoming pregnant and during the first trimester of pregnancy, with one meta-analysis indicating that around 25% of women did so. An estimated 14,600 NTD pregnancies may have been prevented if the European countries had implemented fortification at the level adopted by the USA in 1998 and 25% of women took folic acid supplements. An estimated 19,500 NTD pregnancies would have been prevented if no women took folic acid supplements.

Conclusions: This study suggests that failure to implement mandatory folic acid fortification in the 28 European countries has caused, and continues to cause, neural tube defects to occur in almost 1,000 pregnancies every year.
Unsupervised Hierarchical Clustering Identifies Immune Gene Subtypes in Gastric Cancer
Authors: Cao Jing , Gong Jiao , Li Xinhua , Hu Zhaoxia , Xu Yingjun , Shi Hong , Li Danyang , Liu Guangjian , Jie Yusheng , Hu Bo , Chong Yutian
Published: June 2021

Objectives: The pathogenesis of heterogeneity in gastric cancer (GC) is not clear and presents as a significant obstacle in providing effective drug treatment. We aimed to identify subtypes of GC and explore the underlying pathogenesis.

Methods: We collected two microarray datasets from GEO (GSE84433 and GSE84426), performed an unsupervised cluster analysis based on gene expression patterns, and identified related immune and stromal cells. Then, we explored the possible molecular mechanisms of each subtype by functional enrichment analysis and identified related hub genes.

Results: First, we identified three clusters of GC by unsupervised hierarchical clustering, with average silhouette width of 0.96, and also identified their related representative genes and immune cells. We validated our findings using dataset GSE84426. Subtypes associated with the highest mortality (subtype 2 in the training group and subtype C in the validation group) showed high expression of SPARC, COL3A1, and CCN. Both subtypes also showed high infiltration of fibroblasts, endothelial cells, hematopoietic stem cells, and a high stromal score. Furthermore, subtypes with the best prognosis (subtype 3 in the training group and subtype A in the validation group) showed high expression of FGL2, DLGAP1-AS5, and so on. Both subtypes also showed high infiltration of CD4+ T cells, CD8+ T cells, NK cells, pDC, macrophages, and CD4+ T effector memory cells.

Conclusion: We found that GC can be classified into three subtypes based on gene expression patterns and cell composition. Findings of this study help us better understand the tumor microenvironment and immune milieu associated with heterogeneity in GC and provide practical information to guide personalized treatment.
In vivo / in vitro Correlation of Pharmacokinetics of Gentamicin, Vancomycin, Teicoplanin and Doripenem in a Bovine Blood Hemodialysis Model
Authors: Vossen M G , Pferschy S , Milacek C , Haidinger M , Karolyi Mario , Vass Zoltan , Burgmann Heinz , Maier-Salamon Alexandra , Wicha S G , Jäger W , Zeitlinger M , Stimpfl T , Wittek T , Thalhammer F
Published: June 2021

Background: Elimination of a drug during renal replacement therapy is not only dependent on flow rates, molecular size and protein binding, but is often influenced by difficult to predict drug membrane interactions. In vitro models allow for extensive profiling of drug clearance using a wide array of hemofilters and flow rates. We present a bovine blood based in vitro pharmacokinetic model for intermittent renal replacement therapy.

Methods: Four different drugs were analyzed: gentamicin, doripenem, vancomicin and teicoplanin. The investigated drug was added to a bovine blood reservoir connected to a hemodialysis circuit. In total seven hemofilter models were analyzed using commonly employed flow rates. Pre-filter, post-filter and dialysate samples were drawn, plasmaseparated and analyzed using turbidimetric assays or HPLC. Protein binding of doripenem and vancomycin was measured in bovine plasma and compared to previously published values for human plasma.

