bluuebunny/crossref_metadata_2025 huggingface dataset:
ANGPT2 and NOS3 Polymorphisms and Clinical Outcome in Advanced Hepatocellular Carcinoma Patients Receiving Sorafenib
Authors: Marisi Giorgia , Petracci Elisabetta , Raimondi Francesco , Faloppi Luca , Foschi Francesco Giuseppe , Lauletta Gianfranco , Iavarone Massimo , Canale Matteo , Valgiusti Martina , Neri Luca Maria , Ulivi Paola , Orsi Giulia , Rovesti Giulia , Vukotic Ranka , Conti Fabio , Cucchetti Alessandro , Ercolani Giorgio , Andrikou Kalliopi , Cascinu Stefano , Scartozzi Mario , Casadei-Gardini Andrea
Published: July 2019

Sorafenib represents the standard of care for advanced hepatocellular carcinoma (HCC), even though a large number of patients have reported limited efficacy. The aim of the present study was to evaluate the prognostic value of single-nucleotide polymorphisms on angiopoietin-2 (ANGPT2) and endothelial-derived nitric oxide synthase (NOS3) genes in 135 patients with advanced HCC receiving sorafenib. Eight ANGPT2 polymorphisms were analyzed by direct sequencing in relation to overall survival (OS) and progression-free survival (PFS). In univariate analysis, ANGPT2rs55633437 and NOS3 rs2070744 were associated with OS and PFS. In particular, patients with ANGPT2rs55633437 TT/GT genotypes had significantly lower median OS (4.66 vs. 15.5 months, hazard ratio (HR) 4.86, 95% CI 2.73–8.67, p < 0.001) and PFS (1.58 vs. 6.27 months, HR 4.79, 95% CI 2.73–8.35, p < 0.001) than those homozygous for the G allele. Moreover, patients with NOS3 rs2070744 TC/CC genotypes had significantly higher median OS (15.6 vs. 9.1 months, HR 0.65, 95% CI 0.44–0.97; p = 0.036) and PFS (7.03 vs. 3.5 months, HR 0.43, 95% CI 0.30–0.63; p < 0.001) than patients homozygous for the T allele. Multivariate analysis confirmed these polymorphisms as independent prognostic factors. Our results suggest that ANGPT2rs55633437 and NOS3 rs2070744 polymorphisms could identify a subset of HCC patients more resistant to sorafenib.
PD-1/PD-L1 Targeting in Breast Cancer: The First Clinical Evidences are Emerging—A Literature Review
Authors: Planes-Laine Gabrielle , Rochigneux Philippe , Bertucci François , Chrétien Anne-Sophie , Viens Patrice , Sabatier Renaud , Gonçalves Anthony
Published: July 2019

Recently, the development of immunotherapy through the immune checkpoint blockade led to long-lasting responses in several types of cancers that are refractory to conventional treatments, such as melanoma or non-small cell lung cancer. Immunotherapy has also demonstrated significant improvements in various other types of cancers. However, breast cancer remains one of the tumors that have not experienced the explosion of immunotherapy yet. Indeed, breast cancer was traditionally considered as being weakly immunogenic with a lower mutational load compared to other tumor types. In the last few years, anti-PD1/PD-L1 (Programmed death-ligand 1) agents have been evaluated in breast cancer, particularly in the triple negative subtype, with promising results observed when delivered as monotherapy or in combination with conventional treatments. In this review, we will report the results of the most recent studies evaluating immune checkpoint inhibitors in breast cancer. In addition, we will discuss the concomitant development of possible biomarkers, which is required for improving the selection of patients with the highest probability of benefiting from these agents.
Degradation of Sulfamethoxazole Using Iron-Doped Titania and Simulated Solar Radiation
Authors: Tsiampalis Athanasios , Frontistis Zacharias , Binas Vassilios , Kiriakidis George , Mantzavinos Dionissios
Published: July 2019

This work examined the photocatalytic destruction of sulfamethoxazole (SMX), a widely used antibiotic, under simulated solar radiation using iron-doped titanium dioxide as the photocatalyst. Amongst the various iron/titania ratios examined (in the range 0%–2%), the catalyst at 0.04% Fe/TiO2 molar ratio exhibited the highest photocatalytic efficiency. The reaction rate followed pseudo-first-order kinetics, where the apparent kinetic constant was reduced as the initial concentration of SMX or humic acid increased. The photodecomposition of SMX was favored in natural pH but retarded at alkaline conditions. Unexpectedly, the presence of bicarbonates (in the range of 0.125–2 g/L) improved the removal of SMX, however, experiments conducted in real environmental matrices showed that process efficiency decreased as the complexity of the water matrix increased. The presence of sodium persulfate as an electron acceptor enhanced the reaction rate. However, only a small synergy was observed between the two individual processes. On the contrary, the addition of tert-butanol, a well-known hydroxyl radical scavenger, hindered the reaction, indicating the significant contribution of these radicals to the photocatalytic degradation of SMX. The photocatalyst retained half of its initial activity after five successive experiments.
Bench-Scale Steam Reforming of Methane for Hydrogen Production
Authors: Park Hae-Gu , Han Sang-Young , Jun Ki-Won , Woo Yesol , Park Myung-June , Kim Seok Ki
Published: July 2019

