bluuebunny/crossref_metadata_2025 huggingface dataset:
Effect of Tff3 Deficiency and ER Stress in the Liver
Authors: Šešelja Kate , Bazina Iva , Welss Jessica , Schicht Martin , Paulsen Friedrich , Bijelić Nikola , Rođak Edi , Horvatić Anita , Gelemanović Andrea , Mihalj Martina , Baus Lončar Mirela
Published: September 2019

Endoplasmic reticulum (ER) stress, a cellular condition caused by the accumulation of unfolded proteins inside the ER, has been recognized as a major pathological mechanism in a variety of conditions, including cancer, metabolic and neurodegenerative diseases. Trefoil factor family (TFFs) peptides are present in different epithelial organs, blood supply, neural tissues, as well as in the liver, and their deficiency has been linked to the ER function. Complete ablation of Tff3 expression is observed in steatosis, and as the most prominent change in the early phase of diabetes in multigenic mouse models of diabesity. To elucidate the role of Tff3 deficiency on different pathologically relevant pathways, we have developed a new congenic mouse model Tff3−/−/C57BL6/N from a mixed background strain (C57BL6/N /SV129) by using a speed congenics approach. Acute ER stress was evoked by tunicamycin treatment, and mice were sacrificed after 24 h. Afterwards the effect of Tff3 deficiency was evaluated with regard to the expression of relevant oxidative and ER stress genes, relevant proinflammatory cytokines/chemokines, and the global protein content. The most dramatic change was noticed at the level of inflammation-related genes, while markers for unfolded protein response were not significantly affected. Ultrastructural analysis confirmed that the size of lipid vacuoles was affected as well. Since the liver acts as an important metabolic and immunological organ, the influence of Tff3 deficiency and physiological function possibly reflects on the whole organism.
Targeting ROS and cPLA2/COX2 Expressions Ameliorated Renal Damage in Obese Mice with Endotoxemia
Authors: Chang Jia-Feng , Yeh Jih-Chen , Ho Chun-Ta , Liu Shih-Hao , Hsieh Chih-Yu , Wang Ting-Ming , Chang Shu-Wei , Lee I-Ta , Huang Kuo-Yang , Wang Jen-Yu , Lin Wei-Ning
Published: September 2019

Obesity is associated with metabolic endotoxemia, reactive oxygen species (ROS), chronic inflammation, and obese kidney fibrosis. Although the fat–intestine–kidney axis has been documented, the pathomechanism and therapeutic targets of obese kidney fibrosis remain unelucidated. To mimic obese humans with metabolic endotoxemia, high-fat-diet-fed mice (HF group) were injected with lipopolysaccharide (LPS) to yield the obese kidney fibrosis–metabolic endotoxemia mouse model (HL group). Therapeutic effects of ROS, cytosolic phospholipases A2 (cPLA2) and cyclooxygenase-2 (COX-2) inhibitors were analyzed with a quantitative comparison of immunohistochemistry stains and morphometric approach in the tubulointerstitium of different groups. Compared with basal and HF groups, the HL group exhibited the most prominent obese kidney fibrosis, tubular epithelial lipid vacuoles, and lymphocyte infiltration in the tubulointerstitium. Furthermore, inhibitors of nonspecific ROS, cPLA2 and COX-2 ameliorated the above renal damages. Notably, the ROS-inhibitor-treated group ameliorated not only oxidative injury but also the expression of cPLA2 and COX-2, indicating that ROS functions as the upstream signaling molecule in the inflammatory cascade of obese kidney fibrosis. ROS acts as a key messenger in the signaling transduction of obese kidney fibrosis, activating downstream cPLA2 and COX-2. The given antioxidant treatment ameliorates obese kidney fibrosis resulting from a combined high-fat diet and LPS—ROS could serve as a potential therapeutic target of obese kidney fibrosis with metabolic endotoxemia.
Social Learning of Acquiring Novel Feeding Habit in Mandarin Fish (Siniperca chuatsi)
Authors: Peng Jian , Dou Ya-Qi , Liang Hui , He Shan , Liang Xu-Fang , Shi Lin-Jie
Published: September 2019

Social learning plays important roles in gaining new foraging skills and food preferences. However, the potential role and molecular mechanism of social learning in acquiring new feeding habits is less clear in fish. In the present study, we examined the success rate of feeding habit domestication from live prey fish to dead prey fish, as well as the food intake of dead prey fish in mandarin fish with or without feeders of dead prey fish as demonstrators. Here, we found that mandarin fish can learn from each other how to solve novel foraging tasks, feeding on dead prey fish. In addition, the analysis of gene expressions and signaling pathways of learning through Western blotting and transcriptome sequencing shows that the expression of the c-fos, fra2, zif268, c/ebpd and sytIV genes were significantly increased, and the anorexigenic pomc and leptin a expressions were decreased in fish of the learning group. The phosphorylation levels of protein kinase A (PKA) and Ca2+/calmodulin-dependent protein kinase II (CaMKII) in the learning group were significantly higher than those of the control group, while the phosphorylation level of S6 ribosomal protein (S6) was lower. With the inhibitors of PKA and CaMKII signaling and the chromatin immunoprecipitation (ChIP) assay, we further found that the social learning of new feeding habits in mandarin fish could be attributed to the activation of the CaMKII signaling pathway and then the stimulation of the expression of the c-fos gene, which might be an important transcriptional factor to inhibit the expression of the anorexigenic gene pomc, resulting in the food intake of dead prey fish in mandarin fish. Altogether, our results support the hypothesis that social learning could facilitate the acquisition of novel feeding habits in fish, and it considerably increases the rate of subsequent individual food intake and domestication through the interaction between the learning gene c-fos and the appetite control gene pomc.
The Interaction of Helicobacter pylori with TFF1 and Its Role in Mediating the Tropism of the Bacteria Within the Stomach
Authors: Clyne Marguerite , May Felicity E. B.
Published: September 2019

