Search results for: molecular marker

Authors: Taek Hwan Lee, Moon Ho Do, Lalita Subedi, Young Un Park, Sun Yeou Kim

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Natural and artificial toxic substances namely neurotoxins induce the bitter effect in the nervous system termed as neurotoxicity. It can modulate the normal functioning of the nervous system either hyperactivate it or damage homeostasis of neuronal system. Neurotoxins induced toxicity ultimately kills the neuron. The present study investigated the neuroprotective effects of germinated Dolichos lablab on 6-hydroxydopamine (6-OHDA)-induced neurotoxicity using SH-SY5Y neuroblastoma cells. Germination is a process of plant growth from a seed. Sprouting of a seedling from a seed induced many molecular changes in the seed in order to prepare it for further growth. Because of these molecular and chemical changes, the neuroprotective effect of Dolichos lablab is higher in the germinated form than in the normal condition. SH-SY5Y cells were treated with Dolichos lablab extract (50, 100 g/ml) followed by 6-OHDA (25M) induced toxicity. Cell Viability was measured to check the cell survival against 6-OHDA induced toxicity using MTT assay. Dolichos lablab showed a neuroprotective effect against 6-OHDA induced neuronal cell death in neuroblastoma cell at a higher concentration of 100g/ml however the effect is much better even at the lower concentration after germination 50g/ml. Cell survival was increased dramatically after 15 h of germination and increased with time of germination in concentration dependent manner. Trigonelline as a representative compound was validated in germinated Dolichos lablab by HPLC analysis that might enhance the neuroprotective effect of Dolichos lablab. This result suggests that Dolichos lablab possess neuroprotective effect in neuroblastoma cells against 6-OHDA however its activity was more potent in the germinated form.

Keywords: dolichos lablab, germination, neuroprotection, trigonelline

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Authors: Ekta Yadav, Sukanta Bhattacharya, Brijesh Yadav, Ariel Hus, Jagjit Yadav

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Background and Significance: Respiratory exposure to toxicants (chemicals or particulates) causes disruption of lung homeostasis leading to lung toxicity/injury manifested as pulmonary inflammation, edema, and/or other effects depending on the type and extent of exposure. This emphasizes the need for investigating toxicant type-specific mechanisms to understand therapeutic targets. Aquaporins, aka water channels, are known to play a role in lung homeostasis. Particularly, the two major lung aquaporins AQP5 and AQP1 expressed in alveolar epithelial and vasculature endothelia respectively allow for movement of the fluid between the alveolar air space and the associated vasculature. In view of this, the current study is focused on understanding the regulation of lung aquaporins and other targets during inhalation exposure to toxic chemicals (Cigarette smoke chemicals) versus toxic particles (Carbon nanoparticles) or co-exposures to understand their relevance as markers of injury and intervention. Methodologies: C57BL/6 mice (5-7 weeks old) were used in this study following an approved protocol by the University of Cincinnati Institutional Animal Care and Use Committee (IACUC). The mice were exposed via oropharyngeal aspiration to multiwall carbon nanotube (MWCNT) particles suspension once (33 ugs/mouse) followed by housing for four weeks or to Cigarette smoke Extract (CSE) using a daily dose of 30µl/mouse for four weeks, or to co-exposure using the combined regime. Control groups received vehicles following the same dosing schedule. Lung toxicity/injury was assessed in terms of homeostasis changes in the lung tissue and lumen. Exposed lungs were analyzed for transcriptional expression of specific targets (AQPs, surfactant protein A, Mucin 5b) in relation to tissue homeostasis. Total RNA from lungs extracted using TRIreagent kit was analyzed using qRT-PCR based on gene-specific primers. Total protein in bronchoalveolar lavage (BAL) fluid was determined by the DC protein estimation kit (BioRad). GraphPad Prism 5.0 (La Jolla, CA, USA) was used for all analyses. Major findings: CNT exposure alone or as co-exposure with CSE increased the total protein content in the BAL fluid (lung lumen rinse), implying compromised membrane integrity and cellular infiltration in the lung alveoli. In contrast, CSE showed no significant effect. AQP1, required for water transport across membranes of endothelial cells in lungs, was significantly upregulated in CNT exposure but downregulated in CSE exposure and showed an intermediate level of expression for the co-exposure group. Both CNT and CSE exposures had significant downregulating effects on Muc5b, and SP-A expression and the co-exposure showed either no significant effect (Muc5b) or significant downregulating effect (SP-A), suggesting an increased propensity for infection in the exposed lungs. Conclusions: The current study based on the lung toxicity mouse model showed that both toxicant types, particles (CNT) versus chemicals (CSE), cause similar downregulation of lung innate defense targets (SP-A, Muc5b) and mostly a summative effect when presented as co-exposure. However, the two toxicant types show differential induction of aquaporin-1 coinciding with the corresponding differential damage to alveolar integrity (vascular permeability). Interestingly, this implies the potential of AQP1 as a differential marker of toxicant type-specific lung injury.

Keywords: aquaporin, gene expression, lung injury, toxicant exposure

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Authors: Vagolu S. Krishna, Shan Zheng, Estharla M. Rekha, Luke W. Guddat, Dharmarajan Sriram

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Tuberculosis (TB) remains a major threat to human health. This due to the fact that current drug treatments are less than optimal as well as the rising occurrence of multi drug-resistant and extensively drug-resistant strains of the etiological agent, Mycobacterium tuberculosis (Mt). Given the wide-spread significance of this disease, we have undertaken a design and evaluation program to discover new anti-TB drug leads. Here, our attention is focused on ketol-acid reductoisomerase (KARI), the second enzyme in the branched-chain amino acid biosynthesis pathway. Importantly, this enzyme is present in bacteria but not in humans, making it an attractive proposition for drug discovery. In the present work, we used high-throughput virtual screening to identify seventeen potential inhibitors of KARI using the Birla Institute of Technology and Science in-house database. Compounds were selected based on high docking scores, which were assigned as the result of favourable interactions between the compound and the active site of KARI. The Ki values for two leads, compounds 14 and 16 are 3.71 and 3.06 µM, respectively for Mt KARI. To assess the mode of binding, 100 ns molecular dynamics simulations for these two compounds in association with Mt KARI were performed and showed that the complex was stable with an average RMSD of less than 2.5 Å for all atoms. Compound 16 showed an MIC of 2.06 ± 0.91 µM and a 1.9 fold logarithmic reduction in the growth of Mt in an infected macrophage model. The two compounds exhibited low toxicity against murine macrophage RAW 264.7 cell lines. Thus, both compounds are promising candidates for development as an anti-TB drug leads.

