bluuebunny/crossref_metadata_2025 huggingface dataset:
Cross-Sectional and Longitudinal Effects of PCB Exposure on Human Stress Hormones in the German HELPcB Surveillance Program
Authors: Gaum Petra Maria , Vida Viktoria Stefanie , Schettgen Thomas , Esser André , Kraus Thomas , Gube Monika , Lang Jessica
Published: June 2020

Multiple pathological associations are attributed to PCBs (polychlorinated biphenyls). Research shows a positive association of PCBs with dehydroepiandrosterone sulfate (DHEAS) concentration but the results on the stress hormone cortisol have been inconsistent so far. This study is the first to examine not only the cross-sectional but also the longitudinal effects of PCB exposure on the stress hormones DHEAS and cortisol. Over a period of three years, 112 former employees occupationally exposed to PCBs were tested for their body burden with different types of PCBs (lower and higher chlorinated, dioxin-like and hydroxylated) and for their stress hormone concentration. Highly exposed employees showed a significantly higher risk for higher DHEAS values. Multiple linear regression analysis revealed a positive relationship between the exposure to lower chlorinated PCBs and DHEAS. Mixed models also revealed a significantly positive correlation between lower chlorinated PCBs with DHEAS when controlled for a cross-section. However, an effect for cortisol was not found. These results suggest a causal pathophysiological relationship between PCB exposure and DHEAS concentration, but not with cortisol. The health consequences of high DHEAS concentrations are discussed.
Assessment of Ketamine and its Enantiomers in an Organophosphate-Based Rat Model for Features of Gulf War Illness
Authors: Zhu Jackie , Hawkins Elisa , Phillips Kristin , Deshpande Laxmikant S.
Published: June 2020

Approximately 33% of U.S. soldiers from the first Gulf War suffer from a multi-system disorder known as the Gulf War Illness (GWI). GW veterans suffer from a cluster of symptoms that prominently include fatigue and can include mood-related symptoms. Compared to traditional antidepressants, ketamine (KET) produces a fast-onset and long-lasting antidepressant response, but assessments of KET for GWI-related depression are lacking. The etiology of GWI is multi-factorial and exposure to organophosphates (OP) during deployment is one of the factors underlying GWI development. Here, male Sprague-Dawley rats were repeatedly exposed to an OP DFP and three months later these rats, when assessed on a battery of rodent behavioral assays, displayed signs consistent with aspects of GWI characteristics. When treated with a sub-anesthetic dose of KET (3, 5, or 10 mg/kg, i.p.), DFP-treated rats exhibited a significant improvement in immobility time, open-arm exploration, and sucrose consumption as early as 1 h and much of these effects persisted at 24-h post-KET injection. KET’s stereoisomers, R-KET and S-KET, also exhibited such effects in DFP rats, with R-KET being the more potent isomer. Our studies provide a starting point for further assessment of KET for GWI depression.
The UK Pregnancies Better Eating and Activity Trial (UPBEAT); Pregnancy Outcomes and Health Behaviours by Obesity Class
Authors: Peacock Lucy , Seed Paul T. , Dalrymple Kathryn V. , White Sara L. , Poston Lucilla , Flynn Angela C.
Published: June 2020

The effectiveness of antenatal intervention in women with increasing obesity is unknown. This study investigated whether there was a differential effect of antenatal intervention on diet, physical activity and pregnancy outcomes in women stratified by obesity class using data from the UK Pregnancies Better Eating and Activity Trial (UPBEAT) (n = 1555). The stratification was by World Health Organization classifications: Class I, II and III (30–34.9 kg/m2, 35–39.9 kg/m2 and ≥40 kg/m2). Using linear and logistic regression, adjusted for confounders, outcomes were assessed post-intervention (27+0–28+6 weeks’ gestation) and in late pregnancy (34+0–36+0 weeks’ gestation). Interactions between obesity class and the intervention were explored. Compared to the standard care arm, class III intervention women had lower gestational weight gain (GWG) (−1.87 kg; 95% CI −3.29 to −0.47, p = 0.009), and the effect of the intervention was greater in class III compared to class I, by −2.01 kg (95% CI −3.45 to −0.57, p = 0.006). Class I and II intervention women reported significantly lower dietary glycaemic load and saturated fat intake across their pregnancy. This differential effect of the intervention suggests antenatal interventions for women with obesity should stratify outcomes by obesity severity. This would inform evidence-based antenatal strategies for high-risk groups, including women with a BMI ≥ 40 kg/m2.
Tailoring EHRs for Specific Working Environments Improves Work Well-Being of Physicians
Authors: Vainiomäki Suvi , Heponiemi Tarja , Vänskä Jukka , Hyppönen Hannele
Published: June 2020