Helicobacter pylori colonises the human stomach and has tropism for the gastric mucin, MUC5AC. The majority of organisms live in the adherent mucus layer within their preferred location, close to the epithelial surface where the pH is near neutral. Trefoil factor 1 (TFF1) is a small trefoil protein co-expressed with the gastric mucin MUC5AC in surface foveolar cells and co-secreted with MUC5AC into gastric mucus. Helicobacter pylori binds with greater avidity to TFF1 dimer, which is present in gastric mucus, than to TFF1 monomer. Binding of H. pylori to TFF1 is mediated by the core oligosaccharide subunit of H. pylori lipopolysaccharide at pH 5.0–6.0. Treatment of H. pylori lipopolysaccharide with mannosidase or glucosidase inhibits its interaction with TFF1. Both TFF1 and H. pylori have a propensity for binding to mucins with terminal non-reducing α- or β-linked N-acetyl-d-glucosamine or α-(2,3) linked sialic acid or Gal-3-SO42−. These findings are strong evidence that TFF1 has carbohydrate-binding properties that may involve a conserved patch of aromatic hydrophobic residues on the surface of its trefoil domain. The pH-dependent lectin properties of TFF1 may serve to locate H. pylori deep in the gastric mucus layer close to the epithelium rather than at the epithelial surface. This restricted localisation could limit the interaction of H. pylori with epithelial cells and the subsequent host signalling events that promote inflammation.
Claudin-19 Is Regulated by Extracellular Osmolality in Rat Kidney Inner Medullary Collecting Duct Cells
Authors: Ziemens Annalisa , Sonntag Svenja , Wulfmeyer Vera , Edemir Bayram , Bleich Markus , Himmerkus Nina
Published: September 2019

The inner medullary collecting duct (IMCD) is subject to severe changes in ambient osmolality and must either allow water transport or be able to seal the lumen against a very high osmotic pressure. We postulate that the tight junction protein claudin-19 is expressed in IMCD and that it takes part in epithelial adaptation to changing osmolality at different functional states. Presence of claudin-19 in rat IMCD was investigated by Western blotting and immunofluorescence. Primary cell culture of rat IMCD cells on permeable filter supports was performed under different osmotic culture conditions and after stimulation by antidiuretic hormone (AVP). Electrogenic transepithelial transport properties were measured in Ussing chambers. IMCD cells cultivated at 300 mosm/kg showed high transepithelial resistance, a cation selective paracellular pathway and claudin-19 was mainly located in the tight junction. Treatment by AVP increased cation selectivity but did not alter transepithelial resistance or claudin-19 subcellular localization. In contrast, IMCD cells cultivated at 900 mosm/kg had low transepithelial resistance, anion selectivity, and claudin-19 was relocated from the tight junctions to intracellular vesicles. The data shows osmolality-dependent transformation of IMCD epithelium from tight and sodium-transporting to leaky, with claudin-19 expression in the tight junction associated to tightness and cation selectivity under low osmolality.
Immune and Inflammatory Cells in Thyroid Cancer Microenvironment
Authors: Ferrari Silvia Martina , Fallahi Poupak , Galdiero Maria Rosaria , Ruffilli Ilaria , Elia Giusy , Ragusa Francesca , Paparo Sabrina Rosaria , Patrizio Armando , Mazzi Valeria , Varricchi Gilda , Marone Gianni , Antonelli Alessandro
Published: September 2019

A hallmark of cancer is the ability of tumor cells to avoid immune destruction. Activated immune cells in tumor microenvironment (TME) secrete proinflammatory cytokines and chemokines which foster the proliferation of tumor cells. Specific antigens expressed by cancer cells are recognized by the main actors of immune response that are involved in their elimination (immunosurveillance). By the recruitment of immunosuppressive cells, decreasing the tumor immunogenicity, or through other immunosuppressive mechanisms, tumors can impair the host immune cells within the TME and escape their surveillance. Within the TME, cells of the innate (e.g., macrophages, mast cells, neutrophils) and the adaptive (e.g., lymphocytes) immune responses are interconnected with epithelial cancer cells, fibroblasts, and endothelial cells via cytokines, chemokines, and adipocytokines. The molecular pattern of cytokines and chemokines has a key role and could explain the involvement of the immune system in tumor initiation and progression. Thyroid cancer-related inflammation is an important target for diagnostic procedures and novel therapeutic strategies. Anticancer immunotherapy, especially immune checkpoint inhibitors, unleashes the immune system and activates cytotoxic lymphocytes to kill cancer cells. A better knowledge of the molecular and immunological characteristics of TME will allow novel and more effective immunotherapeutic strategies in advanced thyroid cancer.
Changes in the Substrate Source Reveal Novel Interactions in the Sediment-Derived Methanogenic Microbial Community
Authors: Szafranek-Nakonieczna Anna , Pytlak Anna , Grządziel Jarosław , Kubaczyński Adam , Banach Artur , Górski Andrzej , Goraj Weronika , Kuźniar Agnieszka , Gałązka Anna , Stępniewska Zofia
Published: September 2019

