Search results for: specific binding

Authors: Sahar Javadi-Novashnagh, Mohammad Moradi-Shahrbabak, Mostafa Sadeghi, Katarzyna Ropka-Molik, Hossein Moradi-Shahrbabak, Maria Consuelo Mura

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The objective of this study was to investigate two single nucleotide polymorphisms located in exon 2 (g.939A > G) and intron 3 (g.4349A > G) of fatty acid binding protein 3 (FABP3) gene in two Iranian sheep breeds, Lori-Bakhtiari and Zel, using polymerase chain reaction -restriction fragment length polymorphism (PCR-RFLP) approach. The association of the polymorphisms with growth traits and blood parameters was also examined. Results revealed a g.939A > G SNP (single nucleotide polymorphism) in the exon 2 exhibiting three genotypes: AA, AG, and GG. Statistical analysis indicated that this polymorphism significantly influenced blood triglyceride (P < 0.05) and cholesterol (P < 0.08) levels as well as weaning weight (P < 0.05). Animals with AG genotype had the highest blood triglyceride level and weaning weight while the highest amount of blood cholesterol was observed in animals with GG genotype. On the other hand, no significant effect was observed on birth and fat-tail weight traits. The intron 3 (g.4349A > G) was monomorphic across the studied samples. Lori-Bakhtiari breed showed significantly higher blood triglyceride and cholesterol levels, as also birth and weaning weight compared to Zel breed (P < 0.01). Considering that the literature is bereft of any report on the association study between FABP3 SNPs and sheep growth traits and blood parameters, our findings suggest that the investigated polymorphism might be one of the main genetic factors affecting growth and physiological traits in sheep.

Keywords: FABP3 gene, fatness, weaning weight, blood triglyceride, cholesterol, Zel, Lori-Bakhtiari

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Authors: T. H. N. Nguyen, A. Khodan, M. Amamra, J-V. Vignes, A. Kanaev

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The ultraporous nanofibrous alumina (NOA, Al2O3·nH2O) was synthesized by oxidation of laminated aluminium plates through a liquid mercury-silver layer in a humid atmosphere ~80% at 25°C. The material has an extremely high purity (99%), porosity (90%) and specific area (300 m2/g). The subsequent annealing of raw NOA permits obtaining pure transition phase (γ and θ) nanostructured materials. In this combination, we report on chemical, structural and phase transformations of pure and modified NOA by an impregnation of trimethylethoxysilane (TMES) and tetraethoxysilane (TEOS) during thermal annealing in the temperature range between 20 and 1650°C. The mass density, specific area, average diameter and specific area are analysed. The 3D model of pure NOA monoliths and silica modified NOA is proposed, which successfully describes the evolution of specific area, mass density and phase transformations. Activation energies of the mass transport in two regimes of surface diffusion and bulk sintering were obtained based on this model. We conclude about a common origin of modifications of the NOA morphology, chemical composition and phase transition.

Keywords: nanostructured materials, alumina (Al₂O₃), morphology, phase transitions

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Authors: Sidra Shaw, Sarenna Shaw, Chae Joon Lee, Irimpan Mathews, Eric Koehn

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One of the biggest public health concerns of our time is increasing antimicrobial resistance. As of 2019, the CDC has documented more than 2.8 million serious antibiotic resistant infections in the United States. Currently, antibiotic resistant infections are directly implicated in over 750,000 deaths per year globally. On our current trajectory, British economist Jim O’Neill predicts that by 2050, an additional 10 million people (about half the population of New York) will die annually due to drug resistant infections. As a result, new biochemical pathways must be targeted to generate next generation antibiotic drugs that will be effective against drug resistant bacteria. One enticing target is the biosynthesis of DNA within bacteria, as few drugs interrupt this essential life process. Thymidylate synthase enzymes are essential for life as they catalyze the synthesis of a DNA building block, 2′-deoxythymidine-5′-monophosphate (dTMP). In humans, the thymidylate synthase enzyme (TSase) has been shown to be distinct from the flavin-dependent thymidylate synthase (FDTS) produced by many pathogenic bacteria. TSase and FDTS have distinct structures and mechanisms of catalysis, which should allow selective inhibition of FDTS over human TSase. Currently, C. diff is one of the most antibiotic resistant bacteria, and no drugs that target thymine biosynthesis exist for C. diff. Here we present the initial biochemical characterization of FDTS from C. diff. Specifically, we examine enzyme kinetics and binding features of this enzyme to determine the nature of interaction with ligands/inhibitors and understand the molecular mechanism of catalysis. This research will provide more insight into the targetability of the C. diff FDTS enzyme for novel antibiotic drugs.

Keywords: flavin-dependent thymidylate synthase, FDTS, clostridioides difficile, C. diff, antibiotic resistance, DNA synthesis, enzyme kinetics, binding features

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Authors: Bezuglov Eduard, Ryland Morgans, Talibov Oleg, Kalinin Evgeny, Butovsky Mikhail, Savin Evgeny, Tzgoev Eduard, Artemii Lazarev, Bekzhan Pirmakhanov, Anthony C. Hackney

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Currently, there is conflicting evidence regarding the efficacy of citrulline for physical performance and post-exercise recovery. Moreover, the vast majority of studies conducted used physically active volunteers from the general population and heterogeneous exercise protocols that are not specific to most sports. A single use of citrulline, regardless of the dose, will not have a significant effect on physical performance and post-exercise recovery in highly trained soccer players performing sport-specific exercises at maximum intensity. To evaluate the effectiveness of a single administration of citrulline at various doses in adult male professional soccer players performing sport-specific exercise at maximum intensity. A randomized, double-blind, placebo-controlled study analyzing eighteen soccer players from the top divisions of several European countries. The participants were randomized into three groups of six and performed a field-based soccer-specific test at 115% VO2max for 18-minutes. Comparative analysis of the cardiovascular system, physical activity, subjective perceived fatigue and post-exercise recovery was conducted. There were no statistically significant differences in more than one analyzed parameter. A single application of 3 to 6 grams of citrulline does not affect physical performance, subjective feeling of fatigue and post-exercise recovery in adult professional soccer players who have performed a sport-specific test. Currently, citrulline cannot be recommended for use as a supplement in adult professional soccer players

Keywords: citrulline, performance, recovery, soccer players

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Authors: B. Varaprasad, C. Srinivasa Rao

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Hard turning has been explored as an alternative to the conventional one used for manufacture of Parts using tool steels. In the present study, the effects of cutting speed, feed rate and Depth of Cut (DOC) on cutting forces, specific cutting force, power and surface roughness in the hard turning are experimentally investigated. Experiments are carried out using mixed ceramic(Al2O3+TiC) cutting tool of corner radius 0.8mm, in turning operations on AISI H13 tool steel, heat treated to a hardness of 62 HRC. Based on Design of Experiments (DOE), a total of 20 tests are carried out. The range of each one of the three parameters is set at three different levels, viz, low, medium and high. The validity of the model is checked by Analysis of variance (ANOVA). Predicted models are derived from regression analysis. Comparison of experimental and predicted values of specific cutting force, power and surface roughness shows that good agreement has been achieved between them. Therefore, the developed model may be recommended to be used for predicting specific cutting force, power and surface roughness in hard turning of tool steel that is AISI H13 steel.