Results: Clearance values were heavily impacted by choice of membrane material and surface as well as by dialysis parameters such as blood flow rate. Gentamicin clearance ranged from a minimum of 90.12 ml/min in a Baxter CAHP-170 diacetate hemofilter up to a maximum of 187.90 ml/min in a Fresenius medical company Fx80 polysulfone model (blood flow rate 400 ml/min, dialysate flow rate 800 ml/min). Clearance of Gentamicin vs Vancomicin over the F80s hemofilter model using the same flow rates was 137.62 mL vs 103.25 ml/min. Doripenem clearance with the Fx80 was 141.25 ml/min.

Conclusion: Clearance values corresponded very well to previously published data from clinical pharmacokinetic trials. In conjunction with in silico pharmacometric models. This model will allow precise dosing recommendations without the need of large scale clinical trials.
Investigating the Association of Wallerian Degeneration and Diaschisis After Ischemic Stroke With BOLD Cerebrovascular Reactivity
Authors: van Niftrik C. H. B. , Sebök M. , Muscas G. , Wegener S. , Luft A. R. , Stippich C. , Regli L. , Fierstra J.
Published: June 2021

Introduction

Wallerian degeneration and diaschisis are considered separate remote entities following ischemic stroke. They may, however, share common neurophysiological denominators, since they are both related to disruption of fiber tracts and brain atrophy over time. Therefore, with advanced multimodal neuroimaging, we investigate Wallerian degeneration and its association with diaschisis.

Methods

In order to determine different characteristics of Wallerian degeneration, we conducted examinations on seventeen patients with chronic unilateral ischemic stroke and persisting large vessel occlusion, conducting high-resolution anatomical magnetic resonance imaging (MRI) and blood oxygenation-level dependent cerebrovascular reactivity (BOLD-CVR) tests, as well as Diamox 15(O)–H2O–PET hemodynamic examinations. Wallerian degeneration was determined using a cerebral peduncle asymmetry index (% difference of volume of ipsilateral and contralateral cerebral peduncle) of more than two standard deviations away from the average of age-matched, healthy subjects (Here a cerebral peduncle asymmetry index > 11%). Diaschisis was derived from BOLD-CVR to assess the presence of ipsilateral thalamus diaschisis and/or crossed cerebellar diaschisis.

Results

Wallerian degeneration, found in 8 (47%) subjects, had a strong association with ipsilateral thalamic volume reduction (r2 = 0.60) and corticospinal-tract involvement of stroke (p < 0.001). It was also associated with ipsilateral thalamic diaschisis (p = 0.021), No cerebral peduncular hemodynamic differences were found in patients with Wallerian degeneration. In particular, no CBF decrease or BOLD-CVR impairment was found.

Conclusion

We show a strong association between Wallerian degeneration and ipsilateral thalamic diaschisis, indicating a structural pathophysiological relationship.
NMDA Receptor Hypofunction in the Aging-Associated Malfunction of Peripheral Tissue
Authors: Rivera-Villaseñor Angélica , Higinio-Rodríguez Frida , Nava-Gómez Laura , Vázquez-Prieto Bárbara , Calero-Vargas Isnarhazni , Olivares-Moreno Rafael , López-Hidalgo Mónica
Published: June 2021

Glutamatergic transmission through NMDA receptors (NMDARs) is important for the function of peripheral tissues. In the bone, NMDARs and its co-agonist, D-serine participate in all the phases of the remodeling. In the vasculature, NMDARs exerts a tonic vasodilation decreasing blood perfusion in the corpus cavernosum and the filtration rate in the renal glomerulus. NMDARs are relevant for the skin turnover regulating the proliferation and differentiation of keratinocytes and the formation of the cornified envelope (CE). The interference with NMDAR function in the skin leads to a slow turnover and repair. As occurs with the brain and cognitive functions, the manifestations of a hypofunction of NMDARs resembles those observed during aging. This raises the question if the deterioration of the glomerular vasculature, the bone remodeling and the skin turnover associated with age could be related with a hypofunction of NMDARs. Furthermore, the interference of D-serine and the effects of its supplementation on these tissues, suggest that a decrease of D-serine could account for this hypofunction pointing out D-serine as a potential therapeutic target to reduce or even prevent the detriment of the peripheral tissue associated with aging.
Orchid Root Associated Bacteria: Linchpins or Accessories?
Authors: Kaur Jaspreet , Sharma Jyotsna
Published: June 2021

