bluuebunny/crossref_metadata_2025 huggingface dataset:
RETRACTED: MicroRNA-326 Functions as a Tumor Suppressor in Breast Cancer by Targeting ErbB/PI3K Signaling Pathway
Authors: Ghaemi Zahra , Soltani Bahram Mohammad , Mowla Seyed Javad
Published: July 2019

Breast cancer represents the most common malignancy in women worldwide and the ErbB/PI3K pathway has been found to play a crucial role in regulation of the cancer cell growth. MicroRNAs have been implicated in regulating diverse cellular pathways and therefore, understanding the link between the regulatory microRNAs and the ErbB/PI3K signaling pathway could potentially be helpful for breast cancer prevention and treatment. The aim of this study is to examine the regulatory effect of miR-326 on ErbB/PI3K signaling pathway in breast cancer development and progression. The results of qRT-PCR, RNA seq, and array data indicated that miR-326 was remarkably down-regulated in breast tumor tissues and correlated with poor survival outcome. Importantly, very low levels of miR-326 expression were found in aggressive breast cells compared to less-aggressive cell types. Mechanistically, a gene network including EGFR, ErbB2, ErbB3, AKT1, AKT2, and AKT3 targeted by miR-326, thereby providing suppression of ErbB/PI3K pathway, detected by RT-qPCR, and dual luciferase assay. In addition, Western blot analysis revealed that miR-326 upregulation decreased PI3K signaling activity by decreasing total AKT and p-AKT protein level in SKBR3 cell lines. Interestingly, up regulation of ErbB2 rescued the effect of miR-326 on miR-326 target genes. Further functional assays demonstrated that up regulation of miR-326 significantly suppressed cell growth as evidenced by cell cycle, cell cycle associated genes expression, colony formation and MTT assays and induced apoptosis, detected by Annexin V-PI. In addition, EMT markers RT-qPCR, scratch, and Transwell assays showed inhibited cellular migration and invasion following miR-326 upregulation. Altogether, our results revealed that miR-326 play a tumor-suppressive role in breast cancer through inhibiting ErbB/PI3K pathway and miR-326 may serve as a potential therapeutic target for the treatment of patients with breast cancer.
Claves fundamentales en terapia de pareja: Una guía de navegación para la práctica
Authors: Montesano Adrian
Published: July 2019

En las últimas décadas, la terapia de pareja ha experimentado una creciente demanda social. La mayoría de los psicoterapeutas la ejercen en algún momento de su trayectoria profesional y muchos de ellos la practican regularmente. Sin embargo, la terapia de pareja es una de las modalidades más difíciles que existen, con un alto índice de fracaso, que requiere de una formación específica muchas veces inexistente. En el presente texto se ofrecen algunas coordenadas clave para orientar la práctica clínica. Concretamente, (a) se delinean los rasgos distintivos de la terapia de pareja como modalidad terapéutica independiente, (b) se comenta su evolución revisando los principales resultados de la investigación,  y (c)  se especifican siete coordenadas fundamentales para el desarrollo de una buena práctica.
A Critical Analysis of Valve-Compensated Hydrostatic Actuators: Qualitative Investigation
Authors: Koury Costa Gustavo , Sepehri Nariman
Published: July 2019

Hydrostatic actuation has gained interest from both academia and industry due to the unquestionable energetic advantages when compared to valve-controlled actuators; the main feature being the absence of throttling losses due to the direct control of the cylinder by the pump. However, the fact that the great majority of applications are based on single-rod cylinders has been both a challenge and a source of inspiration for a variety of different circuit designs. In an attempt to compensate for the uneven flows coming in and out of differential cylinders, several solutions have been proposed, including the use of hydraulic transformers, individual pumps connected to the cylinder ports or pumps with unmatched input and output flows. The simplest approach, however, seems to be the use of compensation valves in the circuit, which is the focus of this paper. Here, we analyse some representative circuits proposed along the years in a direct and elucidative manner, showing that the definitive solution to the single-rod actuator control problem has been established, paving the road for introducing stable and trustworthy circuits, which can be commercially used in the near future.
Special Issue “8th EASN–CEAS Workshop on Manufacturing for Growth and Innovation”
Authors: Pantelakis Spiros , Kontis Konstantinos
Published: July 2019

This Special Issue contains selected papers from works presented at the 8th EASN–CEAS (European Aeronautics Science Network–Council of European Aerospace Societies) Workshop on Manufacturing for Growth and Innovation, which was held in Glasgow, UK, 4–7 September 2018 [...]
Loci Controlling Adaptation to Heat Stress Occurring at the Reproductive Stage in Durum Wheat
Authors: El Hassouni Khaoula , Belkadi Bouchra , Filali-Maltouf Abdelkarim , Tidiane-Sall Amadou , Al-Abdallat Ayed , Nachit Miloudi , Bassi Filippo M.
Published: July 2019

