bluuebunny/crossref_metadata_2025_split huggingface dataset:
Using a chimeric respiratory chain and EPR spectroscopy to determine the origin of semiquinone species previously assigned to mitochondrial complex I
Authors: Wright John J. , Fedor Justin G. , Hirst Judy , Roessler Maxie M. 
Published: May 2020

Abstract
Background
For decades, semiquinone intermediates have been suggested to play an essential role in catalysis by one of the most enigmatic proton-pumping enzymes, respiratory complex I, and different mechanisms have been proposed on their basis. However, the difficulty in investigating complex I semiquinones, due to the many different enzymes embedded in the inner mitochondrial membrane, has resulted in an ambiguous picture and no consensus.

Results
In this paper, we re-examine the highly debated origin of semiquinone species in mitochondrial membranes using a novel approach. Our combination of a semi-artificial chimeric respiratory chain with pulse EPR spectroscopy (HYSCORE) has enabled us to conclude, unambiguously and for the first time, that the majority of the semiquinones observed in mitochondrial membranes originate from complex III. We also identify a minor contribution from complex II.

Conclusions
We are unable to attribute any semiquinone signals unambiguously to complex I and, reconciling our observations with much of the previous literature, conclude that they are likely to have been misattributed to it. We note that, for this earlier work, the tools we have relied on here to deconvolute overlapping EPR signals were not available. Proposals for the mechanism of complex I based on the EPR signals of semiquinone species observed in mitochondrial membranes should thus be treated with caution until future work has succeeded in isolating any complex I semiquinone EPR spectroscopic signatures present.
Interventionist videothermometry: a new model of cardiac ischemia evaluation
Authors: da Silva Tomas Ottoni Barroso , de Moura Vidal Leonardo Waldstein , Cabral Paula Gebe Abreu , da Mota Costa Matheus Roberto , Cadena Silvia Marcela Ruiz , dos Santos Junior Marcelo Borges , Antunes Fernanda , de Abreu Oliveira André Lacerda 
Published: May 2020

Abstract
Background
The purpose of the present study was to evaluate, through videothermometry, the temperature variation in the hearts of rabbits, that underwent induced myocardial ischemia and reperfusion.

Results
A total of 20 female rabbits were divided into two groups: a treated group and a sham group, the treatment group underwent 5 min of cardiac arrest and reperfusion, using the inflow occlusion technique. Throughout the experiment, the animals were monitored by videothermometry, observing the thermal variations of the myocardial tissue. During the experiment, at different times, blood gas tests and tests to evaluate the lactate concentrations were performed. At the end of the experiment, each heart was submitted to histopathological evaluation. In the treated group, there was a reduction in temperature of the myocardial tissue during the circulatory arrest compared to the sham group. Additionally, a colder area next to the caudal vena cava ostium and the right atrium was observed. Notably, despite the 5 min of cardiac arrest in the treated group, both the lactate and bicarbonate levels were maintained without significant variation. However, there was an increase in PaCO2 and pH reduction, featuring respiratory acidosis. In relation to the histopathological study, the presence of hydropic degeneration in the myocardium of animals in the treated group was observed.

Conclusions
Based on these results, the videothermometry was efficient in identifying the range of myocardial tissue temperature, suggesting that the first areas to suffer due to cardiac arrest were the caudal vena cava ostium and the right atrium. However, in regard to the angiographic coronary thermography, the study was not feasible due to the small size of the coronary. There was no variation between the groups regarding the presence of myocardial infarction, myocardial congestion, myocardial edema and myocardial hemorrhage.
Key factors affecting ammonium production by an Azotobacter vinelandii strain deregulated for biological nitrogen fixation
Authors: Plunkett Mary H. , Knutson Carolann M. , Barney Brett M. 
Published: May 2020

Abstract
Background
The obligate aerobe Azotobacter vinelandii is a model organism for the study of biological nitrogen fixation (BNF). This bacterium regulates the process of BNF through the two component NifL and NifA system, where NifA acts as an activator, while NifL acts as an anti-activator based on various metabolic signals within the cell. Disruption of the nifL component in the nifLA operon in a precise manner results in a deregulated phenotype that produces levels of ammonium that far surpass the requirements within the cell, and results in the release of up to 30 mM of ammonium into the growth medium. While many studies have probed the factors affecting growth of A. vinelandii, the features important to maximizing this high-ammonium-releasing phenotype have not been fully investigated.