Keywords: ketol-acid reductoisomerase, macrophage, molecular docking and dynamics, tuberculosis

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Authors: Singh Baljinder, Sharma Navneet

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Microalbuminuria is the earliest detectable marker of diabetic nephropathy. We planned to evaluate the prevalence of microalbuminuria in type 1 diabetics and correlate with various risk factor. We randomly selected 100 type 1 diabetic patients after inclusion and exclusion criteria from DCRC, S. P. Medical College, Bikaner. Clinical examinations for anthropometeric parameters, hypertension, retinopathy, glycaemic status, lipid profile were done and microalbuminuria was estimated by micral test. Microalbuminuria was seen in 38% patients. The mean urinary albumin concentration was 96.61 mg/l in microalbuminuria positive cases, 134 mg/L in hypertensive patients while 74.5 mg/L in normal patients. Mean diabetic duration was 6.43 years in microalbuminurics. Albumin excretion increased significantly with age at onset of 10-18 years and declined thereafter. Microalbuminuria cases exhibited mean cholesterol 181.63 mg%, TG 130.94 mg%, LDL 109.87 mg%, HDL 57.5 mg% and VLDL 30.64 mg%. Mean urinary albumin concentration in patients with retinopathy was 160.52 mg/L while 78.66 mg/L without retinopathy. In multiple stepwise logistic regression analysis, a strong positive association was seen between microalbuminuria and hypertension (OR=5.087, CI=2.1319-12.101), fasting blood sugar (OR=3. 491, CI=1.138-10.70), duration of diabetes (OR=3.41, CI=1.360-8.55) and HbA1c (OR=2.381, CI-=1.1-5.64). The present study indicates that microalbuminuria is a common complication of type 1 diabetes mellitus and can be prevented by careful management of risk factors.

Keywords: type 1 diabetes, microalbuminuria, diabetic nephropathy, retinopathy, hypertension

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Authors: Sang-Myung Jung, Jeong Hyun Ju, Gwang Heum Yoon, Hwa Sung Shin

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Central nervous system (CNS) consists of neuronal cell and supporting cells. Astrocytes are the most common supporting cells and play roles in metabolism between neurons and blood vessel. For this function, engineered astrocytes have been studied as a therapeutic source for CNS injury. In neural tissue engineering, nanofiber has been suggested as an effective scaffold for providing structure and mechanical properties influencing physiology. Cellulose acetate (CA) has been investigated for material to fabricate scaffold because of its biocompatibility, biodegradability and fine thermal stability. In this research, CA nanofiber was modified via heat treatment and its effect on astrocyte activity was evaluated. Adhesion and viability of astrocyte were increased in proportion to stiffness. Additionally, expression of GFAP, a marker of astrocyte activation, was increased via stiffness of scaffold. This research suggests a simple modification method to change stiffness of CA nanofiber and shows cellular behavior affecting stiffness of three-dimensional scaffold independently. For the results, we highlight that the stiffness is a factor to regulate astrocyte activity.

Keywords: astrocyte, cellulose acetate, cell therapy, stiffness of scaffold

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Authors: Varsha Shinde, Belle Damodara Shenoy

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Tarballs are crude oil remnants found in oceans after long term weathering process and are a global concern since several decades as potential marine pollutant. Being complicated in structure microbial remediation of tarballs in natural environment is a slow process. They are rich in high molecular weight alkanes and poly aromatic hydrocarbons which are resistant to microbial attack and other environmental factors, therefore remain in environment for long time. However, it has been found that many bacteria and fungi inhabit on tarballs for nutrients and shelter. Many of them are supposed to be oil degraders, while others are supposed to be getting benefited by byproducts formed during hydrocarbon metabolism. Thus tarballs are forming special interesting ecological niche of microbes. This work aimed to study diversity of bacteria and fungi from tarballs and to see their potential application in crude oil degradation. The samples of tarballs were collected from Betul beach of south Goa (India). Different methods were used to isolate culturable fraction of bacteria and fungi from it. Those were sequenced for 16S rRNA gene and ITS for molecular level identification. The 16S rRNA gene sequence analysis revealed the presence of 13 bacterial genera/clades (Alcanivorax, Brevibacterium, Bacillus, Cellulomonas, Enterobacter, Klebsiella, Marinobacter, Nitratireductor, Pantoea, Pseudomonas, Pseudoxanthomonas, Tistrella and Vibrio), while the ITS sequence analysis placed the fungi in 8 diverse genera/ clades (Aspergillus, Byssochlamys, Monascus, Paecilomyces, Penicillium, Scytalidium/ Xylogone, Talaromyces and Trichoderma). All bacterial isolates were screened for oil degradation capacity. Potential strains were subjected to crude oil degradation experiment for quantification. Results were analyzed by GC-MS-MS.

Keywords: bacteria, biodegradation, crude oil, diversity, fungi, tarballs

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Authors: Byeal-I Han, Michael Lee

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Ageing is associated with an increased risk of diseases such as cancer, and neurodegenerative disorders. Increased autophagy delays ageing and extends longevity. In this study, we investigated the role of autophagy in longevity using human foreskin fibroblast HS68 cells, in which a senescence-like growth arrest can be induced. In particular, cellular senescence is manifested by the irreversible cell cycle arrest, and may contribute to the ageing of organisms. The senescence state was measured with staining for senescence-associated β-galactosidase (SA-β-gal) activity that represents a sensitive and reliable marker to quantify senescent cells. We detected a significantly increased percentage (%) of SA-β-gal positive cells in HS68 cultures at passage 40 (63%) when compared with younger ones at passage 15 (0.5%). As expected, HS68 cells at passage 40 exhibited much lower proliferation rate than cells at passage 15. The basal levels of LC3 were measured by immunoblotting showing a comparison of LC3-I and LC3-II levels at 3 age-points in serially passaged HS68 cells. LC3-II/LC3-I ratio at different passage levels relative to β-actin levels of each band confirmed that cells at passage 34 showed lower conversion of non-autophagic LC3-I to autophagic LC3-II than the cells at passage 16. Furthermore, Cyto-ID autophagy assay also revealed that late passage cells showed lower autophagy than the early passage cells. Together, our findings suggest that senescence induction might be associated with decreased autophagy.