Methanogenesis occurs in many natural environments and is used in biotechnology for biogas production. The efficiency of methane production depends on the microbiome structure that determines interspecies electron transfer. In this research, the microbial community retrieved from mining subsidence reservoir sediment was used to establish enrichment cultures on media containing different carbon sources (tryptone, yeast extract, acetate, CO2/H2). The microbiome composition and methane production rate of the cultures were screened as a function of the substrate and transition stage. The relationships between the microorganisms involved in methane formation were the major focus of this study. Methanogenic consortia were identified by next generation sequencing (NGS) and functional genes connected with organic matter transformation were predicted using the PICRUSt approach and annotated in the KEGG. The methane production rate (exceeding 12.8 mg CH4 L−1 d−1) was highest in the culture grown with tryptone, yeast extract, and CO2/H2. The analysis of communities that developed on various carbon sources casts new light on the ecophysiology of the recently described bacterial phylum Caldiserica and methanogenic Archaea representing the genera Methanomassiliicoccus and Methanothrix. Furthermore, it is hypothesized that representatives of Caldiserica may support hydrogenotrophic methanogenesis.
Reconstitution in Proteoliposomes of the Recombinant Human Riboflavin Transporter 2 (SLC52A2) Overexpressed in E. coli
Authors: Console Lara , Tolomeo Maria , Colella Matilde , Barile Maria , Indiveri Cesare
Published: September 2019

Background: the SLC52A2 gene encodes for the riboflavin transporter 2 (RFVT2). This transporter is ubiquitously expressed. It mediates the transport of Riboflavin across cell membranes. Riboflavin plays a crucial role in cells since its biologically active forms, FMN and FAD, are essential for the metabolism of carbohydrates, amino acids, and lipids. Mutation of the Riboflavin transporters is a risk factor for anemia, cancer, cardiovascular disease, neurodegeneration. Inborn mutations of SLC52A2 are associated with Brown-Vialetto-van Laere syndrome, a rare neurological disorder characterized by infancy onset. In spite of the important metabolic and physio/pathological role of this transporter few data are available on its function and regulation. Methods: the human recombinant RFVT2 has been overexpressed in E. coli, purified and reconstituted into proteoliposomes in order to characterize its activity following the [3H]Riboflavin transport. Results: the recombinant hRFVT2 showed a Km of 0.26 ± 0.07 µM and was inhibited by lumiflavin, FMN and Mg2+. The Riboflavin uptake was also regulated by Ca2+. The native protein extracted from fibroblast and reconstituted in proteoliposomes also showed inhibition by FMN and lumiflavin. Conclusions: proteoliposomes represent a suitable model to assay the RFVT2 function. It will be useful for screening the mutation of RFVT2.
Advances in Molecular Biology and Targeted Therapy of Mantle Cell Lymphoma
Authors: Klener Pavel
Published: September 2019

Mantle cell lymphoma (MCL) is a heterogeneous malignancy with a broad spectrum of clinical behavior from indolent to highly aggressive cases. Despite the fact that MCL remains in most cases incurable by currently applied immunochemotherapy, our increasing knowledge on the biology of MCL in the last two decades has led to the design, testing, and approval of several innovative agents that dramatically changed the treatment landscape for MCL patients. Most importantly, the implementation of new drugs and novel treatment algorithms into clinical practice has successfully translated into improved outcomes of MCL patients not only in the clinical trials, but also in real life. This review focuses on recent advances in our understanding of the pathogenesis of MCL, and provides a brief survey of currently used treatment options with special focus on mode of action of selected innovative anti-lymphoma molecules. Finally, it outlines future perspectives of patient management with progressive shift from generally applied immunotherapy toward risk-stratified, patient-tailored protocols that would implement innovative agents and/or procedures with the ultimate goal to eradicate the lymphoma and cure the patient.
Ethanol Elevates Excitability of Superior Cervical Ganglion Neurons by Inhibiting Kv7 Channels in a Cell Type-Specific and PI(4,5)P2-Dependent Manner
Authors: Kim Kwon-Woo , Kim Keetae , Lee Hyosang , Suh Byung-Chang
Published: September 2019

Alcohol causes diverse acute and chronic symptoms that often lead to critical health problems. Exposure to ethanol alters the activities of sympathetic neurons that control the muscles, eyes, and blood vessels in the brain. Although recent studies have revealed the cellular targets of ethanol, such as ion channels, the molecular mechanism by which alcohol modulates the excitability of sympathetic neurons has not been determined. Here, we demonstrated that ethanol increased the discharge of membrane potentials in sympathetic neurons by inhibiting the M-type or Kv7 channel consisting of the Kv7.2/7.3 subunits, which were involved in determining the membrane potential and excitability of neurons. Three types of sympathetic neurons, classified by their threshold of activation and firing patterns, displayed distinct sensitivities to ethanol, which were negatively correlated with the size of the Kv7 current that differs depending on the type of neuron. Using a heterologous expression system, we further revealed that the inhibitory effects of ethanol on Kv7.2/7.3 currents were facilitated or diminished by adjusting the amount of plasma membrane phosphatidylinositol 4,5-bisphosphate (PI(4,5)P2). These results suggested that ethanol and PI(4,5)P2 modulated gating of the Kv7 channel in superior cervical ganglion neurons in an antagonistic manner, leading to regulation of the membrane potential and neuronal excitability, as well as the physiological functions mediated by sympathetic neurons.
Development of a Combined Genetic Engineering Vaccine for Porcine Circovirus Type 2 and Mycoplasma Hyopneumoniae by a Baculovirus Expression System
Authors: Tao Yu , Li Gaojian , Zheng Wenqian , Shu Jianhong , Chen Jian , Yang Fang , Wu Yuehong , He Yulong
Published: September 2019