Electronic health records (EHRs) have an impact on physicians’ well-being and stress levels. We studied physicians’ experiences with EHRs and their experienced time pressure and self-rated stress by an electronic questionnaire sent to Finnish physicians aged under 65 in 2017. Our sample was 2980 physicians working in the public sector, health care centers (35.5%) or hospitals (64.5%). Experienced technical problems were positively associated with experienced time pressure, whereas user-friendliness of the EHRs was negatively associated with experienced time pressure. Low perceived support for internal cooperation was associated with high levels of time pressure in hospitals. Those experiencing high levels of technical problems were 1.3 times more likely to experience stress compared to those experiencing low levels of technical problems. Better user-friendliness of the EHRs was associated with lower levels of self-rated stress. In both working environments but more strongly in primary health care, technical problems were associated with self-rated stress. Technical problems and user-friendliness of EHRs are the main factors associated with time pressure and self-rated stress. Health care environments differ in the nature of workflow having different demands on the EHRs. Developing EHR systems should consider the special needs of different environments and workflows, enabling better work well-being amongst physicians.
Anti-Inflammatory Potential of Cultured Ginseng Roots Extract in Lipopolysaccharide-Stimulated Mouse Macrophages and Adipocytes
Authors: Park Hyun Ju , Jo Sang-Mi , Seo Seok Hee , Lee Myoungsook , Lee Yunkyoung , Kang Inhae
Published: June 2020

Wild ginseng, Panax ginseng Meyer, is a traditional medicine widely used in Asia. Due to low reward and high costs, wild ginseng is produced by a plant cell culture technique called cultured ginseng roots (GR). The health benefits of wild ginseng have been well studied, but the potential health effects of GR are largely unknown. Thus, we investigated the role of a GR extract (GRE) on inflammatory responses. We firstly investigated the anti-inflammatory potential of GRE in lipopolysaccharide (LPS)-stimulated RAW264.7 cells. GRE (100 μg/mL) dampened pro-inflammatory gene expression, cytokine release, reactive oxygen species (ROS) production, and mitogen-activated protein kinase (MAPK) activation. These anti-inflammatory responses by GRE were confirmed in mouse bone marrow-derived macrophages (BMDMs), which showed that GRE could inhibit inflammation with the induction of antioxidant levels. LPS was recently reported to impair mitochondrial bioenergetics in mouse macrophages. We next measured the mitochondrial oxygen consumption rate (OCR), determining mitochondrial function. LPS treatment downregulated OCR; however, GRE partially restored the LPS-mediated energy homeostasis defects. Furthermore, GRE-pretreated conditioned media (CM) obtained from mouse macrophages decreased CM-mediated adipocyte inflammation. Collectively, these data suggested that GRE attenuated LPS-induced inflammation, and it might be partially involved in the protection from mitochondrial dysfunction in macrophages and adipocytes.
Health Care Costs Associated to Type of Feeding in the First Year of Life
Authors: Lechosa-Muñiz Carolina , Paz-Zulueta María , Sáez de Adana Herrero María , Cornejo del Rio Elsa , Mateo Sota Sonia , Llorca Javier , Cabero-Perez María J.
Published: June 2020

Background: Breastfeeding is associated with lower risk of infectious diseases, leading to fewer hospital admissions and pediatrician consultations. It is cost saving for the health care system, however, it is not usually estimated from actual cohorts but via simulation studies. Methods: A cohort of 970 children was followed-up for twelve months. Data on mother characteristics, pregnancy, delivery and neonate characteristics were obtained from medical records. The type of neonate feeding at discharge, 2, 4, 6, 9 and 12 months of life was reported by the mothers. Infectious diseases diagnosed in the first year of life, hospital admissions, primary care and emergency room consultations and drug treatments were obtained from neonate medical records. Health care costs were attributed using public prices and All Patients Refined–Diagnosis Related Groups (APR–DRG) classification. Results: Health care costs in the first year of life were higher in children artificially fed than in those breastfed (1339.5€, 95% confidence interval (CI): 903.0–1775.0 for artificially fed vs. 443.5€, 95% CI: 193.7–694.0 for breastfed). The breakdown of costs also shows differences in primary care consultations (295.7€ for formula fed children vs. 197.9€ for breastfed children), emergency room consultations (260.1€ for artificially fed children vs. 196.2€ for breastfed children) and hospital admissions (791.6€ for artificially fed children vs. 86.9€ for breastfed children). Conclusions: Children artificially fed brought about more health care costs related to infectious diseases than those exclusively breastfed or mixed breastfed. Excess costs were caused in hospital admissions, primary care consultations, emergency room consultations and drug consumption.
“It’s Just a Band-Aid on Something No One Really Wants to See or Acknowledge”: A Photovoice Study with Transitional Aged Youth Experiencing Homelessness to Examine the Roots of San Diego’s 2016–2018 Hepatitis A Outbreak
Authors: Felner Jennifer K. , Kieu Talia , Stieber Andrew , Call Hunter , Kirkland Daniel , Farr Amanda , Calzo Jerel P.
Published: June 2020

San Diego, California is consistently ranked among regions with the highest rates of homelessness in the United States. From 2016 to 2018, San Diego experienced an unprecedented outbreak of hepatitis A virus (HAV), largely attributed in media and public health discourse to the region’s growing population of people experiencing homelessness. Little attention, however, was devoted to examining the experiences and needs of this population, particularly transitional aged youth (TAY, aged 18–24) experiencing homelessness who may have been uniquely affected by the outbreak. This community-based participatory research study leveraged diverse qualitative methods, principally photovoice, to explore how the social and built environment shapes health among TAY experiencing homelessness in San Diego, how these environments may have contributed to the HAV outbreak, and TAY’s perceptions of HAV-related public health interventions. Emergent findings include stigmatization of TAY and other people experiencing homelessness, interventions that failed to address root causes of the outbreak, and interactions with housing-related and other social support resources that limit rather than support economic and social mobility. Findings have implications for understanding how media and public discourse, public health interventions, and availability and delivery of resources can contribute to and perpetuate stigma and health inequities faced by TAY experiencing homelessness.
Seeing the Finish Line? Retirement Perceptions and Wellbeing among Social Workers
Authors: Moriarty John , Gillen Patricia , Mallett John , Manthorpe Jill , Schröder Heike , McFadden Paula
Published: June 2020

