bluuebunny/crossref_metadata_2025 huggingface dataset:
Rutin Modulates MAPK Pathway Differently from Quercetin in Angiotensin II-Induced H9c2 Cardiomyocyte Hypertrophy
Authors: Siti Hawa Nordin , Jalil Juriyati , Asmadi Ahmad Yusof , Kamisah Yusof
Published: May 2021

Rutin is a flavonoid with antioxidant property. It has been shown to exert cardioprotection against cardiomyocyte hypertrophy. However, studies regarding its antihypertrophic property are still lacking, whether it demonstrates similar antihypertrophic effect to its metabolite, quercetin. Hence, this study aimed to investigate the effects of both flavonoids on oxidative stress and mitogen-activated protein kinase (MAPK) pathway in H9c2 cardiomyocytes that were exposed to angiotensin II (Ang II) to induce hypertrophy. Cardiomyocytes were exposed to Ang II (600 nM) with or without quercetin (331 μM) or rutin (50 μM) for 24 h. A group given vehicle served as the control. The concentration of the flavonoids was chosen based on the reported effective concentration to reduce cell hypertrophy or cardiac injury in H9c2 cells. Exposure to Ang II increased cell surface area, intracellular superoxide anion level, NADPH oxidase and inducible nitric oxide synthase activities, and reduced cellular superoxide dismutase activity and nitrite level, which were similarly reversed by both rutin and quercetin. Rutin had no significant effects on phosphorylated proteins of extracellular signal-related kinases (ERK1/2) and p38 but downregulated phosphorylated c-Jun N-terminal kinases (JNK1/2), which were induced by Ang II. Quercetin, on the other hand, had significantly downregulated the phosphorylated proteins of ERK1/2, p38, and JNK1/2. The quercetin inhibitory effect on JNK1/2 was stronger than the rutin. In conclusion, both flavonoids afford similar protective effects against Ang II-induced cardiomyocyte hypertrophy, but they differently modulate MAPK pathway.
Ectopic Overexpression of Histone H3K4 Methyltransferase CsSDG36 from Tea Plant Decreases Hyperosmotic Stress Tolerance in Arabidopsis thaliana
Authors: Chen Qinghua , Guo Linghui , Yuan Yanwen , Hu Shuangling , Guo Fei , Zhao Hua , Yun Zhenyu , Wang Yu , Wang Mingle , Ni Dejiang , Zhao Lin , Wang Pu
Published: May 2021

Histone methylation plays an important regulatory role in the drought response of many plants, but its regulatory mechanism in the drought response of the tea plant remains poorly understood. Here, drought stress was shown to induce lower relative water content and significantly downregulate the methylations of histone H3K4 in the tea plant. Based on our previous analysis of the SET Domain Group (SDG) gene family, the full-length coding sequence (CDS) of CsSDG36 was cloned from the tea cultivar ‘Fuding Dabaicha’. Bioinformatics analysis showed that the open reading frame (ORF) of the CsSDG36 gene was 3138 bp, encoding 1045 amino acids and containing the conserved structural domains of PWWP, PHD, SET and PostSET. The CsSDG36 protein showed a close relationship to AtATX4 of the TRX subfamily, with a molecular weight of 118,249.89 Da, and a theoretical isoelectric point of 8.87, belonging to a hydrophilic protein without a transmembrane domain, probably located on the nucleus. The expression of CsSDG36 was not detected in the wild type, while it was clearly detected in the over-expression lines of Arabidopsis. Compared with the wild type, the over-expression lines exhibited lower hyperosmotic resistance by accelerating plant water loss, increasing reactive oxygen species (ROS) pressure, and increasing leaf stomatal density. RNA-seq analysis suggested that the CsSDG36 overexpression caused the differential expression of genes related to chromatin assembly, microtubule assembly, and leaf stomatal development pathways. qRT-PCR analysis revealed the significant down-regulation of stomatal development-related genes (BASL, SBT1.2(SDD1), EPF2, TCX3, CHAL, TMM, SPCH, ERL1, and EPFL9) in the overexpression lines. This study provides a novel sight on the function of histone methyltransferase CsSDG36 under drought stress.
Temperature-Dependent Structural Variability of Prion Protein Amyloid Fibrils
Authors: Ziaunys Mantas , Sakalauskas Andrius , Mikalauskaite Kamile , Snieckute Ruta , Smirnovas Vytautas
Published: May 2021

Prion protein aggregation into amyloid fibrils is associated with the onset and progression of prion diseases—a group of neurodegenerative amyloidoses. The process of such aggregate formation is still not fully understood, especially regarding their polymorphism, an event where the same type of protein forms multiple, conformationally and morphologically distinct structures. Considering that such structural variations can greatly complicate the search for potential antiamyloid compounds, either by having specific propagation properties or stability, it is important to better understand this aggregation event. We have recently reported the ability of prion protein fibrils to obtain at least two distinct conformations under identical conditions, which raised the question if this occurrence is tied to only certain environmental conditions. In this work, we examined a large sample size of prion protein aggregation reactions under a range of temperatures and analyzed the resulting fibril dye-binding, secondary structure and morphological properties. We show that all temperature conditions lead to the formation of more than one fibril type and that this variability may depend on the state of the initial prion protein molecules.
The Role of Inflammation in Breast and Prostate Cancer Metastasis to Bone
Authors: Göbel Andy , Dell’Endice Stefania , Jaschke Nikolai , Pählig Sophie , Shahid Amna , Hofbauer Lorenz C. , Rachner Tilman D.
Published: May 2021