Mycoplasma hyopneumoniae (Mhp) and porcine circovirus type 2 (PCV2) are the main pathogens for mycoplasmal pneumonia of swine (MPS) and post-weaning multisystemic wasting syndrome (PMWS), respectively. Infection by these pathogens often happens together and causes great economic losses. In this study, a kind of recombinant baculovirus that can display P97R1P46P42 chimeric protein of Mhp and the capsid (Cap) protein of PCV2 was developed, and the protein location was identified. Another recombinant baculovirus was constructed without tag proteins (EGFP, mCherry) and was used to evaluate the immune effect in experiments with BALB/c mice and domestic piglets. Antigen proteins P97R1P46P42 and Cap were expressed successfully; both were anchored on the plasma membrane of cells and the viral envelope. It should be emphasized that in piglet immunization, the recombinant baculovirus vaccine achieved similar immunological effects as the mixed commercial vaccine. Both the piglet and mouse experiments showed that the recombinant baculovirus was able to induce humoral and cellular responses effectively. The results of this study indicate that this recombinant baculovirus is a potential candidate for the further development of more effective combined genetic engineering vaccines against MPS and PMWS. This experiment also provides ideas for vaccine development for other concomitant diseases using the baculovirus expression system.
TRPM6 N-Terminal CaM- and S100A1-Binding Domains
Authors: Zouharova Monika , Herman Petr , Hofbauerová Kateřina , Vondrasek Jiri , Bousova Kristyna
Published: September 2019

Transient receptor potential (TRPs) channels are crucial downstream targets of calcium signalling cascades. They can be modulated either by calcium itself and/or by calcium-binding proteins (CBPs). Intracellular messengers usually interact with binding domains present at the most variable TRP regions—N- and C-cytoplasmic termini. Calmodulin (CaM) is a calcium-dependent cytosolic protein serving as a modulator of most transmembrane receptors. Although CaM-binding domains are widespread within intracellular parts of TRPs, no such binding domain has been characterised at the TRP melastatin member—the transient receptor potential melastatin 6 (TRPM6) channel. Another CBP, the S100 calcium-binding protein A1 (S100A1), is also known for its modulatory activities towards receptors. S100A1 commonly shares a CaM-binding domain. Here, we present the first identified CaM and S100A1 binding sites at the N-terminal of TRPM6. We have confirmed the L520-R535 N-terminal TRPM6 domain as a shared binding site for CaM and S100A1 using biophysical and molecular modelling methods. A specific domain of basic amino acid residues (R526/R531/K532/R535) present at this TRPM6 domain has been identified as crucial to maintain non-covalent interactions with the ligands. Our data unambiguously confirm that CaM and S100A1 share the same binding domain at the TRPM6 N-terminus although the ligand-binding mechanism is different.
Biophysical Insight on the Membrane Insertion of an Arginine-Rich Cell-Penetrating Peptide
Authors: Jobin Marie-Lise , Vamparys Lydie , Deniau Romain , Grélard Axelle , Mackereth Cameron , Fuchs Patrick , Alves Isabel
Published: September 2019

Cell-penetrating peptides (CPPs) are short peptides that can translocate and transport cargoes into the intracellular milieu by crossing biological membranes. The mode of interaction and internalization of cell-penetrating peptides has long been controversial. While their interaction with anionic membranes is quite well understood, the insertion and behavior of CPPs in zwitterionic membranes, a major lipid component of eukaryotic cell membranes, is poorly studied. Herein, we investigated the membrane insertion of RW16 into zwitterionic membranes, a versatile CPP that also presents antibacterial and antitumor activities. Using complementary approaches, including NMR spectroscopy, fluorescence spectroscopy, circular dichroism, and molecular dynamic simulations, we determined the high-resolution structure of RW16 and measured its membrane insertion and orientation properties into zwitterionic membranes. Altogether, these results contribute to explaining the versatile properties of this peptide toward zwitterionic lipids.
Nonalcoholic Fatty Liver Disease (NAFLD), But not Its Susceptibility Gene Variants, Influences the Decrease of Kidney Function in Overweight/Obese Children
Authors: Di Costanzo Alessia , Pacifico Lucia , D’Erasmo Laura , Polito Luca , Di Martino Michele , Perla Francesco Massimo , Iezzi Ludovica , Chiesa Claudio , Arca Marcello
Published: September 2019

Nonalcoholic fatty liver disease (NAFLD) is associated with an increased risk of kidney disease in adults and children. However, it is uncertain whether this association is influenced by major NAFLD susceptibility genes. In a sample of 230 overweight/obese children, 105 with NAFLD (hepatic fat fraction ≥5% by magnetic resonance imaging) and 125 without NAFLD, rs738409 in PNPLA3, rs58542926 in TM6SF2, rs1260326 in GCKR, and rs641738 in MBOAT7 were genotyped. Abnormal kidney function was defined as estimated glomerular filtration rate (eGFR) < 90 mL/min/1.73 m2 and/or the presence of microalbuminuria (24 h urinary albumin excretion between 30 and 300 mg). In comparison with children without NAFLD, those with NAFLD showed increased prevalence of reduced eGFR (13.3% vs. 1.6%; p < 0.001) and microalbuminuria (8.6% vs. 3.4%, p = 0.025). TM6SF2, GCKR, and MBOAT7 risk alleles did not show any impact on kidney function, while the PNPLA3 G allele was associated with lower eGFR, but only in children with NAFLD (p = 0.003). After adjustment for confounders, NAFLD (OR, 4.7; 95% CI, 1.5–14.8; padj = 0.007), but not the PNPLA3 gene variant, emerged as the main independent predictor of renal dysfunction. Overall, our findings suggest that NAFLD remains the main determinant of decline in kidney function in overweight/obese children, while the PNPLA3 rs738409 prosteatogenic variant has a small impact, if any.
Seasonal Abundance of Psyllid Species on Carrots and Potato Crops in Spain
Authors: Antolínez Carlos A. , Moreno Aranzazu , Ontiveros Irene , Pla Sandra , Plaza María , Sanjuan Susana , Palomo José L. , Sjölund M. Jennifer , Sumner-Kalkun Jason C. , Arnsdorf Yvonne M. , Jeffries Colin J. , Ouvrard David , Fereres Alberto
Published: September 2019