Heat stress occurring during the reproductive stage of wheat has a detrimental effect on productivity. A durum wheat core set was exposed to simulated terminal heat stress by applying plastic tunnels at the time of flowering over two seasons. Mean grain yield was reduced by 54% compared to control conditions, and grain number was the most critical trait for tolerance to this stress. The combined use of tolerance indices and grain yield identified five top performing elite lines: Kunmiki, Berghouata1, Margherita2, IDON37-141, and Ourgh. The core set was also subjected to genome wide association study using 7652 polymorphic single nucleotide polymorphism (SNPs) markers. The most significant genomic regions were identified in association with spike fertility and tolerance indices on chromosomes 1A, 5B, and 6B. Haplotype analysis on a set of 208 elite lines confirmed that lines that carried the positive allele at all three quantitative trait loci (QTLs) had a yield advantage of 8% when field tested under daily temperatures above 31° C. Three of the QTLs were successfully validated into Kompetitive Allele Specific PCR (KASP) markers and explained >10% of the phenotypic variation for an independent elite germplasm set. These genomic regions can now be readily deployed via breeding to improve resilience to climate change and increase productivity in heat-stressed areas.
Harvesting Regimes Affect Brown Midrib Sorghum-Sudangrass and Brown Midrib Pearl Millet Forage Production and Quality
Authors: Machicek Joshua A. , Blaser Brock C. , Darapuneni Murali , Rhoades Marty B.
Published: July 2019

As water levels in the Ogallala Aquifer continue to decline in the Texas High Plains, alternative forage crops that utilize less water must be identified to meet the forage demand of the livestock industry in this region. A two-year (2016 and 2017) study was conducted at West Texas A&M University Nance Ranch near Canyon, TX to evaluate the forage production and quality of brown midrib (BMR) sorghum-sudangrass (SS) (Sorghum bicolor (L.) Moench ssp. Drummondii) and BMR pearl millet (PM) (Pennisetum glaucum (L.) Leeke)) harvested under three regimes (three 30-d, two 45-d, and one 90-d harvests). Sorghum-sudangrass consistently out yielded PM in total DM production in both tested years (yield range 3.96 to 6.28 Mg DM ha−1 vs. 5.38 to 11.19 Mg DM ha−1 in 2016 and 6.00 to 9.87 Mg DM ha−1 vs. 6.53 to 15.51 Mg DM ha−1 in 2017). Water use efficiency was higher in PM compared to SS. The 90-d harvesting regime maximized the water use efficiency and DM production compared to other regimes in both crops; however, some forage quality may be sacrificed. In general, the higher forage quality was achieved in shorter interval harvesting regimes (frequent cuttings). The selection of suitable forage crop and harvesting regime based on this research can be extremely beneficial to the producers of Texas High Plains to meet their individual forage needs and demand.
Contribution of CaBPM4, a BTB Domain–Containing Gene, to the Response of Pepper to Phytophthora capsici Infection and Abiotic Stresses
Authors: He Yu-Mei , Liu Ke-Ke , Zhang Huai-Xia , Cheng Guo-Xin , Ali Muhammad , Ul Haq Saeed , Wei Ai-Min , Gong Zhen-Hui
Published: July 2019

The Broad-complex Tramtrack and Bric-a-brac (BTB) domain participates in plant responses to biotic and abiotic stresses, however its role is unknown in pepper plants. CaBPM4 has meprin and TRAF homology (MATH) and BTB domains at its N- and C-termini, respectively, and it contains a 1589-bp full-length cDNA that encodes a protein containing 403 amino acids. In this study, the pepper gene CaBPM4 (Capsicum annuum BTB-POZ and MATH domain protein) was cloned, and its role in responses to Phytophthora capsici, cold, drought, and salt stress were characterized. The results of quantitative RT-PCR revealed that CaBPM4 was down-regulated under P. capsici infection, salicylic acid, H2O2, and abscisic acid treatments, while abiotic stresses, including salt, cold, and drought, enhanced its transcript level. Furthermore, CaBPM4 silencing significantly impaired resistance to P. capsici, apparently by altering the transcript level of defense-related genes CaPR1, CaDEF1, and CaSAR82 and reducing root activity. However, CaBPM4-silenced plants exhibited remarkably increased peroxidase activity and decreased malondialdehyde concentrations, indicating that CaBPM4 may enhance resistance to salt and drought stress. Further study should focus on the mechanism by which CaBPM4 regulates the defense response to P. capsici infection and abiotic stresses.
The Effects of Root Aeration and Different Soil Conditioners on the Nutritional Values, Yield, and Water Productivity of Potato in Clay Loam Soil
Authors: Abuarab Mohamed E. , El-Mogy Mohamed M. , Hassan Ahmed M. , Abdeldaym Emad A. , Abdelkader Noha H. , B. I. El-Sawy Mohamed
Published: July 2019

A field study was conducted in 2016–2017 and 2017–2018 to evaluate the effects of air injection into an irrigation stream during the subsurface drip irrigation (SDI) process on the nutritional values and productivity of potato grown in clay loam soil. Two irrigation treatments (non-aerated and aerated) and six fertilizer applications (chicken, cow, rabbit, compost, mineral, and chicken + biochar) were compared. In the first growing season, the maximum yield occurred under aerated treatment with cow fertilizer (36.25 ton ha−1), while the minimum yield occurred under non-aerated treatment with chicken fertilizer (24.00 ton ha−1). On the other hand, the maximum and minimum yields in the second growing season were 35.00 and 24.74 ton ha−1 under aerated and non-aerated treatments with cow fertilizer, respectively. Maximum water productivity was achieved under aerated treatment with cow fertilizer (10.04 and 9.13 kg m−3 for the first and second growing seasons, respectively), while minimum water productivity was achieved under the non-aerated treatment with chicken + biochar fertilizer (5.91 and 5.26 kg m−3 for the first and second growing seasons, respectively). Fertilization using aerated treatment yielded the best results and the highest coupling after air injection, compared with the traditional methods of adding soil fertilizer without aeration. The plant growth parameters significantly increased following aeration relative to non-aerated treatments for all fertilizer applications in both growing seasons. Air injection into the soil for potatoes, unsurprisingly, not only benefitted the crop by increasing the soil–air exchange rate but also promoted water infiltration rates and nutrient absorption and reduced drainage water, thus increasing water productivity and reducing the overall irrigation requirements.
Antibiotic-Resistant Septicemia in Pediatric Oncology Patients Associated with Post-Therapeutic Neutropenic Fever
Authors: Vázquez-López Rosalino , Rivero Rojas Omar , Ibarra Moreno Andrea , Urrutia Favila José Erik , Peña Barreto Adan , Ortega Ortuño Guadalupe Lizeth , Abello Vaamonde Jorge Andrés , Aguilar Velazco Ivanka Alejandra , Félix Castro José Marcos , Solano-Gálvez Sandra Georgina , Barrientos Fortes Tomás , González-Barrios Juan Antonio
Published: July 2019