Keywords: ageing, autophagy, senescence, HS68

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Authors: Dong Zhao

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Even though the recent claim of room temperature superconductivity by LK-99 was confirmed an unsuccessful attempt, this work reawakened people’s century striving to get applicable superconductors with Tc of room temperature or higher and under ambient pressure. One of the efforts was focusing on exploring the thorium salts. This is because certain thorium compounds revealed an unusual property of having both high electrical conductivity and diamagnetism or the so-called “coexistence of high electrical conductivity and diamagnetism.” It is well known that this property of the coexistence of high electrical conductivity and diamagnetism is held by superconductors because of the electron pairings. Consequently, the likelihood for these thorium compounds to have superconducting properties becomes great. However, as a surprise, these thorium salts possess this property at room temperature and atmosphere pressure. This gives rise to solid evidence for these thorium compounds to be room-temperature superconductors without a need for external pressure. Among these thorium compound superconductors claimed in that work, thorium di-iodide (ThI₂) is a unique one and has received comprehensive discussion. ThI₂ was synthesized and structurally analyzed by the single crystal diffraction method in the 1960s. Its special property of coexistence of high electrical conductivity and diamagnetism was revealed. Because of this unique property, a special molecular configuration was sketched. Except for an ordinary oxidation of +2 for the thorium cation, the thorium’s oxidation state in ThI₂ is +4. According to the experimental results, ThI₂‘s actual molecular configuration was determined as an unusual one of [Th4+(e-)2](I-)2. This means that the ThI₂ salt’s cation is composed of a [Th4+(e-)2]2+ cation core. In other words, the cation of ThI₂ is constructed by combining an oxidation state +4 of the thorium atom and a pair of electrons or an electron lone pair located on the thorium atom. This combination of the thorium atom and the electron lone pair leads to an oxidation state +2 for the [Th4+(e-)2]2+ cation core. This special construction of the thorium cation is very distinctive, which is believed to be the factor that grants ThI₂ the room temperature superconductivity. Actually, the key for ThI₂ to become a room-temperature superconductor is this characteristic electron lone pair residing on the thorium atom along with the formation of a network constructed by the thorium atoms. This network specializes in a way that allows the electron lone pairs to hop over it and, thus, to generate the supercurrent. This work will discuss, in detail, the special electrical and magnetic properties of ThI₂ as well as its structural features at ambient conditions. The exploration of how the electron pairing in combination with the structurally specialized network works together to bring ThI₂ into a superconducting state. From the experimental results, strong evidence has definitely pointed out that the ThI₂ should be a superconductor, at least at room temperature and under atmosphere pressure.

Keywords: co-existence of high electrical conductivity and diamagnetism, electron lone pair, room temperature superconductor, special molecular configuration of thorium di-iodide ThI₂

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Authors: Monika Kallubai, Shreya Dubey, Rajagopal Subramanyam

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Our study is all about the biological interactions of synthesized 5β-dihydrocortisol (Dhc) and 5β-dihydrocortisol acetate (DhcA) molecules with carrier protein Human Serum Albumin (HSA). The cytotoxic study was performed on breast cancer cell line (MCF-7) normal human embryonic kidney cell line (HEK293), the IC50 values for MCF-7 cells were 28 and 25 µM, respectively, whereas no toxicity in terms of cell viability was observed with HEK293 cell line. The further experiment proved that Dhc and DhcA induced 35.6% and 37.7% early apoptotic cells and 2.5%, 2.9% late apoptotic cells respectively. Morphological observation of cell death through TUNEL assay revealed that Dhc and DhcA induced apoptosis in MCF-7 cells. The complexes of HSA–Dhc and HSA–DhcA were observed as static quenching, and the binding constants (K) was 4.7±0.03×104 M-1 and 3.9±0.05×104 M-1, and their binding free energies were found to be -6.4 and -6.16 kcal/mol, respectively. The displacement studies confirmed that lidocaine 1.4±0.05×104 M-1 replaced Dhc, and phenylbutazone 1.5±0.05×104 M-1 replaced by DhcA, which explains domain I and domain II are the binding sites for Dhc and DhcA. Further, CD results revealed that the secondary structure of HSA was altered in the presence of Dhc and DhcA. Furthermore, the atomic force microscopy and transmission electron microscopy showed that the dimensions like height and molecular sizes of the HSA–Dhc and HSA–DhcA complex were larger compared to HSA alone. Detailed analysis through molecular dynamics simulations also supported the greater stability of HSA–Dhc and HSA–DhcA complexes, and root-mean-square-fluctuation interpreted the binding site of Dhc as domain IB and domain IIA for DhcA. This information is valuable for the further development of steroid derivatives with improved pharmacological significance as novel anti-cancer drugs.

Keywords: apoptosis, dihydrocortisol, fluorescence quenching, protein conformations

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Authors: Jiajia Yao, GuanLin Wu, Fang liu, JunShuai Xue, JinCheng Zhang, Yue Hao

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Due to its outstanding material properties like high thermal conductivity and ultra-wide bandgap, Aluminum nitride (AlN) has the promising potential to provide high breakdown voltage and high output power among III-nitrides for various applications in electronics and optoelectronics. This work presents material growth and characterization of strained channel Aluminum nitride/Gallium nitride (AlN/GaN) heterostructures grown by plasma-assisted molecular beam epitaxy (PA-MBE) on AlN-on-sapphire templates. To improve the crystal quality and manifest the ability of the PA-MBE approach, a thick AlN buffer with a thickness of 180 nm is first grown on AlN template, which acts as a back-barrier to enhance the breakdown characteristic and isolates the leakage path existing in the interface between AlN epilayer and AlN template, as well as improve the heat dissipation. The grown AlN buffer features a root-mean-square roughness of 0.2 nm over a scanned area of 2×2 µm2 measured by atomic force microscopy (AFM), and exhibits full-width at half-maximum of 95 and 407 arcsec for the (002) and (102) plane the X-ray rocking curve, respectively, tested by high resolution x-ray diffraction (HR-XRD). With a thin and strained GaN channel, the electron mobility of 294 cm2 /Vs. with a carrier concentration of 2.82×1013 cm-2 at room temperature is achieved in AlN/GaN double-channel heterostructures, and the depletion capacitance is as low as 14 pF resolved by the capacitance-voltage, which indicates the promising opportunities for future applications in next-generation high temperature, high-frequency and high-power electronics with a further increased electron mobility by optimization of heterointerface quality.