Psyllids (Hemiptera: Psylloidea) can transmit the phloem restricted bacterium ‘Candidatus Liberibacter solanacearum’ (Lso). In Europe, Lso causes severe losses to carrot and represents a threat to the potato industry. A rising concern is Lso transmission from carrot to potato and within potato, and this has driven the need for monitoring populations of psyllid species which could serve as vectors on both crops. This would provide a fundamental understanding of the epidemiology of Lso. Different sampling methods were used to survey populations of psyllid species in commercial carrot and potato fields in central and eastern mainland Spain from 2015 to 2017. Two psyllid species, Bactericera trigonica and Bactericera nigricornis were found on carrot and potato crops. In carrot fields the most abundant species was B. trigonica (occurring from crop emergence to harvest); whereas in potato crops the most abundant psyllid species was B. nigricornis. Depending on field location, the maximum psyllid populations occurred between June and October. Since B. nigricornis was found on both carrot and potato and is the only psyllid species able to feed and reproduce on both these crops in Europe, there is the potential risk of Lso transmission from carrot to potato.
Neo Sex Chromosomes, Colour Polymorphism and Male-Killing in the African Queen Butterfly, Danaus chrysippus (L.)
Authors: Smith David A.S. , Traut Walther , Martin Simon H. , Ireri Piera , Omufwoko Kennedy S. , ffrench-Constant Richard , Gordon Ian J.
Published: September 2019

Danaus chrysippus (L.), one of the world’s commonest butterflies, has an extensive range throughout the Old-World tropics. In Africa it is divided into four geographical subspecies which overlap and hybridise freely in the East African Rift: Here alone a male-killing (MK) endosymbiont, Spiroplasma ixodetis, has invaded, causing female-biased populations to predominate. In ssp. chrysippus, inside the Rift only, an autosome carrying a colour locus has fused with the W chromosome to create a neo-W chromosome. A total of 40–100% of Rift females are neo-W and carry Spiroplasma, thus transmitting a linked, matrilineal neo-W, MK complex. As neo-W females have no sons, half the mother’s genes are lost in each generation. Paradoxically, although neo-W females have no close male relatives and are thereby forced to outbreed, MK restricts gene flow between subspecies and may thus promote speciation. The neo-W chromosome originated in the Nairobi region around 2.2 k years ago and subsequently spread throughout the Rift contact zone in some 26 k generations, possibly assisted by not having any competing brothers. Our work on the neo-W chromosome, the spread of Spiroplasma and possible speciation is ongoing.
Oncogenic Role of Secreted Engrailed Homeobox 2 (EN2) in Prostate Cancer
Authors: Gómez-Gómez Enrique , Jiménez-Vacas Juan M. , Pedraza-Arévalo Sergio , López-López Fernando , Herrero-Aguayo Vicente , Hormaechea-Agulla Daniel , Valero-Rosa José , Ibáñez-Costa Alejandro , León-González Antonio J. , Sánchez-Sánchez Rafael , González-Serrano Teresa , Requena-Tapia Maria J. , Castaño Justo P. , Carrasco-Valiente Julia , Gahete Manuel D. , Luque Raúl M.
Published: September 2019

Engrailed variant-2 (EN2) has been suggested as a potential diagnostic biomarker; however, its presence and functional role in prostate cancer (PCa) cells is still controversial or unknown. Here, we analyzed 1) the expression/secretion profile of EN2 in five independent samples cohorts from PCa patients and controls (prostate tissues and/or urine) to determine its utility as a PCa biomarker; and 2) the functional role of EN2 in normal (RWPE1) and tumor (LNCaP/22Rv1/PC3) prostate cells to explore its potential value as therapeutic target. EN2 was overexpressed in our two cohorts of PCa tissues compared to control and in tumor cell lines compared with normal-like prostate cells. This profile was corroborated in silico in three independent data sets [The Cancer Genome Atlas(TCGA)/Memorial Sloan Kettering Cancer Center (MSKCC)/Grasso]. Consistently, urine EN2 levels were elevated and enabled discrimination between PCa and control patients. EN2 treatment increased cell proliferation in LNCaP/22Rv1/PC3 cells, migration in RWPE1/PC3 cells, and PSA secretion in LNCaP cells. These effects were associated, at least in the androgen-sensitive LNCaP cells, with increased AKT and androgen-receptor phosphorylation levels and with modulation of key cancer-associated genes. Consistently, EN2 treatment also regulated androgen-receptor activity (full-length and splicing variants) in androgen-sensitive 22Rv1 cells. Altogether, this study demonstrates the potential utility of EN2 as a non-invasive diagnostic biomarker for PCa and provides novel and valuable information to further investigate its putative utility to develop new therapeutic tools in PCa.
Improved Quality of Life Following Addiction Treatment Is Associated with Reductions in Substance Use
Authors: Manning Victoria , Garfield Joshua B. B. , Lam Tina , Allsop Steve , Berends Lynda , Best David , Buykx Penny , Room Robin , Lubman Dan I.
Published: September 2019