Death in cancer patients can be caused by the progression of tumors, their malignity, or other associated conditions such as sepsis, which is a multiphasic host response to a pathogen that can be significantly amplified by endogenous factors. Its incidence is continuously rising, which reflects the increasing number of sick patients at a higher risk of infection, especially those that are elderly, pediatric, or immunosuppressed. Sepsis appears to be directly associated with oncological treatment and fatal septic shock. Patients with a cancer diagnosis face a much higher risk of infections after being immunosuppressed by chemotherapy, radiotherapy, or anti-inflammatory therapy, especially caused by non-pathogenic, Gram-negative, and multidrug-resistant pathogens. There is a notorious difference between the incidence and mortality rates related to sepsis in pediatric oncologic patients between developed and developing countries: they are much higher in developing countries, where investment for diagnosis and treatment resources, infrastructure, medical specialists, cancer-related control programs, and post-therapeutic care is insufficient. This situation not only limits but also reduces the life expectancy of treated pediatric oncologic patients, and demands higher costs from the healthcare systems. Therefore, efforts must aim to limit the progression of sepsis conditions, applying the most recommended therapeutic regimens as soon as the initial risk factors are clinically evident—or even before they are, as when taking advantage of machine learning prediction systems to analyze data.
Cytokine Expression Patterns and Single Nucleotide Polymorphisms (SNPs) in Patients with Chronic Borreliosis
Authors: Hein Tabea M. , Sander Philip , Giryes Anwar , Reinhardt Jan-Olaf , Hoegel Josef , Schneider E. Marion
Published: July 2019

(1) Background: Genetically based hyperinflammation may play a role in pathogen defense. We here questioned whether alterations in circulating monocytes/macrophages, inflammatory biomarkers and a functional SNP (single nucleotide polymorphisms) of the Interleukin-6 (IL-6) promotor might play a role in patients with persistent, and treatment resistant borreliosis. (2) Methods: Leukocyte subpopulations were studied by flow cytometry; plasma cytokines were determined by a chemiluminescence based ELISA (Immulite®), and genotypes of the IL-6 promotor SNP rs1800795 were determined by pyrosequencing. (3) Results: In a cohort of n = 107 Lyme borreliosis patients, who concomitantly manifested either malignant diseases (group 1), autoimmune disorders (group 2), neurological diseases (group 3), or morbidities caused by multiple other infectious complications (group 4), we found decreased numbers of anti-inflammatory CD163-positive macrophages, elevated concentrations of inflammatory cytokines, and an imbalance of IL-6 promotor SNP rs1800795 genotypes. The most prominently upregulated cytokines were IL-1β, and IL-8. (4) Conclusions: Increased pro-inflammatory phenotypes identified by monocyte/macrophage subtypes and concomitantly increased cytokines appear to be valid to monitor disease activity in patients with persistent Lyme borreliosis. Patterns may vary by additional co-morbidities. In patients with autoimmune diseases, increased frequencies of a heterozygous IL-6 promotor SNP rs1800795 were identified. This functional SNP may guide chronic inflammation, impacting other cytokines to trigger trigger chronicity and therapeutic resistance in Lyme borreliosis.
Paraoxonases (PON) 1, 2, and 3 Polymorphisms and PON-1 Activities in Patients with Sickle Cell Disease
Authors: Reichert Cadiele Oliana , de Macedo Carolina Garcia , Levy Débora , Sini Bruno Carnevale , Monteiro Andréia Moreira , Gidlund Magnus , Maselli Luciana Morganti Ferreira , Gualandro Sandra Fátima Menosi , Bydlowski Sérgio Paulo
Published: July 2019

(1) Background: Oxidative stress, chronic inflammation, vasoocclusion, and free iron are all features present in sickle cell disease. Paraoxonases (PON) are a family (PON-1, PON-2, PON-3) of antioxidant enzymes with anti-inflammatory action. Here, for the first time, we described PON-1 activities and PON-1, PON-2, PON-3 polymorphisms in patients with sickle cell disease, homozygous for HbSS, compared with healthy controls. (2) Methods: The groups were matched for age and gender. PON-1 activities (arylesterase and paraoxonase) were determined by enzymatic hydrolysis of phenylcetate and paraoxon, respectively. Polymorphisms were determined by Restriction Fragment Length Polymorphism- Polymerase Chain Reaction (RFLP-PCR). (3) Results: Plasma cholesterol and fractions, ApoA1 and ApoB levels were all decreased in sickle cell disease patients, while anti-oxidized low-density lipoprotein (LDL) antibodies and C-reactive protein were increased. Serum arylesterase activity was lower in sickle cell disease patients when compared with healthy controls. In patients, paraoxonase activity was higher in those with PON-1 RR Q192R polymorphism. In these patients, the increase of serum iron and ferritin levels and transferrin saturation were less pronounced than those observed in patients with QQ or QR polymorphism. No differences were observed with PON-1 L55M, and PON-2 and PON-3 polymorphisms. Multivariate regression analysis showed that transferrin and ferritin concentrations correlated with arylesterase and paraoxonase activities. (4) Conclusions: Both transferrin and ferritin were the main predictors of decreased arylesterase and paraoxonase activities in patients with sickle cell disease. LDL oxidation increased, and RR PON-1 Q192R polymorphism is likely to be a protective factor against oxidative damage in these patients.
The Influence of Film and Storage on the Phenolic and Antioxidant Properties of Red Raspberries (Rubus idaeus L.) cv. Erika
Authors: Giuffrè Angelo Maria , Louadj Lamia , Rizzo Paola , De Salvo Emanuela , Sicari Vincenzo
Published: July 2019