The effects of reaction parameters, including reaction temperature and space velocity, on hydrogen production via steam reforming of methane (SRM) were investigated using lab- and bench-scale reactors to identify critical factors for the design of large-scale processes. Based on thermodynamic and kinetic data obtained using the lab-scale reactor, a series of SRM reactions were performed using a pelletized catalyst in the bench-scale reactor with a hydrogen production capacity of 10 L/min. Various temperature profiles were tested for the bench-scale reactor, which was surrounded by three successive cylindrical furnaces to simulate the actual SRM conditions. The temperature at the reactor bottom was crucial for determining the methane conversion and hydrogen production rates when a sufficiently high reaction temperature was maintained (>800 °C) to reach thermodynamic equilibrium at the gas-hourly space velocity of 2.0 L CH4/(h·gcat). However, if the temperature of one or more of the furnaces decreased below 700 °C, the reaction was not equilibrated at the given space velocity. The effectiveness factor (0.143) of the pelletized catalyst was calculated based on the deviation of methane conversion between the lab- and bench-scale reactions at various space velocities. Finally, an idling procedure was proposed so that catalytic activity was not affected by discontinuous operation.
CoSe2 Clusters as Efficient Co-Catalyst Modified CdS Nanorod for Enhance Visible Light Photocatalytic H2 Evolution
Authors: Gan Ruizhou , Ma Xiaohua , Wang Guorong , Jin Zhiliang
Published: July 2019

CoSe2, as a kind of co-catalyst, would replace noble metals element to dope pure CdS. The CoSe2/CdS photocatalyst could be synthesized by simple physical mixing. With the introduction of CoSe2, especially 30% CoSe2/CdS, hydrogen production would be about 500 μmol within 5 h, five times that of pure CdS under the same conditions. The CoSe2/CdS photocatalyst could bear four cycles of hydrogen evolution and sustain the hydrogen production, with a minor decrease. In other words, the electron transition velocity would surge along with the introduction of CoSe2 particles. The CoSe2 could be deemed as the predator and exit of electrons to inspire the detachment of the hole-electron pairs and relieve the recombination of the hole-electron pairs.
Application of Response Surface Methodology for Ethanol Conversion into Hydrocarbons Using ZSM-5 Zeolites
Authors: Souza de Carvalho Filho José Faustino , Maciel Pereira Marcelo , Gomes Aranda Donato Alexandre , Monnerat Araujo Ribeiro de Almeida João , Falabella Sousa-Aguiar Eduardo , Nothaft Romano Pedro
Published: July 2019

The ethanol conversion into hydrocarbons (light olefins and aromatics) using alkali-treated HZSM-5 with different SiO2/Al2O3 ratios (23, 38, and 53) zeolites was evaluated. The desilicated SAR 38 zeolite exhibited significant growth on the external surface area (61–212 m2/g) and the mesopore volume (0.07–0.37 cm3/g) without significate reduction on XRD crystallinity (93%). All catalysts were active on the ethanol conversion into hydrocarbons. At the same set of variables, the alkali-treated HZSM-5 zeolites showed a better conversion and a high selectivity to C4–C9 hydrocarbons when compared to the parent microporous zeolites. Only the parent HZSM-5 zeolite (SAR 53) was chosen for the statistical study using the standard response surface methodology in combination with the central composite design. It was found that maximum BTEX (benzene, toluene, ethylbenzene, and xylenes) and minimum ethylene production were reached for the following conditions: temperature 450 °C, pressure 20 bar, and WHSV (weight hourly space velocity) 5 h−1.
The Effect of CeO2 Preparation Method on the Carbon Pathways in the Dry Reforming of Methane on Ni/CeO2 Studied by Transient Techniques
Authors: Damaskinos Constantinos M. , Vasiliades Michalis A. , Stathopoulos Vassilis N. , Efstathiou Angelos M.
Published: July 2019

The present work discusses the effect of CeO2 synthesis method (thermal decomposition (TD), precipitation (PT), hydrothermal (HT), and sol-gel (SG)) on the carbon pathways of dry reforming of methane with carbon dioxide (DRM) applied at 750 °C over 5 wt% Ni/CeO2. In particular, specific transient and isotopic experiments (use of 13CO, 13CO2, and 18O2) were designed and conducted in an attempt at providing insights about the effect of support’s preparation method on the concentration (mg gcat−1), reactivity towards oxygen, and transient evolution rates (μmol gcat−1 s−1) of the inactive carbon formed under (i) CH4/He (methane decomposition), (ii) CO/He (reverse Boudouard reaction), and (iii) the copresence of the two (CH4/CO/He, use of 13CO). Moreover, important information regarding the relative contribution of CH4 and CO2 activation routes towards carbon formation under DRM reaction conditions was derived by using isotopically labelled 13CO2 in the feed gas stream. Of interest was also the amount, and the transient rate, of carbon removal via the participation of support’s labile active oxygen species.
Advances in Autophagy, Tissue Injury, and Homeostasis: Cells Special Issue
Authors: Lin Pei-Hui
Published: July 2019

Macroautophagy (hereafter referred to as autophagy, a word derived from Greek meaning “auto-digestion”) is a lysosome-dependent quality control process to degrade and turnover damaged or senescent organelles and proteins for cellular renewal [...]
Melatonin and (−)-Epigallocatechin-3-Gallate: Partners in Fighting Cancer
Authors: Zhang Lingyun , He Yufeng , Wu Ximing , Zhao Guangshan , Zhang Ke , Yang Chung S. , Reiter Russel J. , Zhang Jinsong
Published: July 2019