Results
In this work, we report the effect of temperature, medium composition, and oxygen requirements on sustaining and maximizing elevated levels of ammonium production from a nitrogenase deregulated strain. We further investigated several pathways, including ammonium uptake through the transporter AmtB, which could limit yields through energy loss or futile recycling steps. Following optimization, we compared sugar consumption and ammonium production, to attain correlations and energy requirements to drive this process in vivo. Ammonium yields indicate that between 5 and 8% of cellular protein is fully active nitrogenase MoFe protein (NifDK) under these conditions.

Conclusions
These findings provide important process optimization parameters, and illustrate that further improvements to this phenotype can be accomplished by eliminating futile cycles.
The functional capacity of plantaricin-producing Lactobacillus plantarum SF9C and S-layer-carrying Lactobacillus brevis SF9B to withstand gastrointestinal transit
Authors: Butorac Katarina , Banić Martina , Novak Jasna , Leboš Pavunc Andreja , Uroić Ksenija , Durgo Ksenija , Oršolić Nada , Kukolj Marina , Radović Slobodanka , Scalabrin Simone , Žučko Jurica , Starčević Antonio , Šušković Jagoda , Kos Blaženka 
Published: May 2020

Abstract
Background
We evaluated the functional capacity of plantaricin-producing Lactobacillus plantarum SF9C and S-layer-carrying Lactobacillus brevis SF9B to withstand gastrointestinal transit and to compete among the gut microbiota in vivo. Considering the probiotic potential of Lb. brevis SF9B, this study aims to investigate the antibacterial activity of Lb. plantarum SF9C and their potential for in vivo colonisation in rats, which could be the basis for the investigation of their synergistic functionality.

Results
A plantaricin-encoding cluster was identified in Lb. plantarum SF9C, a strain which efficiently inhibited the growth of Listeria monocytogenes ATCC® 19111™ and Staphylococcus aureus 3048. Homology-based three-dimensional (3D) structures of SF9C plantaricins PlnJK and PlnEF were predicted using SWISS-MODEL workspace and the helical wheel representations of the plantaricin peptide helices were generated by HELIQUEST. Contrary to the plantaricin-producing SF9C strain, the S-layer-carrying SF9B strain excluded Escherichia coli 3014 and Salmonella enterica serovar Typhimurium FP1 from the adhesion to Caco-2 cells. Finally, PCR-DGGE analysis of the V2–V3 regions of the 16S rRNA gene confirmed the transit of the two selected lactobacilli through the gastrointestinal tract (GIT). Microbiome profiling via the Illumina MiSeq platform revealed the prevalence of Lactobacillus spp. in the gut microbiota of the Lactobacillus-treated rats, even on the 10th day after the Lactobacillus application, compared to the microbiota of the healthy and AlCl3-exposed rats before Lactobacillus treatment.

Conclusion
The combined application of Lb. plantarum SF9C and Lb. brevis SF9B was able to influence the intestinal microbiota composition in rats, which was reflected in the increased abundance of Lactobacillus genus, but also in the altered abundances of other bacterial genera, either in the model of healthy or aberrant gut microbiota of rats. The antibacterial activity and capacity to withstand in GIT conditions contributed to the functional aspects of SF9C and SF9B strains that could be incorporated in the probiotic-containing functional foods with a possibility to positively modulate the gut microbiota composition.
circRNA-miRNA-mRNA regulatory network in human lung cancer: an update
Authors: Liang Zhuo-Zheng , Guo Cheng , Zou Man-Man , Meng Ping , Zhang Tian-Tuo 
Published: May 2020

AbstractCircular RNAs, as hopeful diagnosis markers and therapeutic molecules, have been studied, probed and applied into several diseases, such as cardiovascular diseases, systemic lupus erythematosus, leukemia, pulmonary tuberculosis, and cancer especially. Recently, mounting evidence has supported that circRNAs play a key role in the tumorigenesis, progress, invasion and metastasis in lung cancer. Its special structure—3′–5′ covalent loop—allow it to execute several special functions in both normal eukaryotic cells and cancer cells. Our review summaries the latest studies on characteristics and biogenesis of circRNAs, and highlight the regulatory functions about miRNA sponge of lung-cancer-related circRNAs. In addition, the interaction of the circRNA-miRNA-mRNA regulatory network will also be elaborated in detail in this review. Therefore, this review can provide a new idea or strategy for further development and application in clinical setting in terms of early-diagnosis and better treatment.
EZH2 inhibitors-mediated epigenetic reactivation of FOSB inhibits triple-negative breast cancer progress
Authors: Zhang Ruishan , Li Xiang , Liu Zhuangkai , Wang Yuying , Zhang Hao , Xu Hong 
Published: May 2020

Abstract
Background
Triple-negative breast cancer (TNBC) is the most aggressive subtype of breast cancer that lacks expression of estrogen receptor (ER) and progesterone receptor (PR) and the human epidermal growth factor receptor 2 (HER2) gene. Chemotherapy remains the standard of care for TNBC treatment, but considerable patients are very resistant to chemotherapy. Mutations or aberrant upregulation of EZH2 occur frequently, and EZH2 inhibitor (EZH2i) showed some preclinic antitumor effects in TNBC.