People seeking treatment for substance use disorders (SUD) ultimately aspire to improve their quality of life (QOL) through reducing or ceasing their substance use, however the association between these treatment outcomes has received scant research attention. In a prospective, multi-site treatment outcome study (‘Patient Pathways’), we recruited 796 clients within one month of intake from 21 publicly funded addiction treatment services in two Australian states, 555 (70%) of whom were followed-up 12 months later. We measured QOL at baseline and follow-up using the WHOQOL-BREF (physical, psychological, social and environmental domains) and determined rates of “SUD treatment success” (past-month abstinence or a statistically reliable reduction in substance use) at follow-up. Mixed effects linear regression analyses indicated that people who achieved SUD treatment success also achieved significantly greater improvements in QOL, relative to treatment non-responders (all four domains p < 0.001). Paired t-tests indicated that non-responders significantly improved their social (p = 0.007) and environmental (p = 0.033) QOL; however, their psychological (p = 0.088) and physical (p = 0.841) QOL did not significantly improve. The findings indicate that following treatment, QOL improved in at least some domains, but that reduced substance use was associated with both stronger and broader improvements in QOL. Addressing physical and psychological co-morbidities during treatment may facilitate reductions in substance use.
A-Ring-Modified Triterpenoids and Their Spermidine–Aldimines with Strong Antibacterial Activity
Authors: Kazakova Oxana B. , Brunel Jean Michel , Khusnutdinova Elmira F. , Negrel Sophie , Giniyatullina Gulnara V. , Lopatina Tatyana V. , Petrova Anastasiya V.
Published: September 2019

Synthesis of A-ring-modified lupane, oleanane and ursane type triterpenoid conjugates with spermidine through an aldimine linkage or diethylentriamine via an amide bond is described. These derivatives were evaluated for their in vitro antimicrobial properties against human pathogens. Except for derivatives 1 and 7, all compounds have moderate to weak minimum inhibitory concentrations (MICs) against Gram-positive Staphylococcus aureus bacteria, with MICs varying from 3.125 to 200 µM. Compound 11 is efficient against Escherichia coli and Pseudomonas aeruginosa, with MICs of 25 and 50 µM, respectively, while all other derivatives do not possess important antimicrobial activities against these Gram-negative bacteria.
Vibrational Spectroscopy Fingerprinting in Medicine: from Molecular to Clinical Practice
Authors: Balan Vera , Mihai Cosmin-Teodor , Cojocaru Florina-Daniela , Uritu Cristina-Mariana , Dodi Gianina , Botezat Doru , Gardikiotis Ioannis
Published: September 2019

In the last two decades, Fourier Transform Infrared (FTIR) and Raman spectroscopies turn out to be valuable tools, capable of providing fingerprint-type information on the composition and structural conformation of specific molecular species. Vibrational spectroscopy’s multiple features, namely highly sensitive to changes at the molecular level, noninvasive, nondestructive, reagent-free, and waste-free analysis, illustrate the potential in biomedical field. In light of this, the current work features recent data and major trends in spectroscopic analyses going from in vivo measurements up to ex vivo extracted and processed materials. The ability to offer insights into the structural variations underpinning pathogenesis of diseases could provide a platform for disease diagnosis and therapy effectiveness evaluation as a future standard clinical tool.
A Bio-Hygromorph Fabricated with Fish Swim Bladder Hydrogel and Wood Flour-Filled Polylactic Acid Scaffold by 3D Printing
Authors: Li Peng , Pan Ling , Liu Dexi , Tao Yubo , Shi Sheldon Q.
Published: September 2019

Non-powered adaptive systems are attractive in the construction of environment actuators, meteorosensitive architectures, biomedical devices, and soft robotics. Combining hydrophilic materials and anisotropic structures to mimic self-morphing plant structures has been demonstrated as an effective approach to creating artificial hygromorphs. The convenience of 3D printing technologies in shaping programmable complex structures facilitates the imitation of complex anisotropic plant structures. In this research, we constructed a bio-hygromorph using fish swim bladder hydrogel as the hydrophilic material and wood flour-filled polylactic acid (WPLA) scaffold, which was printed with fused deposition modeling (FDM) 3D printing technology (3DP). The environmental benign bio-hygromorph displayed morphing abilities triggered by moisture content changes, as the fish swim bladder hydrogel swelled and shrunk during absorption and desorption cycles. The strain disproportion of the two-layered composite structure in the bio-hygromorph drove the bending deformation. Stress analyses performed with finite element analysis (FEA) also revealed the mechanism behind the moisture content driven morphing of the bio-hygromorph. Notably, the bio-hygromorph exhibited faster response times to moisture absorption than desorption, which may donate actuators’ different attributes in distinct moisture conditions.
Doped Nanoscale NMC333 as Cathode Materials for Li-Ion Batteries
Authors: Hashem Ahmed M. , Abdel-Ghany Ashraf E. , Scheuermann Marco , Indris Sylvio , Ehrenberg Helmut , Mauger Alain , Julien Christian M.
Published: September 2019

A series of Li(Ni1/3Mn1/3Co1/3)1−xMxO2 (M = Al, Mg, Zn, and Fe, x = 0.06) was prepared via sol-gel method assisted by ethylene diamine tetra acetic acid as a chelating agent. A typical hexagonal α-NaFeO2 structure (R-3m space group) was observed for parent and doped samples as revealed by X-ray diffraction patterns. For all samples, hexagonally shaped nanoparticles were observed by scanning electron microscopy and transmission electron microscopy. The local structure was characterized by infrared, Raman, and Mössbauer spectroscopy and 7Li nuclear magnetic resonance (Li-NMR). Cyclic voltammetry and galvanostatic charge-discharge tests showed that Mg and Al doping improved the electrochemical performance of LiNi1/3Mn1/3Co1/3O2 in terms of specific capacities and cyclability. In addition, while Al doping increases the initial capacity, Mg doping is the best choice as it improves cyclability for reasons discussed in this work.
Methodology for Evaluation of Residual Stress Effect on Small Corner-Crack Initiation and Growth
Authors: Kim Janghwan , Kang Jun Won , Lee Dong-Eun , Kim Dae Young
Published: September 2019

