bluuebunny/crossref_metadata_2025 huggingface dataset:
Gene Delivery Therapeutics in the Treatment of Periodontitis and Peri-Implantitis: A State of the Art Review
Authors: Goker Funda , Larsson Lena , Del Fabbro Massimo , Asa’ad Farah
Published: July 2019

Background: Periodontal disease is a chronic inflammatory condition that affects supporting tissues around teeth, resulting in periodontal tissue breakdown. If left untreated, periodontal disease could have serious consequences; this condition is in fact considered as the primary cause of tooth loss. Being highly prevalent among adults, periodontal disease treatment is receiving increased attention from researchers and clinicians. When this condition occurs around dental implants, the disease is termed peri-implantitis. Periodontal regeneration aims at restoring the destroyed attachment apparatus, in order to improve tooth stability and thus reduce disease progression and subsequent periodontal tissue breakdown. Although many biomaterials have been developed to promote periodontal regeneration, they still have their own set of disadvantages. As a result, regenerative medicine has been employed in the periodontal field, not only to overcome the drawbacks of the conventional biomaterials but also to ensure more predictable regenerative outcomes with minimal complications. Regenerative medicine is considered a part of the research field called tissue engineering/regenerative medicine (TE/RM), a translational field combining cell therapy, biomaterial, biomedical engineering and genetics all with the aim to replace and restore tissues or organs to their normal function using in vitro models for in vivo regeneration. In a tissue, cells are responding to different micro-environmental cues and signaling molecules, these biological factors influence cell differentiation, migration and cell responses. A central part of TE/RM therapy is introducing drugs, genetic materials or proteins to induce specific cellular responses in the cells at the site of tissue repair in order to enhance and improve tissue regeneration. In this review, we present the state of art of gene therapy in the applications of periodontal tissue and peri-implant regeneration. Purpose: We aim herein to review the currently available methods for gene therapy, which include the utilization of viral/non-viral vectors and how they might serve as therapeutic potentials in regenerative medicine for periodontal and peri-implant tissues.
Cardiac Insulin Resistance in Heart Failure: The Role of Mitochondrial Dynamics
Authors: Saotome Masao , Ikoma Takenori , Hasan Prottoy , Maekawa Yuichiro
Published: July 2019

Heart failure (HF) frequently coexists with conditions associated with glucose insufficiency, such as insulin resistance and type 2 diabetes mellitus (T2DM), and patients with T2DM have a significantly high incidence of HF. These two closely related diseases cannot be separated on the basis of their treatment. Some antidiabetic drugs failed to improve cardiac outcomes in T2DM patients, despite lowering glucose levels sufficiently. This may be, at least in part, due to a lack of understanding of cardiac insulin resistance. Basic investigations have revealed the significant contribution of cardiac insulin resistance to the pathogenesis and progression of HF; however, there is no clinical evidence of the definition or treatment of cardiac insulin resistance. Mitochondrial dynamics play an important role in cardiac insulin resistance and HF because they maintain cellular homeostasis through energy production, cell survival, and cell proliferation. The innovation of diagnostic tools and/or treatment targeting mitochondrial dynamics is assumed to improve not only the insulin sensitivity of the myocardium and cardiac metabolism, but also the cardiac contraction function. In this review, we summarized the current knowledge on the correlation between cardiac insulin resistance and progression of HF, and discussed the role of mitochondrial dynamics on the pathogenesis of cardiac insulin resistance and HF. We further discuss the possibility of mitochondria-targeted intervention to improve cardiac metabolism and HF.
Purification, Characterization of Two Polysaccharides from Pinelliae Rhizoma Praeparatum Cum Alumine and Their Anti-Inflammatory Effects on Mucus Secretion of Airway Epithelium
Authors: Hu Meibian , Liu Yujie , Wang Li , Wang Jiaolong , Li Lin , Wu Chunjie
Published: July 2019

Pinelliae Rhizoma Praeparatum cum Alumine (PRPCA) is an important traditional processed herbal medicine mainly used for treating phlegm in China for more than 2000 years. In our previous studies, extraction optimization, characterization, and bioactivities of total polysaccharides from PRPCA were investigated. In this study, further purification of these polysaccharides was performed. Two polysaccharides named neutral fraction of total polysaccharides-II (TPN-II) and acidic fraction of total polysaccharides-II (TPA-II) were obtained by gradient ion-exchange chromatography followed by gel-permeation chromatography. Results of scanning electron microscopy (SEM) analysis in the present study showed that TPN-II had a tight structure with a rough and uneven surface, while TPA-II had a relative homogeneous surface and a loose structure. Further studies indicated that TPN-II was a homosaccharide mainly composed by glucose with a molecular weight of 8.0 kDa. TPA-II was mainly composed of mannose, rhamnose, glucuronic acid, galacturonic acid, glucose, galactose and arabinose in a molar ratio of 2.1, 2.3, 1.7, 10.6, 2.6, 14.2, and 2.5, with a molecular weight of 1250 kDa. The nuclear magnetic resonance (NMR) results indicated that α and β form glycoside bonds existed in TPN-II and TPA-II, and TPN-II was composed of α-glucopyranose. In addition, both purified polysaccharides have significant anti-inflammatory effects on mucus secretion of human airway epithelial NCI-H292 cells without cytotoxicity. Compared with TPN-II, TPA-II exhibited more significant anti-inflammatory effects on lipopolysaccharide (LPS)-induced airway inflammation by regulating levels of interleukin-4 (IL-4) and interferon-γ (IFN-γ) and inhibiting mucus secretion. The results suggest that polysaccharides from PRPCA could be explored as therapeutic agents in treating inflammation and over secretion of mucus in asthma.
Sphingolipid-Transporting Proteins as Cancer Therapeutic Targets
Authors: Samaha Doaa , Hamdo Housam H. , Wilde Max , Prause Kevin , Arenz Christoph
Published: July 2019

