bluuebunny/crossref_metadata_2025 huggingface dataset:
The Endocannabinoid System in the Retina: From Physiology to Practical and Therapeutic Applications
Authors: Schwitzer Thomas , Schwan Raymund , Angioi-Duprez Karine , Giersch Anne , Laprevote Vincent
Published: January 2016

Cannabisis one of the most prevalent drugs used in industrialized countries. The main effects ofCannabisare mediated by two major exogenous cannabinoids: ∆9-tetrahydroxycannabinol and cannabidiol. They act on specific endocannabinoid receptors, especially types 1 and 2. Mammals are endowed with a functional cannabinoid system including cannabinoid receptors, ligands, and enzymes. This endocannabinoid signaling pathway is involved in both physiological and pathophysiological conditions with a main role in the biology of the central nervous system. As the retina is a part of the central nervous system due to its embryonic origin, we aim at providing the relevance of studying the endocannabinoid system in the retina. Here, we review the distribution of the cannabinoid receptors, ligands, and enzymes in the retina and focus on the role of the cannabinoid system in retinal neurobiology. This review describes the presence of the cannabinoid system in critical stages of retinal processing and its broad involvement in retinal neurotransmission, neuroplasticity, and neuroprotection. Accordingly, we support the use of synthetic cannabinoids as new neuroprotective drugs to prevent and treat retinal diseases. Finally, we argue for the relevance of functional retinal measures in cannabis users to evaluate the impact of cannabis use on human retinal processing.
Revisiting Epithelial‐to‐Mesenchymal Transition in Liver Fibrosis: Clues for a Better Understanding of the “Reactive” Biliary Epithelial Phenotype
Authors: Fabris Luca , Brivio Simone , Cadamuro Massimiliano , Strazzabosco Mario
Published: January 2016

Whether liver epithelial cells contribute to the development of hepatic scarring by undergoing epithelial‐to‐mesenchymal transition (EMT) is a controversial issue. Herein, we revisit the concept of EMT in cholangiopathies, a group of severe hepatic disorders primarily targeting the bile duct epithelial cell (cholangiocyte), leading to progressive portal fibrosis, the main determinant of liver disease progression. Unfortunately, therapies able to halt this process are currently lacking. In cholangiopathies, fibrogenesis is part of ductular reaction, a reparative complex involving epithelial, mesenchymal, and inflammatory cells. Ductular reactive cells (DRC) are cholangiocytes derived from the activation of the hepatic progenitor cell compartment. These cells are arranged into irregular strings and express a “reactive” phenotype, which enables them to extensively crosstalk with the other components of ductular reaction. We will first discuss EMT in liver morphogenesis and then highlight how some of these developmental programs are partly reactivated in DRC. Evidence for “bona fide” EMT changes in cholangiocytes is lacking, but expression of some mesenchymal markers represents a fundamental repair mechanism in response to chronic biliary damage with potential harmful fibrogenetic effects. Understanding microenvironmental cues and signaling perturbations promoting these changes in DRC may help to identify potential targets for new antifibrotic therapies in cholangiopathies.
Effects of the van der Waals Force on the Dynamics Performance for a Micro Resonant Pressure Sensor
Authors: Xu Lizhong , Liu Yulei , Fu Xiaorui
Published: January 2016

The micro resonant pressure sensor outputs the frequency signals where the distortion does not take place in a long distance transmission. As the dimensions of the sensor decrease, the effects of the van der Waals forces should be considered. Here, a coupled dynamic model of the micro resonant pressure sensor is proposed and its coupled dynamic equation is given in which the van der Waals force is considered. By the equation, the effects of the van der Waals force on the natural frequencies and vibration amplitudes of the micro resonant pressure sensor are investigated. Results show that the natural frequency and the vibrating amplitudes of the micro resonant pressure sensor are affected significantly by van der Waals force for a small clearance between the film and the base plate, a small initial tension stress of the film, and some other conditions.
Analytic Solution for Nonlinear Multimode Beam Vibration Using a Modified Harmonic Balance Approach and Vieta’s Substitution
Authors: Lee Y. Y.
Published: January 2016

This paper presents a modified harmonic balance solution method incorporated with Vieta’s substitution technique for nonlinear multimode damped beam vibration. The aim of the modification in the solution procedures is to develop the analytic formulations, which are used to calculate the vibration amplitudes of a nonlinear multimode damped beam without the need of nonlinear equation solver for the nonlinear algebraic equations generated in the harmonic balance processes. The result obtained from the proposed method shows reasonable agreement with that from a previous numerical integration method. In general, the results can show the convergence and prove the accuracy of the proposed method.
Hijacking the Cellular Mail: Exosome Mediated Differentiation of Mesenchymal Stem Cells
Authors: Narayanan Raghuvaran , Huang Chun-Chieh , Ravindran Sriram
Published: January 2016