Tumor metastasis to bone is a common event in multiple forms of malignancy. Inflammation holds essential functions in homeostasis as a defense mechanism against infections and is a strategy to repair injured tissue and to adapt to stress conditions. However, exaggerated and/or persistent (chronic) inflammation may eventually become maladaptive and evoke diseases such as autoimmunity, diabetes, inflammatory tissue damage, fibrosis, and cancer. In fact, inflammation is now considered a hallmark of malignancy with prognostic relevance. Emerging studies have revealed a central involvement of inflammation in several steps of the metastatic cascade of bone-homing tumor cells through supporting their survival, migration, invasion, and growth. The mechanisms by which inflammation favors these steps involve activation of epithelial-to-mesenchymal transition (EMT), chemokine-mediated homing of tumor cells, local activation of osteoclastogenesis, and a positive feedback amplification of the protumorigenic inflammation loop between tumor and resident cells. In this review, we summarize established and evolving concepts of inflammation-driven tumorigenesis, with a special focus on bone metastasis.
Contemporary Transposon Tools: A Review and Guide through Mechanisms and Applications of Sleeping Beauty, piggyBac and Tol2 for Genome Engineering
Authors: Sandoval-Villegas Nicolás , Nurieva Wasifa , Amberger Maximilian , Ivics Zoltán
Published: May 2021

Transposons are mobile genetic elements evolved to execute highly efficient integration of their genes into the genomes of their host cells. These natural DNA transfer vehicles have been harnessed as experimental tools for stably introducing a wide variety of foreign DNA sequences, including selectable marker genes, reporters, shRNA expression cassettes, mutagenic gene trap cassettes, and therapeutic gene constructs into the genomes of target cells in a regulated and highly efficient manner. Given that transposon components are typically supplied as naked nucleic acids (DNA and RNA) or recombinant protein, their use is simple, safe, and economically competitive. Thus, transposons enable several avenues for genome manipulations in vertebrates, including transgenesis for the generation of transgenic cells in tissue culture comprising the generation of pluripotent stem cells, the production of germline-transgenic animals for basic and applied research, forward genetic screens for functional gene annotation in model species and therapy of genetic disorders in humans. This review describes the molecular mechanisms involved in transposition reactions of the three most widely used transposon systems currently available (Sleeping Beauty, piggyBac, and Tol2), and discusses the various parameters and considerations pertinent to their experimental use, highlighting the state-of-the-art in transposon technology in diverse genetic applications.
The Ratio of C-Reactive Protein to Albumin Is an Independent Predictor of Malignant Intraductal Papillary Mucinous Neoplasms of the Pancreas
Authors: Serafini Simone , Friziero Alberto , Sperti Cosimo , Vallese Lorenzo , Grego Andrea , Piangerelli Alfredo , Belluzzi Amanda , Moletta Lucia
Published: May 2021

There is growing evidence to indicate that inflammatory reactions are involved in cancer progression. The aim of this study is to assess the significance of systemic inflammatory biomarkers, such as the neutrophil-to-lymphocyte ratio (NLR), the platelet-to-lymphocyte ratio (PLR), the ratio of C-reactive protein to albumin ratio (CAR), the prognostic nutritional index (PNI) and the modified Glasgow prognostic score (mGps) in the diagnosis and prognosis of malignant intraductal papillary mucinous neoplasms (IPMNs) of the pancreas. Data were obtained from a retrospective analysis of patients who underwent pancreatic resection for IPMNs from January 2005 to December 2015. Univariate and multivariate analyses were performed, considering preoperative inflammatory biomarkers, clinicopathological variables, and imaging features. Eighty-three patients with histologically proven IPMNs of the pancreas were included in the study, 37 cases of low-grade or intermediate dysplasia and 46 cases of high-grade dysplasia (HGD) or invasive carcinoma. Univariate analysis showed that obstructive jaundice (p = 0.02) and a CAR of >0.083 (p = 0.001) were predictors of malignancy. On multivariate analysis, only the CAR was a statistically significant independent predictor of HGD or invasive carcinoma in pancreatic IPMNs, identifying a subgroup of patients with a poor prognosis. Combining the CAR with patients’ imaging findings, clinical features and tumor markers can be useful in the clinical management of IPMNs. Their value should be tested in prospective studies.
Extension of Public Smoking Ban Was Not Associated with Any Immediate Effect on Stroke Occurrence in Finland
Authors: Sipilä Jussi O. T. , Ruuskanen Jori O. , Posti Jussi P. , Rautava Päivi , Kytö Ville
Published: May 2021

We investigated the association between the widening of a nationwide restaurant smoking ban, enacted on 1 June 2007, and stroke admissions. All acute stroke admissions between 1 May 2005 and 30 June 2009 were retrieved from a mandatory registry covering mainland Finland. Patients aged ≥18 years were included. One annual admission per patient was included. Negative binomial regression accounting for the at-risk population was applied. We found no difference in stroke occurrence before and after the smoking ban within 7 days (p = 0.217), 30 days (p = 0.176), or the whole study period (p = 0.998). Results were comparable for all stroke subtypes (ischemic stroke, intracerebral hemorrhage, and subarachnoid hemorrhage). There was no sign of decreased occurrence in June 2007 compared to June in 2005–2006, and all subtypes of stroke occurred at least as frequently in both May and June of 2008 as in May and June of 2007. In conclusion, the nationwide restaurant smoking ban Finland enacted in June 2007 was not associated with any immediate reduction in stroke occurrence.
Identification of a Novel Biosynthetic Gene Cluster in Aspergillus niger Using Comparative Genomics
Authors: Evdokias Gregory , Semper Cameron , Mora-Ochomogo Montserrat , Di Falco Marcos , Nguyen Thi Truc Minh , Savchenko Alexei , Tsang Adrian , Benoit-Gelber Isabelle
Published: May 2021