In this paper, the effect of the packaging material and storage method on red raspberries produced at Reggio Calabria (Italy) was studied. For this purpose, the fruits were stored immediately after harvest in different conditions: in the fridge at 1 °C and in the freezer at −20 °C, using different packaging materials, two new patented films (nanoactive A) and (nanoactive B), one common packaging film (polyethylene terephthalate), and other fruits were left without any packaging material. Chemical parameters were analysed at harvest to have the initial characteristics without any conditioned storage and to distinguish the post-harvest effect on the fruits, then daily for storage in the fridge and monthly for storage in the freezer. The aims of our project were first to determine the qualitative characterization of these red raspberries, the optimization of their shelf-life during time in the fridge or freezer, using the different types of packaging materials and finally to highlight the usefulness of the new patented packaging materials. Nanoactive A film showed the best shelf-life in the fridge, and after 14 days the values, given as mg/100 g fresh weight, were: total phenolics (166.70), monomeric anthocyanin content (50.82), flavonoids (24.64), ascorbic acid (32.42), and 1, 1-diphenyl-2-picrylhydrazyl (DPPH) assay (95.93).
Addition of Olive Leaf Extract (OLE) for Producing Fortified Fresh Pasteurized Milk with an Extended Shelf Life
Authors: Palmeri Rosa , Parafati Lucia , Trippa Daniela , Siracusa Laura , Arena Elena , Restuccia Cristina , Fallico Biagio
Published: July 2019

An olive leaf extract (OLE) has been tested in vitro for its antibacterial activity and ability to inhibit α-glucosidase enzyme. OLE was also evaluated for its potential, when added to pasteurized milk, to preserve nutritional parameters and to limit microbial growth, thus prolonging shelf life. In vitro assays demonstrated a strong antibacterial efficacy of OLE mainly against Bacillus cereus and the capacity to inhibit α-glucosidase enzyme (IC50) when used at 0.2 mg oleuropein/mL. The milk fortification with OLE at 3.6 mg of oleuropein/mL of milk reduced total mesophilic bacteria at undetectable level after 6 d (expiration date) and by 1 log CFU/mL after 10 d. Moreover, OLE addition at 1.44 and 3.6 mg of oleuropein/mL of milk significantly reduced fat and lactose losses up to 10 d. The results motivate the use of the OLE to make a new functional milk with an extended shelf life.
Smart Fault-Tolerant Control System Based on Chaos Theory and Extension Theory for Locating Faults in a Three-Level T-Type Inverter
Authors: Chao Kuei-Hsiang , Chang Long-Yi , Xu Fu-Qiang
Published: July 2019

This study proposes a smart fault-tolerant control system based on the theory of Lorenz chaotic system and extension theory for locating faults and executing tolerant control in a three-level T-type inverter. First, the system constantly monitors the fault states of the 12 power transistor switches of the three-level T-type inverter; if a power transistor fails, the corresponding output phase voltage waveform is converted by a Lorenz chaotic system. Chaos eye coordinates are then extracted from a scatter diagram of chaotic dynamic states and considered as fault characteristics. The system then executes fault diagnosis based on extension theory. The fault characteristic value is used as the input signal for correlation analysis; thus, the faulty power transistor can be located and the fault diagnosis can be achieved for the inverter. The fault-tolerant control system can maintain the three-phase balanced output of the three-level T-type inverter, thereby improving the reliability of the motor drive system. The feasibility of the proposed smart fault-tolerant control system was assessed by conducting simulations in this study, and the results verified its feasibility. Accordingly, after the occurrence of the fault in power switches, the balanced three-phase output line voltage remained unchanged, and the quality of the output voltage was not reduced by using the integration of the proposed fault diagnosis system and fault-tolerant control system for a three-level T-type Inverter.
AR Pointer: Advanced Ray-Casting Interface Using Laser Pointer Metaphor for Object Manipulation in 3D Augmented Reality Environment
Authors: Ro Hyocheol , Byun Jung-Hyun , Park Yoon Jung , Lee Nam Kyu , Han Tack-Don
Published: July 2019