Keywords: hard turning, specific cutting force, power, surface roughness, AISI H13, mixed ceramic

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Authors: Sakshi Piplani, Ajit Kumar

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Valproic acid (VPA) is the first synthetic therapeutic agent used to treat epileptic disorders, which account for affecting nearly 1% world population. Teratogenicity caused by VPA has prompted the search for next generation drug with better efficacy and lower side effects. Recent studies have posed HDAC8 as direct target of VPA that causes the teratogenic effect in foetus. We have employed molecular dynamics (MD) and docking simulations to understand the binding mode of VPA and their analogues onto HDAC8. A total of twenty 3D-structures of human HDAC8 isoforms were selected using BLAST-P search against PDB. Multiple sequence alignment was carried out using ClustalW and PDB-3F07 having least missing and mutated regions was selected for study. The missing residues of loop region were constructed using MODELLER and energy was minimized. A set of 216 structural analogues (>90% identity) of VPA were obtained from Pubchem and ZINC database and their energy was optimized with Chemsketch software using 3-D CHARMM-type force field. Four major neurotransmitters (GABAt, SSADH, α-KGDH, GAD) involved in anticonvulsant activity were docked with VPA and its analogues. Out of 216 analogues, 75 were selected on the basis of lower binding energy and inhibition constant as compared to VPA, thus predicted to have anti-convulsant activity. Selected hHDAC8 structure was then subjected to MD Simulation using licenced version YASARA with AMBER99SB force field. The structure was solvated in rectangular box of TIP3P. The simulation was carried out with periodic boundary conditions and electrostatic interactions and treated with Particle mesh Ewald algorithm. pH of system was set to 7.4, temperature 323K and pressure 1atm respectively. Simulation snapshots were stored every 25ps. The MD simulation was carried out for 20ns and pdb file of HDAC8 structure was saved every 2ns. The structures were analysed using castP and UCSF Chimera and most stabilized structure (20ns) was used for docking study. Molecular docking of 75 selected VPA-analogues with PDB-3F07 was performed using AUTODOCK4.2.6. Lamarckian Genetic Algorithm was used to generate conformations of docked ligand and structure. The docking study revealed that VPA and its analogues have more affinity towards ‘hydrophobic active site channel’, due to its hydrophobic properties and allows VPA and their analogues to take part in van der Waal interactions with TYR24, HIS42, VAL41, TYR20, SER138, TRP137 while TRP137 and SER138 showed hydrogen bonding interaction with VPA-analogues. 14 analogues showed better binding affinity than VPA. ADMET SAR server was used to predict the ADMET properties of selected VPA analogues for predicting their druggability. On the basis of ADMET screening, 09 molecules were selected and are being used for in-vivo evaluation using Danio rerio model.

Keywords: HDAC8, docking, molecular dynamics simulation, valproic acid

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Authors: Dileep K. Verma, Sunil K. Lal

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Influenza still remains one of the most challenging diseases posing significant threat to public health causing seasonal epidemics and pandemics. Previous studies suggest that influenza hemagglutinin is essential for viral attachment to host sialic acid receptors and concentrate in lipid rafts for efficient viral fusion. Studies also reported selective nature of Influenza virus to utilize rafts micro-domain for efficient virus assembly and budding. However, the detailed mechanism of Influenza A Virus (IAV) binding to host cell membrane and entry inside the host remains elusive. In the present study, we investigated if host membrane lipid rafts play any significant role in early life cycle events of influenza A virus. Role of host lipid rafts was studied using raft disruption method by extraction of cholesterol and Methyl-β-Cyclodextrin was used to remove membrane cholesterol. We observed co-localization of Influenza A Virus to lipid rafts by visualization of known lipid raft marker GM1 on host cell membrane. Co-localization suggest direct involvement of these micro-domain in initiation of IAV life cycle. We found significant reduction in influenza A virus adsorption in raft disrupted target host cells indicating poor binding and attachment in absence of coherent membrane rafts. Taken together, the results of present study provide evidence for critical involvement of host lipid rafts and its constituents in adsorption process of Influenza A Virus and suggests crucial involvement in other early events of IAV life cycle. The present study opens a new domain to study influenza virus-host interaction and to combat flu at the very early steps of viral life cycle.

Keywords: lipid raft, adsorption, cholesterol, methyl-β-cyclodextrin, GM1

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Authors: Mahesh M. Patil, K. A. Anu-Appaiah

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Overweight and obesity is a serious medical problem, increasing in prevalence, and affecting millions worldwide. Investigators have been trying from decades to articulate the burden of obesity and related risk factors. To answer this problem, we suggest a new therapeutic anti-obesity compounds from Garcinia xanthochymus fruit. However, there is little published scientific information on non-hydroxycitric acid Garcinia species. Our findings include biochemical characterization of the fruit; in vivo toxicity and bio-efficacy study of G. xanthochymus in high fat diet wistar rat model. We observed that Garcinia pericarp is a rich source of organic acids, polyphenols, mono- (40.63%) and poly-unsaturated fatty acids (16.45%; omega-3: 10.02%). Toxicological studies have showed that Garcinia is safe and had no observed adverse effect level up to 400 mg/kg/day. Body weight and food intake was significantly (P<0.05) reduced in oral gavage treated rats (sonicated Garcinia powder) in 13 weeks. Subcutaneous fat was significantly (P<0.05) reduced in Garcinia treated rats. Hepatocytes significantly (p<0.05) overexpressed sterol regulatory element binding protein 2, liver X receptor- α, liver X receptor- β, lipoprotein lipase and monoacylglycerol lipase. Fatty acid binding protein 1 and peroxisome proliferator activated receptor- α were down regulated as assessed by real time qPCR. Currently our research is focused on the adipocyte obesity related gene expressions, effect of Garcinia on 3T3-adipocyte cell lines and high fat diet induced mice model. This in vivo pre-clinical data suggests that G. xanthochymus may have clinical utility for the treatment of obesity. However, further studies are required to establish its potency.