Bone transplantation is one of the most widely performed clinical procedures. Consequently, bone regeneration using mesenchymal stem cells and tissue engineering strategies is one of the most widely researched fields in regenerative medicine. Recent scientific consensus indicates that a biomimetic approach is required to achieve proper regeneration of any tissue. Exosomes are nanovesicles secreted by cells that act as messengers that influence cell fate. Although exosomal function has been studied with respect to cancer and immunology, the role of exosomes as inducers of stem cell differentiation has not been explored. We hypothesized that exosomes can be used as biomimetic tools for regenerative medicine. In this study we have explored the use of cell‐generated exosomes as tools to induce lineage specific differentiation of stem cells. Our results indicate that proosteogenic exosomes isolated from cell cultures can induce lineage specific differentiation of naïve MSCs in vitro and in vivo. Additionally, exosomes can also bind to matrix proteins such as type I collagen and fibronectin enabling them to be tethered to biomaterials. Overall, the results from this study show the potential of cell derived exosomes in bone regenerative medicine and opens up new avenues for future research.
Synergistic Effects of Cilostazol and Probucol on ER Stress‐Induced Hepatic Steatosis via Heme Oxygenase‐1‐Dependent Activation of Mitochondrial Biogenesis
Authors: Chen Yingqing , Pandiri Indira , Joe Yeonsoo , Kim Hyo Jeong , Kim Seul-Ki , Park Jeongmin , Ryu Jinhyun , Cho Gyeong Jae , Park Jeong Woo , Ryter Stefan W. , Chung Hun Taeg
Published: January 2016

The selective type‐3 phosphodiesterase inhibitor cilostazol and the antihyperlipidemic agent probucol have antioxidative, anti‐inflammatory, and antiatherogenic properties. Moreover, cilostazol and probucol can regulate mitochondrial biogenesis. However, the combinatorial effect of cilostazol and probucol on mitochondrial biogenesis remains unknown. Endoplasmic reticulum (ER) stress is a well‐known causative factor of nonalcoholic fatty liver disease (NAFLD) which can impair mitochondrial function in hepatocytes. Here, we investigated the synergistic effects of cilostazol and probucol on mitochondrial biogenesis and ER stress‐induced hepatic steatosis. A synergistic effect of cilostazol and probucol on HO‐1 and mitochondrial biogenesis gene expression was found in human hepatocellular carcinoma cells (HepG2) and murine primary hepatocytes. Furthermore, in an animal model of ER stress involving tunicamycin, combinatorial treatment with cilostazol and probucol significantly increased the expression of HO‐1 and mitochondrial biogenesis‐related genes and proteins, whereas it downregulated serum ALT, eIF2 phosphorylation, and CHOP expression, as well as the lipogenesis‐related genes SREBP‐1c and FAS. Based on these results, we conclude that cilostazol and probucol exhibit a synergistic effect on the activation of mitochondrial biogenesis via upregulation of HO‐1, which confers protection against ER stress‐induced hepatic steatosis.
Stem Cell Mobilization with G‐CSF versus Cyclophosphamide plus G‐CSF in Mexican Children
Authors: Meraz José Eugenio Vázquez , Arellano-Galindo José , Avalos Armando Martínez , Mendoza-García Emma , Jiménez-Hernández Elva
Published: January 2016

Fifty‐six aphaereses were performed in 23 pediatric patients with malignant hematological and solid tumors, following three different protocols for PBPC mobilization and distributed as follows: A: seventeen mobilized with 4 g/m2 of cyclophosphamide (CFA) and 10 μg/kg/day of granulocyte colony stimulating factor (G‐CSF), B: nineteen with CFA + G‐CSF, and C: twenty only with G‐CSF when the WBC count exceeded 10 × 109/L. The average number of MNC/kg body weight (BW)/aphaeresis was 0.4 × 108 (0.1–1.4), 2.25 × 108 (0.56–6.28), and 1.02 × 108 (0.34–2.5) whereas the average number of CD34+ cells/kg BW/aphaeresis was 0.18 × 106/kg (0.09–0.34), 1.04 × 106 (0.19–9.3), and 0.59 × 106 (0.17–0.87) and the count of CFU/kg BW/aphaeresis was 1.11 × 105 (0.31–2.12), 1.16 × 105 (0.64–2.97), and 1.12 × 105 (0.3–6.63) in groups A, B, and C, respectively. The collection was better in group B versus group A (p = 0.007 and p = 0.05, resp.) and in group C versus group A (p = 0.08 and p = 0.05, resp.). The collection of PBPCs was more effective in the group mobilized with CFM + G‐CSF when the WBC exceeded 10 × 103/μL in terms of MNC and CD34+ cells and there was no toxicity of the chemotherapy.
The Three-Dimensional Culture System with Matrigel and Neurotrophic Factors Preserves the Structure and Function of Spiral Ganglion NeuronIn Vitro
Authors: Sun Gaoying , Liu Wenwen , Fan Zhaomin , Zhang Daogong , Han Yuechen , Xu Lei , Qi Jieyu , Zhang Shasha , Gao Bradley T. , Bai Xiaohui , Li Jianfeng , Chai Renjie , Wang Haibo
Published: January 2016

Whole organ culture of the spiral ganglion region is a resourceful model system facilitating manipulation and analysis of live sprial ganglion neurons (SGNs). Three-dimensional (3D) cultures have been demonstrated to have many biomedical applications, but the effect of 3D culture in maintaining the SGNs structure and function in explant culture remains uninvestigated. In this study, we used the matrigel to encapsulate the spiral ganglion region isolated from neonatal mice. First, we optimized the matrigel concentration for the 3D culture system and found the 3D culture system protected the SGNs against apoptosis, preserved the structure of spiral ganglion region, and promoted the sprouting and outgrowth of SGNs neurites. Next, we found the 3D culture system promoted growth cone growth as evidenced by a higher average number and a longer average length of filopodia and a larger growth cone area. 3D culture system also significantly elevated the synapse density of SGNs. Last, we found that the 3D culture system combined with neurotrophic factors had accumulated effects in promoting the neurites outgrowth compared with 3D culture or NFs treatment only groups. Together, we conclude that the 3D culture system preserves the structure and function of SGN in explant culture.
Nonlinear Vibroimpact Characteristics of a Planetary Gear Transmission System
Authors: Zhou Jianxing , Sun Wenlei , Yuan Liang
Published: January 2016