We have demonstrated previously that melatonin attenuates hepatotoxicity triggered by high doses of (−)-epigallocatechin-3-gallate (EGCG) in mice. The current work investigated the influence of melatonin on the oncostatic activity of EGCG in two cancer cell lines, wherein melatonin induced an opposite response of p21. In human tongue cancer TCA8113 cells, melatonin-induced p21 and EGCG-mediated formation of quinoproteins were positively associated with the oncostatic effects of melatonin and EGCG. Melatonin-stimulated an increase in p21 which was correlated with a pronounced nuclear translocation of thioredoxin 1 and thioredoxin reductase 1, both of which are known to induce p21 via promoting p53 trans-activation. Melatonin did not influence the EGCG-mediated increase of quinoprotein formation nor did EGCG impair melatonin-induced p21 up-regulation. Co-treatment with both agents enhanced the cell-killing effect as well as the inhibitory activities against cell migration and colony formation. It is known that p21 also plays a powerful anti-apoptotic role in some cancer cells and confers these cells with a survival advantage, making it a target for therapeutic suppression. In human hepatocellular carcinoma HepG2 cells, melatonin suppressed p21 along with the induction of pro-survival proteins, PI3K and COX-2. However, EGCG prevented against melatonin-induced PI3K and COX-2, and melatonin probably sensitized HepG2 cells to EGCG cytotoxicity via down-regulating p21, Moreover, COX-2 and HO-1 were significantly reduced only by the co-treatment, and melatonin aided EGCG to achieve an increased inhibition on Bcl2 and NFκB. These events occurring in the co-treatment collectively resulted in an enhanced cytotoxicity. In addition, the co-treatment also enhanced the inhibitory activities against cell migration and colony formation. Overall, the results gathered from these two cancer cell lines with a divergent p21 response to melatonin show that the various oncostatic activities of melatonin and EGCG together are more robust than each agent alone, suggesting that they may be useful partners in fighting cancer.
Roscovitine Attenuates Microglia Activation and Monocyte Infiltration via p38 MAPK Inhibition in the Rat Frontoparietal Cortex Following Status Epilepticus
Authors: Kim Ji-Eun , Park Hana , Choi Seo-Hyeon , Kong Min-Jeong , Kang Tae-Cheon
Published: July 2019

Under physiological conditions, microglia are unique immune cells resident in the brain that is isolated from the systemic immune system by brain-blood barrier. Following status epilepticus (SE, a prolonged seizure activity), microglia are rapidly activated and blood-derived monocytes that infiltrate the brain; therefore, the regulations of microglia activation and monocyte infiltration are one of the primary therapeutic strategies for inhibition of undesirable consequences from SE. Roscovitine, a potent (but not selective) cyclin-dependent kinase 5 (CDK5) inhibitor, has been found to exert anti-inflammatory and microglia-inhibiting actions in several in vivo models, although the underlying mechanisms have not been clarified. In the present study, roscovitine attenuated SE-induces monocyte infiltration without vasogenic edema formation in the frontoparietal cortex (FPC), accompanied by reducing expressions of monocyte chemotactic protein-1 (MCP-1) and lysosome-associated membrane protein 1 (LAMP1) in resident microglia, while it did not affect microglia transformation to amoeboid form. Furthermore, roscovitine ameliorated the up-regulation of p38 mitogen-activated protein kinase (p38 MAPK) phosphorylation, but not nuclear factor-κB-S276 phosphorylation. Similar to roscovitine, SB202190, a p38 MAPK inhibitor, mitigated monocyte infiltration and microglial expressions of MCP-1 and LAMP1 in the FPC following SE. Therefore, these findings suggest for the first time that roscovitine may inhibit SE-induced neuroinflammation via regulating p38 MAPK-mediated microglial responses.
Macrophage-Mediated Subversion of Anti-Tumour Immunity
Authors: Quaranta Valeria , Schmid Michael C.
Published: July 2019

Despite the incredible clinical benefits obtained by the use of immune checkpoint blockers (ICBs), resistance is still common for many types of cancer. Central for ICBs to work is activation and infiltration of cytotoxic CD8+ T cells following tumour-antigen recognition. However, it is now accepted that even in the case of immunogenic tumours, the effector functions of CD8+ T cells are highly compromised by the presence of an immunosuppressive tumour microenvironment (TME) at the tumour site. Tumour-associated macrophages (TAMs) are among the most abundant non-malignant stromal cell types within the TME and they are crucial drivers of tumour progression, metastasis and resistance to therapy. TAMs are able to regulate either directly or indirectly various aspects of tumour immunity, including T cell recruitment and functions. In this review we discuss the mechanisms by which TAMs subvert CD8+ T cell immune surveillance and how their targeting in combination with ICBs represents a very powerful therapeutic strategy.
Golgi Fragmentation in Neurodegenerative Diseases: Is There a Common Cause?
Authors: Martínez-Menárguez José Ángel , Tomás Mónica , Martínez-Martínez Narcisa , Martínez-Alonso Emma
Published: July 2019

In most mammalian cells, the Golgi complex forms a continuous ribbon. In neurodegenerative diseases, the Golgi ribbon of a specific group of neurons is typically broken into isolated elements, a very early event which happens before clinical and other pathological symptoms become evident. It is not known whether this phenomenon is caused by mechanisms associated with cell death or if, conversely, it triggers apoptosis. When the phenomenon was studied in diseases such as Parkinson’s and Alzheimer’s or amyotrophic lateral sclerosis, it was attributed to a variety of causes, including the presence of cytoplasmatic protein aggregates, malfunctioning of intracellular traffic and/or alterations in the cytoskeleton. In the present review, we summarize the current findings related to these and other neurodegenerative diseases and try to search for clues on putative common causes.
Autoantibodies Specific to ERα are Involved in Tamoxifen Resistance in Hormone Receptor Positive Breast Cancer
Authors: Maselli Angela , Parlato Stefania , Puglisi Rossella , Raggi Carla , Spada Massimo , Macchia Daniele , Pontecorvi Giada , Iessi Elisabetta , Pagano Maria Teresa , Cirulli Francesca , Gabriele Lucia , Carè Alessandra , Vici Patrizia , Pizzuti Laura , Barba Maddalena , Matarrese Paola , Pierdominici Marina , Ortona Elena
Published: July 2019