Previously, DNA microarrays analysis showed that, in co-culture with Bacillus subtilis, a biosynthetic gene cluster anchored with a nonribosomal peptides synthetase of Aspergillus niger is downregulated. Based on phylogenetic and synteny analyses, we show here that this gene cluster, NRRL3_00036-NRRL3_00042, comprises genes predicted to encode a nonribosomal peptides synthetase, a FAD-binding domain-containing protein, an uncharacterized protein, a transporter, a cytochrome P450 protein, a NAD(P)-binding domain-containing protein and a transcription factor. We overexpressed the in-cluster transcription factor gene NRRL3_00042. The overexpression strain, NRRL3_00042OE, displays reduced growth rate and production of a yellow pigment, which by mass spectrometric analysis corresponds to two compounds with masses of 409.1384 and 425.1331. We deleted the gene encoding the NRRL3_00036 nonribosomal peptides synthetase in the NRRL3_00042OE strain. The resulting strain reverted to the wild-type phenotype. These results suggest that the biosynthetic gene cluster anchored by the NRRL3_00036 nonribosomal peptides synthetase gene is regulated by the in-cluster transcriptional regulator gene NRRL3_00042, and that it is involved in the production of two previously uncharacterized compounds.
Personalized Medicine for Neuroblastoma: Moving from Static Genotypes to Dynamic Simulations of Drug Response
Authors: Han Jeremy , Hastings Jordan , Phimmachanh Monica , Fey Dirk , Kolch Walter , Croucher David
Published: May 2021

High-risk neuroblastoma is an aggressive childhood cancer that is characterized by high rates of chemoresistance and frequent metastatic relapse. A number of studies have characterized the genetic and epigenetic landscape of neuroblastoma, but due to a generally low mutational burden and paucity of actionable mutations, there are few options for applying a comprehensive personalized medicine approach through the use of targeted therapies. Therefore, the use of multi-agent chemotherapy remains the current standard of care for neuroblastoma, which also conceptually limits the opportunities for developing an effective and widely applicable personalized medicine approach for this disease. However, in this review we outline potential approaches for tailoring the use of chemotherapy agents to the specific molecular characteristics of individual tumours by performing patient-specific simulations of drug-induced apoptotic signalling. By incorporating multiple layers of information about tumour-specific aberrations, including expression as well as mutation data, these models have the potential to rationalize the selection of chemotherapeutics contained within multi-agent treatment regimens and ensure the optimum response is achieved for each individual patient.
Radiomics Analysis of 3D Dose Distributions to Predict Toxicity of Radiotherapy for Cervical Cancer
Authors: Lucia François , Bourbonne Vincent , Visvikis Dimitris , Miranda Omar , Gujral Dorothy M. , Gouders Dominique , Dissaux Gurvan , Pradier Olivier , Tixier Florent , Jaouen Vincent , Bert Julien , Hatt Mathieu , Schick Ulrike
Published: May 2021

Standard treatment for locally advanced cervical cancer (LACC) is chemoradiotherapy followed by brachytherapy. Despite radiation therapy advances, the toxicity rate remains significant. In this study, we compared the prediction of toxicity events after radiotherapy for locally advanced cervical cancer (LACC), based on either dose-volume histogram (DVH) parameters or the use of a radiomics approach applied to dose maps at the voxel level. Toxicity scores using the Common Terminology Criteria for Adverse Events (CTCAE v4), spatial dose distributions, and usual clinical predictors for the toxicity of 102 patients treated with chemoradiotherapy followed by brachytherapy for LACC were used in this study. In addition to usual DVH parameters, 91 radiomic features were extracted from rectum, bladder and vaginal 3D dose distributions, after discretization into a fixed bin width of 1 Gy. They were evaluated for predictive modelling of rectal, genitourinary (GU) and vaginal toxicities (grade ≥ 2). Logistic Normal Tissue Complication Probability (NTCP) models were derived using clinical parameters only or combinations of clinical, DVH and radiomics. For rectal acute/late toxicities, the area under the curve (AUC) using clinical parameters was 0.53/0.65, which increased to 0.66/0.63, and 0.76/0.87, with the addition of DVH or radiomics parameters, respectively. For GU acute/late toxicities, the AUC increased from 0.55/0.56 (clinical only) to 0.84/0.90 (+DVH) and 0.83/0.96 (clinical + DVH + radiomics). For vaginal acute/late toxicities, the AUC increased from 0.51/0.57 (clinical only) to 0.58/0.72 (+DVH) and 0.82/0.89 (clinical + DVH + radiomics). The predictive performance of NTCP models based on radiomics features was higher than the commonly used clinical and DVH parameters. Dosimetric radiomics analysis is a promising tool for NTCP modelling in radiotherapy.
Land Administration Maintenance: A Review of the Persistent Problem and Emerging Fit-for-Purpose Solutions
Authors: Bennett Rohan Mark , Unger Eva-Maria , Lemmen Christiaan , Dijkstra Paula
Published: May 2021