Planning for future health and social services (HSS) workforces must be informed by an understanding of how workers view their work within the context of their life and the challenges they will face across the course of life. There is a range of policies and provisions that states and organisations can adopt to create sustainable careers, support wellbeing at work, and extend working lives where appropriate, but the potential impact of these policies on the make-up of the workforce remains under investigation. This paper makes the case that service planners need to appreciate complex interplay between wellbeing and career decisions when planning the future workforce. It makes use of a recent survey of United Kingdom (UK) social workers (n = 1434) to illustrate this interplay in two ways. First, we present the analysis of how social workers’ perception of retirement and extended working lives are associated with dimensions of Work-Related Quality of Life (WRQL). We find that social workers who agreed that a flexible working policy would encourage them to delay their retirement scored lower on the Home-Work Interface and Control at Work dimensions of WRQL, while social workers who indicated a perception that their employer would not wish them to work beyond a certain age had lower Job and Career Satisfaction scores. Second, we propose a new typology of retirement outlooks using latent class analysis of these attitudinal measures. An 8-class solution is proposed, and we demonstrate the predictive utility of this scheme. Results are discussed in terms of the challenges for ageing Western populations and the usefulness of analysis such as this in estimating the potential uptake and impact of age-friendly policies and provisions.
A Whey Fraction Rich in Immunoglobulin G Combined with Bifidobacterium longum subsp. infantis ATCC 15697 Exhibits Synergistic Effects against Campylobacter jejuni
Authors: Quinn Erinn M. , Kilcoyne Michelle , Walsh Dan , Joshi Lokesh , Hickey Rita M.
Published: June 2020

Evidence that whey proteins and peptides have health benefits beyond basic infant nutrition has increased dramatically in recent years. Previously, we demonstrated that a whey-derived immunoglobulin G-enriched powder (IGEP) enhanced adhesion of Bifidobacterium longum subsp. infantis ATCC 15697 (B. infantis) to HT-29 cells. In this study, we investigated the synergistic effect of IGEP-treated B. infantis on preventing the attachment of highly invasive Campylobacter jejuni 81–176 (C. jejuni) to intestinal HT-29 cells. The combination decreased the adherence of C. jejuni to the HT-29 cells by an average of 48% compared to the control (non-IGEP-treated B. infantis). We also confirmed that treatment of IGEP with sodium metaperiodate, which disables the biological recognition of the conjugated oligosaccharides, reduced adhesion of B. infantis to the intestinal cells. Thus, glycosylation of the IGEP components may be important in enhancing B. infantis adhesion. Interestingly, an increased adhesion phenotype was not observed when B. infantis was treated with bovine serum-derived IgG, suggesting that bioactivity was unique to milk-derived immunoglobulin-rich powders. Notably, IGEP did not induce growth of B. infantis within a 24 hours incubation period, as demonstrated by growth curves and metabolite analysis. The current study provides insight into the functionality of bovine whey components and highlights their potential in positively impacting the development of a healthy microbiota.
New Insight into the Composition of Wheat Seed Microbiota
Authors: Kuźniar Agnieszka , Włodarczyk Kinga , Grządziel Jarosław , Woźniak Małgorzata , Furtak Karolina , Gałązka Anna , Dziadczyk Ewa , Skórzyńska-Polit Ewa , Wolińska Agnieszka
Published: June 2020

Endophytes are associated with host plants throughout their life history from seed germination to fruit development. One of the most important plant organs colonized by endophytic microbiota is the seed. The aim of this study was to determine the structure of the seed core microbiome inhabiting the endosperms and embryos of eight wheat cultivars with the use of a culture-independent technique. The seeds of Triticum aestivum L. cv. Hondia, Wilejka, STH, Opcja, Tybalt, Euforia and Triticum spelta L. cv. Rokosz and Schwabencorn (producer: Plant Breeding Strzelce Sp. z o.o. Group IHAR) were studied. Rokosz and Hondia were cultured in vitro and in vivo to identify obligatory bacterial endophytes. A restrictive analysis of reads originating from the in vitro plants has demonstrated that the bacterial genera Paenibacillus and Propionibacterium inhabiting Rokosz and Hondia plants have a status of obligatory microorganisms. Greater biodiversity of seed-borne endophytes was found in the seed endosperms than in the embryos. The multiple comparison analysis of the OTU abundance indicated that the seed part significantly influenced the relative abundance. The seed-born microbiome is not statistically significantly dependent on the wheat cultivars; however, it cannot be claimed that every wheat seed is the same.
Hydroxytyrosol Inhibits Protein Oligomerization and Amyloid Aggregation in Human Insulin
Authors: Sirangelo Ivana , Borriello Margherita , Vilasi Silvia , Iannuzzi Clara
Published: June 2020