Besides the plant-fungus symbiosis in arbuscular mycorrhizal (AM) and ectomycorrhizal (EM) plants, many endorhizal and rhizosphere bacteria (Root Associated Bacteria, or RAB) also enhance plant fitness, diversity, and coexistence among plants via bi- or tripartite interactions with plant hosts and mycorrhizal fungi. Assuming that bacterial associations are just as important for the obligate mycorrhizal plant family Orchidaceae, surprisingly little is known about the RAB associated with orchids. Herein, we first present the current, underwhelming state of RAB research including their interactions with fungi and the influence of holobionts on plant fitness. We then delineate the need for novel investigations specifically in orchid RAB ecology, and sketch out questions and hypotheses which, when addressed, will advance plant-microbial ecology. We specifically discuss the potential effects of beneficial RAB on orchids as: (1) Plant Growth Promoting Rhizobacteria (PGPR), (2) Mycorrhization Helper Bacteria (MHB), and (3) constituents of an orchid holobiont. We further posit that a hologenomic view should be considered as a framework for addressing co-evolution of the plant host, their obligate Orchid Mycorrhizal Fungi (OMF), and orchid RAB. We conclude by discussing implications of the suggested research for conservation of orchids, their microbial partners, and their collective habitats.
High-Density GBS-Based Genetic Linkage Map Construction and QTL Identification Associated With Yellow Mosaic Disease Resistance in Bitter Gourd (Momordica charantia L.)
Authors: Kaur Gurpreet , Pathak Mamta , Singla Deepak , Sharma Abhishek , Chhuneja Parveen , Sarao Navraj Kaur
Published: June 2021

Yellow mosaic disease (YMD) in bitter gourd (Momordica charantia) is a devastating disease that seriously affects its yield. Although there is currently no effective method to control the disease, breeding of resistant varieties is the most effective and economic option. Moreover, quantitative trait locus (QTL) associated with resistance to YMD has not yet been reported. With the objective of mapping YMD resistance in bitter gourd, the susceptible parent “Punjab-14” and the resistant parent “PAUBG-6” were crossed to obtain F4 mapping population comprising 101 individuals. In the present study, the genotyping by sequencing (GBS) approach was used to develop the genetic linkage map. The map contained 3,144 single nucleotide polymorphism (SNP) markers, consisted of 15 linkage groups, and it spanned 2415.2 cM with an average marker distance of 0.7 cM. By adopting the artificial and field inoculation techniques, F4:5 individuals were phenotyped for disease resistance in Nethouse (2019), Rainy (2019), and Spring season (2020). The QTL analysis using the genetic map and phenotyping data identified three QTLs qYMD.pau_3.1, qYMD.pau_4.1, and qYMD.pau_5.1 on chromosome 3, 4, and 5 respectively. Among these, qYMD.pau_3.1, qYMD.pau_4.1 QTLs were identified during the rainy season, explaining the 13.5 and 21.6% phenotypic variance respectively, whereas, during the spring season, qYMD.pau_4.1 and qYMD.pau_5.1 QTLs were observed with 17.5 and 22.1% phenotypic variance respectively. Only one QTL qYMD.pau_5.1 was identified for disease resistance under nethouse conditions with 15.6% phenotypic variance. To our knowledge, this is the first report on the identification of QTLs associated with YMD resistance in bitter gourd using SNP markers. The information generated in this study is very useful in the future for fine-mapping and marker-assisted selection for disease resistance.
The Role of Grass MUTE Orthologs in GMC Progression and GC Morphogenesis
Authors: Serna Laura
Published: June 2021