Keywords: AlN/GaN, HEMT, MBE, homoepitaxy

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Authors: Lopamudra Ray, Malla Padma, Dibya Bhol, Samir Ranjan Mishra, A. N. Panda, Gurdeep Rastogi, T. K. Adhya, Ajit Kumar Pattnaik, Mrutyunjay Suar, Vishakha Raina

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Chilika Lake is the largest coastal estuarine brackish water lagoon in Asia situated on the east coast of India and is a designated Ramsar site. In the current study, several chitinolytic microorganisms were isolated and screened by appearance of clearance zone on 0.5% colloidal chitin agar plate. A strain designated as RC 1830 displayed maximum colloidal chitin degradation by release of 112 μmol/ml/min of N-acetyl D-glucosamine (GlcNAc) in 48h. The strain was taxonomically identified by polyphasic approach based on a range of phenotypic and genotypic properties and was found to be a novel species named Streptomyces chilikensis RC1830. The organism was halophilic (12% NaCl w/v), alkalophilic (pH10) and was capable of hydrolyzing chitin, starch, cellulose, gelatin, casein, tributyrin and tween 80. The partial purification of chitinase enzymes from RC1830 was performed by DEAE Sephacel anion exchange chromatography which revealed the presence of a very low molecular weight chitinase(10.5kD) which may be a probable chitobiosidase enzyme. The study reports the presence of a low MW chitinase (10.5kD) and a chitin decaetylase from a novel Streptomyces strain RC1830 isolated from Chilika Lake. Previously chitinases less than 20.5kD have not been reported from any other Streptomyces species. The enzymes was characterized with respect to optimum pH, temperature, and substrate specificity and temperature stability.

Keywords: chitinases, chitobiosidase, Chilika Lake, India

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Authors: Nicole C. Valdez, Vincent L. Borromeo, Conrad C. Chong, Ahmad F. Mazahery

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Breast cancer is the most prevalent cancer worldwide, where the majority of cases are estrogen-receptor positive and involve 2 receptor proteins. The binding of estrogen to estrogen receptor alpha (ERα) promotes breast cancer growth, while it's binding to estrogen-receptor beta (ERβ) inhibits tumor growth. While natural products have been a promising source of chemotherapeutic agents, the challenge remains in finding a bioactive compound that specifically targets cancer cells, minimizing side effects on normal cells. Flavonoids are natural products that act as phytoestrogens and induce the same response as estrogen. They are able to compete with estrogen for binding to ERα; however, it has a higher binding affinity for ERβ. Their abundance in nature and low toxicity make them a potential candidate for breast cancer treatment. This study aimed to determine which particular flavonoids can specifically recognize ERβ and potentially be used for breast cancer treatment through molecular docking. A total of 206 flavonoids comprised of 97 isoflavones and 109 flavanones were collected from ZINC15, while the 3D structures of ERβ and ERα were obtained from Protein Data Bank. These flavonoid subclasses were chosen as they bind more strongly to ERs due to their chemical structure. The structures of the flavonoid ligands were converted using Open Babel, while the estrogen receptor protein structures were prepared using Autodock MGL Tools. The optimal binding site was found using BIOVIA Discovery Studio Visualizer before docking all flavonoids on both ERβ and ERα through Autodock Vina. Genistein is a flavonoid that exhibits anticancer effects by binding to ERβ, so its binding affinity was used as a baseline. Eriodictyol and 4”,6”-Di-O-Galloylprunin both exceeded genistein’s binding affinity for ERβ and was lower than its binding affinity for ERα. Of the two, eriodictyol was pursued due to its antitumor properties on a lung cancer cell line and on glioma cells. It is able to arrest the cell cycle at the G2/M phase by inhibiting the mTOR/PI3k/Akt cascade and is able to induce apoptosis via the PI3K/Akt/NF-kB pathway. Protein pathway and gene analysis were also conducted using ChEMBL and PANTHER and it was shown that eriodictyol might induce anticancer effects through the ROS1, CA7, KMO, and KDM1A genes which are involved in cell proliferation in breast cancer, non-small cell lung cancer, and other diseases. The high binding affinity of eriodictyol to ERβ, as well as its potential affected genes and antitumor effects, therefore, make it a candidate for the development of new breast cancer treatment. Verification through in vitro experiments such as checking the upregulation and downregulation of genes through qPCR and checking cell cycle arrest using a flow cytometry assay is recommended.

Keywords: breast cancer, estrogen receptor, flavonoid, molecular docking

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Authors: Panomporn Wisuthseriwong, Hatairuk Tungkasen, Siyaporn Namsongsan, Chanikarn Srinark, Mayuva Youngsabanant-Areekijseree

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The objective of the present study was to evaluate the morphology of porcine cumulus-oocyte complexes (pCOCs) and follicular fluid during follicular development. The samples were obtained from local slaughterhouses in Nakorn Pathom Province, Thailand. Pigs were classified as either in the follicular phase or luteal phase. Porcine follicles (n = 3,510) were categorized as small (1-3 mm in diameters; n=2,910), medium (4-6 mm in diameters; n=530) and large (7-8 mm in diameters; n=70). Then pCOCs and follicular fluid were collected. Finally, we found that the oocytes can be categorized into intact cumulus cells layer oocyte, multi-cumulus cells layer oocyte, partial cumulus cells layer oocyte, completely denuded oocyte and degenerated oocyte. They showed high percentage of intact and multi-cumulus cells layer oocytes from small follicles (54.68%) medium follicles (69.06%) and large follicles (68.57%), which have high potential to develop into matured oocytes in vitro. Protein composition of the follicular fluid was separated by SDS-PAGE technique. The result shows that the protein molecular weight in the small and medium follicles are 23, 50, 66, 75, 92, 100, 132, 163, 225 and >225 kDa. Meanwhile, protein molecular weight in large follicles are 12, 16, 23, 50, 66, 75, 92, 100, 132, 163, 225 and >225 kDa. All proteins play an important role in promotion and regulation on development, maturation of oocytes and regulation of ovulation. We conclude that the results of discovery can be used porcine secretion proteins for supplement in IVM/IVF technology. Acknowledgements: The project was funded by a grant from Silpakorn University Research and Development Institute (SURDI) and Faculty of Science, Silpakorn University, Thailand.