Tamoxifen resistance is a major hurdle in the treatment of estrogen receptor (ER)-positive breast cancer. The mechanisms of tamoxifen resistance are not fully understood although several underlying molecular events have been suggested. Recently, we identified autoantibodies reacting with membrane-associated ERα (anti-ERα Abs) in sera of breast cancer patients, able to promote tumor growth. Here, we investigated whether anti-ERα Abs purified from sera of ER-positive breast cancer patients could contribute to tamoxifen resistance. Anti-ERα Abs inhibited tamoxifen-mediated effects on cell cycle and proliferation in MCF-7 cells. Moreover, anti-ERα Abs hampered the tamoxifen-mediated reduction of tumor growth in SCID mice xenografted with breast tumor. Notably, simvastatin-mediated disaggregation of lipid rafts, where membrane-associated ERα is embedded, restored tamoxifen sensitivity, preventing anti-ERα Abs effects. In conclusion, detection of serum anti-ERα Abs may help predict tamoxifen resistance and concur to appropriately inform therapeutic decisions concerning hormone therapy in ER-positive breast cancer patients.
HLA-DQA1 and HLA-DQB1 Alleles, Conferring Susceptibility to Celiac Disease and Type 1 Diabetes, Are More Expressed Than Non-Predisposing Alleles and Are Coordinately Regulated
Authors: Farina Federica , Picascia Stefania , Pisapia Laura , Barba Pasquale , Vitale Serena , Franzese Adriana , Mozzillo Enza , Gianfrani Carmen , Del Pozzo G Giovanna
Published: July 2019

HLA DQA1*05 and DQB1*02 alleles encoding the DQ2.5 molecule and HLA DQA1*03 and DQB1*03 alleles encoding DQ8 molecules are strongly associated with celiac disease (CD) and type 1 diabetes (T1D), two common autoimmune diseases (AD). We previously demonstrated that DQ2.5 genes showed a higher expression with respect to non-CD associated alleles in heterozygous DQ2.5 positive (HLA DR1/DR3) antigen presenting cells (APC) of CD patients. This differential expression affected the level of the encoded DQ2.5 molecules on the APC surface and established the strength of gluten-specific CD4+ T cells response. Here, we expanded the expression analysis of risk alleles in patients affected by T1D or by T1D and CD comorbidity. In agreement with previous findings, we found that DQ2.5 and DQ8 risk alleles are more expressed than non-associated alleles also in T1D patients and favor the self-antigen presentation. To investigate the mechanism causing the high expression of risk alleles, we focused on HLA DQA1*05 and DQB1*02 alleles and, by ectopic expression of a single mRNA, we modified the quantitative equilibrium among the two transcripts. After transfection of DR7/DR14 B-LCL with HLA-DQA1*05 cDNA, we observed an overexpression of the endogenous DQB1*02 allele. The DQ2.5 heterodimer synthesized was functional and able to present gluten antigens to cognate CD4+ T cells. Our results indicated that the high expression of alpha and beta transcripts, encoding for the DQ2.5 heterodimeric molecules, was strictly coordinated by a mechanism acting at a transcriptional level. These findings suggested that, in addition to the predisposing HLA-DQ genotype, also the expression of risk alleles contributed to the establishment of autoimmunity.
Transcription Factors Indirectly Regulate Genes through Nuclear Colocalization
Authors: Dai Zhiming
Published: July 2019

Various types of data, including genomic sequences, transcription factor (TF) knockout data, TF-DNA interaction and expression profiles, have been used to decipher TF regulatory mechanisms. However, most of the genes affected by knockout of a particular TF are not bound by that factor. Here, I showed that this interesting result can be partially explained by considering the nuclear positioning of TF knockout affected genes and TF bound genes. I found that a statistically significant number of TF knockout affected genes show nuclear colocalization with genes bound by the corresponding TF. Although these TF knockout affected genes are not directly bound by the corresponding TF; the TF tend to be in the same cellular component with the TFs that directly bind these genes. TF knockout affected genes show co-expression and tend to be involved in the same biological process with the spatially adjacent genes that are bound by the corresponding TF. These results demonstrate that TFs can regulate genes through nuclear colocalization without direct DNA binding, complementing the conventional view that TFs directly bind DNA to regulate genes. My findings will have implications in understanding TF regulatory mechanisms.
Myeloid Dendritic Cells Are Enriched in Lymph Node Tissue of Early Rheumatoid Arthritis Patients but not in At Risk Individuals
Authors: Ramwadhdoebe T.H. , Ramos M.I. , Maijer K.I. , van Lienden K.P. , Maas M. , Gerlag D.M. , Tak P.P. , Lebre M.C. , van Baarsen L.G.M.
Published: July 2019