The understanding of the role of sphingolipid metabolism in cancer has tremendously increased in the past ten years. Many tumors are characterized by imbalances in sphingolipid metabolism. In many cases, disorders of sphingolipid metabolism are also likely to cause or at least promote cancer. In this review, sphingolipid transport proteins and the processes catalyzed by them are regarded as essential components of sphingolipid metabolism. There is much to suggest that these processes are often rate-limiting steps for metabolism of individual sphingolipid species and thus represent potential target structures for pharmaceutical anticancer research. Here, we summarize empirical and biochemical data on different proteins with key roles in sphingolipid transport and their potential role in cancer.
RcAP1, a Homolog of APETALA1, is Associated with Flower Bud Differentiation and Floral Organ Morphogenesis in Rosa chinensis
Authors: Han Yu , Tang Aoying , Yu Jiayao , Cheng Tangren , Wang Jia , Yang Weiru , Pan Huitang , Zhang Qixiang
Published: July 2019

Rosa chinensis is one of the most popular flower plants worldwide. The recurrent flowering trait greatly enhances the ornamental value of roses, and is the result of the constant formation of new flower buds. Flower bud differentiation has always been a major topic of interest among researchers. The APETALA1 (AP1) MADS-box (Mcm1, Agamous, Deficiens and SRF) transcription factor-encoding gene is important for the formation of the floral meristem and floral organs. However, research on the rose AP1 gene has been limited. Thus, we isolated AP1 from Rosa chinensis ‘Old Blush’. An expression analysis revealed that RcAP1 was not expressed before the floral primordia formation stage in flower buds. The overexpression of RcAP1 in Arabidopsis thaliana resulted in an early-flowering phenotype. Additionally, the virus-induced down-regulation of RcAP1 expression delayed flowering in ‘Old Blush’. Moreover, RcAP1 was specifically expressed in the sepals of floral organs, while its expression was down-regulated in abnormal sepals and leaf-like organs. These observations suggest that RcAP1 may contribute to rose bud differentiation as well as floral organ morphogenesis, especially the sepals. These results may help for further characterization of the regulatory mechanisms of the recurrent flowering trait in rose.
Autophagy: New Insights into Mechanisms of Action and Resistance of Treatment in Acute Promyelocytic leukemia
Authors: Moosavi Mohammad Amin , Djavaheri-Mergny Mojgan
Published: July 2019

Autophagy is one of the main cellular catabolic pathways controlling a variety of physiological processes, including those involved in self-renewal, differentiation and death. While acute promyelocytic leukemia (APL) cells manifest low levels of expression of autophagy genes associated with reduced autophagy activity, the introduction of all-trans retinoid acid (ATRA)—a differentiating agent currently used in clinical settings—restores autophagy in these cells. ATRA-induced autophagy is involved in granulocytes differentiation through a mechanism that involves among others the degradation of the PML-RARα oncoprotein. Arsenic trioxide (ATO) is another anti-cancer agent that promotes autophagy-dependent clearance of promyelocytic leukemia retinoic acid receptor alpha gene (PML-RARα) in APL cells. Hence, enhancing autophagy may have therapeutic benefits in maturation-resistant APL cells. However, the role of autophagy in response to APL therapy is not so simple, because some autophagy proteins have been shown to play a pro-survival role upon ATRA and ATO treatment, and both agents can activate ETosis, a type of cell death mediated by the release of neutrophil extracellular traps (ETs). This review highlights recent findings on the impact of autophagy on the mechanisms of action of ATRA and ATO in APL cells. We also discuss the potential role of autophagy in the development of resistance to treatment, and of differentiation syndrome in APL.
Unique Phase Transition of Exogenous Fusion Elastin-like Polypeptides in the Solution Containing Polyethylene Glycol
Authors: Ge Zhongqi , Xiong Ziyang , Zhang Dandan , Li Xialan , Zhang Guangya
Published: July 2019

Elastin-Like polypeptides (ELPs), as well-known temperature-controlled bio-macromolecules, are widely used. However, little is known about the interactions between ELPs and macromolecules, which is an important yet neglected problem. Here, the phase transition characteristics of an ELPs-SpyCatcher fusion protein (E-C) in the presence of polyethylene glycol (PEG) in single salts (Na2CO3, Na2SO4, NaCl) solutions were investigated using a UV spectrophotometer, DLC, and fluorescence spectroscopy, and we got some interesting results. The phases transition of E-C occurred at a concentration lower than 0.5 mol/L Na2CO3/PEG2000, while in single Na2CO3 (<0.5 mol/L), the phase transition of E-C did not occur. In the Na2CO3/PEG solution, we observed a unique two-step phase transition of E-C when the Na2CO3 concentration was 0.5 mol/L and PEG2000 concentration was less than 0.15 g/mL, respectively. In the Na2CO3/PEG2000 solution, the phase-transition temperature of E-C decreased with the increase of PEG concentration, but increased in the Na2SO4/PEG2000 solution, while it remained unchanged in the NaCl/PEG2000 solution. However, the phase-transition temperature of the linear ELPs40 decreased under the same salts/PEG2000 solutions. We also addressed the possible molecular mechanism of the interesting results. In contrast to the current well-understood salts-ELPs interactions, this work provides some new insights into the interaction between the PEG-salts-ELPs in solution.
The Atherogenic Role of Circulating Modified Lipids in Atherosclerosis
Authors: Summerhill Volha I. , Grechko Andrey V. , Yet Shaw-Fang , Sobenin Igor A. , Orekhov Alexander N.
Published: July 2019