Keywords: Garcinia xanthochymus, anti-obesity, high fat diet, real time qPCR

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Authors: A. S. Lunev, A. A. Larenkov, O. E. Klementyeva, G. E. Kodina

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Background and aims: 68Ga-citrate is one of prospective radiopharmaceutical for PET-imaging of inflammation and infection. 68Ga-citrate is 67Ga-citrate analogue using since 1970s for SPECT-imaging. There's known rebinding reaction occurs past Ga-citrate injection and gallium (similar iron Fe3+) binds with blood transferrin. Then radiolabeled protein complex is delivered to pathological foci (inflammation/infection sites). But excessive gallium bindings with transferrin are cause of slow blood clearance, long accumulation time in foci (24-72 h) and exception of application possibility of the short-lived gallium-68 (T½ = 68 min). Injection of additional chemical agents (e.g. Fe3+ compounds) competing with radioactive gallium to the blood transferrin joining (blocking of its metal binding capacity) is one of the ways to solve formulated problem. This phenomenon can be used for correction of 68Ga-citrate pharmacokinetics for increasing of the blood clearance and accumulation in foci. The aim of real studying is research of effect of stable Fe-citrate on 68Ga-citrate tissue distribution. Materials and methods: 68Ga-citrate without/with extra injection of stable Fe-citrate (III) was injected nonlinear mice with inflammation models (aseptic soft tissue inflammation, lung infection, osteomyelitis). PET/X-RAY Genisys4 (Sofie Bioscience, USA) was used for non-invasive PET imaging (for 30, 60, 120 min past injection 68Ga-citrate) with subsequent reconstruction of imaging and their analysis (value of clearance, distribution volume). Scanning time is 10 min. Results and conclusions: I. v. injection of stable Fe-citrate blocks the metal-binding capability of transferrin serum and allows decreasing gallium-68 radioactivity in blood significantly and increasing accumulation in inflammation (3-5 time). It allows receiving more informative PET-images of inflammation early (for 30-60 min after injection). Pharmacokinetic parameters prove it. Noted there is no statistically significant difference between 68Ga-citrate accumulation for different inflammation model because PET imaging is indication of pathological processes and is not their identification.

Keywords: 68Ga-citrate, Fe-citrate, PET imaging, mice, inflammation, infection

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Authors: J. U. Santhosh Kumar, V. Krishna, Sebin Sebastian, G. S. Seethapathy, G. Ravikanth, R. Uma Shaanker

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Food is one of the basic needs of human beings. It requires the normal function of the body part and a healthy growth. Recently, food adulteration increases day by day to increase the quantity and make more benefit. Animal source foods can provide a variety of micronutrients that are difficult to obtain in adequate quantities from plant source foods alone. Particularly in the meat industry, products from animals are susceptible targets for fraudulent labeling due to the economic profit that results from selling cheaper meat as meat from more profitable and desirable species. This work presents an overview of the main PCR-based techniques applied to date to verify the authenticity of beef meat and meat products from beef species. We were analyzed 25 market beef samples in South India. We examined PCR methods based on the sequence of the cytochrome b gene for source species identification. We found all sample were sold as beef meat as Bos Taurus. However, interestingly Male meats are more valuable high price compare to female meat, due to this reason most of the markets samples are susceptible. We were used sex determination gene of cattle like TSPY(Y-encoded, testis-specific protein TSPY is a Y-specific gene). TSPY homologs exist in several mammalian species, including humans, horses, and cattle. This gene is Y coded testis protein genes, which only amplify the male. We used multiple PCR products form species-specific “fingerprints” on gel electrophoresis, which may be useful for meat authentication. Amplicons were obtained only by the Cattle -specific PCR. We found 13 market meat samples sold as female beef samples. These results suggest that the species-specific PCR methods established in this study would be useful for simple and easy detection of adulteration of meat products.

Keywords: authentication, meat products, species-specific, TSPY

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Authors: Felice Elefant, Akanksha Bhatnaghar, Keegan Krick, Elizabeth Heller

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Context: The severity of Alzheimer’s Disease (AD) progression involves an interplay of genetics, age, and environmental factors orchestrated by histone acetyltransferase (HAT) mediated neuroepigenetic mechanisms. While disruption of Tip60 HAT action in neural gene control is implicated in AD, alternative mechanisms underlying Tip60 function remain unexplored. Altered RNA splicing has recently been highlighted as a widespread hallmark in the AD transcriptome that is implicated in the disease. Research Aim: The aim of this study was to identify a novel RNA binding/splicing function for Tip60 in human hippocampus and impaired in brains from AD fly models and AD patients. Methodology/Analysis: The authors used RNA immunoprecipitation using RNA isolated from 200 pooled wild type Drosophila brains for each of the 3 biological replicates. To identify Tip60’s RNA targets, they performed genome sequencing (DNB-SequencingTM technology, BGI genomics) on 3 replicates for Input RNA and RNA IPs by Tip60. Findings: The authors' transcriptomic analysis of RNA bound to Tip60 by Tip60-RNA immunoprecipitation (RIP) revealed Tip60 RNA targets enriched for critical neuronal processes implicated in AD. Remarkably, 79% of Tip60’s RNA targets overlap with its chromatin gene targets, supporting a model by which Tip60 orchestrates bi-level transcriptional regulation at both the chromatin and RNA level, a function unprecedented for any HAT to date. Since RNA splicing occurs co-transcriptionally and splicing defects are implicated in AD, the authors investigated whether Tip60-RNA targeting modulates splicing decisions and if this function is altered in AD. Replicate multivariate analysis of transcript splicing (rMATS) analysis of RNA-Seq data sets from wild-type and AD fly brains revealed a multitude of mammalian-like AS defects. Strikingly, over half of these altered RNAs were bonafide Tip60-RNA targets enriched for in the AD-gene curated database, with some AS alterations prevented against by increasing Tip60 in fly brain. Importantly, human orthologs of several Tip60-modulated spliced genes in Drosophila are well characterized aberrantly spliced genes in human AD brains, implicating disruption of Tip60’s splicing function in AD pathogenesis. Theoretical Importance: The authors' findings support a novel RNA interaction and splicing regulatory function for Tip60 that may underlie AS impairments that hallmark AD etiology. Data Collection: The authors collected data from RNA immunoprecipitation experiments using RNA isolated from 200 pooled wild type Drosophila brains for each of the 3 biological replicates. They also performed genome sequencing (DNBSequencingTM technology, BGI genomics) on 3 replicates for Input RNA and RNA IPs by Tip60. Questions: The question addressed by this study was whether Tip60 has a novel RNA binding/splicing function in human hippocampus and whether this function is impaired in brains from AD fly models and AD patients. Conclusions: The authors' findings support a novel RNA interaction and splicing regulatory function for Tip60 that may underlie AS impairments that hallmark AD etiology.