Lymph nodes (LNs) are highly organized structures where specific immune responses are initiated by dendritic cells (DCs). We investigated the frequency and distribution of human myeloid (mDCs) and plasmacytoid (pDCs) in LNs and blood during the earliest phases of rheumatoid arthritis (RA). We included 22 RA-risk individuals positive for IgM rheumatoid factor and/or anti-citrullinated protein antibodies, 16 biological-naïve RA patients and 8 healthy controls (HCs). DC subsets (CD1c+ mDCs and CD304+ pDCs) in LN tissue and paired peripheral blood were analyzed using flow cytometry and confocal microscopy. In blood of RA patients a significant decreased frequency of pDCs was found, with a similar trend for mDCs. In contrast, mDC frequencies were higher in RA compared with HCs and RA-risk individuals, especially in LN. Frequency of mDCs seemed higher in LNs compared to paired blood samples in all donors, while pDCs were higher in LNs only in RA patients. As expected, both mDCs and pDCs localized mainly in T-cell areas of LN tissue. In conclusion, compared with RA-risk individuals, mDCs and pDCs were enriched in the LN tissue of early-RA patients, while their frequency in RA-risk individuals was comparable to HCs. This may suggest that other antigen-presenting cells are responsible for initial breaks of tolerance, while mDCs and pDCs are involved in sustaining inflammation.
Copine A Interacts with Actin Filaments and Plays a Role in Chemotaxis and Adhesion
Authors: Buccilli Matthew J. , Ilacqua April N. , Han Mingxi , Banas Andrew A. , Wight Elise M. , Mao Hanqian , Perry Samantha P. , Salter Tasha S. , Loiselle David R. , Haystead Timothy A.J. , Damer Cynthia K.
Published: July 2019

Copines make up a family of calcium-dependent, phospholipid-binding proteins found in numerous eukaryotic organisms. Copine proteins consist of two C2 domains at the N-terminus followed by an A domain similar to the von Willebrand A domain found in integrins. We are studying copine protein function in the model organism, Dictyostelium discoideum, which has six copine genes, cpnA-cpnF. Previous research showed that cells lacking the cpnA gene exhibited a cytokinesis defect, a contractile vacuole defect, and developmental defects. To provide insight into the role of CpnA in these cellular processes, we used column chromatography and immunoprecipitation to isolate proteins that bind to CpnA. These proteins were identified by mass spectrometry. One of the proteins identified was actin. Purified CpnA was shown to bind to actin filaments in a calcium-dependent manner in vitro. cpnA− cells exhibited defects in three actin-based processes: chemotaxis, cell polarity, and adhesion. These results suggest that CpnA plays a role in chemotaxis and adhesion and may do so by interacting with actin filaments.
The Intrinsic GDP/GTP Exchange Activities of Cdc42 and Rac1 Are Critical Determinants for Their Specific Effects on Mobilization of the Actin Filament System
Authors: Aspenström Pontus
Published: July 2019

The Rho GTPases comprise a subfamily of the Ras superfamily of small GTPases. Their importance in regulation of cell morphology and cell migration is well characterized. According to the prevailing paradigm, Cdc42 regulates the formation of filopodia, Rac1 regulates the formation of lamellipodia, and RhoA triggers the assembly of focal adhesions. However, this scheme is clearly an oversimplification, as the Rho subfamily encompasses 20 members with diverse effects on a number of vital cellular processes, including cytoskeletal dynamics and cell proliferation, migration, and invasion. This article highlights the importance of the catalytic activities of the classical Rho GTPases Cdc42 and Rac1, in terms of their specific effects on the dynamic reorganization of the actin filament system. GTPase-deficient mutants of Cdc42 and Rac1 trigger the formation of broad lamellipodia and stress fibers, and fast-cycling mutations trigger filopodia formation and stress fiber dissolution. The filopodia response requires the involvement of the formin family of actin nucleation promotors. In contrast, the formation of broad lamellipodia induced by GTPase-deficient Cdc42 and Rac1 is mediated through Arp2/3-dependent actin nucleation.
Neurological Enhancement Effects of Melatonin against Brain Injury-Induced Oxidative Stress, Neuroinflammation, and Neurodegeneration via AMPK/CREB Signaling
Authors: Rehman Shafiq , Ikram Muhammad , Ullah Najeeb , Alam Sayed , Park Hyun , Badshah Haroon , Choe Kyonghwan , Ok Kim Myeong
Published: July 2019

Oxidative stress and energy imbalance strongly correlate in neurodegenerative diseases. Repeated concussion is becoming a serious public health issue with uncontrollable adverse effects in the human population, which involve cognitive dysfunction and even permanent disability. Here, we demonstrate that traumatic brain injury (TBI) evokes oxidative stress, disrupts brain energy homeostasis, and boosts neuroinflammation, which further contributes to neuronal degeneration and cognitive dysfunction in the mouse brain. We also demonstrate that melatonin (an anti-oxidant agent) treatment exerts neuroprotective effects, while overcoming oxidative stress and energy depletion and reducing neuroinflammation and neurodegeneration. Male C57BL/6N mice were used as a model for repetitive mild traumatic brain injury (rmTBI) and were treated with melatonin. Protein expressions were examined via Western blot analysis, immunofluorescence, and ELISA; meanwhile, behavior analysis was performed through a Morris water maze test, and Y-maze and beam-walking tests. We found elevated oxidative stress, depressed phospho-5′AMP-activated protein kinase (p-AMPK) and phospho- CAMP-response element-binding (p-CREB) levels, and elevated p-NF-κB in rmTBI mouse brains, while melatonin treatment significantly regulated p-AMPK, p-CREB, and p-NF-κB in the rmTBI mouse brain. Furthermore, rmTBI mouse brains showed a deregulated mitochondrial system, abnormal amyloidogenic pathway activation, and cognitive functions which were significantly regulated by melatonin treatment in the mice. These findings provide evidence, for the first time, that rmTBI induces brain energy imbalance and reduces neuronal cell survival, and that melatonin treatment overcomes energy depletion and protects against brain damage via the regulation of p-AMPK/p-CREB signaling pathways in the mouse brain.
Immediate Effect of a Yoga Breathing Practice on Attention and Anxiety in Pre-Teen Children
Authors: Telles Shirley , Gupta Ram Kumar , Gandharva Kumar , Vishwakarma Babita , Kala Niranjan , Balkrishna Acharya
Published: July 2019