Lipid accumulation in the arterial wall is a crucial event in the development of atherosclerotic lesions. Circulating low-density lipoprotein (LDL) is the major source of lipids that accumulate in the atherosclerotic plaques. It was discovered that not all LDL is atherogenic. In the blood plasma of atherosclerotic patients, LDL particles are the subject of multiple enzymatic and non-enzymatic modifications that determine their atherogenicity. Desialylation is the primary and the most important atherogenic LDL modification followed by a cascade of other modifications that also increase blood atherogenicity. The enzyme trans-sialidase is responsible for the desialylation of LDL, therefore, its activity plays an important role in atherosclerosis development. Moreover, circulating modified LDL is associated with immune complexes that also have a strong atherogenic potential. Moreover, it was shown that antibodies to modified LDL are also atherogenic. The properties of modified LDL were described, and the strong evidence indicating that it is capable of inducing intracellular accumulation of lipids was presented. The accumulated evidence indicated that the molecular properties of modified LDL, including LDL-containing immune complexes can serve as the prognostic/diagnostic biomarkers and molecular targets for the development of anti-atherosclerotic drugs.
Vitamin D Alleviates Rotavirus Infection through a Microrna-155-5p Mediated Regulation of the TBK1/IRF3 Signaling Pathway In Vivo and In Vitro
Authors: Zhao Ye , Ran Zhiming , Jiang Qin , Hu Ningming , Yu Bing , Zhu Li , Shen Linyuan , Zhang Shunhua , Chen Lei , Chen Hong , Jiang Jun , Chen Daiwen
Published: July 2019

(1) Background: Vitamin D (VD) plays a vital role in anti-viral innate immunity. However, the role of VD in anti-rotavirus and its mechanism is still unclear. The present study was performed to investigate whether VD alleviates rotavirus (RV) infection through a microRNA-155-5p (miR-155-5p)-mediated regulation of TANK-binding kinase 1 (TBK1)/interferon regulatory factors 3 (IRF3) signaling pathway in vivo and in vitro. (2) Methods: The efficacy of VD treatment was evaluated in DLY pig and IPEC-J2. Dual-luciferase reporter activity assay was performed to verify the role of miR-155-5p in 1α,25-dihydroxy-VD3 (1,25D3) mediating the regulation of the TBK1/IRF3 signaling pathway. (3) Results: A 5000 IU·kg–1 dietary VD3 supplementation attenuated RV-induced the decrease of the villus height and crypt depth (p < 0.05), and up-regulated TBK1, IRF3, and IFN-β mRNA expressions in the jejunum (p < 0.05). Incubation with 1,25D3 significantly decreased the RV mRNA expression and the RV antigen concentration, and increased the TBK1 mRNA and protein levels, and the phosphoprotein IRF3 (p-IRF3) level (p < 0.05). The expression of miR-155-5p was up-regulated in response to an RV infection in vivo and in vitro (p < 0.05). 1,25D3 significantly repressed the up-regulation of miR-155-5p in vivo and in vitro (p < 0.05). Overexpression of miR-155-5p remarkably suppressed the mRNA and protein levels of TBK1 and p-IRF3 (p < 0.01), while the inhibition of miR-155-5p had an opposite effect. Luciferase activity assays confirmed that miR-155-5p regulated RV replication by directly targeting TBK1, and miR-155-5p suppressed the TBK1 protein level (p < 0.01). (4) Conclusions: These results indicate that miR-155-5p is involved in 1,25D3 mediating the regulation of the TBK1/IRF3 signaling pathway by directly targeting TBK1.
High Mobility Group Box 1 Mediates TMAO-Induced Endothelial Dysfunction
Authors: Singh Gurinder Bir , Zhang Yang , Boini Krishna M. , Koka Saisudha
Published: July 2019

The intestinal microbe-derived metabolite trimethylamine N-oxide (TMAO) is implicated in the pathogenesis of cardiovascular diseases (CVDs). The molecular mechanisms of how TMAO induces atherosclerosis and CVDs’ progression are still unclear. In this regard, high-mobility group box protein 1 (HMGB1), an inflammatory mediator, has been reported to disrupt cell–cell junctions, resulting in vascular endothelial hyper permeability leading to endothelial dysfunction. The present study tested whether TMAO associated endothelial dysfunction results via HMGB1 activation. Biochemical and RT-PCR analysis showed that TMAO increased the HMGB1 expression in a dose-dependent manner in endothelial cells. However, prior treatment with glycyrrhizin, an HMGB1 binder, abolished the TMAO-induced HMGB1 production in endothelial cells. Furthermore, Western blot and immunofluorescent analysis showed significant decrease in the expression of cell–cell junction proteins ZO-2, Occludin, and VE-cadherin in TMAO treated endothelial cells compared with control cells. However, prior treatment with glycyrrhizin attenuated the TMAO-induced cell–cell junction proteins’ disruption. TMAO increased toll-like receptor 4 (TLR4) expression in endothelial cells. Inhibition of TLR4 expression by TLR4 siRNA protected the endothelial cells from TMAO associated tight junction protein disruption via HMGB1. In conclusion, our results demonstrate that HMGB1 is one of the important mediators of TMAO-induced endothelial dysfunction.
The Maize Clade A PP2C Phosphatases Play Critical Roles in Multiple Abiotic Stress Responses
Authors: He Zhenghua , Wu Jinfeng , Sun Xiaopeng , Dai Mingqiu
Published: July 2019