Keywords: Alzheimer's disease, cognition, aging, neuroepigenetics

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Authors: Kyung Jin Kim, Jiwon Kwak, Jae-Hoon Lee, Soo Suk Lee

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We describe an innovative method for highly specific detection of miRNAs using a specially modified method of poly(A) adaptor RT-qPCR. We use uniquely designed specific extension sequence, which plays important role in providing an opportunity to affect high specificity of miRNA detection. This method involves two steps of reactions as like previously reported and which are poly(A) tailing and reverse-transcription followed by real-time PCR. Firstly, miRNAs are extended by a poly(A) tailing reaction and then converted into cDNA. Here, we remarkably reduced the reaction time by the application of short length of poly(T) adaptor. Next, cDNA is hybridized to the 3’-end of a specific extension sequence which contains miRNA sequence and results in producing a novel PCR template. Thereafter, the SYBR Green-based RT-qPCR progresses with a universal poly(T) adaptor forward primer and a universal reverse primer. The target miRNA, miR-106b in human brain total RNA, could be detected quantitatively in the range of seven orders of magnitude, which demonstrate that the assay displays a dynamic range of at least 7 logs. In addition, the better specificity of this novel extension-based assay against well known poly(A) tailing method for miRNA detection was confirmed by melt curve analysis of real-time PCR product, clear gel electrophoresis and sequence chromatogram images of amplified DNAs.

Keywords: microRNA(miRNA), specific extension sequence, RT-qPCR, poly(A) tailing assay, reverse transcription

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Authors: Seher Arslankaya, Merve Si̇mge Usuk

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Lean manufacturing, which is based on the Toyota Production System, has focused on increasing the performance in various fields by eliminating the waste. By waste elimination, the lead time is reduced significantly and lean manufacturing provides companies with an important privilege under today's competitive conditions. The initial point of lean thinking is the value. This notion create of a specific product with specific properties for which the customer is ready to pay and which satisfies his needs within a specific time frame and at a specific price. Considering this, the final customer determines the value but the manufacturer creates this value of the product. The value stream is the whole set of activities required for each product. These activities may or may not be essential for the value. Through value stream mapping, all employees can see the sources of waste and develop future cases to eliminate it. This study focused on manufacturing to eliminate the waste which created a cost but did not create any value. The study was carried out at the Department of Assembly/Logistics at Toyota Motor Manufacturing Turkey from the automotive industry with a high product mix and variable demands. As a result of the value stream analysis, improvements are planned for the future cases. The process was improved by applying these suggestions.

Keywords: lead time, lean manufacturing, performance improvement, value stream papping

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Authors: Niharika Keot, Manabendra Sarma

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A thorough investigation of Ln3+ complexes with more than one inner-sphere water molecule is crucial for designing high relaxivity contrast agents (CAs) used in magnetic resonance imaging (MRI). This study accomplished a comparative stability analysis of two hexadentate (H3cbda and H3dpaa) and two heptadentate (H4peada and H3tpaa) ligands with Ln3+ ions. The higher stability of the hexadentate H3cbda and heptadentate H4peada ligands has been confirmed by the binding affinity and Gibbs free energy analysis in aqueous solution. In addition, energy decomposition analysis (EDA) reveals the higher binding affinity of the peada4− ligand than the cbda3− ligand towards Ln3+ ions due to the higher charge density of the peada4− ligand. Moreover, a mechanistic overview of water exchange kinetics has been carried out based on the strength of the metal–water bond. The strength of the metal–water bond follows the trend Gd–O47 (w) > Gd–O39 (w) > Gd–O36 (w) in the case of the tris-aquated [Gd(cbda)(H2O)3] and Gd–O43 (w) > Gd–O40 (w) for the bis-aquated [Gd(peada)(H2O)2]− complex, which was confirmed by bond length, electron density (ρ), and electron localization function (ELF) at the corresponding bond critical points. Our analysis also predicts that the activation energy barrier decreases with the decrease in bond strength; hence kex increases. The 17O and 1H hyperfine coupling constant values of all the coordinated water molecules were different, calculated by using the second-order Douglas–Kroll–Hess (DKH2) approach. Furthermore, the ionic nature of the bonding in the metal–ligand (M–L) bond was confirmed by the Quantum Theory of Atoms-In-Molecules (QTAIM) and ELF along with energy decomposition analysis (EDA). We hope that the results can be used as a basis for the design of highly efficient Gd(III)-based high relaxivity MRI contrast agents for medical applications.

Keywords: MRI contrast agents, lanthanide chemistry, thermodynamic stability, water exchange kinetics