In order to research the vibroimpact characteristics of a planetary gear transmission system under high speed and lightly loaded conditions, a new modeling method is proposed. In the modeling process, linear spring was used to simulate gear mesh elasticity under heavy load cases, and Hertz contact theory was used to calculate the contact force of gear pair under light load cases. Then, effects of the working conditions on the system vibroimpact characteristics are analyzed. The results show that, with input speed growing, the mesh force produced obvious fluctuations on the resonance frequencies of the sun gear and carrier torsion vibration, ring gear’s transverse vibration under the heavy load. Under light load condition, the collision vibration occurs in the gear pair; the changing trend of the contact force shows strongly nonlinear characteristics. The time of mesh-apart in gears pair decreases gradually as the load is increased; until it reaches collision vibration threshold value, the gear pair is no longer mesh-apart. With increasing of the input speed, the time of mesh-apart is decreased gradually; the fluctuation amplitude of contact force shows a linearly increasing trend. The study provides useful theoretical guideline for planetary gear transmission low-noise design.
Gmelina arboreaRoxb. (Family: Verbenaceae) Extract Upregulates theβ-Cell Regeneration in STZ Induced Diabetic Rats
Authors: Attanayake Anoja Priyadarshani , Jayatilaka Kamani Ayoma Perera Wijewardana , Pathirana Chitra , Mudduwa Lakmini Kumari Boralugoda
Published: January 2016

Gmelina arboreaRoxb. (common name: Et-demata, Family: Verbenaceae) has been used traditionally in Sri Lanka as a remedy against diabetes mellitus. The objective of the present study was to evaluate antidiabetic mechanisms of the aqueous bark extract ofG. arboreain streptozotocin induced (STZ) diabetic male Wistar rats. Aqueous bark extract ofG. arborea(1.00 g/kg) and glibenclamide as the standard drug (0.50 mg/kg) were administered orally using a gavage to STZ diabetic rats (65 mg/kg, ip) for 30 days. The antidiabetic mechanisms of aqueous extract ofG. arborea(1.00 g/kg) were determined at the end of the experiment. The fasting blood glucose concentration was significantly lowered and the serum insulin and C-peptide concentrations were increased by 57% and 39% in plant extract treated rats on day 30, respectively (p<0.05). The histopathology and immunohistochemistry results of the plant extract treated group showed a regenerative effect onβ-cells of the pancreas in diabetic rats. In addition, serum lipid parameters were improved inG. arboreaextract treated diabetic rats. The results revealed that the aqueous stem bark extract ofG. arborea(1.00 g/kg) showed beneficial effects against diabetes mellitus through upregulating theβ-cell regeneration and biosynthesis of insulin in diabetic rats.
The Neuroprotective Effect of the Association of Aquaporin-4/Glutamate Transporter-1 against Alzheimer’s Disease
Authors: Lan Yu-Long , Zou Shuang , Chen Jian-Jiao , Zhao Jie , Li Shao
Published: January 2016

Alzheimer’s disease (AD) is a progressive neurodegenerative disorder that is characterized by memory loss and cognitive dysfunction. Aquaporin-4 (AQP4), which is primarily expressed in astrocytes, is the major water channel expressed in the central nervous system (CNS). This protein plays an important role in water and ion homeostasis in the normal brain and in various brain pathological conditions. Emerging evidence suggests that AQP4 deficiency impairs learning and memory and that this may be related to the expression of glutamate transporter-1 (GLT-1). Moreover, the colocalization of AQP4 and GLT-1 has long been studied in brain tissue; however, far less is known about the potential influence that the AQP4/GLT-1 complex may have on AD. Research on the functional interaction of AQP4 and GLT-1 has been demonstrated to be of great significance in the study of AD. Here, we review the interaction of AQP4 and GLT-1 in astrocytes, which might play a pivotal role in the regulation of distinct cellular responses that involve neuroprotection against AD. The association of AQP4 and GLT-1 could greatly supplement previous research regarding neuroprotection against AD.
Cartilage Regeneration in Human with Adipose Tissue-Derived Stem Cells: Current Status in Clinical Implications
Authors: Pak Jaewoo , Lee Jung Hun , Kartolo Wiwi Andralia , Lee Sang Hee
Published: January 2016

Osteoarthritis (OA) is one of the most common debilitating disorders among the elderly population. At present, there is no definite cure for the underlying causes of OA. However, adipose tissue-derived stem cells (ADSCs) in the form of stromal vascular fraction (SVF) may offer an alternative at this time. ADSCs are one type of mesenchymal stem cells that have been utilized and have demonstrated an ability to regenerate cartilage. ADSCs have been shown to regenerate cartilage in a variety of animal models also. Non-culture-expanded ADSCs, in the form of SVF along with platelet rich plasma (PRP), have recently been used in humans to treat OA and other cartilage abnormalities. These ADSCs have demonstrated effectiveness without any serious side effects. However, due to regulatory issues, only ADSCs in the form of SVF are currently allowed for clinical uses in humans. Culture-expanded ADSCs, although more convenient, require clinical trials for a regulatory approval prior to uses in clinical settings. Here we present a systematic review of currently available clinical studies involving ADSCs in the form of SVF and in the culture-expanded form, with or without PRP, highlighting the clinical effectiveness and safety in treating OA.
Tissue‐Related Hypoxia Attenuates Proinflammatory Effects of Allogeneic PBMCs on Adipose‐Derived Stromal Cells In Vitro
Authors: Bobyleva Polina I. , Andreeva Elena R. , Gornostaeva Aleksandra N. , Buravkova Ludmila B.
Published: January 2016