Hydroxytyrosol (HT), one of the main phenolic components of olive oil, has attracted considerable interest for its biological properties, including a remarkable antioxidant and anti-inflammatory power and, recently, for its ability to interfere with the amyloid aggregation underlying several human diseases. We report here a broad biophysical approach and cell biology techniques that allowed us to characterize the molecular mechanisms by which HT affects insulin amyloid aggregation and the related cytotoxicity. Our data show that HT is able to fully inhibit insulin amyloid aggregation and this property seems to be ascribed to the stabilization of the insulin monomeric state. Moreover, HT completely reverses the toxic effect produced by amyloid insulin aggregates in neuroblastoma cell lines by fully inhibiting the production of toxic amyloid species. These findings suggest that the beneficial effects of olive oil polyphenols, including HT, may arise from multifunctional activities and suggest possible a application of this natural compound in the prevention or treatment of amyloid-associated diseases.
Inhibition of Ovarian Cancer Cell Spheroid Formation by Synthetic Peptides Derived from Nectin-4
Authors: Boylan Kristin L.M. , Manion Rory D. , Shah Heena , Skubitz Keith M. , Skubitz Amy P. N.
Published: June 2020

The formation of 3D multicellular spheroids in the ascites fluid of ovarian cancer patients is an understudied component of the disease progression. Spheroids are less sensitive to chemotherapy, in part due to the protection afforded by their structure, but also due to their slower proliferation rate. Previous studies suggest that the cell adhesion molecule Nectin-4 plays a key role in the formation of ovarian cancer spheroids. In this study, we further examined the role of Nectin-4 at early time points in spheroid formation using real-time digital photography. Human NIH:OVCAR5 ovarian cancer cells formed aggregates within 8 h, which further contracted into compact spheroids over 24 h. In contrast, Nectin-4 knockdown cells did not form tightly compacted spheroids. Synthetic peptides derived from Nectin-4 were tested for their ability to alter spheroid formation in two ovarian cancer cell lines. Nectin-4 peptide 10 (N4-P10) had an immediate effect on disrupting ovarian cancer spheroid formation, which continued for over 24 h, while a scrambled version of the peptide had no effect. N4-P10 inhibited spheroid formation in a concentration-dependent manner and was not cytotoxic; suggesting that N4-P10 treatment could maintain the cancer cells as single cells which may be more sensitive to chemotherapy.
Influence of Herbal Medicines on HMGB1 Release, SARS-CoV-2 Viral Attachment, Acute Respiratory Failure, and Sepsis. A Literature Review
Authors: Wyganowska-Swiatkowska Marzena , Nohawica Michal , Grocholewicz Katarzyna , Nowak Gerard
Published: June 2020

By attaching to the angiotensin converting enzyme 2 (ACE2) protein on lung and intestinal cells, Sudden Acute Respiratory Syndrome (SARS-CoV-2) can cause respiratory and homeostatic difficulties leading to sepsis. The progression from acute respiratory failure to sepsis has been correlated with the release of high-mobility group box 1 protein (HMGB1). Lack of effective conventional treatment of this septic state has spiked an interest in alternative medicine. This review of herbal extracts has identified multiple candidates which can target the release of HMGB1 and potentially reduce mortality by preventing progression from respiratory distress to sepsis. Some of the identified mixtures have also been shown to interfere with viral attachment. Due to the wide variability in chemical superstructure of the components of assorted herbal extracts, common motifs have been identified. Looking at the most active compounds in each extract it becomes evident that as a group, phenolic compounds have a broad enzyme inhibiting function. They have been shown to act against the priming of SARS-CoV-2 attachment proteins by host and viral enzymes, and the release of HMGB1 by host immune cells. An argument for the value in a nonspecific inhibitory action has been drawn. Hopefully these findings can drive future drug development and clinical procedures.
NRF2 Knockdown Resensitizes 5-Fluorouracil-Resistant Pancreatic Cancer Cells by Suppressing HO-1 and ABCG2 Expression
Authors: Kim Eui Joo , Kim Yoon Jae , Lee Hye In , Jeong Seok-Hoo , Nam Hyo Jung , Cho Jae Hee
Published: June 2020

Chemoresistance is a leading cause of morbidity and mortality in patients with pancreatic cancer and remains an obstacle to successful treatment. The antioxidant transcription factor nuclear factor (erythroid-derived 2)-related factor 2 (NRF2), which plays important roles in tumor angiogenesis and invasiveness, is upregulated in pancreatic ductal adenocarcinoma (PDAC), where it correlates with poor survival. Here, we investigated the role of NRF2 in two 5-Fluourouracil-resistant (5-FUR) PDAC cell lines: BxPC-3 and CFPAC-1. Levels of NRF2 and antioxidants, such as heme oxygenase 1 (HO-1), NAD(P)H quinone dehydrogenase 1 (NQO1), and superoxide dismutase 2 (SOD2), were higher in the chemoresistant cells than in their chemosensitive counterparts. Expression of epithelial mesenchymal transition (EMT) markers, stemness markers, including Nanog, Oct4, and CD133, and that of the drug transporter ATP binding cassette, subfamily G, member A2 (ABCG2) was also upregulated in 5-FUR PDAC cells. NRF2 knockdown reversed 5-FU resistance of PDAC cells via suppression of ABCG2 and HO-1. In summary, these data indicate that NRF2 is a potential target for resensitizing 5-FUR PDAC cells to 5-FU to improve treatment outcomes in patients with pancreatic cancer.
Metabolic Shift of an Isogenic Strain of Enterococcus faecalis 14, Deficient in Its Own Bacteriocin Synthesis, as Revealed by a Transcriptomic Analysis
Authors: Ladjouzi Rabia , Lucau-Danila Anca , Drider Djamel
Published: June 2020