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Authors: Manuel Jose Oyson

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The Intergovernmental Panel on Climate Change (IPCC) warned in its most recent report for the entire world “to both mitigate and adapt to climate change if it is to effectively avoid harmful climate impacts.” The IPCC observed “with high confidence” a more rapid rise in total anthropogenic greenhouse gas emissions (GHG) emissions from 2000 to 2010 than in the past three decades that “were the highest in human history”, which if left unchecked will entail a continuing process of global warming and can alter the climate system. Current efforts, however, to respond to the threat of global warming, such as the United Nations Framework Convention on Climate Change and the Kyoto Protocol, have focused on states, and fail to involve Transnational Corporations (TNCs) which are responsible for a vast amount of GHG emissions. Involving TNCs in the search for solutions to climate change is consistent with an acknowledgment by contemporary international law that there is an international role for other international persons, including TNCs, and departs from the traditional “state-centric” response to climate change. Putting the focus of GHG emissions away from states recognises that the activities of TNCs “are not bound by national borders” and that the international movement of goods meets the needs of consumers worldwide. Although there is no legally-binding instrument that covers TNC activities or legal responsibilities generally, TNCs have increasingly been made legally responsible under international law for violations of human rights, exploitation of workers and environmental damage, but not for climate change damage. Imposing on TNCs a legally-binding obligation to reduce their GHG emissions or a legal liability for climate change damage is arguably formidable and unlikely in the absence a recognisable source of obligation in international law or municipal law. Instead a recourse to “soft law” and non-legally binding instruments may be a way forward for TNCs to reduce their GHG emissions and help in addressing climate change. Positive effects have been noted by various studies to voluntary approaches. TNCs have also in recent decades voluntarily committed to “soft law” international agreements. This development reflects a growing recognition among corporations in general and TNCs in particular of their corporate social responsibility (CSR). While CSR used to be the domain of “small, offbeat companies”, it has now become part of mainstream organization. The paper argues that TNCs must voluntarily commit to reducing their GHG emissions and helping address climate change as part of their CSR. One, as a serious “global commons problem”, climate change requires international cooperation from multiple actors, including TNCs. Two, TNCs are not innocent bystanders but are responsible for a large part of GHG emissions across their vast global operations. Three, TNCs have the capability to help solve the problem of climate change. Assuming arguendo that TNCs did not strongly contribute to the problem of climate change, society would have valid expectations for them to use their capabilities, knowledge-base and advanced technologies to help address the problem. It would seem unthinkable for TNCs to do nothing while the global environment fractures.

Keywords: climate change law, corporate social responsibility, greenhouse gas emissions, transnational corporations

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Authors: H. K. Ratre, M. Roy, S. Roy, M. S. Parmar, V. Bhagat

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Mastitis is a common problem of dairy industries. Reduction in milk production and an irreparable damage to the udder associated with the disease are common causes of culling of dairy cows. Milk from infected animals is not suitable for drinking and for making different milk products. So, it has a major economic importance in dairy cattle. The aims of this study were to investigate the bacteriological panorama in milk from udder quarters with subclinical mastitis and to carried out for the molecular characterization of the major isolated organisms, from subclinical mastitis-affected cows in and around Durg and Rajnandgaon district of Chhattisgarh. Isolation and identification of bacteria from the milk samples of subclinical mastitis-affected cows were done by standard and routine culture procedures. A total of 78 isolates were obtained from cows and among the various bacteria isolated, Staphylococcus spp. occupied prime position with occurrence rate of 51.282%. However, other bacteria isolated includeStreptococcus spp. (20.512%), Micrococcus spp. (14.102%), E. coli (8.974%), Klebsiela spp. (2.564%), Salmonella spp. (1.282%) and Proteus spp. (1.282%). Staphylococcus spp. was isolated as the major causative agent of subclinical mastitis in the studied area. Molecular characterization of Staphylococus aureusisolates was done for genetic expression of the virulence genes like ‘nuc’ encoding thermonucleaseexoenzyme, coa and spa by PCR amplification of the respective genes in 25 Staphylococcus isolates. In the present study, 15 isolates (77.27%) out of 20 coagulase positive isolates were found to be genotypically positive for ‘nuc’ where as 20 isolates (52.63%) out of 38 CNS expressed the presence of the same virulence gene. In the present study, three Staphylococcus isolates were found to be genotypically positive for coa gene. The Amplification of the coa gene yielded two different products of 627, 710 bp. The amplification of the gene segment encoding the IgG binding region of protein A (spa) revealed a size of 220 and 253bp in twostaphylococcus isolates. The X-region binding of the spa gene produced an amplicon of 315 bp in one Staphylococcal isolates. Staphylococcus aureus was found to be major isolate (51.28%) responsible for causing subclinical mastitis in cows which also showed expression of virulence genesnuc, coa and spa.

Keywords: mastitis, bacteria, characterization, expression, gene

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Authors: F. Garousi, Sz. Veres, É. Bódi, Sz. Várallyay, B. Kovács

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Specific leaf area (SLA; cm2leaf g-1leaf) is a key ecophysiological parameter influencing leaf physiology, photosynthesis, and whole plant carbon gain and also can be used as a rapid and diagnostic tool. In this study, two species of soluble inorganic selenium forms, selenite (SeIV) and selenate (SeVI) at different concentrations were investigated on maize plants that were growing in nutrient solutions during 2 weeks and at the end of the experiment, amounts of SLA for first and second leaves of maize were measured. In accordance with the results we observed that our regarded Se concentrations in both forms of SeIV and SeVI were not effective on maize plants’ SLA significantly although high level of 3 mg.kg-1 SeIV had negative affect on growth of the samples that had been treated by it but about SeVI samples we did not observe this state and our different considered SeVI concentrations were not toxic for maize plants.

Keywords: maize, sodium selenate, sodium selenite, specific leaf area

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Authors: Per Blomqvist

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This study is part of a larger research project on creativity and writing cultures in upper secondary schools in Sweden, with the purpose of exploring how formative assessment practices can be developed to better support students' writing of subject-specific texts. The purpose of the study is to shed light on how writing has changed over time in the subjects of Social Studies and Swedish, especially regarding changes in the formative assessment practice in relation to students opportunities to take part in creative writing processes that can develop their subject specific-writing. Theoretically, the study is based on concepts and models concerning creativity, writing instructions and formative assessment, especially regarding scaffolding in relation to the development of students' subject-specific writing. The empirical data consists of video recordings of teacher groups' conversations from five upper secondary schools in Sweden, compromising a total of twenty teachers. The conversations were conducted as so-called collective remembering interviews, a method to stimulate the participants' memory through social interaction, and focused on addressing issues on how writing assessment has changed over time. Topic analysis was used to analyze the conversations in order to identify common descriptions and expressions among the teachers in each group. The result highlights two different assessment practices that are described as giving students different opportunities to take part in creative writing processes to develop their writing of subject-specific texts. One of the assessment practices is characterized by teachers focusing on explaining to the students what the grading criteria mean and showing sample texts that correspond to a certain grade. The teachers describe that this assessment practice has led to a formalized, instrumental and product-oriented writing culture that has negative consequences for the student's development of their subject-specific writing, which often lacks independent reasoning, own conclusions and understanding of concepts. The other assessment practice is characterized by students examining text qualities and discussing a variety of sample texts to understand what different texts require. These teachers describe the assessment practice as an exploratory work that leads to more creative writing processes where the students gradually deepen their understanding of subject-specific texts and develop their writing.