Pre-teen children face stressors related to their transition from childhood to adolescence, with a simultaneous increase in academic pressure. The present study compared the immediate effects of 18 min of (i) high frequency yoga breathing with (ii) yoga-based breath awareness and (iii) sitting quietly, on (a) attention and (b) anxiety, in 61 pre-teen children (aged between 11 and 12 years; 25 girls). Attention was assessed using a six letter cancellation task and Spielberger’s State Trait Anxiety Inventory STAI-S was used to measure anxiety before and after the three practices, practiced on separate days. Repeated measures ANOVA, followed by Bonferroni adjusted post-hoc analyses showed an increase in total attempts and net scores after high frequency yoga breathing (p < 0.05), while wrong attempts increased after yoga based breath awareness (p < 0.05). Anxiety decreased comparably after all three interventions. The 25 girls in the group had the same trend of results as the whole group with respect to the attention-based cancellation task, while boys showed no, how since change. For both girls and boys, anxiety decreased after all three 18min interventions. The results suggest that high frequency yoga breathing could be a short, useful school based practice to improve attention and reduce anxiety.
Surface Modification of Hemoglobin-Based Oxygen Carriers Reduces Recognition by Haptoglobin, Immunoglobulin, and Hemoglobin Antibodies
Authors: Prapan Ausanai , Suwannasom Nittiya , Kloypan Chiraphat , Chaiwaree Saranya , Steffen Axel , Xiong Yu , Kao Ijad , Pruß Axel , Georgieva Radostina , Bäumler Hans
Published: July 2019

Hemoglobin-based oxygen carriers (HBOCs) represent a propitious type of blood substitute to transport oxygen throughout the body while acting as a carrier in biomedical applications. However, HBOCs in blood are recognized and rapidly scavenged by the body’s innate immune systems. To overcome this problem, HBOCs require a surface modification that provides protection against detection and elimination in order to prolong their circulation time after administration. In this study, we investigated different surface modifications of hemoglobin submicron particles (HbMPs) by double/triple precipitation, as well as by adsorption of human serum albumin (HSA), hyaluronic acid (HA), and pluronic (Plu) to discover how diverse surface modifications influence the oxygen binding capacity and the binding of anti-hemoglobin (Hb) antibodies, immunoglobulin G (IgG), and haptoglobin (HP) to HbMPs. The particle size and zeta potential of the six types of HbMP modifications were analyzed by zeta sizer, confocal laser scanning microscopy, and transmission electron microscopy (TEM), and were compared to the unmodified HbMPs. The results revealed that all surface-modified HbMPs had a submicron size with a negative charge. A slight decrease in the oxygen binding capacity was noticed. The specific binding of anti-Hb antibodies, IgG, and HP to all surface-modified HbMPs was reduced. This indicates a coating design able to protect the particles from detection and elimination processes by the immune system, and should lead to a delayed clearance and the required and essential increase in half-life in circulation of these particles in order to fulfill their purpose. Our surface modification method reflects a promising strategy for submicron particle design, and can lead the way toward novel biomedical applications.
Predictability of Microbial Adhesion to Dental Materials by Roughness Parameters
Authors: Schubert Andrea , Wassmann Torsten , Holtappels Mareike , Kurbad Oliver , Krohn Sebastian , Bürgers Ralf
Published: July 2019

Microbial adhesion to intraoral biomaterials is associated with surface roughness. For the prevention of oral pathologies, smooth surfaces with little biofilm formation are required. Ideally, appropriate roughness parameters make microbial adhesion predictable. Although a multitude of parameters are available, surface roughness is commonly described by the arithmetical mean roughness value (Ra). The present study investigates whether Ra is the most appropriate roughness parameter in terms of prediction for microbial adhesion to dental biomaterials. After four surface roughness modifications using standardized polishing protocols, zirconia, polymethylmethacrylate, polyetheretherketone, and titanium alloy specimens were characterized by Ra as well as 17 other parameters using confocal microscopy. Specimens of the tested materials were colonized by C. albicans or S. sanguinis for 2 h; the adhesion was measured via luminescence assays and correlated with the roughness parameters. The adhesion of C. albicans showed a tendency to increase with increasing the surface roughness—the adhesion of S. sanguinis showed no such tendency. Although Sa, that is, the arithmetical mean deviation of surface roughness, and Rdc, that is, the profile section height between two material ratios, showed higher correlations with the microbial adhesion than Ra, these differences were not significant. Within the limitations of this in-vitro study, we conclude that Ra is a sufficient roughness parameter in terms of prediction for initial microbial adhesion to dental biomaterials with polished surfaces.
Extrusion Coating of Paper with Poly(3-hydroxybutyrate-co-3-hydroxyvalerate) (PHBV)—Packaging Related Functional Properties
Authors: Sängerlaub Sven , Brüggemann Marleen , Rodler Norbert , Jost Verena , Bauer Klaus Dieter
Published: July 2019