Keywords: porcine follicles, porcine oocyte, follicular fluid, SDS-PAGE

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Authors: Abdel Rahman Mitib Altakhaineh, Abdul Salam Mohamad Alnamer, Sulafah Abdul Salam Alnamer

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This study examines the production of gemination in Emirati Pidgin Arabic (EPA) spoken by blue-collar workers in the United Arab Emirates (UAE). A simple naming test was designed to test the production of geminates and a follow-up discussion was conducted with some of the participants to obtain the complementary qualitative analysis. The goal of the test was to determine whether the EPA speakers would produce a geminated or degeminated phoneme. A semi-structured interview was conducted with a subset of the study cohort to obtain participants’ own explanation where they degeminated the consonants. Our findings suggest that the exercising of this choice functions as a sociolinguistic strategy in a similar manner to that observed by Labov in his study of Martha’s Vineyard. The findings also show that speakers of EPA are inclined to degeminate consonantal geminates to establish themselves as members of a particular social group. Reasons for wanting to achieve this aim were given as: to claim privileges only available to members of this group (such as employment) and to distinguish themselves from the dominant cultural group. The study concludes that degemination in EPA has developed into a sociolinguistic solidarity marker.

Keywords: sociolinguistics, morphophonology, degemination, solidarity, Emirati pidgin Arabic

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Authors: B. Nazari, M. A. Mohammadifar, S. Shojaee-Aliabadi, L. Mirmoghtadaie

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Millets as a new source of plant protein were not used in food applications due to its poor functional properties. In this study, the effect of high intensity ultrasound (frequency: 20 kHz, with contentious flow) (US) in 100% amplitude for varying times (5, 12.5, and 20 min) on solubility, emulsifying activity index (EAI), emulsion stability (ES), foaming capacity (FC), and foaming stability (FS) of millet protein concentrate (MPC) were evaluated. In addition, the structural properties of best treatments such as molecular weight and surface charge were compared with the control sample to prove the US effect. The US treatments significantly (P<0.05) increased the solubility of the native MPC (65.8±0.6%) at all sonicated times with the maximum solubility that is recorded at 12.5 min treatment (96.9±0.82 %). The FC of MPC was also significantly affected by the US treatment. Increase in sonicated time up to 12.5 min significantly increased the FC of native MPC (271.03±4.51 ml), but higher increase reduced it significantly. Minimal improvements were observed in the FS of all sonicated MPC compared to the native MPC. Sonicated time for 12.5 min affected the EAI and ES of the native MPC more markedly than 5 and 20 min that may be attributed to higher increase in proteins tendency to adsorption at the oil and water interfaces after the US treatment at this time. SDS-PAGE analysis showed changes in the molecular weight of MPC that attributed to shearing forces created by cavitation phenomenon. Also, this phenomenon caused an increase in the exposure of more amino acids with negative charge in the surface of US treated MPC, that was demonstrated by Zetasizer data. High intensity ultrasound, as a green technology, can significantly increase the functional properties of MPC and can make this usable for food applications.

Keywords: functional properties, high intensity ultrasound, millet protein concentrate, structural properties

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Authors: Sujitra Ruengdechawiwat, Robert Molloy, Jintana Siripitayananon, Runglawan Somsunan, Paul D. Topham, Brian J. Tighe

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The main aim of this research has been to design and synthesize some completely soluble liquid tin(II) alkoxide initiators for use in the ring-opening polymerisation (ROP) of cyclic ester monomers. This is in contrast to conventional tin(II) alkoxides in solid form which tend to be molecular aggregates and difficult to dissolve. The liquid initiators prepared were bis(tin(II) monooctoate) diethylene glycol ([Sn(Oct)]2DEG) and bis(tin(II) monooctoate) ethylene glycol ([Sn(Oct)]2EG). Their efficiencies as initiators in the bulk ROP of ε-caprolactone (CL) at 130oC were studied kinetically by dilatometry. Kinetic data over the 20-70% conversion range was used to construct both first-order and zero-order rate plots. It was found that the rate data fitted more closely to first-order kinetics with respect to the monomer concentration and gave higher first-order rate constants than the corresponding tin(II) octoate/diol initiating systems normally used to generate the tin(II) alkoxide in situ. Since the ultimate objective of this work is to produce copolymers suitable for biomedical use as absorbable monofilament surgical sutures, poly(L-lactide-co-ε-caprolactone) 75:25 mol %, P(LL-co-CL), copolymers were synthesized using both solid and liquid tin(II) alkoxide initiators at 130°C for 48 hrs. The statistical copolymers were obtained in near-quantitative yields with compositions (from 1H-NMR) close to the initial comonomer feed ratios. The monomer sequencing (from 13C-NMR) was partly random and partly blocky (gradient-type) due to the much differing monomer reactivity ratios (rLL >> rCL). From GPC, the copolymers obtained using the soluble liquid tin(II) alkoxides were found to have higher molecular weights (Mn = 40,000-100,000) than those from the only partially soluble solid initiators (Mn = 30,000-52,000).

Keywords: biodegradable polyesters, poly(L-lactide-co-ε-caprolactone), ring-opening polymerisation, tin(II) alkoxide

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Authors: P. Haldar, P. Ghosh, S. Ghoshdastidar, K. Kargupta

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In polymer electrolyte membrane fuel cells (PEMFC), the membrane electrode assembly (MEA) is consisting of two platinum coated carbon electrodes, sandwiched with one proton conducting phosphoric acid doped polymeric membrane. Due to low mechanical stability, flooding and fuel cell crossover, application of phosphoric acid in polymeric membrane is very critical. Phosphorous and silica based 3D inorganic gel gains the attention in the field of supercapacitors, fuel cells and metal hydrate batteries due to its thermally stable highly proton conductive behavior. Also as a large amount of water molecule and phosphoric acid can easily get trapped in Si-O-Si network cavities, it causes a prevention in the leaching out. In this study, we have performed molecular dynamics (MD) simulation and first principle calculations to understand the structural, electronics and electrochemical and morphological behavior of this inorganic gel at various P to Si ratios. We have used dipole-dipole interactions, H bonding, and van der Waals forces to study the main interactions between the molecules. A 'structure property-performance' mapping is initiated to determine optimum P to Si ratio for best proton conductivity. We have performed the MD simulations at various temperature to understand the temperature dependency on proton conductivity. The observed results will propose a model which fits well with experimental data and other literature values. We have also studied the mechanism behind proton conductivity. And finally we have proposed a structure for the gel paste with optimum P to Si ratio.