Human adipose tissue‐stromal derived cells (ASCs) are considered a perspective tool for regenerative medicine. Depending on the application mode ASC/allogeneic immune cell interaction can occur in the systemic circulation under plenty high concentrations of O2 and in target tissues at lower O2 levels. Here we examined the effects of allogeneic PHA‐stimulated peripheral blood mononuclear cells (PBMCs) on ASCs under ambient (20%) oxygen and “physiological” hypoxia (5% O2). As revealed with microarray analysis ASCs under 20% O2 were more affected by activated PBMCs, which was manifested in differential expression of more than 300 genes, whereas under 5% O2 only 140 genes were changed. Altered gene pattern was only partly overlapped at different O2 conditions. Under O2 ASCs retained their proliferative and differentiative capacities, mesenchymal phenotype, and intracellular organelle’ state. ASCs were proinflammatory activated on transcription level that was confirmed by their ability to suppress activation and proliferation of mitogen‐stimulated PBMCs. ASC/PBMCs interaction resulted in anti‐inflammatory shift of paracrine mediators in conditioning medium with significant increase of immunosuppressive LIF level. Our data indicated that under both ambient and tissue‐related O2 ASCs possessed immunosuppressive potential and maintained functional activity. Under “physiological” hypoxia ASCs were less susceptible to “priming” by allogeneic mitogen‐activated PBMCs.
Fyn Mediates High Glucose-Induced Actin Cytoskeleton Reorganization of Podocytes via Promoting ROCK Activation In Vitro
Authors: Lv Zhimei , Hu Mengsi , Ren Xiaoxu , Fan Minghua , Zhen Junhui , Chen Liqun , Lin Jiangong , Ding Nannan , Wang Qun , Wang Rong
Published: January 2016

Fyn, a member of the Src family of tyrosine kinases, is a key regulator in cytoskeletal remodeling in a variety of cell types. Recent studies have demonstrated that Fyn is responsible for nephrin tyrosine phosphorylation, which will result in polymerization of actin filaments and podocyte damage. Thus detailed involvement of Fyn in podocytes is to be elucidated. In this study, we investigated the potential role of Fyn/ROCK signaling and its interactions with paxillin. Our results presented that high glucose led to filamentous actin (F-actin) rearrangement in podocytes, accompanied by paxillin phosphorylation and increased cell motility, during which Fyn and ROCK were markedly activated. Gene knockdown of Fyn by siRNA showed a reversal effect on high glucose-induced podocyte damage and ROCK activation; however, inhibition of ROCK had no significant effects on Fyn phosphorylation. These observations demonstrate that in vitro Fyn mediates high glucose-induced actin cytoskeleton remodeling of podocytes via promoting ROCK activation and paxillin phosphorylation.
iPSCs: A Minireview from Bench to Bed, including Organoids and the CRISPR System
Authors: Orqueda Andrés Javier , Giménez Carla Alejandra , Pereyra-Bonnet Federico
Published: January 2016

When Dolly the sheep was born, the first probe into an adult mammalian genome traveling back in time and generating a whole new animal appeared. Ten years later, the reprogramming process became a defined method of producing induced pluripotent stem cells (iPSCs) through the overexpression of four transcription factors. iPSCs are capable of originating virtually all types of cells and tissues, including a whole new animal. The reprogramming strategies based on patient‐derived cells should make the development of clinical applications of cell based therapy much more straightforward. Here, we analyze the current state, opportunities, and challenges of iPSCs from bench to bed, including organoids and the CRISPR system.
Dynamics of the Typhoon Haitang Related High Ozone Episode over Hong Kong
Authors: Wei Xiaolin , Lam Ka-se , Cao Chunyan , Li Hui , He Jiajia
Published: January 2016

It has been previously established that photochemical smog occurring in the Pearl River Delta Region (PRD) was associated with stagnant meteorological conditions. However, the photochemical smog (17 July to 20 July 2005) induced by typhoon Haitang was associated with moderate wind speed and nonstagnant meteorological conditions. The dynamic process of this ozone episode was studied using an integrated numerical model, that is, a mesoscale meteorological model and Community Multiscale Air Quality (CMAQ) model. Model performance has been evaluated using both ground-based meteorological and air quality observations. Analysis of simulated wind fields and ozone budget has been performed. This dynamic process is summarized into three physical factors. First, the westerly wind placed Hong Kong directly downwind of the PRD emissions. Second, the convergence of wind flow stimulated a vertical local circulation near the surface layer. This recirculation allowed primary and secondary pollutants to accumulate. Third, the conditions of high air temperature and low humidity resulted in active photochemical reactions. These combined effects resulted in the formation of high ozone in this episode.
Prospect of Stem Cells in Bone Tissue Engineering: A Review
Authors: Yousefi Azizeh-Mitra , James Paul F. , Akbarzadeh Rosa , Subramanian Aswati , Flavin Conor , Oudadesse Hassane
Published: January 2016