The production of antimicrobial molecules often involves complex biological pathways. This study aimed at understanding the metabolic and physiological networks of enterocin EntDD14-associated function, in the bacteriocinogenic strain, Enterococcus faecalis 14. A global and comparative transcriptomic study was carried out on E. faecalis 14 and its isogenic mutant Δbac, inactivated in genes coding for EntDD14. The in vitro ability to form biofilm on polystyrene plates was assessed by the crystal violet method, while the cytotoxicity on human colorectal adenocarcinoma Caco-2 cells was determined by the Cell Counting Kit-8. Transcriptomic data revealed that 71 genes were differentially expressed in both strains. As expected, genes coding for EntDD14 were downregulated in the Δbac mutant, whereas the other 69 genes were upregulated. Upregulated genes were associated with phage-related chromosomal islands, biofilm formation capability, resistance to environmental stresses, and metabolic reprogramming. Interestingly, the Δbac mutant showed an improved bacterial growth, a high capacity to form biofilm on inanimate surfaces and a very weak cytotoxicity level. These multiple metabolic rearrangements delineate a new line of defense to counterbalance the loss of EntDD14.
The Mitochondrial Genome Assembly of Fennel (Foeniculum vulgare) Reveals Two Different atp6 Gene Sequences in Cytoplasmic Male Sterile Accessions
Authors: Palumbo Fabio , Vitulo Nicola , Vannozzi Alessandro , Magon Gabriele , Barcaccia Gianni
Published: June 2020

Cytoplasmic male sterility (CMS) has always aroused interest among researchers and breeders, being a valuable resource widely exploited not only to breed F1 hybrid varieties but also to investigate genes that control stamen and pollen development. With the aim of identifying candidate genes for CMS in fennel, we adopted an effective strategy relying on the comparison between mitochondrial genomes (mtDNA) of both fertile and sterile genotypes. mtDNA raw reads derived from a CMS genotype were assembled in a single molecule (296,483 bp), while a draft mtDNA assembly (166,124 nucleotides, 94 contigs) was performed using male fertile sample (MF) sequences. From their annotation and alignment, two atp6-like sequences were identified. atp6−, the putative mutant copy with a 300 bp truncation at the 5’-end, was found only in the mtDNA of CMS samples, while the wild type copy (atp6+) was detected only in the MF mtDNA. Further analyses (i.e., reads mapping and Sanger sequencing), revealed an atp6+ copy also in CMS samples, probably in the nuclear DNA. However, qPCRs performed on different tissues proved that, despite its availability, atp6+ is expressed only in MF samples, while apt6− mRNA was always detected in CMS individuals. In the light of these findings, the energy deficiency model could explain the pollen deficiency observed in male sterile flower. atp6− could represent a gene whose mRNA is translated into a not-fully functional protein leading to suboptimal ATP production that guarantees essential cellular processes but not a high energy demand process such as pollen development. Our study provides novel insights into the fennel mtDNA genome and its atp6 genes, and paves the way for further studies aimed at understanding their functional roles in the determination of male sterility.
Protein Kinase CK2 Controls CaV2.1-Dependent Calcium Currents and Insulin Release in Pancreatic β-cells
Authors: Scheuer Rebecca , Philipp Stephan Ernst , Becker Alexander , Nalbach Lisa , Ampofo Emmanuel , Montenarh Mathias , Götz Claudia
Published: June 2020

The regulation of insulin biosynthesis and secretion in pancreatic β-cells is essential for glucose homeostasis in humans. Previous findings point to the highly conserved, ubiquitously expressed serine/threonine kinase CK2 as having a negative regulatory impact on this regulation. In the cell culture model of rat pancreatic β-cells INS-1, insulin secretion is enhanced after CK2 inhibition. This enhancement is preceded by a rise in the cytosolic Ca2+ concentration. Here, we identified the serine residues S2362 and S2364 of the voltage-dependent calcium channel CaV2.1 as targets of CK2 phosphorylation. Furthermore, co-immunoprecipitation experiments revealed that CaV2.1 binds to CK2 in vitro and in vivo. CaV2.1 knockdown experiments showed that the increase in the intracellular Ca2+ concentration, followed by an enhanced insulin secretion upon CK2 inhibition, is due to a Ca2+ influx through CaV2.1 channels. In summary, our results point to a modulating role of CK2 in the CaV2.1-mediated exocytosis of insulin.
Phytoene synthase 1 (Psy-1) and lipoxygenase 1 (Lpx-1) Genes Influence on Semolina Yellowness in Wheat Mediterranean Germplasm
Authors: Parada Roberto , Royo Conxita , Gadaleta Agata , Colasuonno Pasqualina , Marcotuli Ilaria , Matus Iván , Castillo Dalma , de Camargo Adriano Costa , Araya-Flores Jorge , Villegas Dolors , Schwember Andrés R.
Published: June 2020