Methods
RNA-seq data of 3 TNBC cell lines either treated with 2 μM GSK343, or stably transduced with shEHZ2, compared to untreated controls (GSE112378) were analyzed by Limma R package. The Kaplan–Meier plotter (KM plotter) database was used to assess the relevance of FOSB mRNA expression to relapse-free survival (RFS) in TNBC. Cell number counting and colony formation assays were used to detect the biological effect of FOSB on the growth of TNBC cells in vitro. The effect of FOSB on TNBC tumor growth in vivo was investigated in a mice tumor xenograft model. Luciferase reporter and chromatin immunoprecipitation (Chip) assays were used to determine the regulatory roles of C/EBPβ on FOSB expression.

Results
We found that FOSB, a member of the activator protein-1 complex, was a direct downstream target of EZH2. FOSB was significantly decreased in TNBC samples and associated with better relapse-free survival (RFS). EZH2-mediated histone 3 trimethylated on lysine 27 (H3K27me3), a marker of silent chromatin conformation, at the FOSB promoter inhibited it expression. Depletion of FOSB in TNBC cells promoted cell proliferation in vitro and tumor growth in vitro by inactivating the p53 pathway and conferred resistant to EZH2 inhibitor (EZH2i). Mechanistically, EZH2i promotes the shift from H3K27me3 to H3K27ac at the FOSB promoter, and recruits the transcription factor C/EBPβ to activate FOSB gene transcription.

Conclusion
Together, our results suggest that EZH2-mediated epigenetic inactivation of FOSB promotes TNBC expression and demonstrate that reactivation of FOSB expression by C/EBPβ underlies the anti-TNBC action of EZH2is.
Israel’s response to the COVID-19 pandemic: tailoring measures for vulnerable cultural minority populations
Authors: Waitzberg Ruth , Davidovitch Nadav , Leibner Gideon , Penn Nadav , Brammli-Greenberg Shuli 
Published: May 2020

AbstractEvery country has vulnerable populations that require special attention from policymakers in their response to a pandemic. This is because those populations may have specific characteristics, culture and behaviours that can accelerate the spread of the virus, and they usually have less access to healthcare, particularly in times of crisis. In order to carry out a comprehensive national intervention plan, policy makers should be sensitive to the needs and lifestyles of these groups, while taking into account structural and cultural gaps.In the context of Israel, the two most prominent and well-defined minority groups are the ultra-Orthodox Jewish community and parts of the Arab population. The government was slow to recognize the unique position of these two groups, public pressure eventually led to a response that was tailored to the ultra-Orthodox community and during the month of Ramadan a similar response has been implemented among the Arab community.
Venezuelan equine encephalitis virus: the problem is not over for tropical America
Authors: Guzmán-Terán Camilo , Calderón-Rangel Alfonso , Rodriguez-Morales Alfonso , Mattar Salim 
Published: May 2020

AbstractThe equine encephalitis viruses, Venezuelan (VEEV), East (EEEV) and West (WEEV), belong to the genus alphavirus, family Togaviridae and still represent a threat for human and animal public health in the Americas. In both, these infections are characterized by high viremia, rash, fever, encephalitis and death. VEEV encephalitis is similar, clinically, to other arboviral diseases, such as dengue, Zika or chikungunya. Most of the alphaviruses are transmitted between vertebrates and mosquitoes. They are able to replicate in a wide number of hosts, including mammals, birds, reptiles, amphibian and arthropods. The VEEV has enzootic and epizootic transmission cycles. At the enzootic one, enzootic strains (subtype I, serotypes D–F and serotypes II–VI) are continuously circulating between mosquitoes and wild rodents in tropical forests and mangroves of the Americas. The main reseroivrs are wild rodent species of the subfamilySigmodontinae. However, bats can be also accidental reservoirs of VEEV. In this article, we reviewed the main features, epidemiology, clinical aspects and the current perspectives of the VEEV.
Circular RNA circMET drives immunosuppression and anti-PD1 therapy resistance in hepatocellular carcinoma via the miR-30-5p/snail/DPP4 axis
Authors: Huang Xiao-Yong , Zhang Peng-Fei , Wei Chuan-Yuan , Peng Rui , Lu Jia-Cheng , Gao Chao , Cai Jia-Bing , Yang Xuan , Fan Jia , Ke Ai-Wu , Zhou Jian , Shi Guo-Ming 
Published: May 2020

