bluuebunny/crossref_metadata_2025 huggingface dataset:
The Regulation of Homologous Recombination by Helicases
Authors: Huselid Eric , Bunting Samuel F.
Published: May 2020

Homologous recombination is essential for DNA repair, replication and the exchange of genetic material between parental chromosomes during meiosis. The stages of recombination involve complex reorganization of DNA structures, and the successful completion of these steps is dependent on the activities of multiple helicase enzymes. Helicases of many different families coordinate the processing of broken DNA ends, and the subsequent formation and disassembly of the recombination intermediates that are necessary for template-based DNA repair. Loss of recombination-associated helicase activities can therefore lead to genomic instability, cell death and increased risk of tumor formation. The efficiency of recombination is also influenced by the ‘anti-recombinase’ effect of certain helicases, which can direct DNA breaks toward repair by other pathways. Other helicases regulate the crossover versus non-crossover outcomes of repair. The use of recombination is increased when replication forks and the transcription machinery collide, or encounter lesions in the DNA template. Successful completion of recombination in these situations is also regulated by helicases, allowing normal cell growth, and the maintenance of genomic integrity.
Development and Transferability of EST-SSR Markers for Pinus koraiensis from Cold-Stressed Transcriptome through Illumina Sequencing
Authors: Li Xiang , Liu Xiaoting , Wei Jiatong , Li Yan , Tigabu Mulualem , Zhao Xiyang
Published: May 2020

Pinus koraiensis has significant economic and ecological value in Northeast China. However, due to the lack of suitable molecular markers, only a few available microsatellite markers were developed for further population genetics studies. In this study, for the first time we developed expressed sequence tag–simple sequence repeat (EST-SSR) markers from the cold-stressed transcriptome of P. koraiensis using Illumina Sequencing. We identified a total of 7,235 EST-SSRs from 97,376 sequences, and we tested their transferability among seven related Pinus species. The results showed that trinucleotides were the most abundant type of repeat (1287, 18.74%) excluding mononucleotides, followed by dinucleotides (1284, 18.7%) and tetranucleotides (72, 1.05%). The most dominant dinucleotides and trinucleotide repeat motifs were AT/AT (535, 7.79%) and AAT/ATT (103, 1.5%). The observed heterozygosity (Ho) and expected heterozygosity (He) ranged from 0.002 to 0.986 and 0.017 to 0.743, respectively, and the polymorphism information content (PIC) values and number of alleles (Na) varied from 0.029 to 0.794 and 2 to 23, respectively. A total of 8 natural P. koraiensis populations were divided into two main genetic clusters. Furthermore, nine of twenty polymorphic primer pairs were successfully amplified in seven Pinus species, and at least 80% of the successful P. koraiensis EST-SSR primers could be amplified in more than four species (16, 80%). Combined results for the development of EST-SSR markers in P. koraiensis and transferability among related species would contribute to improved studies on the genetic diversity and population structure in P. koraiensis and phylogenetic relationships among Pinus species. They would also provide a significant source for quantitative trait locus analysis.
Cognitive Decline in Alzheimer’s Disease: Limited Clinical Utility for GWAS or Polygenic Risk Scores in a Clinical Trial Setting
Authors: Euesden Jack , Gowrisankar Sivakumar , Qu Angela Xiaoyan , St. Jean Pamela , Hughes Arlene R. , Pulford David J.
Published: May 2020

Introduction: Alzheimer’s disease (AD) is a progressive and irreversible neurological disease. The genetics and molecular mechanisms underpinning differential cognitive decline in AD are not well understood; the genetics of AD risk have been studied far more assiduously. Materials and Methods: Two phase III clinical trials measuring cognitive decline over 48 weeks using Alzheimer’s Disease Assessment Scale-cognitive subscale (ADAS-cog, n = 2060) and Clinical Dementia Rating-Sum of Boxes (CDR-SB, n = 1996) were retrospectively genotyped. A Genome-Wide Association Study (GWAS) was performed to identify and replicate genetic variants associated with cognitive decline. The relationship between polygenic risk score (PRS) and cognitive decline was tested to investigate the predictive power of aggregating many variants of individually small effect. Results: No loci met candidate gene or genome-wide significance. PRS explained a very small percentage of variance in rates of cognitive decline (ADAS-cog: 0.54%). Conclusions: These results suggest that incorporating genetic information in the prediction of cognitive decline in AD currently appears to have limited utility in clinical trials, consistent with small effect sizes estimated elsewhere. If AD progression is more heritable soon after disease onset, genetics may have more clinical utility.
Correction: Habibi I. et al. “Clinical and Genetic Findings of Autosomal Recessive Bestrophinopathy (ARB)” Genes, 2019, 10, 953
Authors: Habibi Imen , Falfoul Yosra , Todorova Margarita G. , Wyrsch Stefan , Vaclavik Veronika , Helfenstein Maria , Turki Ahmed , El Matri Khaled , El Matri Leila , Schorderet Daniel F.
Published: May 2020

The authors wish to make a correction to the published version of their paper [...]
Pitfalls in Single Clone CRISPR-Cas9 Mutagenesis to Fine-Map Regulatory Intervals
Authors: Tian Ruoyu , Pan Yidan , Etheridge Thomas H. A. , Deshmukh Harshavardhan , Gulick Dalia , Gibson Greg , Bao Gang , Lee Ciaran M
Published: May 2020