Phytoene synthase 1 (Psy1) and lipoxygenase 1 (Lpx-1) are key genes involved in the synthesis and catalysis of carotenoid pigments in durum wheat, regulating the increase and decrease in these compounds, respectively, resulting in the distinct yellow color of semolina and pasta. Here, we reported new haplotype variants and/or allele combinations of these two genes significantly affecting yellow pigment content in grain and semolina through their effect on carotenoid pigments. To reach the purpose of this work, three complementary approaches were undertaken: the identification of QTLs associated to carotenoid content on a recombinant inbred line (RIL) population, the characterization of a Mediterranean panel of accessions for Psy1 and Lpx-1 genes, and monitoring the expression of Psy1 and Lpx-1 genes during grain filling on two genotypes with contrasting yellow pigments. Our data suggest that Psy1 plays a major role during grain development, contributing to semolina yellowness, and Lpx-1 appears to be more predominant at post-harvest stages and during pasta making.
Remodeling Matrix Synthesis in a Rat Model of Aortocaval Fistula and the Cyclic Stretch: Impaction in Pulmonary Arterial Hypertension-Congenital Heart Disease
Authors: Chang Chi-Jen , Huang Chung-Chi , Chen Po-Ru , Lai Ying-Ju
Published: June 2020

Pulmonary arterial hypertension-congenital heart disease (PAH-CHD) is characterized by systemic to pulmonary arterial shunts and sensitively responds to volume overload and stretch of the vascular wall leading to pulmonary vascular remodeling. We hypothesized that the responses of pulmonary artery smooth muscle cells (PASMCs) to mechanical stress-associated volume overload may promote vascular remodeling in PAH-CHD. Here, we show that significantly increased collagen was in the PA adventitial layer by trichrome staining in PAH-CHD patients and an aortocaval fistula (ACF) rat model in which chronic vascular volume overload induced-PAH. We assessed the gene expression profiles of SMC markers, extracellular matrix, and collagen in isolated SMCs from pulmonary and thoracic vessels with cyclic stretch-triggered responses by real-time PCR analysis. The data corresponded to collagen deposition, which modulated pulmonary vascular remodeling in clinical and experimental PAH-ACF cases as well as in cyclic stretch-triggered SMCs in an in vitro model. We observe that collagen I A2 (COLIA2) is expressed in the control rat, but collagen I A1 (COLIA1) and Notchs remarkably increase in the lungs of ACF rats. Interestingly, closing the left-to-right shunt that leads to a reduced blood volume in the PA system of ACF rats (ACFRs) decreased the expression of COLIA1 and increased that of collagen I A2(COLIA2). This study contributes to the stretch-induced responses of SMCs and provides important future directions for therapies aimed at preventing abnormal matrix protein synthesis in volume overload-induced pulmonary hypertension (PH).
Photosensitive Supramolecular Micelle-Mediated Cellular Uptake of Anticancer Drugs Enhances the Efficiency of Chemotherapy
Authors: Alemayehu Yihalem Abebe , Fan Wen-Lu , Ilhami Fasih Bintang , Chiu Chih-Wei , Lee Duu-Jong , Cheng Chih-Chia
Published: June 2020

The development of stimuli-responsive supramolecular micelles with high drug-loading contents that specifically induce significant levels of apoptosis in cancer cells remains challenging. Herein, we report photosensitive uracil-functionalized supramolecular micelles that spontaneously form via self-assembly in aqueous solution, exhibit sensitive photo-responsive behavior, and effectively encapsulate anticancer drugs at high drug-loading contents. Cellular uptake analysis and double-staining flow cytometric assays confirmed the presence of photo-dimerized uracil groups within the irradiated micelles remarkably enhanced endocytic uptake of the micelles by cancer cells and subsequently led to higher levels of apoptotic cell death, and thus improved the therapeutic effect in vitro. Thus, photo-dimerized uracil-functionalized supramolecular micelles may potentially represent an intelligent nanovehicle to improve the safety, efficacy, and applicability of cancer chemotherapy, and could also enable the development of nucleobase-based supramolecular micelles for multifunctional biomaterials and novel biomedical applications.
Deciphering the Binding of Salicylic Acid to Arabidopsis thaliana Chloroplastic GAPDH-A1
Authors: Pokotylo Igor , Hellal Denis , Bouceba Tahar , Hernandez-Martinez Miguel , Kravets Volodymyr , Leitao Luis , Espinasse Christophe , Kleiner Isabelle , Ruelland Eric
Published: June 2020

Salicylic acid (SA) has an essential role in the responses of plants to pathogens. SA initiates defence signalling via binding to proteins. NPR1 is a transcriptional co-activator and a key target of SA binding. Many other proteins have recently been shown to bind SA. Amongst these proteins are important enzymes of primary metabolism. This fact could stand behind SA’s ability to control energy fluxes in stressed plants. Nevertheless, only sparse information exists on the role and mechanisms of such binding. Glyceraldehyde 3-phosphate dehydrogenase (GAPDH) was previously demonstrated to bind SA both in human and plants. Here, we detail that the A1 isomer of chloroplastic glyceraldehyde 3-phosphate dehydrogenase (GAPA1) from Arabidopsis thaliana binds SA with a KD of 16.7 nM, as shown in surface plasmon resonance experiments. Besides, we show that SA inhibits its GAPDH activity in vitro. To gain some insight into the underlying molecular interactions and binding mechanism, we combined in silico molecular docking experiments and molecular dynamics simulations on the free protein and protein–ligand complex. The molecular docking analysis yielded to the identification of two putative binding pockets for SA. A simulation in water of the complex between SA and the protein allowed us to determine that only one pocket—a surface cavity around Asn35—would efficiently bind SA in the presence of solvent. In silico mutagenesis and simulations of the ligand/protein complexes pointed to the importance of Asn35 and Arg81 in the binding of SA to GAPA1. The importance of this is further supported through experimental biochemical assays. Indeed, mutating GAPA1 Asn35 into Gly or Arg81 into Leu strongly diminished the ability of the enzyme to bind SA. The very same cavity is responsible for the NADP+ binding to GAPA1. More precisely, modelling suggests that SA binds to the very site where the pyrimidine group of the cofactor fits. NADH inhibited in a dose-response manner the binding of SA to GAPA1, validating our data.
Emerging Strategies Targeting Catabolic Muscle Stress Relief
Authors: Scalabrin Mattia , Adams Volker , Labeit Siegfried , Bowen T. Scott
Published: June 2020