Mesenchymal stem cells (MSCs) have been the subject of many studies in recent years, ranging from basic science that looks into MSCs properties to studies that aim for developing bioengineered tissues and organs. Adult bone marrow‐derived mesenchymal stem cells (BM‐MSCs) have been the focus of most studies due to the inherent potential of these cells to differentiate into various cell types. Although, the discovery of induced pluripotent stem cells (iPSCs) represents a paradigm shift in our understanding of cellular differentiation. These cells are another attractive stem cell source because of their ability to be reprogramed, allowing the generation of multiple cell types from a single cell. This paper briefly covers various types of stem cell sources that have been used for tissue engineering applications, with a focus on bone regeneration. Then, an overview of some recent studies making use of MSC‐seeded 3D scaffold systems for bone tissue engineering has been presented. The emphasis has been placed on the reported scaffold properties that tend to improve MSCs adhesion, proliferation, and osteogenic differentiation outcomes.
Vitamin D and the Epithelial to Mesenchymal Transition
Authors: Larriba María Jesús , García de Herreros Antonio , Muñoz Alberto
Published: January 2016

Several studies support reciprocal regulation between the active vitamin D derivative 1α,25‐dihydroxyvitamin D3 (1,25(OH)2D3) and the epithelial to mesenchymal transition (EMT). Thus, 1,25(OH)2D3 inhibits EMT via the induction of a variety of target genes that encode cell adhesion and polarity proteins responsible for the epithelial phenotype and through the repression of key EMT inducers. Both direct and indirect regulatory mechanisms mediate these effects. Conversely, certain master EMT inducers inhibit 1,25(OH)2D3 action by repressing the transcription of VDR gene encoding the high affinity vitamin D receptor that mediates 1,25(OH)2D3 effects. Consequently, the balance between the strength of 1,25(OH)2D3 signaling and the induction of EMT defines the cellular phenotype in each context. Here we review the current understanding of the genes and mechanisms involved in the interplay between 1,25(OH)2D3 and EMT.
Determinants of Cervical Cancer Screening Uptake among Women in Ilorin, North Central Nigeria: A Community-Based Study
Authors: Idowu Ajibola , Olowookere Samuel Anu , Fagbemi Aderonke Tolulope , Ogunlaja Olumuyiwa Ayotunde
Published: January 2016

Introduction. Cancer of the cervix is the leading cause of cancer deaths among women in developing countries. Screening is one of the most cost effective control strategies for the disease. This study assessed the determinants of cervical cancer screening uptake among Nigerian women.Methodology. This cross-sectional study was conducted using multistage sampling technique among 338 participants in Ilorin, North Central Nigeria. A pretested questionnaire was used for data collection and data analysis was done using SPSS version 21. Chi-square test was used for bivariate analysis while binary logistic regression was used for multivariate analysis. Statistical significance was set atp<0.05.Results. Only 8.0% of the respondents had ever been screened for cancer of the cervix. The proportion of women who had ever been screened was significantly higher among those who demonstrated positive attitude to screening (81.5%,p=0.001), respondents who were aware of the disease (100.0%,p=0.001), and those who were aware of cervical cancer screening (88.9%,p=0.001). Respondents who had negative attitude had 63% lesser odds of being screened compared to those who had positive attitudes towards screening (AOR; 0.37, 95% CI; 0.01–0.28).Conclusion. There is urgent need to improve the knowledge base and attitude of Nigerian women to enhance cervical cancer screening uptake among them.
The Application of Human iPSCs in Neurological Diseases: From Bench to Bedside
Authors: Xie Nina , Tang Beisha
Published: January 2016

In principle, induced pluripotent stem cells (iPSCs) are generated from somatic cells by reprogramming and gaining the capacity to self‐renew indefinitely as well as the ability to differentiate into cells of different lineages. Human iPSCs have absolute advantages over human embryonic stem cells (ESCs) and animal models in disease modeling, drug screening, and cell replacement therapy. Since Takahashi and Yamanaka first described in 2007 that iPSCs can be generated from human adult somatic cells by retroviral transduction of the four transcription factors, Oct3/4, Sox2, Klf4, and c‐Myc, disease specific iPSC lines have sprung up worldwide like bamboo shoots after a spring rain, making iPSC one of the hottest and fastest moving topics in modern science. The craze for iPSCs has spread throughout main branches of clinical medicine, covering neurology, hematology, cardiology, endocrinology, hepatology, ophthalmology, and so on. Here in this paper, we will focus on the clinical application of human iPSCs in disease modeling, drug screening, and cell replacement therapy for neurological diseases.
Glioblastoma Stem Cells Microenvironment: The Paracrine Roles of the Niche in Drug and Radioresistance
Authors: Fidoamore Alessia , Cristiano Loredana , Antonosante Andrea , d’Angelo Michele , Di Giacomo Erica , Astarita Carlo , Giordano Antonio , Ippoliti Rodolfo , Benedetti Elisabetta , Cimini Annamaria
Published: January 2016

Among all solid tumors, the high‐grade glioma appears to be the most vascularized one. In fact, “microvascular hyperplasia” is a hallmark of GBM. An altered vascular network determines irregular blood flow, so that tumor cells spread rapidly beyond the diffusion distance of oxygen in the tissue, with the consequent formation of hypoxic or anoxic areas, where the bulk of glioblastoma stem cells (GSCs) reside. The response to this event is the induction of angiogenesis, a process mediated by hypoxia inducible factors. However, this new capillary network is not efficient in maintaining a proper oxygen supply to the tumor mass, thereby causing an oxygen gradient within the neoplastic zone. This microenvironment helps GSCs to remain in a “quiescent” state preserving their potential to proliferate and differentiate, thus protecting them by the effects of chemo‐ and radiotherapy. Recent evidences suggest that responses of glioblastoma to standard therapies are determined by the microenvironment of the niche, where the GSCs reside, allowing a variety of mechanisms that contribute to the chemo‐ and radioresistance, by preserving GSCs. It is, therefore, crucial to investigate the components/factors of the niche in order to formulate new adjuvant therapies rendering more efficiently the gold standard therapies for this neoplasm.
PTF1a Activity in Enriched Posterior Foregut Endoderm, but Not Definitive Endoderm, Leads to Enhanced Pancreatic Differentiation in an In Vitro Mouse ESC‐Based Model
Authors: Nair Gopika G. , Odorico Jon S.
Published: January 2016