The majority of genetic variants affecting complex traits map to regulatory regions of genes, and typically lie in credible intervals of 100 or more SNPs. Fine mapping of the causal variant(s) at a locus depends on assays that are able to discriminate the effects of polymorphisms or mutations on gene expression. Here, we evaluated a moderate-throughput CRISPR-Cas9 mutagenesis approach, based on replicated measurement of transcript abundance in single-cell clones, by deleting candidate regulatory SNPs, affecting four genes known to be affected by large-effect expression Quantitative Trait Loci (eQTL) in leukocytes, and using Fluidigm qRT-PCR to monitor gene expression in HL60 pro-myeloid human cells. We concluded that there were multiple constraints that rendered the approach generally infeasible for fine mapping. These included the non-targetability of many regulatory SNPs, clonal variability of single-cell derivatives, and expense. Power calculations based on the measured variance attributable to major sources of experimental error indicated that typical eQTL explaining 10% of the variation in expression of a gene would usually require at least eight biological replicates of each clone. Scanning across credible intervals with this approach is not recommended.
Investigation of Mating Pheromone–Pheromone Receptor Specificity in Lentinula edodes
Authors: Kim Sinil , Ha Byeongsuk , Kim Minseek , Ro Hyeon-Su
Published: May 2020

The B mating-type locus of Lentinula edodes, a representative edible mushroom, is highly complex because of allelic variations in the mating pheromone receptors (RCBs) and the mating pheromones (PHBs) in both the Bα and Bβ subloci. The complexity of the B mating-type locus, five Bα subloci with five alleles of RCB1 and nine PHBs and three Bβ subloci with 3 alleles of RCB2 and five PHBs, has led us to investigate the specificity of the PHB–RCB interaction because the interaction plays a key role in non-self-recognition. In this study, the specificities of PHBs to RCB1-2 and RCB1-4 from the Bα sublocus and RCB2-1 from the Bb sublocus were investigated using recombinant yeast strains generated by replacing STE2, an endogenous yeast mating pheromone receptor, with the L. edodes RCBs. Fourteen synthetic PHBs with C-terminal carboxymethylation but without farnesylation were added to the recombinant yeast cells and the PHB–RCB interaction was monitored by the expression of the FUS1 gene—a downstream gene of the yeast mating signal pathway. RCB1-2 (Bα2) was activated by PHB1 (4.3-fold) and PHB2 (2.1-fold) from the Bα1 sublocus and RCB1-4 (Bα4) was activated by PHB5 (3.0-fold) and PHB6 (2.7-fold) from the Bα2 sublocus and PHB13 (3.0-fold) from the Bα5 sublocus. In particular, PHB3 from Bβ2 and PHB9 from Bβ3 showed strong activation of RCB2-1 of the Bβ1 sublocus by 59-fold. The RCB–PHB interactions were confirmed in the monokaryotic S1–10 strain of L. edodes by showing increased expression of clp1, a downstream gene of the mating signal pathway and the occurrence of clamp connections after the treatment of PHBs. These results indicate that a single PHB can interact with a non-self RCB in a sublocus-specific manner for the activation of the mating pheromone signal pathways in L. edodes.
Genetic Epidemiology in Latin America: Identifying Strong Genetic Proxies for Complex Disease Risk Factors
Authors: Bonilla Carolina , Novaes Baccarini Lara
Published: May 2020

Epidemiology seeks to determine the causal effects of exposures on outcomes related to the health and wellbeing of populations. Observational studies, one of the most commonly used designs in epidemiology, can be biased due to confounding and reverse causation, which makes it difficult to establish causal relationships. In recent times, genetically informed methods, like Mendelian randomization (MR), have been developed in an attempt to overcome these disadvantages. MR relies on the association of genetic variants with outcomes of interest, where the genetic variants are proxies or instruments for modifiable exposures. Because genotypes are sorted independently and at random at the time of conception, they are less prone to confounding and reverse causation. Implementation of MR depends on, among other things, a strong association of the genetic variants with the exposure, which has usually been defined via genome-wide association studies (GWAS). Because GWAS have been most often carried out in European populations, the limited identification of strong instruments in other populations poses a major problem for the application of MR in Latin America. We suggest potential solutions that can be realized with the resources at hand and others that will have to wait for increased funding and access to technology.
Diagnostic Role of 18F-Fluorodeoxyglucose Positron Emission Tomography in Gastric Mesenchymal Tumors
Authors: Iwamuro Masaya , Miyahara Koji , Sakaguchi Chihiro , Takenaka Ryuta , Kobayashi Sayo , Mouri Hirokazu , Tanaka Shigetomi , Toyokawa Tatsuya , Tanaka Shouichi , Nishimura Mamoru , Yamauchi Kenji , Tanaka Takehiro , Okada Hiroyuki
Published: May 2020

There have been no comparative studies investigating the results of 18F-fluorodeoxyglucose (FDG)-positron emission tomography (PET) in patients with gastric mesenchymal tumors, including leiomyomas, leiomyosarcomas, schwannomas, and gastrointestinal stromal tumors (GISTs). We retrospectively reviewed the data of 142 patients with pathologically diagnosed gastric mesenchymal tumors treated at 11 institutions. We analyzed the correlation between the maximum standardized uptake value (SUVmax) evaluated using fluorodeoxyglucose-positron emission tomography (FDG-PET) and the tumor size. The correlation between the SUVmax and mitotic index was also investigated in GISTs. The SUVmax (mean ± standard deviation) was 0.5 ± 0.6 in very low-risk GISTs (n = 42), 2.1 ± 0.7 in low-risk GISTs (n = 26), 4.9 ± 0.8 in intermediate-risk GISTs (n = 22), 12.3 ± 0.8 in high-risk GISTs (n = 20), 1.0 ± 1.0 in leiomyomas (n = 15), 6.9 ± 1.2 in schwannomas (n = 10), and 3.5 in a leiomyosarcoma (n = 1). The SUVmax of GISTs with an undetermined risk classification was 4.2 ± 1.3 (n = 8). Linear associations were observed between the SUVmax and tumor size in GISTs, leiomyomas, and schwannomas. The SUVmax of GISTs with a high mitotic index was significantly higher than that of GISTs with a low mitotic index (9.6 ± 7.6 vs. 2.4 ± 4.2). In conclusion, we observed positive correlations between the SUVmax and tumor size in GISTs, leiomyomas, and schwannomas. The SUVmax also positively correlated with the mitotic index and risk grade in GISTs. Schwannomas showed a higher FDG uptake than GISTs and leiomyomas.
Elevated Levels of Monocyte Chemotactic Protein-1 in the Follicular Fluid Reveals Different Populations among Women with Severe Endometriosis
Authors: Bouet Pierre-Emmanuel , Chao de la Barca Juan-Manuel , Boucret Lisa , Descamps Philippe , Legendre Guillaume , Hachem Hady El , Blanchard Simon , Jeannin Pascale , Reynier Pascal , May-Panloup Pascale
Published: May 2020