Skeletal muscle wasting represents a common trait in many conditions, including aging, cancer, heart failure, immobilization, and critical illness. Loss of muscle mass leads to impaired functional mobility and severely impedes the quality of life. At present, exercise training remains the only proven treatment for muscle atrophy, yet many patients are too ill, frail, bedridden, or neurologically impaired to perform physical exertion. The development of novel therapeutic strategies that can be applied to an in vivo context and attenuate secondary myopathies represents an unmet medical need. This review discusses recent progress in understanding the molecular pathways involved in regulating skeletal muscle wasting with a focus on pro-catabolic factors, in particular, the ubiquitin-proteasome system and its activating muscle-specific E3 ligase RING-finger protein 1 (MuRF1). Mechanistic progress has provided the opportunity to design experimental therapeutic concepts that may affect the ubiquitin-proteasome system and prevent subsequent muscle wasting, with novel advances made in regards to nutritional supplements, nuclear factor kappa-light-chain-enhancer of activated B cells (NFκB) inhibitors, myostatin antibodies, β2 adrenergic agonists, and small-molecules interfering with MuRF1, which all emerge as a novel in vivo treatment strategies for muscle wasting.
A Census and Categorization Method of Epitranscriptomic Marks
Authors: Mathlin Julia , Le Pera Loredana , Colombo Teresa
Published: June 2020

In the past few years, thorough investigation of chemical modifications operated in the cells on ribonucleic acid (RNA) molecules is gaining momentum. This new field of research has been dubbed “epitranscriptomics”, in analogy to best-known epigenomics, to stress the potential of ensembles of RNA modifications to constitute a post-transcriptional regulatory layer of gene expression orchestrated by writer, reader, and eraser RNA-binding proteins (RBPs). In fact, epitranscriptomics aims at identifying and characterizing all functionally relevant changes involving both non-substitutional chemical modifications and editing events made to the transcriptome. Indeed, several types of RNA modifications that impact gene expression have been reported so far in different species of cellular RNAs, including ribosomal RNAs, transfer RNAs, small nuclear RNAs, messenger RNAs, and long non-coding RNAs. Supporting functional relevance of this largely unknown regulatory mechanism, several human diseases have been associated directly to RNA modifications or to RBPs that may play as effectors of epitranscriptomic marks. However, an exhaustive epitranscriptome’s characterization, aimed to systematically classify all RNA modifications and clarify rules, actors, and outcomes of this promising regulatory code, is currently not available, mainly hampered by lack of suitable detecting technologies. This is an unfortunate limitation that, thanks to an unprecedented pace of technological advancements especially in the sequencing technology field, is likely to be overcome soon. Here, we review the current knowledge on epitranscriptomic marks and propose a categorization method based on the reference ribonucleotide and its rounds of modifications (“stages”) until reaching the given modified form. We believe that this classification scheme can be useful to coherently organize the expanding number of discovered RNA modifications.
Role for Lipids Secreted by Irradiated Peripheral Blood Mononuclear Cells in Inflammatory Resolution in Vitro
Authors: Panahipour Layla , Kochergina Evgeniya , Laggner Maria , Zimmermann Matthias , Mildner Michael , Ankersmit Hendrik J. , Gruber Reinhard
Published: June 2020

Periodontal inflammation is associated with dying cells that potentially release metabolites helping to promote inflammatory resolution. We had shown earlier that the secretome of irradiated, dying peripheral blood mononuclear cells support in vitro angiogenesis. However, the ability of the secretome to promote inflammatory resolution remains unknown. Here, we determined the expression changes of inflammatory cytokines in murine bone marrow macrophages, RAW264.7 cells, and gingival fibroblasts exposed to the secretome obtained from γ-irradiated peripheral blood mononuclear cells in vitro by RT-PCR and immunoassays. Nuclear translocation of p65 was detected by immunofluorescence staining. Phosphorylation of p65 and degradation of IκB was determined by Western blot. The secretome of irradiated peripheral blood mononuclear cells significantly decreased the expression of IL1 and IL6 in primary macrophages and RAW264.7 cells when exposed to LPS or saliva, and of IL1, IL6, and IL8 in gingival fibroblasts when exposed to IL-1β and TNFα. These changes were associated with decreased phosphorylation and nuclear translocation of p65 but not degradation of IκB in macrophages. We also show that the lipid fraction of the secretome lowered the inflammatory response of macrophages exposed to the inflammatory cues. These results demonstrate that the secretome of irradiated peripheral blood mononuclear cells can lower an in vitro simulated inflammatory response, supporting the overall concept that the secretome of dying cells promotes inflammatory resolution.
Real-Time Tweet Analytics Using Hybrid Hashtags on Twitter Big Data Streams
Authors: Gupta Vibhuti , Hewett Rattikorn
Published: June 2020