A contemporary review of land administration, from the perspective of systems maintenance, is provided. A special emphasis is placed on emerging fit-for-purpose land administration solutions. The research synthesis uses reputable sources from the contemporary era. Results show the challenges of maintaining land administration systems and the data held are long recognized. The 1970s–1980s gave the issue impetus as data and processes moved from paper-based and manual to digital and automated. The 1990s recognized concerns on maintenance, albeit as a secondary issue: system establishment was the primary concern. The 2000s placed more emphasis on more holistic sociotechnical systems but, again maintenance was supplementary. The fit-for-purpose era deliveres a vast range of new social and technological innovations; however, scaled and sustainable implementations still struggle with system maintenance. From the findings, a consolidated model for analyzing maintenance problems and solutions at jurisdictional level is developed. Maintenance of a land administration system can be understood by identifying the level of change, method for change, components to change, and options for what to change to. The United Nations-endorsed Framework for Effective Land Administration is then used to identify specific maintenance challenges and available solutions. It is suggested that due to the scope and size of what can be considered maintenance issues, there exists no single solution—instead the country should identify its persistant maintenance problems, and the most appropriate solution set from the suite of available options. Emerging solutions and challenges include ensuring interlinkage to maintenance of spatial planning, land valuation, and marine administration; exploiting survey data ‘back capture’ initiatives; supporting grassroots IT; and giving serious attention to cybersecurity concerns.
Geomorphological Hazard in Active Tectonics Area: Study Cases from Sibillini Mountains Thrust System (Central Apennines)
Authors: Aringoli Domenico , Farabollini Piero , Pambianchi Gilberto , Materazzi Marco , Bufalini Margherita , Fuffa Emy , Gentilucci Matteo , Scalella Gianni
Published: May 2021

In many areas of the Umbria-Marche Apennines, evident traces of huge landslides have been recognized; these probably occurred in the Upper Pleistocene and are conditioned by the tectonic-structural setting of the involved Meso-Cenozoic formations, in a sector of the Sibillini Mountains (central Italy). The present work aimed to focus on a geomorphological hazard in the tectonic-structural setting of a complex area that is the basis of several gravitational occurrences in different types and mechanisms, but nonetheless with very considerable extension and total destabilized volume. An aerophoto-geological analysis and geomorphological survey allowed verification of how the main predisposing factor of these phenomena is connected with the presence in depth of an important tectonic-structural element: the plane of the Sibillini Mountains thrust, which brings the pre-evaporitic member of the Laga Formation in contact with the Cretaceous-Eocene limestone lithotypes (from the Maiolica to the Scaglia Rosata Formations) of the Umbria-Marche sedimentary sequence. Another important element for the mass movements activation is the presence of an important and vast water table and related aquifer, confined prevalently by the different structural elements and in particular by the thrust plane, which has acted and has continued to act, weakening the rocky masses and the overlaying terrains.
Airway Epithelial Nucleotide Release Contributes to Mucociliary Clearance
Authors: van Heusden Catharina , Grubb Barbara , Button Brian , Lazarowski Eduardo
Published: May 2021

Mucociliary clearance (MCC) is a dominant component of pulmonary host defense. In health, the periciliary layer (PCL) is optimally hydrated, thus acting as an efficient lubricant layer over which the mucus layer moves by ciliary force. Airway surface dehydration and production of hyperconcentrated mucus is a common feature of chronic obstructive lung diseases such as cystic fibrosis (CF) and chronic bronchitis (CB). Mucus hydration is driven by electrolyte transport activities, which in turn are regulated by airway epithelial purinergic receptors. The activity of these receptors is controlled by the extracellular concentrations of ATP and its metabolite adenosine. Vesicular and conducted pathways contribute to ATP release from airway epithelial cells. In this study, we review the evidence leading to the identification of major components of these pathways: (a) the vesicular nucleotide transporter VNUT (the product of the SLC17A9 gene), the ATP transporter mediating ATP storage in (and release from) mucin granules and secretory vesicles; and (b) the ATP conduit pannexin 1 expressed in non-mucous airway epithelial cells. We further illustrate that ablation of pannexin 1 reduces, at least in part, airway surface liquid (ASL) volume production, ciliary beating, and MCC rates.
A New Kernel Estimator of Copulas Based on Beta Quantile Transformations
Authors: Bolancé Catalina , Acuña Carlos Alberto
Published: May 2021

A copula is a multivariate cumulative distribution function with marginal distributions Uniform(0,1). For this reason, a classical kernel estimator does not work and this estimator needs to be corrected at boundaries, which increases the difficulty of the estimation and, in practice, the bias boundary correction might not provide the desired improvement. A quantile transformation of marginals is a way to improve the classical kernel approach. This paper shows a Beta quantile transformation to be optimal and analyses a kernel estimator based on this transformation. Furthermore, the basic properties that allow the new estimator to be used for inference on extreme value copulas are tested. The results of a simulation study show how the new nonparametric estimator improves alternative kernel estimators of copulas. We illustrate our proposal with a financial risk data analysis.
Diet Supplementation with Fish-Derived Extracts Suppresses Diabetes and Modulates Intestinal Microbiome in a Murine Model of Diet-Induced Obesity
Authors: Axarlis Konstantinos , Daskalaki Maria G. , Michailidou Sofia , Androulaki Nikolais , Tsoureki Antiopi , Mouchtaropoulou Evangelia , Kolliniati Ourania , Lapi Ioanna , Dermitzaki Eirini , Venihaki Maria , Kousoulaki Katerina , Argiriou Anagnostis , Marsni Zouhir El , Tsatsanis Christos
Published: May 2021