Abstract
Background
Amplification of chromosome 7q21-7q31 is associated with tumor recurrence and multidrug resistance, and several genes in this region are powerful drivers of hepatocellular carcinoma (HCC). We aimed to investigate the key circular RNAs (circRNAs) in this region that regulate the initiation and development of HCC.

Methods
We used qRT-PCR to assess the expression of 43 putative circRNAs in this chromosomal region in human HCC and matched nontumor tissues. In addition, we used cultured HCC cells to modify circRNA expression and assessed the effects in several cell-based assays as well as gene expression analyses via RNA-seq. Modified cells were implanted into immunocompetent mice to assess the effects on tumor development. We performed additional experiments to determine the mechanism of action of these effects.

Results
circMET (hsa_circ_0082002) was overexpressed in HCC tumors, and circMET expression was associated with survival and recurrence in HCC patients. By modifying the expression of circMET in HCC cells in vitro, we found that circMET overexpression promoted HCC development by inducing an epithelial to mesenchymal transition and enhancing the immunosuppressive tumor microenvironment. Mechanistically, circMET induced this microenvironment through the miR-30-5p/Snail/ dipeptidyl peptidase 4(DPP4)/CXCL10 axis. In addition, the combination of the DPP4 inhibitor sitagliptin and anti-PD1 antibody improved antitumor immunity in immunocompetent mice. Clinically, HCC tissues from diabetic patients receiving sitagliptin showed higher CD8+ T cell infiltration than those from HCC patients with diabetes without sitagliptin treatment.

Conclusions
circMET is an onco-circRNA that induces HCC development and immune tolerance via the Snail/DPP4/CXCL10 axis. Furthermore, sitagliptin may enhance the efficacy of anti-PD1 therapy in a subgroup of patients with HCC.
A systematic review and meta-analysis of serum cholesterol and triglyceride levels in patients with Parkinson’s disease
Authors: Fu Xiaoxue , Wang Yu , He Xiaofeng , Li Hongyu , Liu Hong , Zhang Xiangyang 
Published: May 2020

Abstract
Objectives
Numerous studies have reported that lipid metabolic abnormalities may play an important role in the development of Parkinson’s disease (PD), with mixed results. This meta-analysis aims to systematically assess the relationship between serum cholesterol or triglyceride and the PD risk and to further determine the role of dyslipidemia in potential predictive value.

Methods
This research systematically consulted and screened observational studies to evaluate the association of serum lipids with the risk of PD as of April 01, 2020 based on the inclusion and exclusion criteria. Two researchers screened and extracted the data independently. Then this article summarized the characteristics of all clinical studies and collected the corresponding data to perform pooled and sensitivity analyses. The meta-analysis was performed by using the RevMan 5.3 software after data extraction, quality assessment and analysis of publication bias.

Results
Twenty-one related studies (13 case-control and 8 cohort studies) were selected with a total of 980,180 subjects, including 11,188 PD patients. Meta-analysis showed that higher levels of serum triglyceride (S-TG) [standard mean different (SMD) = − 0.26 (95% confidence interval (CI): − 0.39 to − 0.13, p<0.00001), relative risk (RR) = 0.67 (95% CI: 0.60 to 0.75, p<0.00001)] could be considered as protective factors for the pathogenesis of PD. However, there was no significant association between serum high density lipoprotein cholesterol (S-HDL) and the risk of PD. Meanwhile, serum low density lipoprotein cholesterol (S-LDL) [SMD = -0.26 (95% CI: − 0.43 to − 0.07, p = 0.006), RR = 0.76 (95% CI: 0.59 to 0.97, p = 0.03)] and serum total cholesterol (S-TC) levels [SMD = -0.21 (95% CI: − 0.33 to − 0.10, p = 0.0002), RR = 0.86 (95% CI: 0.77 to 0.97, p = 0.01)] were negatively associated with PD risk.