Keywords: first principle calculation, molecular dynamics simulation, phosphorous and silica based 3D inorganic gel, polymer electrolyte membrane fuel cells, proton conductivity

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Authors: A. Monika, Manu Sharma, Hong Boo Lee, Richa Dhingra, Neelima Dhingra

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Nuclear factor-κappa B serve as a molecular lynchpin that links persistent infections and chronic inflammation to increased cancer risk. Inflammation has been recognized as a hallmark and cause of cancer. Natural products present a privileged source of inspiration for chemical probe and drug design. Herbal remedies were the first medicines used by humans due to the many pharmacologically active secondary metabolites produced by plants. Some of the metabolites like Lantadene (pentacyclic triterpenoids) from the weed Lantana camara has been known to inhibit cell division and showed anti-antitumor potential. The C-3 aromatic esters of lantadenes were synthesized, characterized and evaluated for cytotoxicity and inhibitory potential against Tumor necrosis factor alpha-induced activation of Nuclear factor-κappa B in lung cancer cell line A549. The 3-methoxybenzoyloxy substituted lead analogue inhibited kinase activity of the inhibitor of nuclear factor-kappa B kinase in a single-digit micromolar concentration. At the same time, the lead compound showed promising cytotoxicity against A549 lung cancer cells with IC50 ( half maximal inhibitory concentration) of 0.98l µM. Further, molecular docking of 3-methoxybenzoyloxy substituted analogue against Inhibitor of nuclear factor-kappa B kinase (Protein data bank ID: 3QA8) showed hydrogen bonding interaction involving oxygen atom of 3-methoxybenzoyloxy with the Arginine-31 and Glutamine-110. Encouraging results indicate the Lantadene’s potential to be developed as anticancer agents.

Keywords: anticancer, lantadenes, pentacyclic triterpenoids, weed

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Authors: Fatemeh Keshavarz

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Background: Rheumatoid arthritis (RA) is one of the most common autoimmune diseases, often leading to joint damage and physical disability. This study aimed to investigate the relationship of serum levels of interleukin 17 and anti-CCP factor with disease severity in RA patients. Materials and Methods: Fifty-four patients with RA confirmed by clinical and laboratory criteria were recruited. A 5 ml venous blood sample was taken from every patient, its serum was separated. Based on clinical data and severity of symptoms, patients were classified into three groups of those with mild, moderate, and severe symptoms. Serum levels of IL-17 and anti-CCP in all samples were measured using ELISA. Results: Analysis of IL-17 serum levels in different groups showed that its amount was higher in the group with mild clinical symptoms than in other groups. Comparison of IL-17 serum levels between mild and moderate disease severity groups showed a statistically significant relationship. There was also a positive linear relationship between anti-CCP and serum IL-17 levels in different groups of the disease, and serum IL-17 levels were inversely related to the duration of exposure to the disease. Conclusion: Higher IL-17 serum levels in patients with mild symptom severity confirm that this highly specific marker is involved in the pathogenesis of RA and may be effective in initiating patients’ clinical symptoms.

Keywords: IL-17, anti-CCP, rheumatoid arthritis, autoimmune

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Authors: Muhammad Fiaz, Muhammad Saqlain, Bernard M. Y. Cheung, S. M. Saqlan Naqvi, Ghazala Kaukab Raja

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Background: Association of C allele of rs662799 SNP of APOA5 gene with metabolic syndrome (MetS) has been reported in different populations around the world. A case control study was conducted to explore the relationship of rs662799 variants (T/C) with the MetS and the associated risk phenotypes in a population of Pakistani origin. Methods: MetS was defined according to the IDF criteria. Blood samples were collected from the Pakistan Institute of Medical Sciences, Islamabad, Pakistan for biochemical profiling and DNA extraction. Genotyping of rs662799 was performed using mass ARRAY, iPEX Gold technology. A total of 712 unrelated case and control subjects were genotyped. Data were analyzed using Plink software and SPSS 16.0. Results: The risk allele C of rs662799 showed highly significant association with MetS (OR=1.5, Ρ=0.002). Among risk phenotypes, dyslipidemia, and obesity showed strong association with SNP (OR=1.49, p=0.03; OR =1.46, p=0.01) respectively in models adjusted for age and gender. Conclusion: The rs662799C allele is a significant risk marker for MetS in the local Pakistani population studied. The effect of the SNP is more on dyslipidemia than the other components of the MetS.

Keywords: metabolic syndrome, APOA5, rs662799, dyslipidemia, obesity

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Authors: Gajanan M. Sonwane

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Nowadays, the entire pharmaceutical industry is facing the challenge of increasing efficiency and innovation. The major hurdles are the growing cost of research and development and a concurrent stagnating number of new chemical entities (NCEs). Hence, the challenge is to select the most druggable targets and to search the equivalent drug-like compounds, which also possess specific pharmacokinetic and toxicological properties that allow them to be developed as drugs. The present research work includes the studies of developing new anticancer heterocycles by using molecular modeling techniques. The heterocycles synthesized through such methodology are much effective as various physicochemical parameters have been already studied and the structure has been optimized for its best fit in the receptor. Hence, on the basis of the literature survey and considering the need to develop newer anticancer agents, new phenazinamine derivatives were designed by subjecting the nucleus to molecular modeling, viz., GQSAR analysis and docking studies. Simultaneously, these designed derivatives were subjected to in silico prediction of biological activity through PASS studies and then in silico toxicity risk assessment studies. In PASS studies, it was found that all the derivatives exhibited a good spectrum of biological activities confirming its anticancer potential. The toxicity risk assessment studies revealed that all the derivatives obey Lipinski’s rule. Amongst these series, compounds 4c, 5b and 6c were found to possess logP and drug-likeness values comparable with the standard Imatinib (used for anticancer activity studies) and also with the standard drug methotrexate (used for antimitotic activity studies). One of the most notable mutations is the threonine to isoleucine mutation at codon 315 (T315I), which is known to be resistant to all currently available TKI. Enzyme assay planned for confirmation of target selective activity.