Metabolic syndrome-related diseases affect millions of people worldwide. It is well established that changes in nutritional habits and lifestyle can improve or prevent metabolic-related pathologies such as type-2 diabetes and obesity. Previous reports have shown that nutritional supplements have the capacity to limit glucose intolerance and suppress diabetes development. In this study, we investigated the effect of dietary supplementation with fish-derived extracts on obesity and type 2 diabetes and their impact on gut microbial composition. We showed that nutritional supplements containing Fish Complex (FC), Fish Complex combined with Cod Powder (FC + CP), or Cod Powder combined with Collagen (CP + C) improved glucose intolerance, independent of abdominal fat accumulation, in a mouse model of diet-induced obesity and type 2 diabetes. In addition, collagen-containing supplements distinctly modulate the gut microbiome in high-fat induced obesity in mice. Our results suggest that fish-derived supplements suppress diet-induced type 2 diabetes, which may be partly mediated through changes in the gut microbiome. Thus, fish-derived supplements and particularly the ones containing fish collagen have potential beneficial properties as dietary supplements in managing type 2 diabetes and metabolic syndrome via modulation of the gut microbiome.
Is the Risk to Develop Osteoradionecrosis of the Jaws Following IMRT for Head and Neck Cancer Related to Co-Factors?
Authors: Rosenfeld Eli , Eid Bassel , Masri Daya , Popovtzer Aron , Mizrachi Aviram , Chaushu Gavriel
Published: May 2021

Background and Objectives: Determine the contribution of coexisting factors to the risk to develop Osteoradionecrosis (ORN) of the jaws among patients who have received radiotherapy by intensity modulated radiation therapy (IMRT) for head and neck cancer (HNC) between 2013 and 2016, in a single medical center. Materials and Methods: The records of all patients treated with IMRT for HNC between 2013 and 2016 in The Davidoff Center for the treatment and Research of Cancer in Rabin Medical Center—Beilinson hospital, Petah-Tikva, Israel were screened. Patients who have received a minimum mean dose of 40 Gy to the oral cavity entered the research and their medical records were retrospectively reviewed. Collected background data included: age, gender, smoking, diabetes mellitus (DM), ASA score, mean and maximal radiation doses (Gy), and diseases characteristics including histological diagnosis, primary tumor site, and disease stage. Results: A total of 1232 patients were surveyed. Out of all screened patients, 93 received a minimum mean dose of 40 Gy to the oral cavity. Out of the 93 patients, 7 (7.52%) developed ORN (ORN+) and 86 did not develop ORN (ORN−). Tumor type in all seven patients in the ORN+ group was Squamous Cell Carcinoma (SCC). In three out of those seven patients (42.9%), the tumor was located in the mandible. Conclusions: within the limits of the relatively small cohort in the current study, we suggest that the development of ORN due to Radiation therapy (RT) with IMRT is related significantly only to the location of a tumor in the mandible. Other co-factors do not significantly increase the risk to develop ORN when RT is delivered via IMRT.
Obstetric and Perinatal Outcomes after Very Early Preterm Premature Rupture of Membranes (PPROM)-A Retrospective Analysis over the Period 2000–2020
Authors: González-Mesa Ernesto , Blasco-Alonso Marta , Benítez María José , Gómez-Muñoz Cristina , Sabonet-Morente Lorena , Gómez-Castellanos Manuel , Ulloa Osmayda , González-Cazorla Ernesto , Puertas-Prieto Alberto , Mozas-Moreno Juan , Jiménez-López Jesús , Lubián-López Daniel
Published: May 2021

Background and Objectives: Pre-term premature rupture of membranes (PPROM) responds for one third of preterm births, and it is associated with other complications that increase the risk of maternal or fetal poor outcome. To reduce uncertainty and provide accurate information to patients, the analysis of the large series is of great importance. In order to learn about the evolution over the time of the obstetric and perinatal outcomes in cases of PPROM at, or before, 28 weeks (very early PPROM) managed with an expectant/conservative protocol, we have designed the present study. Materials and Methods: We retrospectively studied all cases of very early PPROM attended in Malaga University Regional Hospital from 2000 to 2020. Results: Among 119,888 deliveries assisted, 592 cases of PPROM occurred in pregnancies at or before 28 weeks (0.49% of all deliveries, 3.9% of all preterm births and 12.9% of all cases of PPROM). The mean duration of the latency period between PPROM and delivery was 13.5 days (range 0 to 88 days), enlarging over the years. The mean gestational age at delivery was 27 weeks (SD 2.9; range 17–34). The proportion of cesarean deliveries was 52.5%. The overall perinatal mortality rate was 26.5%, decreasing over the period with a significant correlation Pearson’s coefficient −0.128 (p < 0.05). Conclusions: In the period 2000–2020, there was an improvement in the outcomes of very early PPROM cases and perinatal mortality showed a clear trend to decrease.
Effective Distance between Aortic Valve and Conduction System Is an Independent Predictor of Persistent Left Bundle Branch Block during Transcatheter Aortic Valve Implantation
Authors: Poels Thomas T. , Stassen Robert , Kats Suzanne , Veenstra Leo , van Ommen Vincent , Kietselaer Bastiaan , Houthuizen Patrick , Maessen Jos G. , Prinzen Frits W.
Published: May 2021