In this paper, we propose AR Pointer, a new augmented reality (AR) interface that allows users to manipulate three-dimensional (3D) virtual objects in AR environment. AR Pointer uses a built-in 6-degrees of freedom (DoF) inertial measurement unit (IMU) sensor in an off-the-shelf mobile device to cast a virtual ray that is used to accurately select objects. It is also implemented using simple touch gestures commonly used in smartphones for 3D object manipulation, so users can easily manipulate 3D virtual objects using the AR Pointer, without a long training period. To demonstrate the usefulness of AR Pointer, we introduce two use-cases, constructing an AR furniture layout and AR education. Then, we conducted two experiments, performance tests and usability tests, to represent the excellence of the designed interaction methods using AR Pointer. We found that AR Pointer is more efficient than other interfaces, achieving 39.4% faster task completion time in the object manipulation. In addition, the participants gave an average of 8.61 points (13.4%) on the AR Pointer in the usability test conducted through the system usability scale (SUS) questionnaires and 8.51 points (15.1%) on the AR Pointer in the fatigue test conducted through the NASA task load index (NASA-TLX) questionnaire. Previous AR applications have been implemented in a passive AR environment where users simply check and pop up the AR objects those are prepared in advance. However, if AR Pointer is used for AR object manipulation, it is possible to provide an immersive AR environment for the user who want/wish to actively interact with the AR objects.
Systematic Analysis of MYB Family Genes in Potato and Their Multiple Roles in Development and Stress Responses
Authors: Li Xiaoxu , Guo Cun , Ahmad Salman , Wang Qi , Yu Jing , Liu Cheng , Guo Yongfeng
Published: July 2019

The MYB proteins represent a large family of transcription factors and play important roles in development, senescence, and stress responses in plants. In the current study, 233 MYB transcription factor-encoding genes were identified and analyzed in the potato genome, including 119 R1-MYB, 112 R2R3-MYB, and two R1R2R3-MYB members. R2R3-MYB is the most abundant MYB subclass and potato R2R3-MYB members together with their Arabidopsis homologs were divided into 35 well-supported subgroups as the result of phylogenetic analyses. Analyses on gene structure and protein motif revealed that members from the same subgroup shared similar exon/intron and motif organization, further supporting the results of phylogenetic analyses. Evolution of the potato MYB family was studied via syntenic analysis. Forty-one pairs of StMYB genes were predicted to have arisen from tandem or segmental duplication events, which played important roles in the expansion of the StMYB family. Expression profiling revealed that the StMYB genes were expressed in various tissues and several StMYB genes were identified to be induced by different stress conditions. Notably, StMYB030 was found to act as the homolog of AtMYB44 and was significantly up-regulated by salt and drought stress treatments. Furthermore, overexpression of StMYB030 in Arabidopsis enhanced salt stress tolerance of transgenic plants. The results from this study provided information for further functional analysis and for crop improvements through genetic manipulation of these StMYB genes.
Bio-Recognition in Spectroscopy-Based Biosensors for *Heavy Metals-Water and Waterborne Contamination Analysis
Authors: Aloisi Alessandra , Della Torre Antonio , De Benedetto Angelantonio , Rinaldi Rosaria
Published: July 2019

Microsystems and biomolecules integration as well multiplexing determinations are key aspects of sensing devices in the field of heavy metal contamination monitoring. The present review collects the most relevant information about optical biosensors development in the last decade. Focus is put on analytical characteristics and applications that are dependent on: (i) Signal transduction method (luminescence, colorimetry, evanescent wave (EW), surface-enhanced Raman spectroscopy (SERS), Förster resonance energy transfer (FRET), surface plasmon resonance (SPR); (ii) biorecognition molecules employed (proteins, nucleic acids, aptamers, and enzymes). The biosensing systems applied (or applicable) to water and milk samples will be considered for a comparative analysis, with an emphasis on water as the primary source of possible contamination along the food chain.
Anoctamin 3: A Possible Link between Cluster Headache and Ca2+ Signaling
Authors: Ran Caroline , Fourier Carmen , Arafa Donia , Liesecke Franziska , Sjöstrand Christina , Waldenlind Elisabet , Steinberg Anna , Belin Andrea
Published: July 2019

Cluster headache is a severe primary headache characterized by extremely painful attacks of unilateral headache. Verapamil is commonly used as a prophylactic treatment with good effect. In order to search for new pathways involved in the pathophysiology of cluster headache, we analyzed genetic variants that were previously linked to verapamil response in migraine in a Swedish cluster headache case-control sample. We used TaqMan qPCR for genetic screening and performed a gene expression analysis on associated genes in patient-derived fibroblasts, and further investigated which reference genes were suitable for analysis in fibroblasts from cluster headache patients. We discovered a significant association between anoctamin 3, a gene encoding a calcium-activated ion channel, and cluster headache. The association was not dependent on verapamil treatment since the associated variant, rs1531394, was also overrepresented in patients not using verapamil. No difference was found in the anoctamin 3 gene expression between controls and patients. Also, we determined that TBP, IPO8 and PDHB were suitable reference genes in cluster headache fibroblasts. This finding is the first report of an association between a variant in a gene encoding an ion-channel and cluster headache, and the first significant genetic evidence of calcium involvement in cluster headache pathophysiology.
Association between Interictal Epileptiform Discharges and Autistic Spectrum Disorder
Authors: Luz-Escamilla Laura , Morales-González José
Published: July 2019

It has been reported that bioelectric alterations in an electroencephalogram (EEG) may play an etiological role in neurodevelopmental disorders. The clinical impact of interictal epileptiform discharges (IEDs) in association with autistic spectrum disorder (ASD) is unknown. The Autism Diagnostic Interview-Revised (ADI-R) is one of the gold standards for the diagnosis of autistic spectrum disorder. Some studies have indicated high comorbidity of IED and ASD, while other studies have not supported an association between the central symptoms of autism and IED. This review examines the high comorbidity and clinical impact of IED; patients with epilepsy are excluded from the scope of this review. ASD can be disabling and is diagnosed at an average age of 5 years old, at which point the greatest neurological development has occurred. If an association between IED and ASD is identified, a clinical tool that entails an innocuous procedure could enable diagnosis in the first years of life. However, in the absence of reports that prove an association between IED and ASD, patients should not be subjected to expensive treatments, such as the administration of anticonvulsant therapies.
An AHP Analysis on the Habitability Performance toward the Modernized Hanok in Korea
Authors: Lee Mi-Hyang , Cheon Deuk-Youm , Han Seung-Hoon
Published: July 2019