Twitter is a microblogging platform that generates large volumes of data with high velocity. This daily generation of unbounded and continuous data leads to Big Data streams that often require real-time distributed and fully automated processing. Hashtags, hyperlinked words in tweets, are widely used for tweet topic classification, retrieval, and clustering. Hashtags are used widely for analyzing tweet sentiments where emotions can be classified without contexts. However, regardless of the wide usage of hashtags, general tweet topic classification using hashtags is challenging due to its evolving nature, lack of context, slang, abbreviations, and non-standardized expression by users. Most existing approaches, which utilize hashtags for tweet topic classification, focus on extracting hashtag concepts from external lexicon resources to derive semantics. However, due to the rapid evolution and non-standardized expression of hashtags, the majority of these lexicon resources either suffer from the lack of hashtag words in their knowledge bases or use multiple resources at once to derive semantics, which make them unscalable. Along with scalable and automated techniques for tweet topic classification using hashtags, there is also a requirement for real-time analytics approaches to handle huge and dynamic flows of textual streams generated by Twitter. To address these problems, this paper first presents a novel semi-automated technique that derives semantically relevant hashtags using a domain-specific knowledge base of topic concepts and combines them with the existing tweet-based-hashtags to produce Hybrid Hashtags. Further, to deal with the speed and volume of Big Data streams of tweets, we present an online approach that updates the preprocessing and learning model incrementally in a real-time streaming environment using the distributed framework, Apache Storm. Finally, to fully exploit the batch and stream environment performance advantages, we propose a comprehensive framework (Hybrid Hashtag-based Tweet topic classification (HHTC) framework) that combines batch and online mechanisms in the most effective way. Extensive experimental evaluations on a large volume of Twitter data show that the batch and online mechanisms, along with their combination in the proposed framework, are scalable, efficient, and provide effective tweet topic classification using hashtags.
Sleep Quality and Sleep Disturbance Perception in Dual Disorder Patients
Authors: Luca Gianina , Peris Lola
Published: June 2020

Background: Sleep problems are particularly frequent in psychiatric disorders, but their bidirectional intersection is poorly clarified. An especial link between substance use and sleep seems to exist. While dual disorder patients are certainly at higher risk of experiencing sleep problems, very limited research is available today. Methods: Forty-seven dual disorder hospitalized patients were included in this first study. A complete psychiatric evaluation was performed, and sleep habits, patterns and potential disorders were evaluated with specific sleep scales, as well as anxiety. Results: The global prevalence of insomnia symptoms was considerably higher compared with the general population. Different abuse patterns as a function of concurrent psychiatric diagnosis were found, with no significant gender differences. The association between the investigated sleep parameters and any specific substance of abuse was minor. The addict behavior started in more than half of the patients prior to the main psychiatric diagnosis and close to the beginning of sleep problems. Men had a higher prevalence of insomnia symptoms, together with a higher incidence of anxiety. Overall, subjective daytime functioning was not altered as a consequence of poor sleep. Conclusion: Dual disorder patients face significant sleep disturbances, with low sleep quality. The role of sleep in addiction and dual disorders deserves greater research.
Microflow Nanoprecipitation of Positively Charged Gastroresistant Polymer Nanoparticles of Eudragit® RS100: A Study of Fluid Dynamics and Chemical Parameters
Authors: Yus Cristina , Arruebo Manuel , Irusta Silvia , Sebastián Victor
Published: June 2020

The objective of the present work was to produce gastroresistant Eudragit® RS100 nanoparticles by a reproducible synthesis approach that ensured mono-disperse nanoparticles under the size of 100 nm. Batch and micromixing nanoprecipitation approaches were selected to produce the demanded nanoparticles, identifying the critical parameters affecting the synthesis process. To shed some light on the formulation of the targeted nanoparticles, the effects of particle size and homogeneity of fluid dynamics, and physicochemical parameters such as polymer concentration, type of solvent, ratio of solvent to antisolvent, and total flow rate were studied. The physicochemical characteristics of resulting nanoparticles were studied applying dynamic light scattering (DLS) particle size analysis and electron microscopy imaging. Nanoparticles produced using a micromixer demonstrated a narrower and more homogenous distribution than the ones obtained under similar conditions in conventional batch reactors. Besides, fluid dynamics ensured that the best mixing conditions were achieved at the highest flow rate. It was concluded that nucleation and growth events must also be considered to avoid uncontrolled nanoparticle growth and evolution at the collection vial. Further, rifampicin-encapsulated nanoparticles were prepared using both approaches, demonstrating that the micromixing-assisted approach provided an excellent control of the particle size and polydispersity index. Not only the micromixing-assisted nanoprecipitation promoted a remarkable control in the nanoparticle formulation, but also it enhanced drug encapsulation efficiency and loading, as well as productivity. To the best of our knowledge, this was the very first time that drug-loaded Eudragit® RS100 nanoparticles (NPs) were produced in a continuous fashion under 100 nm (16.5 ± 4.3 nm) using microreactor technology. Furthermore, we performed a detailed analysis of the influence of various fluid dynamics and physicochemical parameters on the size and uniformity of the resulting nanoparticles. According to these findings, the proposed methodology can be a useful approach to synthesize a myriad of nanoparticles of alternative polymers.