To determine if a modification of the cytokine profile occurs in the follicular fluid (FF) of women with endometriosis undergoing in vitro fertilization (IVF), we performed a prospective observational study from January 2018 to February 2019. In total, 87 women undergoing IVF were included: 43 for severe endometriosis-related infertility and 40 controls with other causes of infertility. The cytokine profile of the FF was determined by multiplex fluorescent-bead-based technology allowing the measurement of 59 cytokines. Monocyte Chemoattractant Protein 1 (MCP-1) was the only variable retained in the multivariate analysis. We identified two subgroups of patients in the endometriosis group: MCP-1-low group (n = 23), which had FF MCP-1 levels comparable to the control group, and MCP-1-high (n = 20), which had significantly higher FF levels. Only patients in the MCP-1-high group had a significantly altered cytokine profile in the FF, and had a significantly higher serum estradiol level (p = 0.002) and a significantly lower number of oocytes recovered (p = 0.01) compared to the MCP-1-low and the control group. Our study has shown an alteration of the oocyte microenvironment in women with endometriosis associated with high follicular fluid levels of MCP-1, allowing the identification of a subgroup of endometriosis patients with a potentially worse prognosis.
Prognostic Value of Tumor Size in Resected Stage IIIA-N2 Non-Small-Cell Lung Cancer
Authors: Chen Chih-Yu , Wu Bing-Ru , Chen Chia-Hung , Cheng Wen-Chien , Chen Wei-Chun , Liao Wei-Chih , Chen Chih-Yi , Hsia Te-Chun , Tu Chih-Yen
Published: May 2020

The eighth edition of the American Joint Committee on Cancer (AJCC) staging system for lung cancer was introduced in 2017 and included major revisions, especially of stage III. For the subgroup stage IIIA-N2 non-small-cell lung cancer (NSCLC), surgical resection remains controversial due to heterogeneous disease entity. The aim of this study was to evaluate the clinicopathologic features and prognostic factors of patients with completely resected stage IIIA-N2 NSCLC. We retrospectively evaluated 77 consecutive patients with pathologic stage IIIA-N2 NSCLC (AJCC eighth edition) who underwent surgical resection with curative intent in China Medical University Hospital between 2006 and 2014. Survival analysis was conducted, using the Kaplan–Meier method. Prognostic factors predicting overall survival (OS) and disease-free survival (DFS) were analyzed, using log-rank tests and multivariate Cox proportional hazards models. Of the 77 patients with pathologic stage IIIA-N2 NSCLC examined, 35 (45.5%) were diagnosed before surgery and 42 (54.5%) were diagnosed unexpectedly during surgery. The mean age of patients was 59 years, and the mean length of follow-up was 38.1 months. The overall one-, three-, and five-year OS rates were 91.9%, 61.3%, and 33.5%, respectively. Multivariate analysis showed that tumor size <3 cm (hazards ratio (HR): 0.373, p = 0.003) and video-assisted thoracoscopic surgery (VATS) approach (HR: 0.383, p = 0.014) were significant predictors for improved OS. For patients with surgically treated, pathologic stage IIIA-N2 NSCLC, tumor size <3 cm and the VATS approach seemed to be associated with better prognosis.
Significant Remodeling Affects the Circulating Glycosaminoglycan Profile in Adult Patients with both Severe and Mild Forms of Acute Pancreatitis
Authors: Koźma Ewa M. , Kuźnik-Trocha Kornelia , Winsz-Szczotka Katarzyna , Wisowski Grzegorz , Olczyk Paweł , Komosińska-Vassev Katarzyna , Kasperczyk Mariusz , Olczyk Krystyna
Published: May 2020

Acute pancreatitis (AP) manifests itself either as a mild, self-limiting inflammation or a severe, systemic inflammatory process that is associated with various complications and a high mortality rate. It is unknown whether these two forms of the disease can differ in the profile of circulating glycosaminoglycans, which are molecules with huge biological reactivity due to a high density of negative electric charge. Plasma glycosaminoglycans were characterized/quantified in 23 healthy controls, 32 patients with mild AP, and 15 individuals with severe disease using electrophoresis with enzymatic identification (chondroitin sulfate and heparan sulfate) or an ELISA-based test (hyaluronan). Moreover, the correlations between the glycosaminoglycan levels and clinical parameters were evaluated. Both forms of AP showed similar remodeling of the plasma profile of the sulfated glycosaminoglycans. In contrast, only in the patients with mild AP was the level of circulating hyaluronan significantly decreased as compared to the healthy controls. Both forms of AP are associated with systemic changes in the metabolism of glycosaminoglycans. However, the alterations in hyaluronan metabolism may contribute to the disease evolution. The circulating hyaluronan may have some clinical value to predict the severity of AP and to evaluate the clinical status of patients with severe AP.
Diagnostic Utility and Pathogenic Role of Circulating MicroRNAs in Vasospastic Angina
Authors: Park Chan Soon , Kim Inho , Oh Gyu Chul , Han Jung-Kyu , Yang Han-Mo , Park Kyung Woo , Cho Hyun-Jai , Kang Hyun-Jae , Koo Bon-Kwon , Chung Woo-Young , Oh Seil , Lee Hae-Young
Published: May 2020