Transcription factors are tools repetitively used by the embryo to generate a variety of lineages. Hence, their context of activation is an important determinant of their ability to specifically trigger certain cell fates, but not others. The context is also consequential when considering directing differentiation of embryonic stem cells (ESCs). In this study, we sought to assess the context of pancreatic transcription factor 1a (PTF1a) activation in reference to its propancreatic effects in mouse ESCs (mESCs). We hypothesized that an enriched endodermal population would respond to PTF1a and trigger the pancreatic program more effectively than a spontaneously differentiated population. Using an in vitro model of pancreas development that we recently established, we found that inducing PTF1a in highly enriched definitive endoderm did not promote pancreatic differentiation but induction in more differentiated endoderm, specifically posterior foregut endoderm, did form pancreatic progenitors. These progenitors never underwent terminal differentiation to endocrine or acinar phenotype. However, a short 3D culture period, prior to PTF1a induction, led to the generation of monohormonal insulin+ cells and amylase‐expressing cells. Our findings suggest that enriched posterior foregut endoderm is competent to respond to PTF1a’s propancreatic activity; but a 3D culture environment is essential for terminal differentiation of pancreatic progenitors.
Transcriptional Control of Synaptic Plasticity by Transcription Factor NF-κB
Authors: Engelmann Christian , Haenold Ronny
Published: January 2016

Activation of nuclear factor kappa B (NF-κB) transcription factors is required for the induction of synaptic plasticity and memory formation. All components of this signaling pathway are localized at synapses, and transcriptionally active NF-κB dimers move to the nucleus to translate synaptic signals into altered gene expression. Neuron-specific inhibition results in altered connectivity of excitatory and inhibitory synapses and functionally in selective learning deficits. Recent research on transgenic mice with impaired or hyperactivated NF-κB gave important insights into plasticity-related target gene expression that is regulated by NF-κB. In this minireview, we update the available data on the role of this transcription factor for learning and memory formation and comment on cross-sectional activation of NF-κB in the aged and diseased brain that may directly or indirectly affectκB-dependent transcription of synaptic genes.
Bilateral Neck of Femur Fractures in a Bilateral Below-Knee Amputee: A Unique Case
Authors: Lancer Hannah R. , Smitham Peter , Ray Pinak
Published: January 2016

According to the National Hip Fracture Database, over 64,000 patients were admitted with a hip fracture across England, Wales, and Northern Ireland in 2013, but very few are bilateral, and there are no current cases in the literature of bilateral neck of femur fractures in a patient with bilateral below-knee amputations. We present a case of a 69-year-old bilateral below-knee amputee male admitted to the emergency department with bilateral hip pain and radiological evidence of bilateral displaced neck of femur fractures. The patient subsequently underwent synchronous bilateral total hip replacements under general anaesthetic and an epidural and then went on to make a full recovery. He was discharged 27 days after arrival in hospital. Outpatient follow-up at 3 months has shown that the patient has returned to a similar level of preinjury function and is still able to carry out his daily activities with walking aids and bilateral leg prostheses.
Decellularized and Engineered Tendons as Biological Substitutes: A Critical Review
Authors: Lovati Arianna B. , Bottagisio Marta , Moretti Matteo
Published: January 2016

Tendon ruptures are a great burden in clinics. Finding a proper graft material as a substitute for tendon repair is one of the main challenges in orthopaedics, for which the requirement of a biological scaffold would be different for each clinical application. Among biological scaffolds, the use of decellularized tendon‐derived matrix increasingly represents an interesting approach to treat tendon ruptures. We analyzed in vitro and in vivo studies focused on the development of efficient protocols for the decellularization and for the cell reseeding of the tendon matrix to obtain medical devices for tendon substitution. Our review considered also the proper tendon source and preclinical animal models with the aim of entering into clinical trials. The results highlight a wide panorama in terms of allogenic or xenogeneic tendon sources, specimen dimensions, physical or chemical decellularization techniques, and the cell type variety for reseeding from terminally differentiated to undifferentiated mesenchymal stem cells and their static or dynamic culture employed to generate implantable constructs tested in different animal models. We try to identify the most efficient approach to achieve an optimal biological scaffold for biomechanics and intrinsic properties, resembling the native tendon and being applicable in clinics in the near future, with particular attention to the Achilles tendon substitution.
Urban Link Travel Time Estimation Based on Low Frequency Probe Vehicle Data
Authors: Zhou Xiyang , Yang Zhaosheng , Zhang Wei , Tian Xiujuan , Bing Qichun
Published: January 2016