Background and objectives: Persistent left bundle branch block (P-LBBB) has been associated with poor clinical outcomes of transcatheter aortic valve implantation (TAVI) procedures. We hypothesized that the distance from the aortic valve to the proximal conduction system, expressed as the effective distance between the aortic valve and conduction system (EDACS), can predict the occurrence of P-LBBB in patients undergoing a TAVI procedure. Materials and methods: In a retrospective study, data from 269 patients were analyzed. EDACS was determined using two longitudinal CT sections. Results: Sixty-four of the patients developed P-LBBB. EDACS ranged between −3 and +18 mm. EDACS was significantly smaller in P-LBBB than in non-P-LBBB patients (4.6 (2.2–7.1) vs. 8.0 (5.8–10.2) mm, median values (interquartile range); p < 0.05). Receiver operating characteristic analysis showed an area under the curve of 0.78 for predicting P-LBBB based on EDACS. In patients with EDACS of ≤3 mm and >10 mm, the chance of developing P-LBBB was ≥50% and <10%, respectively. Conclusions: A small EDACS increases the risk for the development of P-LBBB during TAVI by a factor of >25. As EDACS can be measured pre-procedurally, it may be a valuable additional factor to weigh the risks of transcatheter and surgical aortic valve replacement.
What the Wild Things Do: Mechanisms of Plant Host Manipulation by Bacterial Type III-Secreted Effector Proteins
Authors: Schreiber Karl J. , Chau-Ly Ilea J. , Lewis Jennifer D.
Published: May 2021

Phytopathogenic bacteria possess an arsenal of effector proteins that enable them to subvert host recognition and manipulate the host to promote pathogen fitness. The type III secretion system (T3SS) delivers type III-secreted effector proteins (T3SEs) from bacterial pathogens such as Pseudomonas syringae, Ralstonia solanacearum, and various Xanthomonas species. These T3SEs interact with and modify a range of intracellular host targets to alter their activity and thereby attenuate host immune signaling. Pathogens have evolved T3SEs with diverse biochemical activities, which can be difficult to predict in the absence of structural data. Interestingly, several T3SEs are activated following injection into the host cell. Here, we review T3SEs with documented enzymatic activities, as well as T3SEs that facilitate virulence-promoting processes either indirectly or through non-enzymatic mechanisms. We discuss the mechanisms by which T3SEs are activated in the cell, as well as how T3SEs modify host targets to promote virulence or trigger immunity. These mechanisms may suggest common enzymatic activities and convergent targets that could be manipulated to protect crop plants from infection.
Evaluation of Antimicrobial, Antioxidant, and Cytotoxic Activity of Phenolic Preparations of Diverse Composition, Obtained from Elaeagnus rhamnoides (L.) A. Nelson Leaf and Twig Extracts
Authors: Stochmal Anna , Skalski Bartosz , Pietukhov Rostyslav , Sadowska Beata , Rywaniak Joanna , Wójcik-Bojek Urszula , Grabarczyk Łukasz , Żuchowski Jerzy , Olas Beata
Published: May 2021

Although the major components of various organs of sea buckthorn have been identified (particularly phenolic compounds), biological properties of many of these phytochemicals still remain poorly characterized. In this study, we focused on the chemical composition and biological activity of preparations that were obtained from sea buckthorn twigs and leaves. The objective was to investigate cytotoxicity of these preparations against human fibroblast line HFF-1, using MTT reduction assay, their anti- or pro-oxidant activities against the effects of a biological oxidant -H2O2/Fe—on human plasma lipids and proteins in vitro (using TBARS and carbonyl groups as the markers of oxidative stress). Antimicrobial activity of the tested preparations against Gram-positive (Staphylococcus aureus, S. epidermidis, Enterococcus faecalis) and Gram-negative bacteria (Escherichia coli, Pseudomonas aeruginosa), as well as against fungi (Candida albicans, C. glabrata) by the EUCAST-approved broth microdilution method, followed by growth on solid media, were also assessed. Our analysis showed significant differences in chemical composition and biological properties of the tested preparations (A–F). All tested preparations from sea buckthorn twigs (D–F) and one preparation from sea buckthorn leaves (preparation C) may be a new source of phenolic antioxidants for pharmacological and cosmetic applications.
The Effects of Statins on Neurotransmission and Their Neuroprotective Role in Neurological and Psychiatric Disorders
Authors: Kosowski Michał , Smolarczyk-Kosowska Joanna , Hachuła Marcin , Maligłówka Mateusz , Basiak Marcin , Machnik Grzegorz , Pudlo Robert , Okopień Bogusław
Published: May 2021

Statins are among the most widely used drug classes in the world. Apart from their basic mechanism of action, which is lowering cholesterol levels, many pleiotropic effects have been described so far, such as anti-inflammatory and antiatherosclerotic effects. A growing number of scientific reports have proven that these drugs have a beneficial effect on the functioning of the nervous system. The first reports proving that lipid-lowering therapy can influence the development of neurological and psychiatric diseases appeared in the 1990s. Despite numerous studies about the mechanisms by which statins may affect the functioning of the central nervous system (CNS), there are still no clear data explaining this effect. Most studies have focused on the metabolic effects of this group of drugs, however authors have also described the pleiotropic effects of statins, pointing to their probable impact on the neurotransmitter system and neuroprotective effects. The aim of this paper was to review the literature describing the impacts of statins on dopamine, serotonin, acetylcholine, and glutamate neurotransmission, as well as their neuroprotective role. This paper focuses on the mechanisms by which statins affect neurotransmission, as well as on their impacts on neurological and psychiatric diseases such as Parkinson’s disease (PD), Alzheimer’s disease (AD), vascular dementia (VD), stroke, and depression. The pleiotropic effects of statin usage could potentially open floodgates for research in these treatment domains, catching the attention of researchers and clinicians across the globe.
The Hydrolysis of Phosphinates and Phosphonates: A Review
Authors: Harsági Nikoletta , Keglevich György
Published: May 2021