The growth behavior of a naturally initiated corner crack under a uniform residual stress field is investigated in this study. A convenient method is proposed to induce and evaluate the uniform residual stress field for a beam-type specimen. Fatigue tests are conducted with a rotary bending fatigue machine to investigate the growth of the corner crack. For this reason, a cylindrical specimen, which is typically used for rotating bending tests, is modified into a beam specimen. The corner crack growth behavior under residual stress is evaluated based on linear elastic fracture mechanics (LEFM) and compared with long through crack data. The test results verify that the corner crack growth under residual stress can be effectively evaluated by LEFM and estimated using long crack data.
Stress Dependence of the Small Angle Magnetization Rotation Signal in Commercial Amorphous Ribbons
Authors: Nowicki Michał
Published: September 2019

The results of the investigation on tensile stress dependence of the SAMR (small angle magnetization rotation) signal in soft magnetic amorphous ribbons are presented. Exemplary results for commercially available, negatively magnetostrictive 2705M, 2714A, and 6030D amorphous ribbons show significant stress dependence, in contrast to positively magnetostrictive 2826MB alloy. The magnetoelastic hysteresis of the obtained characteristics is compared, as well as the influence of the biasing H field and supply current variations. Based on the results, 2705M alloy with near-zero negative magnetostriction is proposed as best suited for a SAMR-based, magnetoelastic force sensor.
Disturbance of the Conformation of DNA Hairpin Containing the 5′-GT-3′ Binding Site Caused by Zn(II)bleomycin-A5 Studied through NMR Spectroscopy
Authors: Covington Kyle L. , Lehmann Teresa
Published: September 2019

The antibiotics known as bleomycins constitute a family of natural products clinically employed for the treatment of a wide spectrum of cancers. These antibiotics have the ability to chelate a metal center, most commonly Fe(II), and cause site-specific DNA cleavage upon oxidation. Bleomycin therapy is a successful course of treatment for some types of cancers. However, the risk of pulmonary fibrosis as an undesirable side effect, limits the use of the antibiotics in cancer chemotherapy. Bleomycins are differentiated by their C-terminal, or tail, regions, which have been shown to closely interact with DNA. Pulmonary toxicity has been correlated to the chemical structure of the bleomycin C-termini through biochemical studies performed in mice. In the present study, we examined the binding of Zn(II)Bleomycin-A5 to a DNA hairpin of sequence 5′-CCAGTATTTTTACTGG-3′, containing the 5′-GT-3′ binding site. The results were compared to those from a previous study that examined the binding of Zn(II)Bleomycin-A2 and Zn(II)Peplomycin to the same DNA hairpin. We provide evidence that, as shown for DNA hairpins containing the 5′-GC-3′ binding site, Zn(II)BLM-A5 causes the most significant structural changes to the oligonucleotide.
Using Machine Learning for Enhancing the Understanding of Bullwhip Effect in the Oil and Gas Industry
Authors: Sousa Ana L. , Ribeiro Tiago P. , Relvas Susana , Barbosa-Póvoa Ana
Published: September 2019

Several suppliers of oil and gas (O & G) equipment and services have reported the necessity of making frequent resources planning adjustments due to the variability of demand, which originates in unbalanced production levels. The occurrence of these specific problems for the suppliers and operators is often related to the bullwhip effect. For studying such a problem, a research proposal is herein presented. Studying the bullwhip effect in the O & G industry requires collecting data from different levels of the supply chain, namely: services, upstream and midstream suppliers, and downstream clients. The first phase of the proposed research consists of gathering the available production and financial data. A second phase will be the statistical treatment of the data in order to evaluate the importance of the bullwhip effect in the oil and gas industry. The third phase of the program involves applying artificial neural networks (ANN) to forecast the demand. At this stage, ANN based on different training methods will be used. Further on, the attained mathematical model will be used to simulate the effects of demand fluctuations and assess the bullwhip effect in an oil and gas supply chain.
Introduction to Survival Analysis in Practice
Authors: Emmert-Streib Frank , Dehmer Matthias
Published: September 2019

The modeling of time to event data is an important topic with many applications in diverse areas. The collective of methods to analyze such data are called survival analysis, event history analysis or duration analysis. Survival analysis is widely applicable because the definition of an ’event’ can be manifold and examples include death, graduation, purchase or bankruptcy. Hence, application areas range from medicine and sociology to marketing and economics. In this paper, we review the theoretical basics of survival analysis including estimators for survival and hazard functions. We discuss the Cox Proportional Hazard Model in detail and also approaches for testing the proportional hazard (PH) assumption. Furthermore, we discuss stratified Cox models for cases when the PH assumption does not hold. Our discussion is complemented with a worked example using the statistical programming language R to enable the practical application of the methodology.
Sparse Recovery Algorithm for Compressed Sensing Using Smoothed l0 Norm and Randomized Coordinate Descent
Authors: Jin Dingfei , Yang Guang , Li Zhenghui , Liu Haode
Published: September 2019