Hanok is a building style in Korean traditional architecture that presently supports a specialty of urban scenery and residential environment for regeneration in Korea. However, it is difficult to review or evaluate for the performance of Hanok, and there is no definite standard that can be applied to it yet. Therefore, it is necessary to establish the evaluation system of the residential performance of Hanok, and its concept model of the habitability performance needs to be derived in order to develop an evaluation system for the residential performance of Hanok. For this study, its evaluation factors have been classified into three major aspects such as the architectural space, the village complex, and the sustainability. This study, then, has attempted to build an evaluation system composed of proven assessment items or factors and performed AHP (Analytic Hierarchy Process) analyses with certified experts in the Hanok field and applied the relative importance among the evaluation items. Finally, this research has proposed an evaluation model of the habitability performance of Hanok. As a result of applying the assessment model for weighted habitability performances, the proposed evaluation system has been implemented as the inherent value of Hanok and its objectivity to be a major sustainable form of regeneration for contemporary residency in Korea.
Innovative Activated Carbon Based on Deep Eutectic Solvents (DES) and H3PO4
Authors: Pam Aloysius Akaangee
Published: July 2019

In this present work, a novel method for synthesis of palm kernel shell activated carbon was established using DES (choline chloride/urea)/H3PO4 as the activating agent. The pore characterization, morphology, and adsorption properties of the activated carbons were investigated. The activated carbon samples made from the same feedstock at two pyrolysis temperatures (500 and 600 °C) were compared for their ability to adsorb Pb(II) in aqueous solution. The results demonstrated that the production of the activated carbon and adsorptive properties were significantly influenced by the pyrolysis temperature and the ratio of precursor to activating agent. DES/H3PO4 activated carbon (having surface area 1413 m2/g and total pore volume 0.6181 cm3/g) demonstrated good Pb(II) removal. Although all the tested activated carbon samples adsorbed Pb(II) from aqueous solution, they demonstrated different adsorption capabilities according to their various properties. The pyrolysis temperature, however, showed little influence on the activated carbon adsorption of Pb(II) when compared to the impregnation ratio. Their good desorption performance perhaps resulted from the porous structure.
The Transcriptional Roles of ALK Fusion Proteins in Tumorigenesis
Authors: Ducray Stephen P. , Natarajan Karthikraj , Garland Gavin D. , Turner Suzanne D. , Egger Gerda
Published: July 2019

Anaplastic lymphoma kinase (ALK) is a tyrosine kinase involved in neuronal and gut development. Initially discovered in T cell lymphoma, ALK is frequently affected in diverse cancers by oncogenic translocations. These translocations involve different fusion partners that facilitate multimerisation and autophosphorylation of ALK, resulting in a constitutively active tyrosine kinase with oncogenic potential. ALK fusion proteins are involved in diverse cellular signalling pathways, such as Ras/extracellular signal-regulated kinase (ERK), phosphatidylinositol 3-kinase (PI3K)/Akt and Janus protein tyrosine kinase (JAK)/STAT. Furthermore, ALK is implicated in epigenetic regulation, including DNA methylation and miRNA expression, and an interaction with nuclear proteins has been described. Through these mechanisms, ALK fusion proteins enable a transcriptional programme that drives the pathogenesis of a range of ALK-related malignancies.
Uveal Melanoma Biopsy: A Review
Authors: Frizziero Luisa , Midena Edoardo , Trainiti Sara , Londei Davide , Bonaldi Laura , Bini Silvia , Parrozzani Raffaele
Published: July 2019

Intraocular tumor diagnosis is based on clinical findings supported by additional imaging tools, such as ultrasound, optical coherence tomography and angiographic techniques, usually without the need for invasive procedures or tissue sampling. Despite improvements in the local treatment of uveal melanoma (UM), the prevention and treatment of the metastatic disease remain unsolved, and nearly 50% of patients develop liver metastasis. The current model suggests that tumor cells have already spread by the time of diagnosis, remaining dormant until there are favorable conditions. Tumor sampling procedures at the time of primary tumor diagnosis/treatment are therefore now commonly performed, usually not to confirm the diagnosis of UM, but to obtain a tissue sample for prognostication, to assess patient’s specific metastatic risk. Moreover, several studies are ongoing to identify genes specific to UM tumorigenesis, leading to several potential targeted therapeutic strategies. Genetic information can also influence the surveillance timing and metastatic screening type of patients affected by UM. In spite of the widespread use of biopsies in general surgical practice, in ophthalmic oncology the indications and contraindications for tumor biopsy continue to be under debate. The purpose of this review paper is to critically evaluate the role of uveal melanoma biopsy in ophthalmic oncology.
Linking Cancer Metabolic Dysfunction and Genetic Instability through the Lens of Iron Metabolism
Authors: Petronek Michael S. , Spitz Douglas R. , Buettner Garry R. , Allen Bryan G.
Published: July 2019