We investigated the diagnostic value and pathophysiological role of circulating microRNA (miR) in vasospastic angina (VA). We enrolled patients who underwent coronary angiography for chest pain to explore the miR’s diagnostic utility. In addition, we investigated the role of miRs in regulating endothelial nitric oxide synthase (eNOS) expression in human coronary artery endothelial cells (hCAECs). Among the 121 patients, 46 were diagnosed with VA (VA group), 26 with insignificant coronary lesions (ICL group), and 49 with atherothrombotic angina (AA group). The VA group showed a significantly higher expression of miR-17-5p, miR-92a-3p, and miR-126-3p than the ICL group. In contrast, miR-221-3p and miR-222-3p were upregulated in the AA group compared to the VA group, and all levels of miR-17-5p, miR-92a-3p, miR-126-3p, miR-145-5p, miR-221-3p, and miR-222-3p differed between the AA group and the ICL group. In the hCAECs, transfection with mimics (pre-miR) of miR-17-5p, miR-92a-3p, and miR-126-3p was associated with eNOS suppression. Additionally, transfection with inhibitors (anti-miR) of miR-92a-3p significantly rescued the eNOS suppression induced by lipopolysaccharide. In conclusion, the circulating miRs not only proved to have diagnostic utility, but also contributed to pathogenesis by eNOS regulation.
A Proteomics-Based Analysis Reveals Predictive Biological Patterns in Fabry Disease
Authors: Tebani Abdellah , Mauhin Wladimir , Abily-Donval Lenaig , Lesueur Céline , Berger Marc G. , Nadjar Yann , Berger Juliette , Benveniste Oliver , Lamari Foudil , Laforêt Pascal , Noel Esther , Marret Stéphane , Lidove Olivier , Bekri Soumeya
Published: May 2020

Background: Fabry disease (FD) is an X-linked progressive lysosomal disease (LD) due to glycosphingolipid metabolism impairment. Currently, plasmatic globotriaosylsphingosine (LysoGb3) is used for disease diagnosis and monitoring. However, this biomarker is inconstantly increased in mild forms and in some female patients. Materials and Methods: We applied a targeted proteomic approach to explore disease-related biological patterns that might explain the disease pathophysiology. Forty proteins, involved mainly in inflammatory and angiogenesis processes, were assessed in 69 plasma samples retrieved from the French Fabry cohort (FFABRY) and from 83 healthy subjects. For predictive performance assessment, we also included other LD samples (Gaucher, Pompe and Niemann Pick C). Results: The study yielded four discriminant proteins that include three angiogenesis proteins (fibroblast growth factor 2 (FGF2), vascular endothelial growth factor A (VEGFA), vascular endothelial growth factor C (VEGFC)) and one cytokine interleukin 7 (IL-7). A clear elevation of FGF2 and IL-7 concentrations was observed in FD compared to other LD samples. No correlation was observed between these proteins and globotriaosylsphingosine (LysoGb3). A significant correlation exists between IL-7 and residual enzyme activity in a non-classical phenotype. This highlights the orthogonal biological information yielded by these proteins that might help in stratifying Fabry patients. Conclusion: This work highlights the potential of using proteomics approaches in exploring FD and enhancing FD diagnosis and therapeutic monitoring performances.
Shape and Enhancement Analysis as a Useful Tool for the Presentation of Blood Hemodynamic Properties in the Area of Aortic Dissection
Authors: Polanczyk Andrzej , Piechota-Polańczyk Aleksandra , Stefanczyk Ludomir , Strzelecki Michal
Published: May 2020

The aim of this study was to create a mathematical approach for blood hemodynamic description with the use of brightness analysis. Medical data was collected from three male patients aged from 45 to 65 years with acute type IIIb aortic dissection that started proximal to the left subclavian artery and involved the renal arteries. For the recognition of wall dissection areas Digital Imaging and Communications in Medicine (DICOM) data were applied. The distance from descending aorta to the diaphragm was analyzed. Each time Feret (DF) and Hydraulic (DHy) diameter were calculated. Moreover, an average brightness (BAV) was analyzed. Finally, to describe blood hemodynamic in the area of aortic wall dissection, mathematical function combining difference in brightness value and diameter for each computed tomography (CT) scan was calculated. The results indicated that DF described common duct more accurately compare to DHy. While, DHy described more accurately true and false ducts. Each time when connection of true and false duct appeared, true duct had lower brightness compare to common duct and false duct. Moreover, false duct characterized with higher brightness compare to common duct. In summary, the proposed algorithm mimics changes in brightness value for patients with acute type IIIb aortic dissection.
Prognostic Implications of Combined Imaging and Histologic Criteria in Squamous Cell Carcinoma with Mandibular Invasion
Authors: Lee Chena , Choi Yoon Joo , Jeon Kug Jin , Kim Dong Wook , Nam Woong , Kim Hyung Jun , Cha In-Ho , Han Sang Sun
Published: May 2020