Compressed sensing theory is widely used in the field of fault signal diagnosis and image processing. Sparse recovery is one of the core concepts of this theory. In this paper, we proposed a sparse recovery algorithm using a smoothed l0 norm and a randomized coordinate descent (RCD), then applied it to sparse signal recovery and image denoising. We adopted a new strategy to express the (P0) problem approximately and put forward a sparse recovery algorithm using RCD. In the computer simulation experiments, we compared the performance of this algorithm to other typical methods. The results show that our algorithm possesses higher precision in sparse signal recovery. Moreover, it achieves higher signal to noise ratio (SNR) and faster convergence speed in image denoising.
Epigenetic Modification and Differentiation Induction of Malignant Glioma Cells by Oligo-Fucoidan
Authors: Liao Chien-Huang , Lai I-Chun , Kuo Hui-Ching , Chuang Shuang-En , Lee Hsin-Lun , Whang-Peng Jacqueline , Yao Chih-Jung , Lai Gi-Ming
Published: September 2019

Malignant glioma (MG) is a poor prognostic brain tumor with inevitable recurrence after multimodality treatment. Searching for more effective treatment is urgently needed. Differentiation induction via epigenetic modification has been proposed as a potential anticancer strategy. Natural products are known as fruitful sources of epigenetic modifiers with wide safety margins. We thus explored the effects of oligo-fucoidan (OF) from brown seaweed on this notion in MG cells including Grade III U87MG cells and Grade IV glioblastoma multiforme (GBM)8401 cells and compared to the immortalized astrocyte SVGp12 cells. The results showed that OF markedly suppress the proliferation of MG cells and only slightly affected that of SVGp12 cells. OF inhibited the protein expressions of DNA methyltransferases 1, 3A and 3B (DNMT1, 3A and 3B) accompanied with obvious mRNA induction of differentiation markers (MBP, OLIG2, S100β, GFAP, NeuN and MAP2) both in U87MG and GBM8401 cells. Accordingly, the methylation of p21, a DNMT3B target gene, was decreased by OF. In combination with the clinical DNMT inhibitor decitabine, OF could synergize the growth inhibition and MBP induction in U87MG cells. Appropriated clinical trials are warranted to evaluate this potential complementary approach for MG therapy after confirmation of the effects in vivo.
Bioactive Aliphatic Sulfates from Marine Invertebrates
Authors: Kellner Filho Luis C. , Picão Bruno W. , Silva Marcio L. A. , Cunha Wilson R. , Pauletti Patricia M. , Dias Gustavo M. , Copp Brent R. , Bertanha Camila S. , Januario Ana H.
Published: September 2019

The occurrence of sulfated steroids and phenolics in marine organisms is quite widespread, being typically reported from Echinoderms. In contrast, alkane and alkene aliphatic sulfates are considerably rarer with examples being reported from a diverse array of organisms including echinoderms, sponges and ascidians. While no ecological roles for these metabolites have been proposed, they do exhibit a diverse array of biological activities including thrombin inhibition; the ability to induce metamorphosis in larvae; antiproliferative, antibacterial and antifungal properties; and metalloproteinase inhibition. Of particular interest and an avenue for future development is the finding of antifouling properties with low or nontoxic effects to the environment. This review focuses on alkyl sulfates and related sulfamates, their structures and biological activities. Spectroscopic and spectrometric techniques that can be used to recognize the presence of sulfate groups are also discussed, data for which will enhance the ability of researchers to recognize this class of chemically- and biologically-interesting marine natural products.
Lay People Esthetic Evaluation of Primary Surgical Repair on Three-Dimensional Images of Cleft Lip and Palate Patients
Authors: Staderini Edoardo , De Luca Marilisa , Candida Ettore , Rizzo Maria Ida , Rajabtork Zadeh Oriana , Bucci Daria , Zama Mario , Lajolo Carlo , Cordaro Massimo , Gallenzi Patrizia
Published: September 2019

Background and Objectives: Previous literature has disclosed that facial attractiveness affects the esthetic evaluation of nose and lip deformity on frontal and lateral photographs. However, it has never been debated if the removal of the external facial features on three-dimensional (3D) models (“cropped assessment bias”) could provide a considerable usefulness in the interpretation and comparison of the results. Additionally, it has been assumed on two-dimensional (2D) studies that esthetic assessment biases with respect to observer gender, and it is not acknowledged if and to the extent that “gender assessment bias” may be influenced by a three-dimensional layout. The aim of this study is to investigate if facial traits and observers’ gender may affect the esthetic ratings of unilateral cleft lip and palate (UCLP) patients after soft tissue reconstruction. Materials and Methods: Three-dimensional images of ten UCLP patients’ images were acquired before the intervention (T0), one-month (T1) and six-months (T2) postoperative. Geomagic® software (version 2014; 3D Systems, Rock Hill, SC, USA) was used to remove the external facial features of 3D surface models. Five-point scale developed by Asher-McDade et al. was used to rate both nasolabial attractiveness and impairment for full-face (FF) and cropped-face (CF) 3D images. Forty-three judges (21 males, 22 females) were enrolled for the esthetic evaluation. Intraclass correlation coefficient (ICC) was used to test intra- and inter-examiner reliability; a value of 0.7 was set as the minimum acceptable level of reliability. Results: When comparing the 2 sets of observations (FF and CF), the ICC ranged from 0.654 to 0.823. Concerning gender assessment bias, the ICC ranged from 0.438 to 0.686 and from 0.722 to 0.788 for males and females, respectively. Concerning inter-examiner reliability, ICC for questions 2–7 ranged from 0.448 to 0.644 and from 0.659 to 0.817 at T0 and T2, respectively. Conclusions: The removal of external facial features provides subtle differences on the esthetic assessment of UCLP patients. Moreover, based on our data, examiners’ gender differences may affect esthetic assessment of UCLP patients. Despite the subjectivity of esthetic judgments, a reliable, validated and reproducible scoring protocol should consider the influence of gender differences on 3D esthetic assessment of UCLP patients.