Keywords: drug design, tyrosine kinases, anticancer, Phenazinamine

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Authors: Michael Dare Asemoloye, Segun Gbolagade Jonathan, Rafiq Ahmad, Odunayo Joseph Olawuyi, D. O. Adejoye

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Fungi have potentials for degrading hydrocarbons through the secretion of different enzymes. Crude oil tolerance and degradation by Trichoderma harzianum was investigated in this study with its ability to produce peroxidase enzymes (LiP and MnP). Many fungal strains were isolated from rhizosphere of grasses growing on a crude oil spilled site, and the most frequent strain based on percentage incidence was further characterized using morphological and molecular characteristics. Molecular characterization was done through the amplification of Ribosomal-RNA regions of 18s (1609-1627) and 28s (287-266) using ITS1 and ITS4 combinations and it was identified using NCBI BLAST tool. The selected fungus was also subjected to an in-vitro tolerance test at crude oil concentrations of 5, 10, 15, 20 and 25% while 0% served as control. In addition, lignin peroxidase genes (lig1-6) and manganese peroxidase gene (mnp) were detected and expressed in this strain using RT-PCR technique, its peroxidase producing activities was also studied in aliquots (U/ml). This strain had highest incidence of 80%, it was registered in NCBI as Trichoderma harzianum asemoJ KY488466. The strain KY488466 responded to crude oil concentrations as it increase, the dose inhibition response percentage (DIRP) increased from 41.67 to 95.41 at 5 to 25 % crude oil concentrations. All the peroxidase genes are present in KY488466, and expressed with amplified 900-1000 bp through RT-PCR technique. In this strain, lig2, lig4 and mnp genes were over-expressed, lig 6 was moderately expressed, while none of the genes was under-expressed. The strain also produced 90±0.87 U/ml lignin peroxidase and 120±1.23 U/mil manganese peroxidase enzymes in aliquots. These results imply that KY488466 can tolerate and survive high crude oil concentration and could be exploited for bioremediation of oil-spilled soils, the produced peroxidase enzymes could also be exploited for other biotechnological experiments.

Keywords: crude oil, enzymes, expression, peroxidase genes, tolerance, Trichoderma harzianum

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Authors: Sandeep Pandey, Nimra Habib, Ranjana Singh, Abbas Ali Mahdi

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Leukemia is a malignancy of blood that mainly affects children and young adults; while advancement in the early diagnosis will have the potential to improve the outcome of diseases. A wide range of disease including leukemia shows inflammatory signals in their pathogenesis. In a pilot study conducted in our laboratory, 52 people were screened, of which 26 had leukemia and 26 were free from any kind of malignancy. We performed the estimation of the inflammatory cytokine Interleukin-8 and it was found significantly raised in all the leukemia patients concerning healthy volunteers who participated in the study. Flow cytometry had been performed for the confirmation of leukemia and further genomic, and proteomic, analyses of the sample revealed that IL-8 levels showed a positive correlation in patients with leukemia. The results had shown constitutive secretion of interleukin-8 by leukemia cells. So, our finding demonstrated that IL-8 is considered to have a role in the pathogenesis of leukemia, and quantification of IL-8 levels in leukemia conditions might be more useful and feasible in the clinical setting for the prediction of drug responses where it may represent a putative target for innovative diagnostic toward effective therapeutic approaches. However, further research explorations in this area are needed that include a greater number of patients with all different forms of leukemia, and estimating their IL-8 levels may hold the key for the additional predictive values on the recurrence of leukemia and its prognosis.

Keywords: T-ALL, IL-8, leukemia pathogenesis, cancer therapeutics

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Authors: Kakali Bhadra

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Binding of small molecules to DNA and recently to RNA, continues to attract considerable attention for developing effective therapeutic agents for control of gene expression. This work focuses towards understanding interaction of harmalol, a dihydro beta-carboline alkaloid, with different nucleic acid motifs viz. double stranded CT DNA, single stranded A-form poly(A), double-stranded A-form of poly(C)·poly(G) and clover leaf tRNAphe by different spectroscopic, calorimetric and molecular modeling techniques. Results of this study converge to suggest that (i) binding constant varied in the order of CT DNA > poly(C)·poly(G) > tRNAphe > poly(A), (ii) non-cooperative binding of harmalol to poly(C)·poly(G) and poly(A) and cooperative binding with CT DNA and tRNAphe, (iii) significant structural changes of CT DNA, poly(C)·poly(G) and tRNAphe with concomitant induction of optical activity in the bound achiral alkaloid molecules, while with poly(A) no intrinsic CD perturbation was observed, (iv) the binding was predominantly exothermic, enthalpy driven, entropy favoured with CT DNA and poly(C)·poly(G) while it was entropy driven with tRNAphe and poly(A), (v) a hydrophobic contribution and comparatively large role of non-polyelectrolytic forces to Gibbs energy changes with CT DNA, poly(C)·poly(G) and tRNAphe, and (vi) intercalated state of harmalol with CT DNA and poly(C)·poly(G) structure as revealed from molecular docking and supported by the viscometric data. Furthermore, with competition dialysis assay it was shown that harmalol prefers hetero GC sequences. All these findings unequivocally pointed out that harmalol prefers binding with ds CT DNA followed by ds poly(C)·poly(G), clover leaf tRNAphe and least with ss poly(A). The results highlight the importance of structural elements in these natural beta-carboline alkaloids in stabilizing different DNA and RNA of various motifs for developing nucleic acid based better therapeutic agents.

Keywords: calorimetry, docking, DNA/RNA-alkaloid interaction, harmalol, spectroscopy

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Authors: Nuray Yilmaz Baran, Mehmet Saçak

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Schiff base polymers are one class of conjugated polymers, also called as poly(azomethines). They have drawn the attention of researchers in recent years due to their some properties such as, optoelectronic, semiconductive, and photovoltaic, antimicrobial activities and high thermal stability. In this study, Poly(2-[[4-(dimethylamino)benzylidene]amino] phenol) P(2-DBAP), which is a Schiff base polymer, was synthesized by an oxidative polycondensation reaction of -[[4-(dimethylamino)benzylidene]amino]phenol (2-DBAP) with oxidants NaOCl, H₂O₂ and O₂ in various organic medium. At the end of the polymerizations carried out at various temperatures and time, maximum conversion of the monomer to the polymer could be obtained as around 93.7 %. The structures of the monomer and polymer were characterized by UV-Vis, FTIR and ¹HNMR techniques. Thermal analysis of the polymer was identified by TG-DTG and DTA techniques, and the thermal degradation behavior was supported by Thermo-IR spectra recorded in the temperature range of 25-800 °C. The number average molecular weight (Mn), weight average molecular weight (Mw) and polydispersity index (PDI) of the polymer were found to be 26337, 9860 g/mol 2.67, respectively. The change of electrical conductivity value of the P(2-DBAP) doped with iodine vapor at different temperatures and time was investigated its maximum was measured by increasing 10¹⁰ fold as 2 x10⁻⁴ Scm⁻¹ after doping for 48 h at 60 °C. Antibacterial and antifungal activities of P(2-DBAP) Schiff base and its polymer were also investigated against Sarcina lutea, Enterobacter aerogenes, Escherichia coli, Enterococcus Faecalis, Klebsiella pneumoniae, Bacillus subtilis, and Candida albicans, Saccharomyces cerevisiae, respectively.