To improve the accuracy and robustness of urban link travel time estimation with limited resources, this research developed a methodology to estimate the urban link travel time using low frequency GPS probe vehicle data. First, focusing on the case without reporting points for the GPS probe vehicle on the target link in the current estimation time window, a virtual report point creation model based on theK-Nearest Neighbour Rule was proposed. Then an improved back propagation neural network model was used to estimate the link travel time. The proposed method was applied to a case study based on an arterial road in Changchun, China: comparisons with the traditional artificial neural network method and the spatiotemporal moving average method revealed that the proposed method offered a higher estimation accuracy and better robustness.
Noninsulin Antidiabetic Drugs for Patients with Type 2 Diabetes Mellitus: Are We Respecting Their Contraindications?
Authors: Ruiz-Tamayo Irene , Franch-Nadal Josep , Mata-Cases Manel , Mauricio Dídac , Cos Xavier , Rodriguez-Poncelas Antonio , Barrot Joan , Coll-de-Tuero Gabriel , Mundet-Tudurí Xavier
Published: January 2016

Aim. To assess prescribing practices of noninsulin antidiabetic drugs (NIADs) in T2DM with several major contraindications according to prescribing information or clinical guidelines: renal failure, heart failure, liver dysfunction, or history of bladder cancer.Methods. Cross-sectional, descriptive, multicenter study. Electronic medical records were retrieved from all T2DM subjects who attended primary care centers pertaining to the Catalan Health Institute in Catalonia in 2013 and were pharmacologically treated with any NIAD alone or in combination.Results. Records were retrieved from a total of 255,499 pharmacologically treated patients. 78% of patients with some degree of renal impairment (glomerular filtration rate (GFR) < 60 mL/min) were treated with metformin and 31.2% with sulfonylureas. Even in the event of severe renal failure (GFR < 30 mL/min), 35.3% and 22.5% of patients were on metformin or sulfonylureas, respectively. Moreover, metformin was prescribed to more than 60% of patients with moderate or severe heart failure.Conclusion. Some NIADs, and in particular metformin, were frequently used in patients at high risk of complications when they were contraindicated. There is a need to increase awareness of potential inappropriate prescribing and to monitor the quality of prescribing patterns in order to help physicians and policymakers to yield better clinical outcomes in T2DM.
Glioma Stem Cells: Signaling, Microenvironment, and Therapy
Authors: Liebelt Brandon D. , Shingu Takashi , Zhou Xin , Ren Jiangong , Shin Seul A. , Hu Jian
Published: January 2016

Glioblastoma remains the most common and devastating primary brain tumor despite maximal therapy with surgery, chemotherapy, and radiation. The glioma stem cell (GSC) subpopulation has been identified in glioblastoma and likely plays a key role in resistance of these tumors to conventional therapies as well as recurrent disease. GSCs are capable of self‐renewal and differentiation; glioblastoma‐derived GSCs are capable of de novo tumor formation when implanted in xenograft models. Further, GSCs possess unique surface markers, modulate characteristic signaling pathways to promote tumorigenesis, and play key roles in glioma vascular formation. These features, in addition to microenvironmental factors, present possible targets for specifically directing therapy against the GSC population within glioblastoma. In this review, the authors summarize the current knowledge of GSC biology and function and the role of GSCs in new vascular formation within glioblastoma and discuss potential therapeutic approaches to target GSCs.
Sulforaphane and Other Nutrigenomic Nrf2 Activators: Can the Clinician’s Expectation Be Matched by the Reality?
Authors: Houghton Christine A. , Fassett Robert G. , Coombes Jeff S.
Published: January 2016

The recognition that food‐derived nonnutrient molecules can modulate gene expression to influence intracellular molecular mechanisms has seen the emergence of the fields of nutrigenomics and nutrigenetics. The aim of this review is to describe the properties of nutrigenomic activators of transcription factor Nrf2 (nuclear factor erythroid 2‐related factor 2), comparing the potential for sulforaphane and other phytochemicals to demonstrate clinical efficacy as complementary medicines. Broccoli‐derived sulforaphane emerges as a phytochemical with this capability, with oral doses capable of favourably modifying genes associated with chemoprevention. Compared with widely used phytochemical‐based supplements like curcumin, silymarin, and resveratrol, sulforaphane more potently activates Nrf2 to induce the expression of a battery of cytoprotective genes. By virtue of its lipophilic nature and low molecular weight, sulforaphane displays significantly higher bioavailability than the polyphenol‐based dietary supplements that also activate Nrf2. Nrf2 activation induces cytoprotective genes such as those playing key roles in cellular defense mechanisms including redox status and detoxification. Both its high bioavailability and significant Nrf2 inducer capacity contribute to the therapeutic potential of sulforaphane‐yielding supplements.
The Rise of CRISPR/Cas for Genome Editing in Stem Cells
Authors: Shui Bing , Hernandez Matias Liz , Guo Yi , Peng Ying
Published: January 2016

Genetic manipulation is a powerful tool to establish the causal relationship between a genetic lesion and a particular pathological phenotype. The rise of CRISPR/Cas9 genome‐engineering tools overcame the traditional technical bottleneck for routine site‐specific genetic manipulation in cells. To create the perfect in vitro cell model, there is significant interest from the stem cell research community to adopt this fast evolving technology. This review addresses this need directly by providing both the up‐to‐date biochemical rationale of CRISPR‐mediated genome engineering and detailed practical guidelines for the design and execution of CRISPR experiments in cell models. Ultimately, this review will serve as a timely and comprehensive guide for this fast developing technology.
Structural Damage Detection by Using Single Natural Frequency and the Corresponding Mode Shape
Authors: Zhao Bo , Xu Zili , Kan Xuanen , Zhong Jize , Guo Tian
Published: January 2016