As the core components of abscisic acid (ABA) signal pathway, Clade A PP2C (PP2C-A) phosphatases in ABA-dependent stress responses have been well studied in Arabidopsis. However, the roles and natural variations of maize PP2C-A in stress responses remain largely unknown. In this study, we investigated the expression patterns of ZmPP2C-As treated with multiple stresses and generated transgenic Arabidopsis plants overexpressing most of the ZmPP2C-A genes. The results showed that the expression of most ZmPP2C-As were dramatically induced by multiple stresses (drought, salt, and ABA), indicating that these genes may have important roles in response to these stresses. Compared with wild-type plants, ZmPP2C-A1, ZmPP2C-A2, and ZmPP2C-A6 overexpression plants had higher germination rates after ABA and NaCl treatments. ZmPP2C-A2 and ZmPP2C-A6 negatively regulated drought responses as the plants overexpressing these genes had lower survival rates, higher leaf water loss rates, and lower proline accumulation compared to wild type plants. The natural variations of ZmPP2C-As associated with drought tolerance were also analyzed and favorable alleles were detected. We widely studied the roles of ZmPP2C-A genes in stress responses and the natural variations detected in these genes have the potential to be used as molecular markers in genetic improvement of maize drought tolerance.
Smooth Muscle Phenotype in Idiopathic Pulmonary Hypertension: Hyper-Proliferative but not Cancerous
Authors: Perros Frédéric , Sentenac Pierre , Boulate David , Manaud Grégoire , Kotsimbos Tom , Lecerf Florence , Lamrani Lilia , Fadel Elie , Mercier Olaf , Londono-Vallejo Arturo , Humbert Marc , Eddahibi Saadia
Published: July 2019

Idiopathic pulmonary arterial hypertension (IPAH) is a complex disease associated with vascular remodeling and a proliferative disorder in pulmonary artery smooth muscle cells (PASMCs) that has been variably described as having neoplastic features. To decode the phenotype of PASMCs in IPAH, PASMCs from explanted lungs of patients with IPAH (IPAH-PASMCs) and from controls (C-PASMCs) were cultured. The IPAH-PASMCs grew faster than the controls; however, both growth curves plateaued, suggesting contact inhibition in IPAH cells. No proliferation was seen without stimulation with exogenous growth factors, suggesting that IPAH cells are incapable of self-sufficient growth. IPAH-PASMCs were more resistant to apoptosis than C-PASMCs, consistent with the increase in the Bcl2/Bax ratio. As cell replication is governed by telomere length, these parameters were assessed jointly. Compared to C-PASMCs, IPAH-PASMCs had longer telomeres, but a limited replicative capacity. Additionally, it was noted that IPAH-PASMCs had a shift in energy production from mitochondrial oxidative phosphorylation to aerobic glycolysis. As DNA damage and genomic instability are strongly implicated in IPAH development a comparative genomic hybridization was performed on genomic DNA from PASMCs which showed multiple break-points unaffected by IPAH severity. Activation of DNA damage/repair factors (γH2AX, p53, and GADD45) in response to cisplatin was measured. All proteins showed lower phosphorylation in IPAH samples than in controls, suggesting that the cells were resistant to DNA damage. Despite the cancer-like processes that are associated with end-stage IPAH-PASMCs, we identified no evidence of self-sufficient proliferation in these cells—the defining feature of neoplasia.
Behavior of Embedded Cation-Exchange Particles in a DC Electric Field
Authors: Vobecká Lucie , Belloň Tomáš , Slouka Zdeněk
Published: July 2019

Electrodialysis and electrodeionization are separation processes whose performance depends on the quality and properties of ion-exchange membranes. One of the features that largely affects these properties is heterogeneity of the membranes both on the macroscopic and microscopic level. Macroscopic heterogeneity is an intrinsic property of heterogeneous ion-exchange membranes. In these membranes, the functional ion-exchange component is dispersed in a non-conductive binder. The functional component is finely ground ion-exchange resin particles. The understanding of the effect of structure on the heterogeneous membrane properties and behavior is thus of utmost importance since it does not only affect the actual performance but also the cost and therefore competitiveness of the aforementioned separation processes. Here we study the electrokinetic behavior of cation-exchange resin particle systems with well-defined geometrical structure. This approach can be understood as a bottom up approach regarding the membrane preparation. We prepare a structured cation-exchange membrane by using its fundamental component, which is the ion exchange resin. We then perform an experimental study with four different experimental systems in which the number of used cation-exchange particles changes from 1 to 4. These systems are studied by means of basic electrochemical characterization measurements, such as measurement of current–voltage curves and direct optical observation of phenomena that occur at the interface between the ion-exchange system and the adjacent electrolyte. Our work aims at better understanding of the relation between the structure and the membrane properties and of how structure affects electrokinetic behavior of these systems.
On the Aqueous Solution Behavior of C-Substituted 3,1,2-Ruthenadicarbadodecaboranes
Authors: Gozzi Marta , Schwarze Benedikt , Coburger Peter , Hey-Hawkins Evamarie
Published: July 2019