Stomata arose about 400 million years ago when plants left their aquatic environment. The last step of stomatal development is shared by all plant groups, and it implies a symmetrical cell division from the guard mother cell (GMC) to produce two guard cells (GCs) flanking a pore. In Arabidopsis, the basic helix-loop-helix transcription factor MUTE controls this step, upregulating cell-cycle regulators of the GMC division, and immediately afterward, repressors of theses regulators like FAMA and FOUR LIPS. Recently, three grass MUTE orthologs (BdMUTE from Brachypodium distachyon, OsMUTE from rice, and ZmMUTE from maize) have been identified and characterized. Mutations in these genes disrupt GMC fate, with bdmute also blocking GC morphogenesis. However, because these genes also regulate subsidiary cell recruitment, which takes place before GMC division, their functions regulating GMC division and GC morphogenesis could be an indirect consequence of that inducing the recruitment of subsidiary cells. Comprehensive data evaluation indicates that BdMUTE, and probably grass MUTE orthologs, directly controls GMC fate. Although grass MUTE proteins, whose genes are expressed in the GMC, move between cells, they regulate GMC fate from the cells where they are transcribed. Grass MUTE genes also regulate GC morphogenesis. Specifically, OsMUTE controls GC shape by inducing OsFAMA expression. In addition, while SCs are not required for GMC fate progression, they are for GC maturation.
Mosaic Arrangement of the 5S rDNA in the Aquatic Plant Landoltia punctata (Lemnaceae)
Authors: Chen Guimin , Stepanenko Anton , Borisjuk Nikolai
Published: June 2021

Duckweeds are a group of monocotyledonous aquatic plants in the Araceae superfamily, represented by 37 species divided into five genera. Duckweeds are the fastest growing flowering plants and are distributed around the globe; moreover, these plants have multiple applications, including biomass production, wastewater remediation, and making pharmaceutical proteins. Dotted duckweed (Landoltia punctata), the sole species in genus Landoltia, is one of the most resilient duckweed species. The ribosomal DNA (rDNA) encodes the RNA components of ribosomes and represents a significant part of plant genomes but has not been comprehensively studied in duckweeds. Here, we characterized the 5S rDNA genes inL. punctataby cloning and sequencing 25 PCR fragments containing the 5S rDNA repeats. No length variation was detected in the 5S rDNA gene sequence, whereas the nontranscribed spacer (NTS) varied from 151 to 524 bp. The NTS variants were grouped into two major classes, which differed both in nucleotide sequence and the type and arrangement of the spacer subrepeats. The dominant class I NTS, with a characteristic 12-bp TC-rich sequence present in 3–18 copies, was classified into four subclasses, whereas the minor class II NTS, with shorter, 9-bp nucleotide repeats, was represented by two identical sequences. In addition to these diverse subrepeats, class I and class II NTSs differed in their representation of cis-elements and the patterns of predicted G-quadruplex structures, which may influence the transcription of the 5S rDNA. Similar to related duckweed species in the genus Spirodela,L. punctatahas a relatively low rDNA copy number, but in contrast to Spirodela and the majority of other plants, the arrangement of the 5S rDNA units demonstrated an unusual, heterogeneous pattern inL. punctata, as revealed by analyzing clones containing double 5S rDNA neighboring units. Our findings may further stimulate the research on the evolution of the plant rDNA and discussion of the molecular forces driving homogenization of rDNA repeats in concerted evolution.
Genetic Divergence and Population Structure in Weedy and Cultivated Broomcorn Millets (Panicum miliaceum L.) Revealed by Specific-Locus Amplified Fragment Sequencing (SLAF-Seq)
Authors: Li Chunxiang , Liu Minxuan , Sun Fengjie , Zhao Xinyu , He Mingyue , Li Tianshu , Lu Ping , Xu Yue
Published: June 2021