Prognosis prediction of squamous cell carcinoma (SCC) with mandibular invasion is controversial, and a more sophisticated staging system to aid prognosis could be developed with imaging characteristics of bone invasion. Imaging-feature analysis provides practical, stratified results for survival prognosis in oral SCC (OSCC) of the mandible, and imaging advances enable more detailed tumor visualization. We retrospectively evaluated significant bone-invasion features associated with poor outcomes in mandibular OSCC to assess the predictive value of staging criteria that combined imaging features and histologic grade (combined imaging–histology (IH) grade) in 65 patients (39 men, 26 women) with mandibular SCC diagnosed from 2006 to 2016. Clinicopathologic features, including T-stage and histologic grade, and prognosis were retrieved. Tumors were classified into three types by extent of mandibular invasion on pretreatment imaging studies. Moreover, we assessed the involvement of the mandibular canal. We examined the correlation of factors associated with locoregional recurrence and overall mortality. The Harrell Concordance Index (C-index) determined prognostic performance of predictors. Nineteen (29%) patients showed locoregional recurrence and 13 (20%) died. For locoregional recurrence and mortality rates, imaging-detected mandibular canal (MC) involvement is a stronger prognostic factor for recurrence (C-index = 0.61 > 0.58) and survival (C-index = 0.58 > 0.63) than histopathologically confirmed perineural invasion, as was the IH grade, especially IH Grade 3, which was significantly associated with worse locoregional recurrence (p < 0.02). Imaging-based staging showed higher prognostic performance than T-staging (C-index = 0.57 (recurrence), 0.60 (death)), when combined with histologic grading (C-index = 0.69 for both) or used alone (C-index = 0.63 (locoregional recurrence), 0.69 (death)). Overall survival was significantly stratified by Imaging type and IH grade. Therefore, analysis of imaging features provided more specific, practical results for survival prognosis in mandibular OSCC. Imaging advances can potentially provide detailed gross views of tumor masses to facilitate development of prognostic criteria for OSCC.
Three-Dimensional Identification of the Medial Longitudinal Fasciculus in the Human Brain: A Diffusion Tensor Imaging Study
Authors: Yeo Sang Seok , Jang Sung Ho , Kwon Jung Won , Cho In Hee
Published: May 2020

Background: The medial longitudinal fasciculus (MLF) interacts with eye movement control circuits involved in the adjustment of horizontal, vertical, and torsional eye movements. In this study, we attempted to identify and investigate the anatomical characteristics of the MLF in human brain, using probabilistic diffusion tensor imaging (DTI) tractography. Methods: We recruited 31 normal healthy adults and used a 1.5-T scanner for DTI. To reconstruct MLFs, a seed region of interest (ROI) was placed on the interstitial nucleus of Cajal at the midbrain level. A target ROI was located on the MLF of the medulla in the reticular formation of the medulla. Mean values of fractional anisotropy, mean diffusivity, and tract volumes of MLFs were measured. Results: The component of the MLF originated from the midbrain MLF, descended through the posterior side of the medial lemniscus (ML) and terminated on the MLF of medulla on the posterior side of the ML in the medulla midline. DTI parameters of right and left MLFs were not significantly different. Conclusion: The tract of the MLF in healthy brain was identified by probabilistic DTI tractography. We believe this study will provide basic data and aid future comparative research on lesion or age-induced MLF changes.
Long-Term Survival Following Surgical Ablation for Atrial Fibrillation Concomitant to Isolated and Combined Coronary Artery Bypass Surgery—Analysis from the Polish National Registry of Cardiac Surgery Procedures (KROK)
Authors: Kowalewski Mariusz , Jasiński Marek , Staromłyński Jakub , Zembala Marian , Widenka Kazimierz , Zembala Michał Oskar , Bartuś Krzysztof , Hirnle Tomasz , Dziembowska Inga , Knapik Piotr , Deja Marek , Wierzba Waldemar , Tobota Zdzisław , Maruszewski Bohdan J. , Suwalski Piotr
Published: May 2020

The current investigation aimed to evaluate long-term survival in patients undergoing isolated and combined coronary artery bypass grafting (CABG) with concomitant surgical ablation for atrial fibrillation (AF). Procedural data from KROK (Polish National Registry of Cardiac Surgery Procedures) were retrospectively collected. Eleven thousand three hundred sixteen patients with baseline AF (72.4% men, mean age 69.6 ± 7.9) undergoing isolated and combined CABG surgery between 2006–2019 in 37 reference centers across Poland and included in the registry were analyzed. The median follow-up was four years (3.7 IQR 1.3–6.8). Over a 12-year study period, there was a significant survival benefit (Hazard Ratio (HR) 0.83; (95% Confidence Interval (CI): 0.73–0.95); p = 0.005) with concomitant ablation as compared to no concomitant ablation. After rigorous propensity matching (LOGIT model, 432 pairs), concomitant surgical ablation was associated with over 25% improved survival in the overall analysis: HR 0.74; (95% CIs: 0.56–0.98); p = 0.036. The benefit of concomitant ablation was maintained in the subgroups, yet the most benefit was appraised in low-risk patients (EuroSCORE < 2, p = 0.003) with the three-vessel disease (p < 0.001) and without other comorbidities. Ablation was further associated with significantly improved survival in patients undergoing CABG with mitral valve surgery (HR 0.62; (95% CIs: 0.52–0.74); p < 0.001) and in patients in whom complete revascularization was not achieved: HR 0.43; (95% CIs: 0.24–0.79); p = 0.006.
The Role of Autophagy in White Adipose Tissue Function: Implications for Metabolic Health
Authors: Clemente-Postigo Mercedes , Tinahones Alberto , El Bekay Rajaa , Malagón María M. , Tinahones Francisco J.
Published: May 2020

White adipose tissue (WAT) is a highly adaptive endocrine organ that continuously remodels in response to nutritional cues. WAT expands to store excess energy by increasing adipocyte number and/or size. Failure in WAT expansion has serious consequences on metabolic health resulting in altered lipid, glucose, and inflammatory profiles. Besides an impaired adipogenesis, fibrosis and low-grade inflammation also characterize dysfunctional WAT. Nevertheless, the precise mechanisms leading to impaired WAT expansibility are yet unresolved. Autophagy is a conserved and essential process for cellular homeostasis, which constitutively allows the recycling of damaged or long-lived proteins and organelles, but is also highly induced under stress conditions to provide nutrients and remove pathogens. By modulating protein and organelle content, autophagy is also essential for cell remodeling, maintenance, and survival. In this line, autophagy has been involved in many processes affected during WAT maladaptation, including adipogenesis, adipocyte, and macrophage function, inflammatory response, and fibrosis. WAT autophagy dysregulation is related to obesity and diabetes. However, it remains unclear whether WAT autophagy alteration in obese and diabetic patients are the cause or the consequence of WAT malfunction. In this review, current data regarding these issues are discussed, focusing on evidence from human studies.
Use of Large and Diverse Datasets for 1H NMR Serum Metabolic Profiling of Early Lactation Dairy Cows
Authors: Luke Timothy D. W. , Pryce Jennie E. , Elkins Aaron C. , J. Wales William , Rochfort Simone J.
Published: May 2020