3,1,2-Ruthenadicarbadodecaborane complexes bearing the [C2B9H11]2− (dicarbollide) ligand are robust scaffolds, with exceptional thermal and chemical stability. Our previous work has shown that these complexes possess promising anti-tumor activities in vitro, and tend to form aggregates (or self-assemblies) in aqueous solutions. Here, we report on the synthesis and characterization of four ruthenium(II) complexes of the type [3-(η6-arene)-1,2-R2-3,1,2-RuC2B9H9], bearing either non-polar (R = Me (2–4)) or polar (R = CO2Me (7)) substituents at the cluster carbon atoms. The behavior in aqueous solution of complexes 2, 7 and the parent unsubstituted [3-(η6-p-cymene)-3,1,2-RuC2B9H11] (8) was investigated via UV-Vis spectroscopy, mass spectrometry and nanoparticle tracking analysis (NTA). All complexes showed spontaneous formation of self-assemblies (108–109 particles mL−1), at low micromolar concentration, with high polydispersity. For perspective applications in medicine, there is thus a strong need for further characterization of the spontaneous self-assembly behavior in aqueous solutions for the class of neutral metallacarboranes, with the ultimate scope of finding the optimal conditions for exploiting this self-assembling behavior for improved biological performance.
The Effects of an Energy Drink on Psychomotor Vigilance in Trained Individuals
Authors: Antonio Jose , Kenyon Madaline , Horn Christopher , Jiannine Lia , Carson Cassandra , Ellerbroek Anya , Roberts Justin , Peacock Corey , Tartar Jaime
Published: July 2019

The psychomotor vigilance test (PVT) measures one’s behavioral alertness. It is a visual test that involves measuring the speed at which a person reacts to visual stimuli over a fixed time frame (e.g., 5 min). The purpose of this study was to assess the effects of an energy drink on psychomotor vigilance as well as a simple measure of muscular endurance (i.e., push-ups). A total of 20 exercise-trained men (n = 11) and women (n = 9) (mean ± SD: age 32 ± 7 years; height 169 ± 10 cm; weight; 74.5 ± 14.5 kg; percent body fat 20.3 ± 6.2%; years of training 14 ± 9; daily caffeine intake 463 ± 510 mg) volunteered for this randomized, double-blind, placebo-controlled, crossover trial. In a randomized counterbalanced order, they consumed either the energy drink (ED) (product: BANG®, Weston Florida) or a similar tasting placebo drink (PL). In the second visit after a 1-week washout period, they consumed the alternate drink. A full 30 min post-consumption, they performed the following tests in this order: a 5-min psychomotor vigilance test, three sets of push-ups, followed once more by a 5-min psychomotor vigilance test. Reaction time was recorded. For the psychomotor vigilance test, lapses, false starts and efficiency score are also assessed. There were no differences between groups for the number of push-ups that were performed or the number of false starts during the psychomotor vigilance test. However, the ED treatment resulted in a significantly lower (i.e., faster) psychomotor vigilance mean reaction time compared to the PL (p = 0.0220) (ED 473.8 ± 42.0 milliseconds, PL 482.4 ± 54.0 milliseconds). There was a trend for the ED to lower the number of lapses (i.e., reaction time > 500 milliseconds) (p = 0.0608). The acute consumption of a commercially available ED produced a significant improvement in psychomotor vigilance in exercise-trained men and women.
Emerging Fungal Infections: New Patients, New Patterns, and New Pathogens
Authors: Friedman Daniel Z.P. , Schwartz Ilan S.
Published: July 2019

The landscape of clinical mycology is constantly changing. New therapies for malignant and autoimmune diseases have led to new risk factors for unusual mycoses. Invasive candidiasis is increasingly caused by non-albicans Candida spp., including C. auris, a multidrug-resistant yeast with the potential for nosocomial transmission that has rapidly spread globally. The use of mould-active antifungal prophylaxis in patients with cancer or transplantation has decreased the incidence of invasive fungal disease, but shifted the balance of mould disease in these patients to those from non-fumigatus Aspergillus species, Mucorales, and Scedosporium/Lomentospora spp. The agricultural application of triazole pesticides has driven an emergence of azole-resistant A. fumigatus in environmental and clinical isolates. The widespread use of topical antifungals with corticosteroids in India has resulted in Trichophyton mentagrophytes causing recalcitrant dermatophytosis. New dimorphic fungal pathogens have emerged, including Emergomyces, which cause disseminated mycoses globally, primarily in HIV infected patients, and Blastomyces helicus and B. percursus, causes of atypical blastomycosis in western parts of North America and in Africa, respectively. In North America, regions of geographic risk for coccidioidomycosis, histoplasmosis, and blastomycosis have expanded, possibly related to climate change. In Brazil, zoonotic sporotrichosis caused by Sporothrix brasiliensis has emerged as an important disease of felines and people.
The Burden of Serious Fungal Infections in Tajikistan
Authors: Bobokhojaev Oktam I. , Osmanov Ali , Aliev Samariddin P. , Radjabzoda Asliddin S. , Avgonov Ziyovuddin T. , Manonov Safarbek T. , Denning David W.
Published: July 2019