Phosphinic and phosphonic acids are useful intermediates and biologically active compounds which may be prepared from their esters, phosphinates and phosphonates, respectively, by hydrolysis or dealkylation. The hydrolysis may take place both under acidic and basic conditions, but the C-O bond may also be cleaved by trimethylsilyl halides. The hydrolysis of P-esters is a challenging task because, in most cases, the optimized reaction conditions have not yet been explored. Despite the importance of the hydrolysis of P-esters, this field has not yet been fully surveyed. In order to fill this gap, examples of acidic and alkaline hydrolysis, as well as the dealkylation of phosphinates and phosphonates, are summarized in this review.
Polarization Dependent Photoinduced Supramolecular Chirality in High-Performance Azo Materials
Authors: Bagatur Sekvan , Schlesag Marcel , Fuhrmann-Lieker Thomas
Published: May 2021

Here, we will show photo-induced supramolecular chirality in thin films of achiral amorphous polymers with azo groups in their side-chain. A matter of particular interest is the effect of various film thicknesses on azimuthal rotation and ellipticity of incident/transmitted polarized light. Furthermore, we investigated the temporal stability of inscribed chirality. By polarimetric measurements, we found out that the azimuthal rotation gets higher with layer thickness. In this scope, we were able to measure a very high azimuthal rotation of Δψ/d=112.5∘/μm. The inscribed chirality was stable for several days. Furthermore, we investigated the time-resolved behavior of incident and transmitted polarization ellipticities for various thicknesses. The time dependency may be explained by a two-step process: (1) fast trans-cis-isomerization resulting in photo-orientation and (2) slow photo-induced mass flow.
Phase Transitions and Structural Changes in DPPC Liposomes Induced by a 1-Carba-Alpha-Tocopherol Analogue
Authors: Neunert Grażyna , Tomaszewska-Gras Jolanta , Baj Aneta , Gauza-Włodarczyk Marlena , Witkowski Stanislaw , Polewski Krzysztof
Published: May 2021

Steady-state emission spectroscopy of 1-anilino-8- naphthalene sulfonate (ANS) and 1,6-diphenyl-1,3,5-hexatriene (DPH), fluorescence anisotropy, and DSC methods were used to characterize the interactions of the newly synthesized 1-carba-alpha-tocopherol (CT) with a 1,2-dipalmitoyl-sn-glycero-3-phosphocholine (DPPC) membrane. The DSC results showed significant perturbations in the DPPC structure for CT concentrations as low as 2 mol%. The main phase transition peak was broadened and shifted to lower temperatures in a concentration-dependent manner, and pretransition was abolished. Increasing CT concentrations induced the formation of new phases in the DPPC structure, leading to melting at lower temperatures and, finally, disruption of the ordered DPPC structure. Hydration and structural changes of the DPPC liposomes using ANS and DPH fluorescent probes, which are selectively located at different places in the bilayer, were studied. With the increased concentration of CT molecules in the DPPC liposomes, structural changes with the simultaneous formation of different phases of such mixture were observed. Temperature studies of such mixtures revealed a decrease in the temperature of the main phase transition and fluidization at decreasing temperatures related to increasing hydration in the bilayer. Contour plots obtained from concentration–temperature data with fluorescent probes allowed for identification of different phases, such as gel, ordered liquid, disordered liquid, and liquid crystalline phases. The CT molecule with a modified chromanol ring embedded in the bilayer led to H-bonding interactions, expelling water molecules from the interphase, thus introducing disorder and structural changes to the highly ordered gel phase.
Ca2+ Regulates ERp57-Calnexin Complex Formation
Authors: Tanikawa Yuya , Kanemura Shingo , Ito Dai , Lin Yuxi , Matsusaki Motonori , Kuroki Kimiko , Yamaguchi Hiroshi , Maenaka Katsumi , Lee Young-Ho , Inaba Kenji , Okumura Masaki
Published: May 2021

ERp57, a member of the protein disulfide isomerase family, is a ubiquitous disulfide catalyst that functions in the oxidative folding of various clients in the mammalian endoplasmic reticulum (ER). In concert with ER lectin-like chaperones calnexin and calreticulin (CNX/CRT), ERp57 functions in virtually all folding stages from co-translation to post-translation, and thus plays a critical role in maintaining protein homeostasis, with direct implication for pathology. Here, we present mechanisms by which Ca2+ regulates the formation of the ERp57-calnexin complex. Biochemical and isothermal titration calorimetry analyses revealed that ERp57 strongly interacts with CNX via a non-covalent bond in the absence of Ca2+. The ERp57-CNX complex not only promoted the oxidative folding of human leukocyte antigen heavy chains, but also inhibited client aggregation. These results suggest that this complex performs both enzymatic and chaperoning functions under abnormal physiological conditions, such as Ca2+ depletion, to effectively guide proper oxidative protein folding. The findings shed light on the molecular mechanisms underpinning crosstalk between the chaperone network and Ca2+.
A Critical Review of the Deviance Detection Theory of Mismatch Negativity
Authors: O’Reilly Jamie A. , O’Reilly Amonrat
Published: May 2021

Mismatch negativity (MMN) is a component of the difference waveform derived from passive auditory oddball stimulation. Since its inception in 1978, this has become one of the most popular event-related potential techniques, with over two-thousand published studies using this method. This is a testament to the ingenuity and commitment of generations of researchers engaging in basic, clinical and animal research. Despite this intensive effort, high-level descriptions of the mechanisms theorized to underpin mismatch negativity have scarcely changed over the past four decades. The prevailing deviance detection theory posits that MMN reflects inattentive detection of difference between repetitive standard and infrequent deviant stimuli due to a mismatch between the unexpected deviant and a memory representation of the standard. Evidence for these mechanisms is inconclusive, and a plausible alternative sensory processing theory considers fundamental principles of sensory neurophysiology to be the primary source of differences between standard and deviant responses evoked during passive oddball stimulation. By frequently being restated without appropriate methods to exclude alternatives, the potentially flawed deviance detection theory has remained largely dominant, which could lead some researchers and clinicians to assume its veracity implicitly. It is important to have a more comprehensive understanding of the source(s) of MMN generation before its widespread application as a clinical biomarker. This review evaluates issues of validity concerning the prevailing theoretical account of mismatch negativity and the passive auditory oddball paradigm, highlighting several limitations regarding its interpretation and clinical application.
Extracting Hypernuclear Properties from the (e, e′K+) Cross Section
Authors: Benhar Omar
Published: May 2021