Keywords: teaching for creativity, writing processes, formative assessment, subject-specific writing

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Authors: Gadiri Sabiha

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Introduction: Current allergy diagnostic tools using Multiplex technology have made it possible to increase the efficiency of the search for specific IgE. This opportunity is provided by the newly developed “Alex Biochip”, consisting of a panel of 282 allergens in native and molecular form, a CCD inhibitor, and the potential for detecting cross-reactive allergens. We evaluated the performance of this technology in detecting cross-reactivity in previously explored patients. Material/Method: The sera of 39 patients presenting sensitization and polysensitization profiles were explored. The search for specific IgE is carried out by the Alex ® IgE Biochip, and the results are analyzed by nature and by molecular family of allergens using specific software. Results/Discussion: The analysis gave a particular profile of cross-reactivity allergens: 33% for the Ole e1 family, 31% for NPC2, 26% for storage proteins, 20% for Tropomyosin, 10% for LTPs, 10% for Arginine Kinase and 10% for Uteroglobin CCDs were absent in all patients. The “Ole e1” allergen is responsible for a pollen-pollen cross allergy. The storage proteins found and LTP are not species-specific, causing cross-pollen-food allergy. The nDer p2 of the NPC2 family is responsible for cross-reactivity between mite species. Conclusion: The cross-reactivities responsible for mixed syndromes at diagnosis in our patients were dominated by pollen-pollen and pollen-food syndromes. They allow the identification of severity factors linked to the prognosis and the best-adapted immunotherapy.

Keywords: specific IgE, allergy, cross reactivity, molecular allergens

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Authors: Hassan Nour, Nouh Mounadi, Oussama Abchir, Belaidi Salah, Samir Chtita

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Cholinesterase enzymes are biological catalysts essential for the transformation of acetylcholine, which is a neurotransmitter implicated in memory and learning, into acetic acid and choline, altering the neurotransmission process in Alzheimer’s disease patients. Therefore, inhibition of cholinesterase enzymes is a relevant strategy for the symptomatic treatment of Alzheimer’s disease. The current investigation aims to explore potential Cholinesterase (ChE) inhibitors through a comprehensive computational approach. Forty-nine phytoconstituents extracted from Cannabis sativa L were in-silico screened using molecular docking, pharmacokinetic and toxicological analysis to evaluate their possible inhibitory effect towards the cholinesterase enzymes. Two phytoconstituents belonging to cannabinoid derivatives were revealed to be promising candidates for Alzheimer therapy by acting as cholinesterase inhibitors. They have exhibited high binding affinities towards the cholinesterase enzymes and showed their ability to interact with key residues involved in cholinesterase enzymatic activity. In addition, they presented good ADMET profiles allowing them to be promising oral drug candidates. Furthermore, molecular dynamics (MD) simulations were executed to explore their interactions stability under mimetic biological conditions and thus support our findings. To corroborate the docking results, the binding free energy corresponding to the more stable ligand-ChE complexes was re-estimated by applying the MM-PBSA method. MD and MM-PBSA studies affirmed that the ligand-ChE recognition is spontaneous reaction leading to stable complexes. The conducted investigations have led to great findings that would strongly guide the pharmaceutical industries towards the rational development of potent anti-Alzheimer agents.

Keywords: alzheimer’s disease, molecular docking, cannabis sativa l, cholinesterase inhibitors

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Authors: Jyh-Yi Shih, Chie-Bein Chen, Kuang-Yi Lin, Yu-Wei Huang

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Because of the trend toward globalization, Taiwanese companies have gradually focused more on overseas market operations. Overseas market performance has gradually increased as a proportion of Taiwanese companies’ total business revenues. Existing international investment theories cannot explain numerous new phenomena in this domain. Opinions are inconsistent, and contradictory positions exist regarding the antecedents of multinational enterprise (MNE) performance. This study applied contemporary internalization theory to establish and extend approaches adopted by previous relevant studies. In the context of the overseas market, the influence that MNE investment in research and development (R&D) and marketing has on enterprise performance was investigated from the firm-specific advantages (FSAs) and country-specific advantages (CSAs) perspectives. CSAs and internationalization speed were addressed as moderators, and hypotheses regarding how internationalization and performance were achieved through MNE overseas market operation were explored to ensure the completeness of the investigation. The list of enterprises was sourced from the Taiwan Economic Journal. After examining the relevant data, the following conclusions were obtained: (a) The relationship between the level of FSAs in R&D and enterprise performance exhibited an S-shaped curve. (b) The relationship between the level of FSAs in marketing and enterprise performance displayed a U-shaped curve. (c) The extent to which potential CFAs were obtained positively moderated the relationship between enterprise investment in R&D to gain FSAs and MNE performance. (d) Internationalization speed positively moderated the relationship between MNEs and enterprise investment in R&D and marketing to gain FSAs.

Keywords: multinational corporation, firm-specific advantages, country-specific advantages, international speed

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Authors: Heri Hermansyah, Annisa Kurnia, A. Vania Anisya, Adi Surjosatyo, Yopi Sunarya, Rita Arbianti, Tania Surya Utami

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Lipase is one of biocatalyst which is applied commercially for the process in industries, such as bioenergy, food, and pharmaceutical industry. Nowadays, biocatalysts are preferred in industries because they work in mild condition, high specificity, and reduce energy consumption (high pressure and temperature). But, the usage of lipase for industry scale is limited by economic reason due to the high price of lipase and difficulty of the separation system. Immobilization of lipase is one of the solutions to maintain the activity of lipase and reduce separation system in the process. Therefore, we conduct a study about lipase immobilization with the adsorption-cross linking method using glutaraldehyde because this method produces high enzyme loading and stability. Lipase is immobilized on different kind of resin with the various functional group. Highest enzyme loading (76.69%) was achieved by lipase immobilized on anion macroporous which have anion functional group (OH^‑). However, highest activity (24,69 U/g support) through olive oil emulsion method was achieved by lipase immobilized on anion macroporous-chitosan which have amino (NH₂) and anion (OH^-) functional group. In addition, it also success to produce biodiesel until reach yield 50,6% through interesterification reaction and after 4 cycles stable 63.9% relative with initial yield. While for Aspergillus, niger lipase immobilized on anion macroporous-kitosan have unit activity 22,84 U/g resin and yield biodiesel higher than commercial lipase (69,1%) and after 4 cycles stable reach 70.6% relative from initial yield. This shows that optimum functional group on support for immobilization with adsorption-cross linking is the support that contains amino (NH₂) and anion (OH^-) functional group because they can react with glutaraldehyde and binding with enzyme prevent desorption of lipase from support through binding lipase with a functional group on support.