Tajikistan is a low-income country in Middle Asia with a population of 8.9 million people. Five percent of the population lives on less than 1.9 USD a day and 54% live on less than 5.5 USD a day. We have estimated the burden of serious fungal infections in Tajikistan. It was estimated that 168,834 Tajik women develop recurrent vulvovaginal candidiasis. Among HIV-positive patients, we estimate 490 patients with oesophageal candidiasis and 1260 patients with oral candidiasis, 41 cases of cryptococcal meningitis and 210 cases of Pneumocystis pneumonia annually. According to our estimations there are 774 cases of chronic pulmonary aspergillosis (CPA) as a sequel of tuberculosis; CPA may occur as a consequence of multiple pulmonary conditions and the total prevalence of 4161 cases was estimated. We have estimated 6008 cased of allergic bronchopulmonary aspergillosis (ABPA) and 7930 cases of severe asthma with fungal sensitisation (SAFS), and 137 fungal asthma deaths annually. We have estimated 445 cases of candidemia a year applying a low European rate. There are approximately 283 cases of invasive aspergillosis annually. There are 189,662 (2.1% of the population) people suffering from serious fungal infections in Tajikistan. Hence, improving diagnostics is the first step of understanding a scale of the fungal burden.
Evidence of the Environmental Kuznets Curve: Unleashing the Opportunity of Industry 4.0 in Emerging Economies
Authors: Koilo Viktoriia
Published: July 2019

This study aims to investigate the relationship of economic development, measured as economic growth, energy use, trade and foreign direct investment, on the one hand, and environmental degradation (carbon dioxide (hereafter CO2) emissions), on the other hand, in eleven emerging Eastern European and Central Asian countries during the period of 1990 to 2014. The empirical results give an evidence of a carbon emission Kuznets curve for these emerging economies. The current income level indicates that not every country has reached the turning point for CO2 emissions reductions. Income elasticities for CO2 are positive for all eleven countries. The paper concludes that within the group, Ukraine and Kazakhstan have the most sensitive change in economic growth in respect to CO2. In addition, it concludes that there is a negative effect of total energy consumption on environment as such consumption increases CO2 emissions. The results also show a positive effect of foreign direct investment (FDI) on CO2 emissions in Eastern European and Central Asian countries. It is expected that the innovative transition to a low-carbon economy offers great opportunities for economic growth and job creation. Technological leadership (the initiative Industry 4.0) should be accompanied by the development and introduction of new technologies throughout Eastern European and Central Asian countries, hence, the paradigm of “sustainable development” should be considered as fatal. Furthermore, Eastern European and Central Asian economies should consider the experience of policy making implications made by other developing countries in gaining sustainable growth. Econometric analyses prove the existence of different impact on energy consumption of the ICT sector, which plays a key supporting role for intelligent manufacturing. Thus, there is a need for further investigations of the relationship between technology use and CO2 emissions.
Some Dynamic and Steady-State Properties of Threshold Auto-Regressions with Applications to Stationarity and Local Explosivity
Authors: Ahmed Muhammad Farid , Satchell Stephen
Published: July 2019

The purpose of this paper is to investigate the dynamics and steady-state properties of threshold autoregressive models with exogenous states that follow Markovian processes. Markovian processes are widely used in applied economics although their statistical properties have not been explored in detail. We use characteristic functions to carry out the analysis, and this allows us to describe limiting distributions for processes not considered in the literature previously. We also calculate analytical expressions for some moments. Furthermore, we see that we can have locally explosive processes that are explosive in one regime whilst being strongly stationary overall. This is explored through simulation analysis, where we also show how the distribution changes when the explosive state becomes more frequent although the overall process remains stationary. In doing so, we are able to relate our analysis to asset prices which exhibit similar distributional properties.
The Effect of the Pivot Stiffness on the Performances of Five-Pad Tilting Pad Bearings
Authors: Dang Phuoc Vinh , Chatterton Steven , Pennacchi Paolo
Published: July 2019

The role of the pivot flexibility in tilting-pad journal bearings (TPJBs) has become essential, particularly for bearings working at high applied load and relatively high rotor speeds. Predictions from a simple bearing model with rigid pivots show incorrect estimation of the dynamic coefficients in comparison with the experimental results. Normally, the more flexible the pad pivot, the lower the dynamic coefficients because the stiffness of the pivot takes in series with the stiffness and damping of the oil film. This paper investigates the influence of pivot stiffness on the dynamic force coefficients of two different five-pad TPJBs as a function of the applied static load and excitation frequency: rocker-backed pivot and spherical pivot bearings. In order to highlight the effect of the pivot stiffness in the spherical pivot bearing, displacement restriction components and elastic copper made shims have been used. Firstly, a thermo-elasto-hydrodynamic model for the static and dynamic characteristics of the two bearings is described. This model takes into account the flexibility of both pad and pivot. The pivot stiffnesses calculated by means of the Hertz theory and those obtained by experiments have been introduced and compared in the model. The clearance profiles of two tested bearing and the shaft center loci obtained by measurement and prediction are also shown. The dynamic coefficients of the two bearings obtained from the numerical simulation were compared with the experimental results. By the analysis it can be concluded that the effect of the pivot flexibility on the clearance profile, the shaft locus and on the dynamic coefficients is very significant. More important, it is important to estimate the pivot stiffness of each single pad using experimental measurements.
Parameter Estimation of Lindley Distribution Based on Progressive Type-II Censored Competing Risks Data with Binomial Removals
Authors: Nie Jiaxin , Gui Wenhao
Published: July 2019