Taking into account the current trend for environmentally friendly solutions, paper coated with a biopolymer presents an interesting field for future packaging applications. This study covers the application of the biopolymer poly(3-hydroxybutyrate-co-3-hydroxyvalerate) (PHBV) on a paper substrate via extrusion coating. The intention of this study is to analyse the effect of a plasticiser on the processability (melting point, film thickness) and the final properties (crystallinity, elongation at break) of PHBV. Up to 15 wt.% of the plasticisers triethyl citrate (TEC) and polyethylene glycol (PEG) were used as additive. The processing (including melt flow rate) as well as the structural properties (melting and crystallisation temperature, surface structure by atomic force microscopy (AFM), polarisation microscopy, scanning electron microscopy (SEM)), mechanical properties (elongation at break, tensile strength, elastic modulus, adhesion), and barrier properties (grease) of these blends and their coating behaviour (thickness on paper), were tested at different extrusion temperatures. The melting temperature (Tm) of PHBV was reduced by the plasticisers (from 172 °C to 164 resp. 169 °C with 15 wt.% TEC resp. PEG). The minimal achieved PHBV film thickness on paper was 30 µm owing to its low melt strength. The elastic modulus decreased with both plasticisers (from 3000 N/mm2 to 1200 resp. 1600 N/mm2 with 15 wt.% TEC resp. PEG). At 15 wt.% TEC, the elongation at break increased to 2.4 length-% (pure PHBV films had 0.9 length-%). The grease barrier (staining) was low owing to cracks in the PHBV layers. The extrusion temperature correlated with the grease barrier, mechanical properties, and bond strength. The bond strength was higher for films extruded with a temperature profile for constant melt flow rate at different plasticiser concentrations. The bond strength was max. 1.2 N/15 mm. Grease staining occurs because of cracks induced by the low elongation at break and high brittleness. Extrusion coating of the used specific PHBV on paper is possible. In further studies, the minimum possible PHBV film thickness needs to be reduced to be cost-effective. The flexibility needs to be increased to avoid cracks, which cause migration and staining.
Physical Unclonable Function (PUF)-Based e-Cash Transaction Protocol (PUF-Cash)
Authors: Calhoun Jeff , Minwalla Cyrus , Helmich Charles , Saqib Fareena , Che Wenjie , Plusquellic Jim
Published: July 2019

Electronic money (e-money or e-Cash) is the digital representation of physical banknotes augmented by added use cases of online and remote payments. This paper presents a novel, anonymous e-money transaction protocol, built based on physical unclonable functions (PUFs), titled PUF-Cash. PUF-Cash preserves user anonymity while enabling both offline and online transaction capability. The PUF’s privacy-preserving property is leveraged to create blinded tokens for transaction anonymity while its hardware-based challenge–response pair authentication scheme provides a secure solution that is impervious to typical protocol attacks. The scheme is inspired from Chaum’s Digicash work in the 1980s and subsequent improvements. Unlike Chaum’s scheme, which relies on Rivest, Shamir and Adlemans’s (RSA’s) multiplicative homomorphic property to provide anonymity, the anonymity scheme proposed in this paper leverages the random and unique statistical properties of synthesized integrated circuits. PUF-Cash is implemented and demonstrated using a set of Xilinx Zynq Field Programmable Gate Arrays (FPGAs). Experimental results suggest that the hardware footprint of the solution is small, and the transaction rate is suitable for large-scale applications. An in-depth security analysis suggests that the solution possesses excellent statistical qualities in the generated authentication and encryption keys, and it is robust against a variety of attack vectors including model-building, impersonation, and side-channel variants.
Synthesis, Structural Features, and Catalytic Activity of an Iron(II) 3D Coordination Polymer Driven by an Ether-Bridged Pyridine-Dicarboxylate
Authors: Zhao Na , Li Yu , Gu Jinzhong , Kirillova Marina V. , Kirillov Alexander M.
Published: July 2019

New iron(II) three-dimensional coordination polymer (3D CP), [Fe(µ3-Hcpna)2]n (1), was assembled under hydrothermal conditions from 5-(4’-carboxyphenoxy)nicotinic acid (H2cpna) as a trifunctional organic N,O-building block. This stable microcrystalline CP was characterized by standard methods for coordination compounds in the solid state (infrared spectroscopy, elemental analysis, thermogravimetric analysis, powder and single-crystal X-ray diffraction). Structure and topology of 1 were examined and permitted an identification of a 3,6-connected framework of the rtl topological type. In addition, compound 1 acts as effective catalyst precursor for oxidative functionalization of alkanes (propane and cyclic C5−C8 alkanes) under homogeneous catalysis conditions, namely for the oxidation of saturated hydrocarbons with H2O2/H+ system to produce ketones and alcohols, and for alkane carboxylation with CO/H2O/S2O82− system to obtain carboxylic acids. The influence of an acid promoter and substrate scope (propane and cyclic C5−C8 alkanes) were investigated.
Triple-Ringed Luminescent Heptanuclear Zn(II) Cluster for Efficient Ag(I) Ion Sensing Materials
Authors: Deng Qian-Jun , Chen Min , Chen Dong-Chu , Zhu Zhong-Hong , Zou Hua-Hong
Published: July 2019

The organic ligands (E)-8-hydroxyquinoline-2-carbaldehyde oxime (H2L1) and furan-2-ylmethanamine (H2L2) were used to react with Zn(NO3)2·6H2O at 140 °C solvothermal for two days to obtain the heptanuclear Zn(II) cluster [Zn7(L1)4(HL1)2(H2L2)(µ2-OH)(µ2-O)(NO3)] (1). The X-ray single crystal diffraction reveals that every five-coordinated Zn(II) ions are surrounded by two N atoms and three O atoms with the N2O3 coordination environment and four-coordinated Zn(II) ion surrounded by one N atom and three O atoms in the NO3 coordinated environment. The photoluminescence of cluster 1 is obvious. Moreover, in the presence of Ag(I) ions, cluster 1 exhibits an efficient recognition ability, and it realizes the recognition of toxic metal ions. Here, we have developed cluster-based sensing materials for the efficient detection of heavy metal ions Ag(I) strategies.
Towards the Fulfillment of a Knowledge Gap: Wood Densities for Species of the Subtropical Atlantic Forest
Authors: Zimermann Oliveira Laio , Felippe Uller Heitor , Renata Klitzke Aline , Roberto Eleotério Jackson , Christian Vibrans Alexander
Published: July 2019