Damage can be identified using generalized flexibility matrix based methods, by using the first natural frequency and the corresponding mode shape. However, the first mode is not always appropriate to be used in damage detection. The contact interface of rod-fastened-rotor may be partially separated under bending moment which decreases the flexural stiffness of the rotor. The bending moment on the interface varies as rotating speed changes, so that the first- and second-modal parameters obtained are corresponding to different damage scenarios. In this paper, a structural damage detection method requiring single nonfirst mode is proposed. Firstly, the system is updated via restricting the first few mode shapes. The mass matrix, stiffness matrix, and modal parameters of the updated system are derived. Then, the generalized flexibility matrix of the updated system is obtained, and its changes and sensitivity to damage are derived. The changes and sensitivity are used to calculate the location and severity of damage. Finally, this method is tested through numerical means on a cantilever beam and a rod-fastened-rotor with different damage scenarios when only the second mode is available. The results indicate that the proposed method can effectively identify single, double, and multiple damage using single nonfirst mode.
Analysis of Residual DSBs in Ataxia-Telangiectasia Lymphoblast Cells Initiating Apoptosis
Authors: Anglada Teresa , Terradas Mariona , Hernández Laia , Genescà Anna , Martín Marta
Published: January 2016

In order to examine the relationship between accumulation of residual DNA double-strand breaks (DSBs) and cell death, we have used a control and an ATM (Ataxia-Telangiectasia Mutated) defective cell line, as Ataxia-Telangiectasia (AT) cells tend to accumulate residual DSBs at long times after damage infliction. After irradiation, AT cells showed checkpoint impairment and a fraction of cells displayed an abnormal centrosome number and tetraploid DNA content, and this fraction increased along with apoptosis rates. At all times analyzed, AT cells displayed a significantly higher rate of radiation-induced apoptosis than normal cells. Besides apoptosis, 70–85% of the AT viable cells (TUNEL-negative) carried ≥10γH2AX foci/cell, while only 12–27% of normal cells did. The fraction of AT and normal cells undergoing early and late apoptosis were isolated by flow cytometry and residual DSBs were concretely scored in these populations. Half of theγH2AX-positive AT cells undergoing early apoptosis carried ≥10γH2AX foci/cell and this fraction increased to 75% in late apoptosis. The results suggest that retention of DNA damage-inducedγH2AX foci is an indicative of lethal DNA damage, as cells undergoing apoptosis are those accumulating more DSBs. Scoring of residualγH2AX foci might function as a predictive tool to assess radiation-induced apoptosis.
An Enhanced PSO-Based Clustering Energy Optimization Algorithm for Wireless Sensor Network
Authors: Vimalarani C. , Subramanian R. , Sivanandam S. N.
Published: January 2016

Wireless Sensor Network (WSN) is a network which formed with a maximum number of sensor nodes which are positioned in an application environment to monitor the physical entities in a target area, for example, temperature monitoring environment, water level, monitoring pressure, and health care, and various military applications. Mostly sensor nodes are equipped with self-supported battery power through which they can perform adequate operations and communication among neighboring nodes. Maximizing the lifetime of the Wireless Sensor networks, energy conservation measures are essential for improving the performance of WSNs. This paper proposes an Enhanced PSO-Based Clustering Energy Optimization (EPSO-CEO) algorithm for Wireless Sensor Network in which clustering and clustering head selection are done by using Particle Swarm Optimization (PSO) algorithm with respect to minimizing the power consumption in WSN. The performance metrics are evaluated and results are compared with competitive clustering algorithm to validate the reduction in energy consumption.
Intraframe Scene Capturing and Speed Measurement Based on Superimposed Image: New Sensor Concept for Vehicle Speed Measurement
Authors: Nemeth Mate , Zarandy Akos
Published: January 2016

A vision based vehicle speed measurement method is presented in this paper. The proposed intraframe method calculates speed estimates based on a single frame of a single camera. With a special double exposure, a superimposed image can be obtained, where motion blur appears significantly only in the bright regions of the otherwise sharp image. This motion blur contains information of the movement of bright objects during the exposure. Most papers in the field of motion blur are aiming at the removal of this image degradation effect. In this work, we utilize it for a novel speed measurement approach. An applicable sensor structure and exposure-control system are also shown, as well as the applied image processing methods and experimental results.
Polymorphisms in DNA Repair GeneXRCC3and Susceptibility to Breast Cancer in Saudi Females
Authors: Ali Alaa Mohammed , AbdulKareem Huda , Al Anazi Mohammad , Reddy Parine Narasimha , Shaik Jilani Purusottapatnam , Alamri Abdullah , Ali Khan Pathan Akbar , Warsy Arjumand
Published: January 2016

We investigated three common polymorphisms (SNPs) in the XRCC3 gene (rs861539, rs1799794, and rs1799796) in 143 Saudi females suffering from breast cancer (median age = 51.4 years) and 145 age matched normal healthy controls. DNA was extracted from whole blood and genotyping was conducted using PCR-RFLP. rs1799794 showed significant association, where AA and AA+AG occurred at a significantly higher frequency in the cancer patients compared to the control group (OR: 28.1; 95% CI: 3.76–21.12;χ2: 22.82;p<0.0001). The G allele was protective and presented with a dominant model. The genotype and allele frequencies of rs861539 C>T and rs1799796 A>G did not show a significant difference when the results in the patients and controls were compared. However, the frequency of rs1799796 differed significantly in patients with different age of diagnosis, tumor grade, and ER and HER2 status. The wild type A allele occurred at a higher frequency in the ER− and HER2− group. Our results among Saudis suggest that some variations in XRCC3 may contribute to breast cancer susceptibility. In conclusion, the results obtained during this study suggest that rs1799794 in XRCC3 shows strong association with breast cancer development in Saudi females.