The competing risk model based on Lindley distribution is discussed under the progressive type-II censored sample data with binomial removals. The maximum likelihood estimation of the unknown parameters of the distribution is established. Using the Lindley approximation method, we also obtain the Bayesian estimation of the unknown parameters of the distribution under different loss functions. The performance of different estimates is studied in this article. A real practical dataset is analyzed for illustration.
The Regularity of Some Families of Circulant Graphs
Authors: Uribe-Paczka Miguel Eduardo , Van Tuyl Adam
Published: July 2019

We compute the Castelnuovo–Mumford regularity of the edge ideals of two families of circulant graphs, which includes all cubic circulant graphs. A feature of our approach is to combine bounds on the regularity, the projective dimension, and the reduced Euler characteristic to derive an exact value for the regularity.
Rapid Metabolome and Bioactivity Profiling of Fungi Associated with the Leaf and Rhizosphere of the Baltic Seagrass Zostera marina
Authors: Petersen Lars-Erik , Marner Michael , Labes Antje , Tasdemir Deniz
Published: July 2019

Zostera marina (eelgrass) is a marine foundation species with key ecological roles in coastal habitats. Its bacterial microbiota has been well studied, but very little is known about its mycobiome. In this study, we have isolated and identified 13 fungal strains, dominated by Penicillium species (10 strains), from the leaf and the root rhizosphere of Baltic Z. marina. The organic extracts of the fungi that were cultured by an OSMAC (One-Strain–Many-Compounds) regime using five liquid culture media under both static and shaking conditions were investigated for their chemical and bioactivity profiles. All extracts showed strong anti-quorum sensing activity, and the majority of the Penicillium extracts displayed antimicrobial or anti-biofilm activity against Gram-negative environmental marine and human pathogens. HPLC-DAD-MS-based rapid metabolome analyses of the extracts indicated the high influence of culture conditions on the secondary metabolite (SM) profiles. Among 69 compounds detected in all Penicillium sp. extracts, 46 were successfully dereplicated. Analysis of SM relatedness in culture conditions by Hierarchical Cluster Analysis (HCA) revealed generally low similarity and showed a strong effect of medium selection on chemical profiles of Penicillium sp. This is the first study assessing both the metabolite and bioactivity profile of the fungi associated with Baltic eelgrass Z. marina.
Cytotoxic Sesquiterpenoid Quinones and Quinols, and an 11-Membered Heterocycle, Kauamide, from the Hawaiian Marine Sponge Dactylospongia elegans
Authors: Neupane Ram P. , Parrish Stephen M. , Bhandari Neupane Jayanti , Yoshida Wesley Y. , Yip M. L. Richard , Turkson James , Harper Mary Kay , Head John D. , Williams Philip G.
Published: July 2019

Several known sesquiterpenoid quinones and quinols (1–9), and kauamide (10), a new polyketide-peptide containing an 11-membered heterocycle, were isolated from the extracts of the Hawaiian marine sponge Dactylospongia elegans. The planar structure of 10 was determined from spectroscopic analyses, and its relative and absolute configurations were established from density functional theory (DFT) calculations of the GIAO NMR shielding tensors, and advanced Marfey’s analysis of the N-MeLeu residue, respectively. Compounds 1 and 3 showed moderate inhibition of β-secretase 1 (BACE1), whereas 1–9 exhibited moderate to potent inhibition of growth of human glioma (U251) cells. Compounds 1–2 and 4–7 were also active against human pancreatic carcinoma (Panc-1) cells.
Abalone Collagen Extracts Potentiate Stem Cell Properties of Human Epidermal Keratinocytes
Authors: Thaweekitphathanaphakdee Sajee , Chanvorachote Pithi , Prateepchinda Sagaw , Khongkow Mattaka , Sucontphunt Apirada
Published: July 2019

Stem cell activities in human tissues are critical for tissue integrity and function. Maintaining keratinocyte stem cells (KSCs) stemness helps sustain healthy skin by supporting keratinocyte renewal, involving the formation of epidermal barriers. In this study, abalone collagen (AC) extracts with molecular weights of 3 kDa (AC 1) and 300 kDa (AC 2) were compared to the epidermal growth factor (EGF) for their effects on cell proliferation, cell migration (wound healing), spheroid formation, and the expression level of stem cell markers on human keratinocytes (HaCaT cells). Cell viability was measured by 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide (MTT) assay and cell proliferation was quantified by ATP and DNA content analysis and Sulforhodamine B (SRB) assays. Cell migration assay was determined using the scratch wound healing test. Spheroid formation was evaluated and the expression level of stem cell markers was investigated by western blot analysis. The results showed that AC 1 at the concentration of 100 µg/mL could stimulate HaCaT cell proliferation, migration, spheroid formation, and the expression level of stem cell markers (keratin 19, β-catenin, ALDH1A1) compared to the control. In conclusion, a smaller molecular weight of abalone collagen extract exhibits a better effect on keratinocytes proliferation, migration, and stemness, which could be a potential active ingredient in cosmeceutical products.
Pinnatoxins’ Deleterious Effects on Cholinergic Networks: From Experimental Models to Human Health
Authors: Delcourt Nicolas , Lagrange Emmeline , Abadie Eric , Fessard Valérie , Frémy Jean-Marc , Vernoux Jean-Paul , Peyrat Marie-Bénédicte , Maignien Thomas , Arnich Nathalie , Molgó Jordi , Mattei César
Published: July 2019