Iron (Fe) is an essential element that plays a fundamental role in a wide range of cellular functions, including cellular proliferation, DNA synthesis, as well as DNA damage and repair. Because of these connections, iron has been strongly implicated in cancer development. Cancer cells frequently have changes in the expression of iron regulatory proteins. For example, cancer cells frequently upregulate transferrin (increasing uptake of iron) and down regulate ferroportin (decreasing efflux of intracellular iron). These changes increase the steady-state level of intracellular redox active iron, known as the labile iron pool (LIP). The LIP typically contains approximately 2% intracellular iron, which primarily exists as ferrous iron (Fe2+). The LIP can readily contribute to oxidative distress within the cell through Fe2+-dioxygen and Fenton chemistries, generating the highly reactive hydroxyl radical (HO•). Due to the reactive nature of the LIP, it can contribute to increased DNA damage. Mitochondrial dysfunction in cancer cells results in increased steady-state levels of hydrogen peroxide and superoxide along with other downstream reactive oxygen species. The increased presence of H2O2 and O2•− can increase the LIP, contributing to increased mitochondrial uptake of iron as well as genetic instability. Thus, iron metabolism and labile iron pools may play a central role connecting the genetic mutational theories of cancer to the metabolic theories of cancer.
Early Colorectal Cancers Provide New Evidence for a Lynch Syndrome-to-CMMRD Phenotypic Continuum
Authors: Fernández-Rozadilla Ceres , Alvarez-Barona Miriam , Schamschula Esther , Bodo Sahra , Lopez-Novo Anael , Dacal Andres , Calviño-Costas Consuelo , Lancho Angel , Amigo Jorge , Bello Xabier , Cameselle-Teijeiro Jose Manuel , Carracedo Angel , Colas Chrystelle , Muleris Martine , Wimmer Katharina , Ruiz-Ponte Clara
Published: July 2019

Lynch syndrome (LS) is the most common hereditary colorectal cancer (CRC) syndrome, caused by heterozygous mutations in the mismatch repair (MMR) genes. Biallelic mutations in these genes lead however, to constitutive mismatch repair deficiency (CMMRD). In this study, we follow the diagnostic journey of a 12-year old patient with CRC, with a clinical phenotype overlapping CMMRD. We perform molecular and functional assays to discard a CMMRD diagnosis then identify by exome sequencing and validation in a cohort of 134 LS patients, a candidate variant in the MLH1 UTR region in homozygosis. We propose that this variant, together with other candidates, could be responsible for age-of-onset modulation. Our data support the idea that low-risk modifier alleles may influence early development of cancer in LS leading to a LS-to-CMMRD phenotypic continuum. Therefore, it is essential that larger efforts are directed to the identification and study of these genetic modifiers, in order to provide optimal cancer prevention strategies to these patients.
Ni Catalysts Based on Attapulgite for Hydrogen Production through the Glycerol Steam Reforming Reaction
Authors: Charisiou Nikolaos D. , Sebastian Victor , Hinder Steven J. , Baker Mark A. , Polychronopoulou Kyriaki , Goula Maria A.
Published: July 2019

Attapulgite (ATP, a natural clay) was used as carrier to produce a nickel-based catalyst (Ni/ATP) for the work that is presented herein. Its catalytic performance was comparatively assessed with a standard Ni/Al2O3 sample for the glycerol steam reforming (GSR) reaction. It was shown that the ATP support led to lower mean Ni crystallite size, i.e., it increased the dispersion of the active phase, to the easier reduction of NiO and also increased the basicity of the catalytic material. It was also shown that it had a significant effect on the distribution of the gaseous products. Specifically, for the Ni/ATP catalyst, the production of liquid effluents was minimal and subsequently, conversion of glycerol into gaseous products was higher. Importantly, the Ni/ATP favored the conversion into H2 and CO2 to the detriment of CO and CH4. The stability experiments, which were undertaken at a low WGFR, showed that the activity of both catalysts was affected with time as a result of carbon deposition and/or metal particle sintering. An examination of the spent catalysts revealed that the coke deposits consisted of filamentous carbon, a type that is known to encapsulate the active phase with fatal consequences.
A Novel Porous Ceramic Membrane Supported Monolithic Cu-Doped Mn–Ce Catalysts for Benzene Combustion
Authors: Cuo Zhaxi , Wang Dongdong , Gong Yan , Zhao Feng , Liu Haidi , Chen Yunfa
Published: July 2019

Porous ceramic membranes (PCMs) are considered as an efficient hot gas filtration material in industrial systems. Functionalization of the PCMs with high-efficiency catalysts for the abatement of volatile organic compounds (VOCs) during dust elimination is a promising way to purify the industrial exhaust gases. In this work, we prepared PCMs (porosity: 70%) in a facile sintering process and integrated Cu-doped Mn–Ce oxides into the PCMs as monolithic catalysts by the sol–gel method for benzene oxidation. Through this method, the catalysts are dispersed evenly throughout the PCMs with excellent adhesion, and the catalytic PCMs provided more active sites for the reactant gases during the catalytic reaction process compared to the powder catalysts. The physicochemical properties of PCMs and catalytic PCMs were characterized systematically, and the catalytic activities were measured in total oxidation of benzene. As a result, all the prepared catalytic PCMs exhibited high catalytic activity for benzene oxidation. Significantly, the monolithic catalyst of Cu0.2Mn0.6Ce0.2/PCMs obtained the lowest temperature for benzene conversion efficiency of 90% (T90) at 212 °C with a high gaseous hourly space velocity of 5000 h−1 and showed strong resistance to high humidity (90 vol.%, 20 °C) with long-term stability in continuous benzene stream, which is caused by abundant active adsorbed oxygen, more surficial oxygen vacancy, and lower-temperature reducibility.
Fabrication of Au Nanoparticle-Decorated MoS2 Nanoslices as Efficient Electrocatalysts for Electrochemical Detection of Dopamine
Authors: Chen Huaiyin , Chen Huaijin , Hong Ruoyu
Published: July 2019