Experimental studies of hypernuclear dynamics, besides being essential for the understanding of strong interactions in the strange sector, have important astrophysical implications. The observation of neutron stars with masses exceeding two solar masses poses a serious challenge to the models of hyperon dynamics in dense nuclear matter, many of which predict a maximum mass incompatible with the data. In this paper, it is argued that valuable new insight can be gained from the forthcoming extension of the experimental studies of kaon electro production from nuclei to include the 208Pb(e,e′K+)Λ208Tl process. A comprehensive framework for the description of kaon electro production, based on factorization of the nuclear cross section and the formalism of the nuclear many-body theory, is outlined. This approach highlights the connection between the kaon production and proton knockout reactions, which will allow us to exploit the available 208Pb(e,e′p)207Tl data to achieve a largely model-independent analysis of the measured cross section.
Enhancing the Cannabidiol (CBD) Compound in Formulated Hemp (Cannabis sativa L.) Leaves through the Application of Hot-Melt Extrusion
Authors: Azad Md Obyedul Kalam , Ryu Byeong Ryeol , Rana Md Soyel , Rahman Md Hafizur , Lim Jung-Dae , Lim Young-Seok
Published: May 2021

Cannabidiol (CBD) is a non-psychoactive cannabinoid compound found in hemp plants that has recently sparked interest in the biomedical and food industries. CBD is a natural decarboxylated product of cannabidiolic acid (CBDA). In this study, processing parameters were developed to enhance the decarboxylation process of CBDA in hemp leaves using hot-melt extrusion (HME). The hemp leaves were formulated with two different acid-based polymers, namely ascorbic acid (AA) and ascorbyl palmitate (AP), before the HME. The results showed that the carboxylation process of CBDA was increased by at least 2.5 times in the extrudate leaves and the content of the CBD was four times higher when formulated with AP (2800 µg/g) compared with the raw leaves (736 µg/g). The total phenolic and total flavonoid content, as well as the DPPH antioxidant capacity, were higher in the AP formulated extrudate. At the same time, the Δ9-tetrahydrocannabinol (THC) content was reduced by half in the extrudate compared with the raw leaves. It was also observed that double HME processing did not increase the decarboxylation process. It was concluded that the HME process significantly improved the conversion rate of CBDA to CBD in formulated hemp leaves with a reduced THC content.
Simulation of Shear-Thickening Liquid Transfer between U-Shaped Cell and Flat Plate
Authors: Dong Ling , Xing Jiefang , Wu Shuang , Guan Xiaomin , Zhu Hongjuan
Published: May 2021

Based on the actual measurement of the shear-thickening properties of water-based inks, in order to improve the ink transfer rate, the PLIC (Piecewise Linear Interface Construction) interface tracking method and the VOF (Volume of Fluid) method are used to simulate the transfer process of the shear-thickening liquid between the U-shaped cell and the upwardly moving plate. The effects of substrate surface wettability, cell contact angle, and cell depth on liquid transfer were studied. The results showed that all can increase the liquid transfer rate, and the change of the cell contact angle also led to the difference in the breaking time of the liquid filament. In addition, the shallow plate effect was discovered in the study of cell depth. The shallow plate effect is a phenomenon by which the amount of liquid transferred and the liquid transfer rate are greatly improved when the depth of the cell decreases to a certain limit value. In addition, for the U-shaped cell, the optimization method combining the shallow printing plate effect and fillet can greatly improve the liquid transfer rate and solve the undesirable problems such as plate blocking. After optimization, a liquid transfer rate of about 85% can be achieved.
Extraction and Quality Evaluation of Biodiesel from Six Familiar Non-Edible Plants Seeds
Authors: Khan Inam Ullah , Chen Hang , Yan Zhenhua , Chen Jun
Published: May 2021

Biodiesel produced from non-edible plant sources is cost-effective, biodegradable, environment friendly, and compatible with petro-diesel, but new sources and extraction processes still need to be discovered. Here, we explored the fuel properties of seeds from six non-edible plant sources, including Sapindus mukorossi (Soapnut, SP), Vernicia fordii (Tung, TO), Ricinus communis (Castor, CA), Toona sinensis (Juss. TS), Ailanthus altissima (Heaven tree, AA), and Linum usitatissimum L. (Lin seed, LS) from China. The optimum extraction conditions were obtained by optimizing the most important variables (reaction temperature, ratio of alcohol to vegetable oil, catalyst, mixing intensity, and purity of reactants) that influence the transesterification reaction of the biodiesel. All six plants contained high seed oil content (SOC; % w/v) with the highest in the TO-54.4% followed by SP-51%, CA-48%, LS-45%, AA-38%, and TS-35%, respectively, and all expressed satisfactory physico-chemical properties as per international standards of ASTM D6751 and EN14214. Our data provide a scientific basis for growing these plants in unproductive agricultural lands as an alternative energy sources for biodiesel production either standalone or blended with petro-diesel.