Most livestock metabolomic studies involve relatively small, homogenous populations of animals. However, livestock farming systems are non-homogenous, and large and more diverse datasets are required to ensure that biomarkers are robust. The aims of this study were therefore to (1) investigate the feasibility of using a large and diverse dataset for untargeted proton nuclear magnetic resonance (1H NMR) serum metabolomic profiling, and (2) investigate the impact of fixed effects (farm of origin, parity and stage of lactation) on the serum metabolome of early-lactation dairy cows. First, we used multiple linear regression to correct a large spectral dataset (707 cows from 13 farms) for fixed effects prior to multivariate statistical analysis with principal component analysis (PCA). Results showed that farm of origin accounted for up to 57% of overall spectral variation, and nearly 80% of variation for some individual metabolite concentrations. Parity and week of lactation had much smaller effects on both the spectra as a whole and individual metabolites (<3% and <20%, respectively). In order to assess the effect of fixed effects on prediction accuracy and biomarker discovery, we used orthogonal partial least squares (OPLS) regression to quantify the relationship between NMR spectra and concentrations of the current gold standard serum biomarker of energy balance, β-hydroxybutyrate (BHBA). Models constructed using data from multiple farms provided reasonably robust predictions of serum BHBA concentration (0.05 ≤ RMSE ≤ 0.18). Fixed effects influenced the results biomarker discovery; however, these impacts could be controlled using the proposed method of linear regression spectral correction.
Oxidative Stress Modulation by Cameroonian Spice Extracts in HepG2 Cells: Involvement of Nrf2 and Improvement of Glucose Uptake
Authors: Atchan Nwakiban Achille Parfait , Cicolari Stefania , Piazza Stefano , Gelmini Fabrizio , Sangiovanni Enrico , Martinelli Giulia , Bossi Lorenzo , Carpentier-Maguire Eugénie , Deutou Tchamgoue Armelle , Agbor Gabriel A. , Kuiaté Jules-Roger , Beretta Giangiacomo , Dell’Agli Mario , Magni Paolo
Published: May 2020

Oxidative stress plays a relevant role in the progression of chronic conditions, including cardiometabolic diseases. Several Cameroonian plants, including spices, are traditionally used as herbal medicines for the treatment of diseases where oxidative stress contributes to insulin resistance, like type 2 diabetes mellitus. This study evaluated the antioxidant capacity and the effects on oxidative-stress-induced impairment of glucose uptake of 11 Cameroonian spice extracts. H2O2-induced reactive oxygen species (ROS) production by human HepG2 cells was significantly reduced by 8/11 extracts. The most effective extracts, Xylopia parviflora, Echinops giganteus, and Dichrostachys glomerata, showed a concentration-dependent ROS-scavenging activity, which involved Nrf2 translocation into the nucleus. Xylopia parviflora, Tetrapleura tetraptera, Dichrostachys glomerata, Aframomum melegueta, and Aframomum citratum extracts showed the highest antioxidant capacity, according to oxygen radical absorbance capacity (ORAC) (2.52–88 μM Trolox Eq/g of extract), ferric-reducing antioxidant power (FRAP) (40.23–233.84 mg gallic acid Eq/g of extract), and total phenol (8.96–32.96% mg gallic acid Eq/g of extract) assays. In HepG2 cells, glucose uptake was stimulated by 4/11 extracts, similarly to insulin and metformin. H2O2-induced oxidative stress reduced glucose uptake, which was rescued by pretreatment with Xylopia aethiopica, Xylopia parviflora, Scorodophloeus zenkeri, Monodora myristica, and Dichrostachys glomerata extracts. The ROS-scavenging ability of the spice extracts may reside in some secondary metabolites observed by phytochemical profiling (reverse-phase high-performance liquid chromatography coupled to a diode array detector (HPLC-UV-DAD)). Further studies are needed to better clarify their biological activities and potential use to control oxidative stress and promote insulin sensitivity.
Recent Advances and the Potential for Clinical Use of Autofluorescence Detection of Extra-Ophthalmic Tissues
Authors: Wizenty Jonas , Schumann Teresa , Theil Donna , Stockmann Martin , Pratschke Johann , Tacke Frank , Aigner Felix , Wuensch Tilo
Published: May 2020

The autofluorescence (AF) characteristics of endogenous fluorophores allow the label-free assessment and visualization of cells and tissues of the human body. While AF imaging (AFI) is well-established in ophthalmology, its clinical applications are steadily expanding to other disciplines. This review summarizes clinical advances of AF techniques published during the past decade. A systematic search of the MEDLINE database and Cochrane Library databases was performed to identify clinical AF studies in extra-ophthalmic tissues. In total, 1097 articles were identified, of which 113 from internal medicine, surgery, oral medicine, and dermatology were reviewed. While comparable technological standards exist in diabetology and cardiology, in all other disciplines, comparability between studies is limited due to the number of differing AF techniques and non-standardized imaging and data analysis. Clear evidence was found for skin AF as a surrogate for blood glucose homeostasis or cardiovascular risk grading. In thyroid surgery, foremost, less experienced surgeons may benefit from the AF-guided intraoperative separation of parathyroid from thyroid tissue. There is a growing interest in AF techniques in clinical disciplines, and promising advances have been made during the past decade. However, further research and development are mandatory to overcome the existing limitations and to maximize the clinical benefits.
From the Kinetic Theory of Gases to the Kinetics of Rate Processes: On the Verge of the Thermodynamic and Kinetic Limits
Authors: Carvalho-Silva Valter H. , Coutinho Nayara D. , Aquilanti Vincenzo
Published: May 2020