Herein, MoS2 nanoslices were simply prepared by using ultrasonic treatment, and were further decorated with Au nanoparticles (AuNPs) through an electrodeposition process to obtain the MoS2/Au nanocomposites. The obtained nanocomposites display synergetic electrocatalytic effect for the oxidation of dopamine due to the large surface area and two-dimensional structure of the MoS2 nanoslices, combining with the high catalytic activity and good conductivity of AuNPs. An electrochemical sensor was constructed based on MoS2/Au-modified carbon paste electrode, for sensitive and quantitative determination of dopamine. The prepared electrochemical sensor proves excellent analytical performances: very high sensitivity, wide linear ranges (0.5–300 μM), and low detection limit (76 nM). Moreover, the dopamine sensor also displays high selectivity, good reproducibility and stability, and can be used in real sample analysis. The method of fabricating high-efficiency electrocatalysts and electrochemical sensors proposed in this study provides a good reference for developing more functionalized nanocomposites and for extending practical applications.
Differential Inhibition of Target Gene Expression by Human microRNAs
Authors: Li Peng , Chen Yi , Juma Conslata Awino , Yang Chengyong , Huang Jinfeng , Zhang Xiaoxiao , Zeng Yan
Published: July 2019

microRNAs (miRNAs) exert their functions by repressing the expression of their target genes, but most miRNA target genes are unknown, and the degree to which a miRNA differentially inhibits the expression of its targets is underappreciated. We selected human miR-1, miR-122, and miR-124 as representatives to investigate the reliability of miRNA target predictions and examine how miRNAs suppress their targets. We constructed miRNA target gene reporter libraries based on prediction programs TargetScan, miRanda, and PicTar, and performed large-scale reporter assays to directly evaluate whether and how strongly a predicted target gene is repressed by its miRNA. We then performed statistical analyses to examine parameters that contributed to the miRNA inhibition of target genes. We found that the three programs have approximately 72–85% success rates in predicting genuine targets and that the miRNA inhibition of different targets varies in extent. We also identified parameters that could predict the degrees of miRNA repression, and further showed that differential miR-124 repression might contribute to differential gene expression in vivo. Our studies systematically investigated hundreds of miRNA target genes, shed light on factors influencing miRNA functions, and suggested a new mechanism by which differential target repression by miRNAs regulates endogenous gene expression.
Mitochondrial Uncoupling: A Key Controller of Biological Processes in Physiology and Diseases
Authors: Demine Stéphane , Renard Patricia , Arnould Thierry
Published: July 2019

Mitochondrial uncoupling can be defined as a dissociation between mitochondrial membrane potential generation and its use for mitochondria-dependent ATP synthesis. Although this process was originally considered a mitochondrial dysfunction, the identification of UCP-1 as an endogenous physiological uncoupling protein suggests that the process could be involved in many other biological processes. In this review, we first compare the mitochondrial uncoupling agents available in term of mechanistic and non-specific effects. Proteins regulating mitochondrial uncoupling, as well as chemical compounds with uncoupling properties are discussed. Second, we summarize the most recent findings linking mitochondrial uncoupling and other cellular or biological processes, such as bulk and specific autophagy, reactive oxygen species production, protein secretion, cell death, physical exercise, metabolic adaptations in adipose tissue, and cell signaling. Finally, we show how mitochondrial uncoupling could be used to treat several human diseases, such as obesity, cardiovascular diseases, or neurological disorders.
Metabolic Dysregulations and Epigenetics: A Bidirectional Interplay that Drives Tumor Progression
Authors: Crispo Fabiana , Condelli Valentina , Lepore Silvia , Notarangelo Tiziana , Sgambato Alessandro , Esposito Franca , Maddalena Francesca , Landriscina Matteo
Published: July 2019

Cancer has been considered, for a long time, a genetic disease where mutations in key regulatory genes drive tumor initiation, growth, metastasis, and drug resistance. Instead, the advent of high-throughput technologies has revolutionized cancer research, allowing to investigate molecular alterations at multiple levels, including genome, epigenome, transcriptome, proteome, and metabolome and showing the multifaceted aspects of this disease. The multi-omics approaches revealed an intricate molecular landscape where different cellular functions are interconnected and cooperatively contribute to shaping the malignant phenotype. Recent evidence has brought to light how metabolism and epigenetics are highly intertwined, and their aberrant crosstalk can contribute to tumorigenesis. The oncogene-driven metabolic plasticity of tumor cells supports the energetic and anabolic demands of proliferative tumor programs and secondary can alter the epigenetic landscape via modulating the production and/or the activity of epigenetic metabolites. Conversely, epigenetic mechanisms can regulate the expression of metabolic genes, thereby altering the metabolome, eliciting adaptive responses to rapidly changing environmental conditions, and sustaining malignant cell survival and progression in hostile niches. Thus, cancer cells take advantage of the epigenetics-metabolism crosstalk to acquire aggressive traits, promote cell proliferation, metastasis, and pluripotency, and shape tumor microenvironment. Understanding this bidirectional relationship is crucial to identify potential novel molecular targets for the implementation of robust anti-cancer therapeutic strategies.