Broomcorn millet (Panicum miliaceum L.) is one of the earliest domesticated crops in the world. Weedy broomcorn millet [Panicum ruderale (Kitag.) Chang or Panicum miliaceum subsp. ruderale (Kitag.) Tzvel] is thought to be the descendant of the wild ancestor or the feral type of this cereal. The genealogical relationships and genetic divergence among these taxa have not been clarified. In this study, the genetic diversity and population structure of weedy and cultivated broomcorn millets were investigated by using the high-throughput sequencing technology, i.e., the specific-locus amplified fragment sequencing (SLAF-seq). Our analyses consistently revealed both the wild and the feral genotypes in the weedy broomcorn millets. The single nucleotide polymorphisms (SNPs) at the genomic level provided useful evidence to distinguish the wild and the endoferal/exoferal types of weedy broomcorn millets. The genetic divergence revealed between the cultivated broomcorn millet from eastern Eurasia and those from central-western Eurasia was probably derived from either the genetic introgression from weedy broomcorn millets along the spread routes or the founder effect, while the limited gene flow of broomcorn millets from eastern and central-western Eurasia was probably due to the different uses of broomcorn millets and eating habits of the local people.
Identification and Characterization of Genes Encoding the Hydroxypyruvate Reductases in Chlamydomonas Reveal Their Distinct Roles in Photorespiration
Authors: Shi Menglin , Zhao Lei , Wang Yong
Published: June 2021

Photorespiration plays an important role in maintaining normal physiological metabolism in higher plants and other oxygenic organisms, such as algae. The unicellular eukaryotic organismChlamydomonasis reported to have a photorespiration system different from that in higher plants, and only two out of nine genes encoding photorespiratory enzymes have been experimentally characterized. Hydroxypyruvate reductase (HPR), which is responsible for the conversion of hydroxypyruvate into glycerate, is poorly understood and not yet explored inChlamydomonas. To identify the candidate genes encoding hydroxypyruvate reductases inChlamydomonas(CrHPR) and uncover their elusive functions, we performed sequence comparison, enzyme activity measurement, subcellular localization, and analysis of knockout/knockdown strains. Together, we identify five proteins to be good candidates for CrHPRs, all of which are detected with the activity of hydroxypyruvate reductase. CrHPR1, a nicotinamide adenine dinucleotide (NADH)-dependent enzyme in mitochondria, may function as the major component of photorespiration. Its deletion causes severe photorespiratory defects. CrHPR2 takes part in the cytosolic bypass of photorespiration as the compensatory pathway of CrHPR1 for the reduction of hydroxypyruvate. CrHPR4, with NADH as the cofactor, may participate in photorespiration by acting as the chloroplastidial glyoxylate reductase in glycolate-quinone oxidoreductase system. Therefore, the results reveal that CrHPRs are far more complex than previously recognized and provide a greatly expanded knowledge base for studies to understand how CrHPRs perform their functions in photorespiration. These will facilitate both modification of photorespiration and genetic engineering for crop improvement by synthetic biology.
Level of Sulfite Oxidase Activity Affects Sulfur and Carbon Metabolism in Arabidopsis
Authors: Oshanova Dinara , Kurmanbayeva Assylay , Bekturova Aizat , Soltabayeva Aigerim , Nurbekova Zhadyrassyn , Standing Dominic , Dubey Arvind Kumar , Sagi Moshe
Published: June 2021

Molybdenum cofactor containing sulfite oxidase (SO) enzyme is an important player in protecting plants against exogenous toxic sulfite. It was also demonstrated that SO activity is essential to cope with rising dark-induced endogenous sulfite levels and maintain optimal carbon and sulfur metabolism in tomato plants exposed to extended dark stress. The response of SO and sulfite reductase to direct exposure of low and high levels of sulfate and carbon was rarely shown. By employing Arabidopsis wild-type, sulfite reductase, and SO-modulated plants supplied with excess or limited carbon or sulfur supply, the current study demonstrates the important role of SO in carbon and sulfur metabolism. Application of low and excess sucrose, or sulfate levels, led to lower biomass accumulation rates, followed by enhanced sulfite accumulation in SO impaired mutant compared with wild-type. SO-impairment resulted in the channeling of sulfite to the sulfate reduction pathway, resulting in an overflow of organic S accumulation. In addition, sulfite enhancement was followed by oxidative stress contributing as well to the lower biomass accumulation in SO-modulated plants. These results indicate that the role of SO is not limited to protection against elevated sulfite toxicity but to maintaining optimal carbon and sulfur metabolism in Arabidopsis plants.
Comparative Analysis of Glycosidic Aroma Compound Profiling in Three Vitis vinifera Varieties by Using Ultra-High-Performance Liquid Chromatography Quadrupole-Time-of-Flight Mass Spectrometry
Authors: Wei Yi , Chen Zhuo , Zhang Xin-Ke , Duan Chang-Qing , Pan Qiu-Hong
Published: June 2021