Conclusions
This systematic review suggests that elevated serum levels of TG, LDL and TC may be protective factors for the pathogenesis of PD. Further longitudinal and well-designed prospective studies with a large sample size are needed to confirm the findings in this meta-analysis.
Proteome-wide identification of arginine methylation in colorectal cancer tissues from patients
Authors: Lim Yongchul , Lee Ju Yeon , Ha Su Jin , Yu Suyeun , Shin Jung Kyong , Kim Hee Cheol 
Published: May 2020

Abstract
Background
Protein arginine methylation reaction is catalyzed by protein arginine methyltransferase (PRMT) and the modification is implicated in various diseases including cancer. Currently, thousands of arginine methylation sites have been identified using high-resolution mass spectrometry-based proteomics technology. However, identification of arginine methylation using clinical samples at proteome level has not been reported yet. The objective of the present study was to identify, monomethyl-arginine (MMA) and asymmetric dimethyl-arginine (ADMA) sites in colorectal cancer (CRC) tissues at proteome level.

Methods
Pooled CRC tissue samples from 10 patients with stage II and III were digested by trypsin and these digests were further processed and lyophilized. Using monomethyl- or asymmetric dimethyl arginine (MMA or ADMA, respectively) motif kits, methylarginine-containing peptides were enriched and subsequently analyzed by high-resolution LC-MS/MS. DLD1 and HCT116 colon cancer cells were treated with type I PRMTs inhibitor (MS023) alone or combined with SN-38, and the effect of the drugs on CRC cell proliferation and apoptosis was measured by water-soluble tetrazolium salt (WST-1) assay and FACS analysis, respectively.

Results
In the present study, 455 MMA sites of 272 proteins and 314 ADMA sites of 155 proteins were identified from CRC tissues acquired from patients. In addition, 216 methylation sites and 75 substrates for PRMTs were newly identified. These results reveal the significant presence of MMA and ADMA sites on nucleic acid binding proteins and protein complexes involved in transcription. To investigate the effect of protein arginine methylation in CRC proliferation and apoptosis, MS023 was treated to two CRC cell lines. After 48 h treatment with various concentrations of MS023, CRC cell proliferation was significantly suppressed, with concomitant apoptosis induction. Furthermore, MS023 treatment significantly enhanced the inhibitory effect of SN-38 on CRC cell proliferation.

Conclusion
This work reports the first comprehensive analysis of arginine methylation with clinical sample and suggests that type I PRMTs are potential therapeutic targets for drug discovery in CRC.
Cost-utility analysis in chronic kidney disease patients undergoing kidney transplant; what pays? A systematic review
Authors: Senanayake Sameera , Graves Nicholas , Healy Helen , Baboolal Keshwar , Kularatna Sanjeewa 
Published: May 2020

AbstractBackgroundHealth systems are under pressure to deliver more effective care without expansion of resources. This is particularly pertinent to diseases like chronic kidney disease (CKD) that are exacting substantial financial burden to many health systems. The aim of this study is to systematically review the Cost Utility Analysis (CUA) evidence generated across interventions for CKD patients undergoing kidney transplant (KT).MethodsA systemic review of CUA on the interventions for CKD patients undergoing KT was carried out using a search of the MEDLINE, CINAHL, EMBASE, PsycINFO and NHS-EED. The CHEERS checklist was used as a set of good practice criteria in determining the reporting quality of the economic evaluation. Quality of the data used to inform model parameters was determined using the modified hierarchies of data sources.ResultsA total of 330 articles identified, 16 met the inclusion criteria. Almost all (n = 15) the studies were from high income countries. Out of the 24 characteristics assessed in the CHEERS checklist, more than 80% of the selected studies reported 14 of the characteristics. Reporting of the CUA were characterized by lack of transparency of model assumptions, narrow economic perspective and incomplete assessment of the effect of uncertainty in the model parameters on the results. The data used for the economic model were satisfactory quality. The authors of 13 studies reported the intervention as cost saving and improving quality of life, whereas three studies were cost increasing and improving quality of life. In addition to the baseline analysis, sensitivity analysis was performed in all the evaluations except one. Transplanting certain high-risk donor kidneys (high risk of HIV and Hepatitis-C infected kidneys, HLA mismatched kidneys, high Kidney Donor Profile Index) and a payment to living donors, were found to be cost-effective.ConclusionsThe quality of economic evaluations reviewed in this paper were assessed to be satisfactory. Implementation of these strategies will significantly impact current systems of KT and require a systematic implementation plan and coordinated efforts from relevant stakeholders.