A variety of current experiments and molecular dynamics computations are expanding our understanding of rate processes occurring in extreme environments, especially at low temperatures, where deviations from linearity of Arrhenius plots are revealed. The thermodynamic behavior of molecular systems is determined at a specific temperature within conditions on large volume and number of particles at a given density (the thermodynamic limit): on the other side, kinetic features are intuitively perceived as defined in a range between the extreme temperatures, which limit the existence of each specific phase. In this paper, extending the statistical mechanics approach due to Fowler and collaborators, ensembles and partition functions are defined to evaluate initial state averages and activation energies involved in the kinetics of rate processes. A key step is delayed access to the thermodynamic limit when conditions on a large volume and number of particles are not fulfilled: the involved mathematical analysis requires consideration of the role of the succession for the exponential function due to Euler, precursor to the Poisson and Boltzmann classical distributions, recently discussed. Arguments are presented to demonstrate that a universal feature emerges: Convex Arrhenius plots (super-Arrhenius behavior) as temperature decreases are amply documented in progressively wider contexts, such as viscosity and glass transitions, biological processes, enzymatic catalysis, plasma catalysis, geochemical fluidity, and chemical reactions involving collective phenomena. The treatment expands the classical Tolman’s theorem formulated quantally by Fowler and Guggenheim: the activation energy of processes is related to the averages of microscopic energies. We previously introduced the concept of “transitivity”, a function that compactly accounts for the development of heuristic formulas and suggests the search for universal behavior. The velocity distribution function far from the thermodynamic limit is illustrated; the fraction of molecules with energy in excess of a certain threshold for the description of the kinetics of low-temperature transitions and of non-equilibrium reaction rates is derived. Uniform extension beyond the classical case to include quantum tunneling (leading to the concavity of plots, sub-Arrhenius behavior) and to Fermi and Bose statistics has been considered elsewhere. A companion paper presents a computational code permitting applications to a variety of phenomena and provides further examples.
Synthesis and Catalytic Application of Two Mononuclear Complexes Bearing Diethylenetriamine Derivative Ligand
Authors: Liu Chao , Yang Zhao , Guo Hao , Zhao Yu-Cai
Published: May 2020

Two mononuclear zero-dimensional Ni(II) and Zn(II) complexes bearing diethylenetriamine derivative ligand, namely [NiL(CH3COO)2(H2O)] (1) and [ZnL(CH3COO)2] (2) [L = N, N’-bis(2-hydroxybenzyl)diethylenetriamine], were synthesized under reflux conditions. The molecular composition and structure of the complexes were identified by IR, PXRD, elemental analyses, and single crystal X-ray diffraction. Complex 1 belongs to a monoclinic crystal system with the P21/n space group, and Complex 2 belongs to a monoclinic crystal system with the C2/c space group. The Henry reaction of nitromethane with aromatic aldehydes was explored with Complexes 1 and 2 as the catalyst. Results from the catalytic reaction revealed that the complexes displayed excellent catalytic activities under the optimized conditions and that the substrate scope of aromatic aldehydes could be extended to a certain extent. In addition, the possible catalytic mechanism of the Henry reaction was also deduced.
Evaluation of the Antibacterial Activity and Efflux Pump Reversal of Thymol and Carvacrol against Staphylococcus aureus and Their Toxicity in Drosophila melanogaster
Authors: Sousa Silveira Zildene de , Macêdo Nair Silva , Sampaio dos Santos Joycy Francely , Sampaio de Freitas Thiago , Rodrigues dos Santos Barbosa Cristina , Júnior Dárcio Luiz de Sousa , Muniz Débora Feitosa , Castro de Oliveira Lígia Claudia , Júnior José Pinto Siqueira , Cunha Francisco Assis Bezerra da , Melo Coutinho Henrique Douglas , Balbino Valdir Queiroz , Martins Natália
Published: May 2020

The antibacterial activity and efflux pump reversal of thymol and carvacrol were investigated against the Staphylococcus aureus IS-58 strain in this study, as well as their toxicity against Drosophila melanogaster. The minimum inhibitory concentration (MIC) was determined using the broth microdilution method, while efflux pump inhibition was assessed by reduction of the antibiotic and ethidium bromide (EtBr) MICs. D. melanogaster toxicity was tested using the fumigation method. Both thymol and carvacrol presented antibacterial activities with MICs of 72 and 256 µg/mL, respectively. The association between thymol and tetracycline demonstrated synergism, while the association between carvacrol and tetracycline presented antagonism. The compound and EtBr combinations did not differ from controls. Thymol and carvacrol toxicity against D. melanogaster were evidenced with EC50 values of 17.96 and 16.97 µg/mL, respectively, with 48 h of exposure. In conclusion, the compounds presented promising antibacterial activity against the tested strain, although no efficacy was observed in terms of efflux pump inhibition.
Beyond Oncological Hyperthermia: Physically Drivable Magnetic Nanobubbles as Novel Multipurpose Theranostic Carriers in the Central Nervous System
Authors: Ficiarà Eleonora , Ansari Shoeb Anwar , Argenziano Monica , Cangemi Luigi , Monge Chiara , Cavalli Roberta , D’Agata Federico
Published: May 2020