Wood density ( ρ ) is a trait involved in forest biomass estimates, forest ecology, prediction of stand stability, wood science, and engineering. Regardless of its importance, data on ρ are scarce for a substantial number of species of the vast Atlantic Forest phytogeographic domain. Given that, the present paper describes a dataset composed of three data tables: (i) determinations of ρ (kg m−3) for 153 species growing in three forest types within the subtropical Atlantic Forest, based on wood samples collected throughout the state of Santa Catarina, southern Brazil; (ii) a list of 719 tree/shrub species observed by a state-level forest inventory and a ρ value assigned to each one of them based on local determinations and on a global database; (iii) the means and standard deviations of ρ for 477 permanent sample plots located in the subtropical Atlantic Forest, covering ∼95,000 km2. The mean ρ over the 153 sampled species is 538.6 kg m−3 (standard deviation = 120.5 kg m−3), and the mean ρ per sample plot, considering the three forest types, is 525.0 kg m−3 (standard error = 1.8 kg m−3). The described dataset has potential to underpin studies on forest biomass, forest ecology, alternative uses of timber resources, as well as to enlarge the coverage of global datasets.
Rethinking ME/CFS Diagnostic Reference Intervals via Machine Learning, and the Utility of Activin B for Defining Symptom Severity
Authors: Lidbury Brett A. , Kita Badia , Richardson Alice M. , Lewis Donald P. , Privitera Edwina , Hayward Susan , de Kretser David , Hedger Mark
Published: July 2019

Biomarker discovery applied to myalgic encephalomyelitis/chronic fatigue syndrome (ME/CFS), a disabling disease of inconclusive aetiology, has identified several cytokines to potentially fulfil a role as a quantitative blood/serum marker for laboratory diagnosis, with activin B a recent addition. We explored further the potential of serum activin B as a ME/CFS biomarker, alone and in combination with a range of routine test results obtained from pathology laboratories. Previous pilot study results showed that activin B was significantly elevated for the ME/CFS participants compared to healthy (control) participants. All the participants were recruited via CFS Discovery and assessed via the Canadian/International Consensus Criteria. A significant difference for serum activin B was also detected for ME/CFS and control cohorts recruited for this study, but median levels were significantly lower for the ME/CFS cohort. Random Forest (RF) modelling identified five routine pathology blood test markers that collectively predicted ME/CFS at ≥62% when compared via weighted standing time (WST) severity classes. A closer analysis revealed that the inclusion of activin B to the panel of pathology markers improved the prediction of mild to moderate ME/CFS cases. Applying correct WST class prediction from RFA modelling, new reference intervals were calculated for activin B and associated pathology markers, where 24-h urinary creatinine clearance, serum urea and serum activin B showed the best potential as diagnostic markers. While the serum activin B results remained statistically significant for the new participant cohorts, activin B was found to also have utility in enhancing the prediction of symptom severity, as represented by WST class.
Multi-Timescale Education Program for Temporal Expansion in Ecocentric Education: Using Fixed-Point Time-Lapse Images for Phenology Observation
Authors: Nakamura Kazuhiko W. , Fujiwara Akio , Kobayashi Hill Hiroki , Saito Kaoru
Published: July 2019

Ecocentric education programs should include a method for the in-depth understanding of multi-scale ecological time concepts. To accomplish this, the common restriction that ecocentric education should pertain only to realistic nature may have to be removed. The purpose of this research was to confirm the validity of a program featuring phenology observation, employing fixed-point time-lapse images as climate change learning, and to obtain suggestions on the influence of the program on the multi-timescale concepts of the learners. An observation sheet listing images of cherry flowering from 16 April to 15 March each year from 1996 to 2017 was created, and the 50-min educational program using the observation sheet was conducted with 189 third year junior high school students. The tendencies among students’ answers to the two questions before and after the program suggest that the program contributed to the students acquiring the hundreds-year timescale concept based on the short-term timescale concept of dynamic nature. The contribution of this research is to visualize long-term and multi-scale ecological time concepts. By combining long-term time-lapse images with everyday nature experiences, the possibility of expanding such emotions as wonder and attachment to nature towards a long-term ecological timescale is achieved.
Study Approaches in Higher Education Mathematics: Investigating the Statistical Behaviour of an Instrument Translated into Norwegian
Authors: Zakariya Yusuf F.
Published: July 2019

The revised two-factor study process questionnaire (R-SPQ-2F) has widely been considered valid and reliable in many contexts for measuring students’ learning approaches. However, its cultural specificity has generated considerable discussion, with inconclusive results when translated to different languages. This paper provides more insights into the construct validity of a Norwegian version of this instrument. The R-SPQ-2F is composed of ten items designed to expose deep learning approaches and 10 items designed to expose surface learning approaches. A survey research design involving a sample of 253 first year university students in a mathematics course was adopted. Ten hypothesized models were compared using a series of confirmatory factor analyses following the model proposals reported in the literature. A weighted least square mean and variance adjusted (WLSMV) estimator was used to enhance model parameter estimations under multiple violations of assumptions inherent in ordinal data. The results favored a two first-order factor model with ten items measuring the deep approach and nine items measuring the surface approach including a deletion of one item from this instrument. The findings of this study provide empirical evidence for the cultural specificity of the instrument that is consistent with the literature. The R-SPQ-2F is therefore recommended to assess students’ approaches to learning, and further studies into its cultural specificity are recommended.