Glycosidic aroma compounds are the important precursors of volatile aroma in grapes, and they can be added with odorous aglycones via enzyme- or acid-catalyzed hydrolysis during wine fermentation and storage. Developing an analytical method for intact glycosides can provide the possibility to study the accumulation of these aroma precursors in grape berries. For this purpose, a Tandem Mass Spectrometry (MS/MS). database based on ultra-high-performance liquid chromatography quadrupole-time-of-flight mass spectrometry was built, covering multiple aglycone classes. Subsequently, the profiles of glycosidic aroma compounds in Vitis vinifera L. cv. Muscat Blanc, Riesling, and Chardonnay berries during maturation were investigated. Pentosyl-hexosides were the most abundant glycosides in all three varieties. Both composition and concentration of glycosidic aroma compounds varied obviously among grape varieties. Except for monoterpenol pentosyl-hexosides, most glycosides were kept almost stable in their concentrations during berry maturation. This research provides an approach to understand the variation of glycosidic aroma components from the perspective of aglycones and glycosides.
Cultural Beliefs and Stakeholder Affiliation Influence Attitudes Towards Responsible Research and Innovation Among United States Stakeholders Involved in Biotechnology and Gene Editing
Authors: Kuzma Jennifer , Cummings Christopher L.
Published: June 2021

Biotech developers are concerned about the future of gene editing having experienced the contentious history of first-generation GM foods. They have also expressed desires to do better with public engagement in gene-editing innovation. The framework of Responsible Research and Innovation (RRI) may provide a way forward to act on their desires for greater public legitimacy. However, in the United States, -there has also been reluctance to incorporate RRI into biotechnology innovation systems like gene editing in food and agriculture. In this article, we investigate individual- and group-level factors, including demographic, sociographic, and cultural factors, that influence attitudes towards RRI among biotechnology United States stakeholders. Using the Advocacy Coalition Framework’s (ACF) hierarchy of beliefs as a theoretical guide, biotechnology stakeholders (n = 110) were surveyed about their cultural (deep-core) beliefs and then about their attitudes towards principles (policy-core beliefs) and practices (secondary beliefs) of RRI applied to biotechnology innovation. Through statistical analysis of the results, we found significant relationships between stronger egalitarian cultural-beliefs and positive attitudes towards both the principles and practices of RRI. We also found that participants with higher levels of experience held more positive attitudes towards principles of RRI. In contrast, we found a significant inverse relationship between professional affiliation with industry or trade organizations and attitudes towards RRI practices. With these results, we present a model of factors that influence RRI attitudes for future testing. In closing, we interpret the results in the context of ACF to examine the potential for building cross-sector coalitions for practicing RRI within United States gene-editing innovation systems.
Prognostic Awareness in Advanced Disease: A Review Update and Concept Analysis
Authors: Kühne Franziska , Hermann Myriel , Preisler Martina , Rohrmoser Amy , Letsch Anne , Goerling Ute
Published: June 2021

Purpose

Although subjective knowledge about the prognosis of an advanced disease is extremely important for coping and treatment planning, the concept of prognostic awareness (PA) remains inconsistently defined. The aims of the scoping review were to synthesize a definition of PA from the most recent literature, describe preconditions, correlates and consequences, and suggest a conceptual model.