Magnetic Oxygen-Loaded Nanobubbles (MOLNBs), manufactured by adding Superparamagnetic Iron Oxide Nanoparticles (SPIONs) on the surface of polymeric nanobubbles, are investigated as theranostic carriers for delivering oxygen and chemotherapy to brain tumors. Physicochemical and cyto-toxicological properties and in vitro internalization by human brain microvascular endothelial cells as well as the motion of MOLNBs in a static magnetic field were investigated. MOLNBs are safe oxygen-loaded vectors able to overcome the brain membranes and drivable through the Central Nervous System (CNS) to deliver their cargoes to specific sites of interest. In addition, MOLNBs are monitorable either via Magnetic Resonance Imaging (MRI) or Ultrasound (US) sonography. MOLNBs can find application in targeting brain tumors since they can enhance conventional radiotherapy and deliver chemotherapy being driven by ad hoc tailored magnetic fields under MRI and/or US monitoring.
Facile Synthesis of NH-Free 5-(Hetero)Aryl-Pyrrole-2-Carboxylates by Catalytic C–H Borylation and Suzuki Coupling
Authors: Kanwal Saba , Ann Noor-ul- , Fatima Saman , Emwas Abdul-Hamid , Alazmi Meshari , Gao Xin , Ibrar Maha , Zaib Saleem Rahman Shah , Chotana Ghayoor Abbas
Published: May 2020

A convenient two-step preparation of NH-free 5-aryl-pyrrole-2-carboxylates is described. The synthetic route consists of catalytic borylation of commercially available pyrrole-2-carboxylate ester followed by Suzuki coupling without going through pyrrole N–H protection and deprotection steps. The resulting 5-aryl substituted pyrrole-2-carboxylates were synthesized in good- to excellent yields. This synthetic route can tolerate a variety of functional groups including those with acidic protons on the aryl bromide coupling partner. This methodology is also applicable for cross-coupling with heteroaryl bromides to yield pyrrole-thiophene, pyrrole-pyridine, and 2,3’-bi-pyrrole based bi-heteroaryls.
Photocatalytic Cleavage of β-O-4 Ether Bonds in Lignin over Ni/TiO2
Authors: Chen Changzhou , Liu Peng , Xia Haihong , Zhou Minghao , Zhao Jiaping , Sharma Brajendra K. , Jiang Jianchun
Published: May 2020

It is of great importance to explore the selective hydrogenolysis of β-O-4 linkages, which account for 45–60% of all linkages in native lignin, to produce valued-added chemicals and fuels from biomass employing UV light as catalyst. TiO2 exhibited satisfactory catalytic performances in various photochemical reactions, due to its versatile advantages involving high catalytic activity, low cost and non-toxicity. In this work, 20 wt.% Ni/TiO2 and oxidant PCC (Pyridinium chlorochromate) were employed to promote the cleavage of β-O-4 alcohol to obtain high value chemicals under UV irradiation at room temperature. The Ni/TiO2 photocatalyst can be magnetically recovered and efficiently reused in the following four consecutive recycling tests in the cleavage of β-O-4 ether bond in lignin. Mechanism studies suggested that the oxidation of β-O-4 alcohol to β-O-4 ketone by oxidant PCC first occurred during the reaction, and was followed by the photocatalysis of the obtained β-O-4 ketone to corresponding acetophenone and phenol derivates. Furthermore, the system was tested on a variety of lignin model substrates containing β-O-4 linkage for the generation of fragmentation products in good to excellent results.
Chemistry and Reactivity of Tannins in Vitis spp.: A Review
Authors: Watrelot Aude A. , Norton Erin L.
Published: May 2020

Tannins are a group of polyphenols found in fruits, leaves, trees, etc., well known in the leather industry and in apples, persimmons and grapes, because of their capacity to interact with other polyphenols or other components either from the food product or from saliva. Prior to being able to interact with other compounds, tannins have to be extracted from the food matrix, which depends on their chemistry, as well as the chemical structure of other components, such as cell wall material and proteins. Vitis vinifera grapes are commonly grown around the world and are used in winemaking, providing good quality wines with different levels of tannins responsible for the final wine’s astringency. Many studies have focused on tannins extractability and retention with cell wall material, and the reactivity of tannins with proteins in Vitis vinifera grapes and wine, but there are very few reports for other Vitis species. However, depending on the environmental characteristics of certain regions, Vitis hybrid grapes are grown and used to produce wines more and more. This review focuses on the comparison of the chemistry of tannins, and their reactivity with other macromolecules in Vitis species.
Fermented Wild Ginseng by Rhizopus oligosporus Improved l-Carnitine and Ginsenoside Contents
Authors: Lee Ganghee , Nguyen Thi Thanh Hanh , Lim Tae Yun , Lim Juho , Park Byeongsu , Lee Seonmin , Mok Il-Kyoon , Pal Kunal , Lim Sangyong , Kim Doman
Published: May 2020

We conducted this study to investigate the beneficial effects of Rhizopus oligosporus fermentation of wild ginseng on ginsenosides, l-carnitine contents and its biological activity. The Rhizopus oligosporus fermentation of wild ginseng was carried out at 30 °C for between 1 and 14 days. Fourteen ginsenosides and l-carnitine were analyzed in the fermented wild ginseng by the ultra high pressure liquid chromatography–mass spectrometry (UPLC–MS) system. Our results showed that the total amount of ginsenosides in ginseng increased from 3274 to 5573 mg/kg after 14 days of fermentation. Among the 14 ginsenosides tested, the amounts of 13 ginsenosides (Rg1, Rb2, Rb3, Rc, Rd, Re, Rf, Rg2, Rg3, Rh1, compound K, F1 and F2) increased, whereas ginsenoside Rb1 decreased, during the fermentation. Furthermore, l-carnitine (630 mg/kg) was newly synthesized in fermented ginseng extract after 14 days. In addition, both total phenol contents and DPPH radical scavenging activities showed an increase in the fermented ginseng with respect to non-fermented ginseng. These results show that the fermentation process reduced the cytotoxicity of wild ginseng against RAW264.7 cells. Both wild and fermented wild ginseng showed anti-inflammatory activity via inhibition of nitric oxide synthesis in RAW264.7 murine macrophage cells.