Pinnatoxins (PnTXs) are emerging neurotoxins that were discovered about 30 years ago. They are solely produced by the marine dinoflagellate Vulcanodinium rugosum, and may be transferred into the food chain, as they have been found in various marine invertebrates, including bivalves. No human intoxication has been reported to date although acute toxicity was induced by PnTxs in rodents. LD50 values have been estimated for the different PnTXs through the oral route. At sublethal doses, all symptoms are reversible, and no neurological sequelae are visible. These symptoms are consistent with impairment of central and peripheral cholinergic network functions. In fact, PnTXs are high-affinity competitive antagonists of nicotinic acetylcholine receptors (nAChRs). Moreover, their lethal effects are consistent with the inhibition of muscle nAChRs, inducing respiratory distress and paralysis. Human intoxication by ingestion of PnTXs could result in various symptoms observed in episodes of poisoning with natural nAChR antagonists. This review updates the available data on PnTX toxicity with a focus on their mode of action on cholinergic networks and suggests the effects that could be extrapolated on human physiology.
Genome Sequencing of the Japanese Eel (Anguilla japonica) for Comparative Genomic Studies on tbx4 and a tbx4 Gene Cluster in Teleost Fishes
Authors: Chen Weiwei , Bian Chao , You Xinxin , Li Jia , Ye Lizhen , Wen Zhengyong , Lv Yunyun , Zhang Xinhui , Xu Junmin , Yang Shaosen , Gu Ruobo , Lin Xueqiang , Shi Qiong
Published: July 2019

Limbs originated from paired fish fins are an important innovation in Gnathostomata. Many studies have focused on limb development-related genes, of which the T-box transcription factor 4 gene (tbx4) has been considered as one of the most essential factors in the regulation of the hindlimb development. We previously confirmed pelvic fin loss in tbx4-knockout zebrafish. Here, we report a high-quality genome assembly of the Japanese eel (Anguilla japonica), which is an economically important fish without pelvic fins. The assembled genome is 1.13 Gb in size, with a scaffold N50 of 1.03 Mb. In addition, we collected 24 tbx4 sequences from 22 teleost fishes to explore the correlation between tbx4 and pelvic fin evolution. However, we observed complete exon structures of tbx4 in several pelvic-fin-loss species such as Ocean sunfish (Mola mola) and ricefield eel (Monopterus albus). More interestingly, an inversion of a special tbx4 gene cluster (brip1-tbx4-tbx2b- bcas3) occurred twice independently, which coincides with the presence of fin spines. A nonsynonymous mutation (M82L) was identified in the nuclear localization sequence (NLS) of the Japanese eel tbx4. We also examined variation and loss of hindlimb enhancer B (HLEB), which may account for pelvic fin loss in Tetraodontidae and Diodontidae. In summary, we generated a genome assembly of the Japanese eel, which provides a valuable genomic resource to study the evolution of fish tbx4 and helps elucidate the mechanism of pelvic fin loss in teleost fishes. Our comparative genomic studies, revealed for the first time a potential correlation between the tbx4 gene cluster and the evolutionary development of toxic fin spines. Because fin spines in teleosts are usually venoms, this tbx4 gene cluster may facilitate the genetic engineering of toxin-related marine drugs.
Magnitude and Determinants of Patients at Risk of Developing Obstructive Sleep Apnea in a Non-Communicable Disease Clinic
Authors: Mathiyalagen Prakash , Govindasamy Venkatesh , Rajagopal Anandaraj , Vasudevan Kavita , Gunasekaran Kalaipriya , Yadav Dhananjay
Published: July 2019

Background and Objective: Obstructive sleep apnea (OSA) is a common chronic disorder worldwide, which can adversely affect the cardiovascular system among non-communicable disease (NCD) patients. It is underdiagnosed—or rather not diagnosed—in primary care settings due to the costly diagnostic techniques involved. This study aimed to assess the number of study participants at risk of developing OSA and to assess and quantify the risk factors associated with this disorder. Materials and Methods: A cross-sectional study was performed in an NCD clinic of a rural health training center, Karikalampakkam, Puducherry of South India from August 2018 to October 2018. A Modified Berlin Questionnaire (MBQ) was used to screen the study participants at risk for OSA. Four-hundred-and-seventy-three people aged 18 years and above were included in the study, using systematic random sampling. Respondents’ socio-demographic and morbidity characteristics, as well as clinical and anthropometric parameters including body weight, height, blood pressure, neck, hip and waist circumference were collected. Data was captured using Epicollect5 and analyzed using SPSS version 20.0. Results: One-fourth (25.8%) of the respondents were at high risk of developing OSA. In terms of gender, 27.9% of the men and 23.8% of the women were at high risk for OSA. In univariate analyses, the risk of developing OSA was significantly associated with a history of diabetes mellitus, hypertension, dyslipidemia and gastro-esophageal reflux disease, weight, body mass index, neck, waist and hip circumference, waist–hip ratio, and systolic and diastolic blood pressure. Multivariate logistic regression analysis showed that a history of dyslipidemia (aOR, 95% CI = 2.34, 1.22–4.48), body mass index (aOR, 95% CI = 1.15, 1.06–1.22) and waist circumference (aOR, 95% CI = 1.10, 1.07–1.14) emerged as significant predictors of risk for OSA. Conclusions: A considerable proportion of NCD patients with easily detectable attributes are at risk of developing OSA, but still remain undiagnosed at a primary health care setting. The results obtained using MBQ in this study were comparable to studies performed using polysomnography. Dyslipidemia, body mass index and waist circumference were independent risk factors for predicting a risk of developing OSA. Prospective studies are needed to confirm whether a reduction in these risk factors could reduce the risk for OSA.