Methods

By using scoping review methodology, we searched the Web of Science and PubMed databases, and included publications, reviews, meta-analyses or guidelines on all physical diagnoses, as well as publications offering a conceptual or an operational definition of PA. The data were analyzed by means of content analysis techniques.

Results

Of the 24 included publications, 21 referred exclusively to cancer, one to patients with hip fractures and two to palliative care in general. The deduced definition of PA comprised the following facets: adequate estimation of chances for recovery, knowledge of limited time to live, adequate estimation of life expectancy, knowledge of therapy goals, and knowledge of the course of the disease. Further content analysis results were mapped graphically and in a detailed table.

Conclusion

There appears to be a lack of theoretical embedding of PA that in turn influences the methods used for empirical investigation. Drawing on a clear conceptual definition, longitudinal or experimental studies would be desirable.
Dealing With the Pandemic of COVID-19 in Portugal: On the Important Role of Positivity, Experiential Avoidance, and Coping Strategies
Authors: Ferreira Maria José , Sofia Rui , Carreno David F. , Eisenbeck Nikolett , Jongenelen Inês , Cruz José Fernando A.
Published: June 2021

The global COVID-19 pandemic crisis has caused an unprecedented impact on most areas of people’s lives. Thus, framed within the scope of Existential Positive Psychology (PP2.0), this study aimed at assessing the psychological distress of adults living in Portugal during the first national lockdown, how they are coping with stress, as well to contribute to a deeper understanding about the role that positivity, experiential avoidance, and coping strategies have in psychological distress and well-being. For this purpose, 586 Portuguese adults (73% females) ranging between 18 and 78 years old (M = 38.96, SD = 12.20) completed an online survey during the initial phase of the pandemic crisis in Portugal. Findings suggest that experiential avoidance was the strongest predictor of a negative response (depression, anxiety, stress, loneliness, and negative emotions), whereas positivity was a better predictor of psychological well-being and lower levels of depression. Additionally, self-blame, behavioral disengagement, and emotional venting were strong risk factors for psychological distress, whereas positive reframing, planning, and acceptance were associated with more positive outcomes. These findings highlight the critical role of experiential avoidance on individuals’ psychological distress and the essential contribution of positive life orientation in promoting flourishing. By offering a better understanding of the complex navigation through the dialectics between positive and negative life features, this study provides important and useful cues for psychological interventions directed at promoting a more positive and adaptive human functioning even through such potential adverse and painful life events.
Identity and Guilt as Mediators of Pro-environmental Spillover
Authors: Truelove Heather Barnes , Carrico Amanda R. , Yeung Kam Leung , Wolff Jennifer M.
Published: June 2021

Policymakers are interested in programs that increase targeted pro-environmental behavior (PEB) and spill over to increase non-targeted PEBs. Theoretically, guilt should lead to negative spillover and identity to positive spillover, though this has rarely been tested empirically. Additionally, little is known about how reminders of past PEB behavior might also lead to downstream spillover effects. Across two studies, participants (Study 1: 377 MTurk workers; Study 2: 172 undergraduates) were randomly assigned to write about a prior PEB, an anti-environmental behavior, or to a control condition. Subsequently, respondents were given an opportunity to perform a PEB2 and completed measures of PEB3 intentions. Results showed some evidence of positive (through increasing identity) and negative (through decreasing guilt) indirect spillover pathways from prior PEB reminders to PEB2 performance and PEB3 curtailment intentions (but not efficiency upgrade intentions). However, there were no overall spillover effects from PEB reminders to PEB2 performance or PEB3 intentions, as the positive and negative indirect effects canceled each other out. Results also showed positive spillover from PEB2 performance to PEB3 curtailment intentions through increasing environmental guilt. The strength of the spillover effects depended on the comparison group for the experimental manipulation, whether environmental guilt or global guilt was measured, and the type of PEB. The results suggest that environmental communications that remind people of their prior PEB may not meaningfully spill over to further PEB performance or intentions.