Keywords: adsorption-cross linking, immobilization, lipase, resin

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Authors: Muhammad Noor Ul Ane, Dong-Soon Kim, Myron P. Zalucki

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Models can be useful to help understand population dynamics of insects under diverse environmental conditions and in developing strategies to manage pest species better. Adult longevity and fecundity of Helicoverpa armigera (Hübner) were evaluated against a wide range of constant temperatures (15, 20, 25, 30, 35 and 37.5ᵒC). The modified Sharpe and DeMichele model described adult aging rate and was used to estimate adult physiological age. Maximum fecundity of H. armigera was 973 egg/female at 25ᵒC decreasing to 72 eggs/female at 37.5ᵒC. The relationship between adult fecundity and temperature was well described by an extreme value function. Age-specific cumulative oviposition rate and age-specific survival rate were well described by a two-parameter Weibull function and sigmoid function, respectively. An oviposition model was developed using three temperature-dependent components: total fecundity, age-specific oviposition rate, and age-specific survival rate. The oviposition model was validated against independent field data and described the field occurrence pattern of egg population of H. armigera very well. Our model should be a useful component for population modeling of H. armigera and can be independently used for the timing of sprays in management programs of this key pest species.

Keywords: cotton bollworm, life table, temperature-dependent adult development, temperature-dependent fecundity

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Authors: Gajanan M. Sonwane

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The computational studies on 2-phenazinamines with their protein targets have been carried out to design compounds with potential anticancer activity. This strategy of designing compounds possessing selectivity over specific tyrosine kinase has been achieved through G-QSAR and molecular docking studies. The objective of this research has been to design newer 2-phenazinamine derivatives as Bcr-Abl tyrosine kinase inhibitors by G-QSAR, molecular docking studies followed by wet-lab studies along with evaluation of their anticancer potential. Computational chemistry was done by using VLife MDS 4.3 and Autodock 4.2 followed by wet-lab experiments for synthesizing 2-phenazinamine derivatives. The chemical structures of ligands in 2D were drawn by employing Chemdraw 2D Ultra 8.0 and were converted into 3D. These were optimized by using a semi-empirical method called MOPAC. The protein structure was retrieved from RCSC protein data bank as a PDB file. The binding interactions of protein and ligands were done by using PYMOL. The molecular properties of the designed compounds were predicted in silico by using Osiris property explorer. The parent compound 2-phenazinamine was synthesized by reduction of 2, 4-dinitro-N-phenyl-benzenamine in the presence of tin chloride followed by cyclization in the presence of nitrobenzene and magnesium sulfate. The derivatization at the amino function of 2-phenazinamine was performed by treating parent compound with various aldehydes in the presence of dicyclohexylcarbodiimide (DCC) and urea to afford 2-(2-chlorophenyl)-3-(phenazine-2-yl) thiazolidine-4-one. Synthesized 39 novel derivatives of 2-phenazinamine and performed antioxidant activity, anti antiproliferative on the bulb of onion and anticancer activity on cell line showing significant competition with marked blockbuster drug imatinib.

Keywords: computer-aided drug design, tyrosin kinases, anticancer, docking

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Authors: Gábor Kocsmárik

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The topic of this is coercive measures against assets in which the factor of the procedure contains a foreign element. We speak of cross-border enforcement if the debtor or the property requesting enforcement or subject to enforcement is not located in the bordering country. Given that the jurisdiction of a country cannot extend beyond its borders, the cooperation of nations and the mutual recognition of their decisions are necessary to eliminate this. In addition, it is essential to create framework rules that are binding and enforceable for each country participating in the convention. During the study, some conventions between countries that are still in force will be presented, which can serve as a starting point for dealing with existing problems.

Keywords: law, execution, civil procedure law, international

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Authors: Reham Khalaf-Nazzal, Imad Dweikat, Paula Gimenez, Iker Oyenarte, Alfonso Martinez-Cruz, Domonik Muller

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Metal cation transport mediator (CNNM) gene family comprises 4 isoforms that are expressed in various human tissues. Structurally, CNNMs are complex proteins that contain an extracellular N-terminal domain preceding a DUF21 transmembrane domain, a ‘Bateman module’ and a C-terminal cNMP-binding domain. Mutations in CNNM2 cause familial dominant hypomagnesaemia. Growing evidence highlights the role of CNNM2 in neurodevelopment. Mutations in CNNM2 have been implicated in epilepsy, intellectual disability, schizophrenia, and others. In the present study, we aim to elucidate the function of CNNM2 in the developing brain. Thus, we present the genetic origin of symptoms in two family cohorts. In the first family, three siblings of a consanguineous Palestinian family in which parents are first cousins, and consanguinity ran over several generations, presented a varying degree of intellectual disability, cone-rod dystrophy, and autism spectrum disorder. Exome sequencing and segregation analysis revealed the presence of homozygous pathogenic mutation in the CNNM2 gene, the parents were heterozygous for that gene mutation. Magnesium blood levels were normal in the three children and their parents in several measurements. They had no symptoms of hypomagnesemia. The CNNM2 mutation in this family was found to locate in the CBS1 domain of the CNNM2 protein. The crystal structure of the mutated CNNM2 protein was not significantly different from the wild-type protein, and the binding of AMP or MgATP was not dramatically affected. This suggests that the CBS1 domain could be involved in pure neurodevelopmental functions independent of its magnesium-handling role, and this mutation could have affected a protein partner binding or other functions in this protein. In the second family, another autosomal dominant CNNM2 mutation was found to run in a large family with multiple individuals over three generations. All affected family members had hypomagnesemia and hypermagnesuria. Oral supplementation of magnesium did not increase the levels of magnesium in serum significantly. Some affected members of this family have defects in fine motor skills such as dyslexia and dyslalia. The detected mutation is located in the N-terminal part, which contains a signal peptide thought to be involved in the sorting and routing of the protein. In this project, we describe heterogenous clinical phenotypes related to CNNM2 mutations and protein functions. In the first family, and up to the authors’ knowledge, we report for the first time the involvement of CNNM2 in retinal photoreceptor development and function. In addition, we report the presence of a neurophenotype independent of magnesium status related to the CNNM2 protein mutation. Taking into account the different modes of inheritance and the different positions of the mutations within CNNM2 and its different structural and functional domains, it is likely that CNNM2 might be involved in a wide spectrum of neuropsychiatric comorbidities with considerable varying phenotypes.

Keywords: magnesium transport, autosomal recessive, autism, neurodevelopment, CBS domain

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Authors: S. Mohamadi, T. Boudina, A. Rouabeh, A. Seridi

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Equivalent linear and non-linear ground response analyses are conducted at many representative sites at the mosque of Algeria, to compare the free field acceleration spectra with local code of practice. Spectral Analysis of Surface Waves (SASW) technique was adopted to measure the in-situ shear wave velocity profile at the representative sites. The seismic movement imposed on the rock is the NS component of Keddara station recorded during the earthquake in Boumerdes 21 May 2003. The site-specific elastic design spectra for each site are determined to further obtain site specific non-linear acceleration spectra. As a case study, the results of site-specific evaluations are presented for two building sites (site of minaret and site of the prayer hall) to demonstrate the influence of local geological conditions on ground response at Algerian sites. A comparison of computed response with the standard code of practice being used currently in Algeria for the seismic zone of Algiers indicated that the design spectra is not able to capture site amplification due to local geological conditions.

Keywords: equivalent linear, non-linear, ground response analysis, design response spectrum

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Authors: Christian Fercher, Jiaul Islam, Simon R. Corrie

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Fluorescence-based immunodiagnostics are an emerging field in biosensor development and exhibit several advantages over traditional detection methods. While various affinity biosensors have been developed to generate a fluorescence signal upon sensing varying concentrations of analytes, reagentless, reversible, and continuous monitoring of complex biological samples remains challenging. Here, we aimed to genetically engineer biosensors based on single-chain antibody fragments (scFv) that are site-specifically labeled with environmentally sensitive fluorescent unnatural amino acids (UAA). A rational design approach resulted in quantifiable analyte-dependent changes in peak fluorescence emission wavelength and enabled antigen detection in vitro. Incorporation of a polarity indicator within the topological neighborhood of the antigen-binding interface generated a titratable wavelength blueshift with nanomolar detection limits. In order to ensure continuous analyte monitoring, scFv candidates with fast binding and dissociation kinetics were selected from a genetic library employing a high-throughput phage display and affinity screening approach. Initial rankings were further refined towards rapid dissociation kinetics using bio-layer interferometry (BLI) and surface plasmon resonance (SPR). The most promising candidates were expressed, purified to homogeneity, and tested for their potential to detect biomarkers in a continuous microfluidic-based assay. Variations of dissociation kinetics within an order of magnitude were achieved without compromising the specificity of the antibody fragments. This approach is generally applicable to numerous antibody/antigen combinations and currently awaits integration in a wide range of assay platforms for one-step protein quantification.

Keywords: antibody engineering, biosensor, phage display, unnatural amino acids

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Authors: Alok Kumar Yadav, Saurabh Saraswat, Preeti Sirohi, Manjoo Rani, Sameer Srivastava, Manish Pratap Singh, Nand K. Singh

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The development of antibiotic resistance in bacteria is increasing at an alarming rate, and this is considered as one of the most serious threats in the history of medicine, and an alternative solution should be derived so as to tackle this problem. In many countries, people use the medicinal plants for the treatment of various diseases as these are cheaper, easily available and least toxic. Syzygium cumini is used for the treatment of various kinds of diseases but their mechanism of action is not reported. The antimicrobial activity of Syzygium cumini was tested by the well diffusion assay and zone of inhibition was reported to be 20.06 mm as compared to control with MIC of 0.3 mg/ml. Genomic DNA fragmentation of Bacillus subtilis revealed apoptosis and FE-SEM indicate cell wall cracking on several intervals of time. Propidium iodide staining results showed that few bacterial cells were stained in the control and population of stained cells increase after exposing them for various period of time. Flow cytometric kinetic data analysis on the membrane permeabilization in bacterial cell showed the significant contribution of antimicrobial potential of the seed extract on antimicrobial-induced permeabilization. Two components of Syzygium cumini methanolic seed extract was found to be quite active against four enzymes like PDB ID- 1W5D, 4OX3, 3MFD and 5E2F which have a very crucial role in membrane synthesis in Bacillus subtilis by in silico analysis. Through in silico analysis, lupeol showed highest binding energy for macromolecule 1W5D and 4OX3 whereas stigmasterol showed the highest binding energy for macromolecule 3MFD and 5E2F respectively. It showed that methanolic seed extract of Syzygium cumini can be used for the inhibition of foodborne infections caused by Bacillus subtilis and also as an alternative of prevalent antibiotics.

Keywords: antibiotics, Bacillus subtilis, inhibition, Syzygium cumini

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Authors: Tong Ming Liu

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Human mesenchymal stem cells (MSCs) represent the most used stem cells for clinical application, which have been used in over 1000 clinical trials to treat over 30 diseases due to multilineage differentiation potential, secretome and immunosuppression. Gene therapies of MSCs hold great promise in the treatment of many diseases due to enhanced MSC-based clinical outcomes. To identify genes for gene therapy of MSCs, by comparing gene expression profile before and after MSC differentiation following by functional screening, we have identified ZNF145 that regulated MSC differentiation. Forced expression of ZNF145 resulted in enhanced in vitro chondrogenesis of MSCs as an upstream factor of SOX9 and improved osteochondral repair upon implant into osteochondral defects in rodents. By comparing gene expression profile during differentiation of iPSCs toward MSCs, we also identified gene HOX regulating MSC stemness, which was much downregulated in late-passaged MSCs. Knockdown of this gene greatly compromised MSC stemness including abolished proliferation, decreased CFU-F, promoted senescence and reduced expression of cell surface antigens linked to the MSC phenotype. In addition, multi-linage differentiation was also greatly impaired. Notably, HOX overexpression resulted in improved multi-lineage differentiation. In the mechanism, HOX expression significantly deceased in late passage of MSCs compared with early passage of MSCs, correlating with MSC important genes. ChIP-seq data shown that HOX binds to genes related to MSC self-renewal and differentiation. Most importantly, most HOX binding sites are lost in late passage of MSCs. HOX exerts its effects by directing binding Twist1, one important gene of MSCs. The identification of the genes regulating MSC differentiation and stemness will provide and promising strategies for gene therapy of MSCs in regenerative medicine.

Keywords: mesenchymal stem cell, novel transcription factor, stemness, gene therapy, cartilage repair, signaling pathway

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