Keywords: conductive properties, polyazomethines, polycondensation reaction, Schiff base polymers, thermal stability

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Authors: Amornnat Thuppia, Pornrut Rabintossaporn, Suphaket Saenthaweesuk, Nuntiya Somparn

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The aim of this present study was to determine the antioxidant effects and its mechanism of aqueous leaves extract of Bauhinia acuminata (BA) in rat. The extract was screened for its phytochemical contents and antioxidant activity in vitro. Moreover, the extract was studied in rats to evaluate its effects in vivo. Rats were orally administered with the extract at the dose of 50, 100 and 200 mg/kg for 28 days. Phytochemical screening of plant extracts showed the presence of saponin, alkaloid, cardiac glycosides, flavonoids, tannin and steroid compounds. The extract contained phenolic compounds 53.36 ± 1.01 mg of gallic acid equivalents per gram BA extract. The free radical scavenging activity assessed by DPPH assay gave IC50 of 44.47 ± 2.83 µg/mL, which is relatively lower than that of BHT with IC50 of 12.34 ± 1.14µg/mL. In the animals, the extract was well tolerated by the animals throughout the 28 days of study as shown by normal serum levels AST, ALP, ALT, BUN and Cr as well as normal histology of liver and pancreatic and kidney tissue. Significantly, reduction of serum oxidative stress markers malondialdehyde (MDA) was found in rat treated with BA extract compared with control. Taken together, this study provides evidence that Bauhinia acuminata (BA) exhibits direct antioxidant properties and induces cytoprotective enzyme in vivo.

Keywords: Bauhinia acuminata, antioxidant, malondialdehyde (MDA), oxidative marker

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Authors: Jesmin Akter, Chang Hyuk Ahn, Ilho Kim, Jaiyeop Lee

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Global pandemic coronavirus disease (COVID-19) caused by Severe acute respiratory syndrome SARS-CoV-2, to control the spread of the COVID-19 pandemic, wastewater surveillance has been used to monitor SARS-CoV2 prevalence in the community. The challenging part is establishing wastewater surveillance; there is a need for a well-equipped laboratory for wastewater sample analysis. According to many previous studies, reverse transcription-polymerase chain reaction (RT-PCR) based molecular tests are the most widely used and popular detection method worldwide. However, the RT-qPCR based approaches for the detection or quantification of SARS-CoV-2 genetic fragments ribonucleic acid (RNA) from wastewater require a specialized laboratory, skilled personnel, expensive instruments, and a workflow that typically requires 6 to 8 hours to provide results for just minimum samples. Rapid and reliable alternative detection methods are needed to enable less-well-qualified practitioners to set up and provide sensitive detection of SARS-CoV-2 within wastewater at less-specialized regional laboratories. Therefore, scientists and researchers are conducting experiments for rapid detection methods of COVID-19; in some cases, the structural and molecular characteristics of SARS-CoV-2 are unknown, and various strategies for the correct diagnosis of COVID-19 have been proposed by research laboratories, which are presented in the present study. The ongoing research and development of these highly sensitive and rapid technologies, namely RT-LAMP, ELISA, Biosensors, GeneXpert, allows a wide range of potential options not only for SARS-CoV-2 detection but also for other viruses as well. The effort of this study is to discuss the above effective and regional rapid detection and quantification methods in community wastewater as an essential step in advancing scientific goals.

Keywords: rapid detection, SARS-CoV-2, sensitive detection, wastewater surveillance

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Authors: Lavinia Ruta, Ileana Farcasanu

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The yeast surface display (YSD) technique enables the expression of proteins on yeast cell surfaces, facilitating the identification and isolation of proteins with targeted binding properties, such as nanobodies. Nanobodies, derived from camelid species, are single-domain antibody fragments renowned for their high affinity and specificity towards target proteins, making them valuable in research and potentially in therapeutics. Their advantages include a compact size (~15 kDa), robust stability, and the ability to target challenging epitopes. The project endeavors to establish and validate a platform for producing Green Fluorescent Protein (GFP) and mCherry nanobodies using the yeast surface display method. mCherry, a prevalent red fluorescent protein sourced from coral species, is commonly utilized as a genetic marker in biological studies due to its vibrant red fluorescence. The GFP-nanobody, a single variable domain of heavy-chain antibodies (VHH), exhibits specific binding to GFP, offering a potent means for isolating and engineering fluorescent protein fusions across various biological research domains. Both GFP and mCherry nanobodies find specific utility in cellular imaging and protein analysis applications.

Keywords: YSD, nanobodies, GFP, Saccharomyces cerevisiae

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Authors: Watchawin Ekphinitphithaya, Patompong Satapornpong

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Introduction: Carbamazepine (CBZ) is one of the most prescribed antiepileptic drugs (AEDs) by neurologists and non-neurologist worldwide. CBZ is usually prescribed along with other drugs, leading to the possibility of severe cutaneous adverse drug reactions (SCARs). The HLA-B*15:02 is strongly associated with CBZ-induced Stevens-Johnson syndrome and toxic epidermal necrolysis (SJS–TEN) in the Han Chinese and other Asian populations but not in European populations, while HLA-A*31:01 allele has been reported to be associated with CBZ-induced SCARs in European population and Japanese. Objective: The aim of this study is to investigate the distribution of pharmacogenetics HLA-A*31:01 marker in a healthy Thai population associated with Carbamazepine-induced SCARs. Materials and Methods: Prospective study, 350 unrelated healthy Thais were recruited in this study. Human leukocyte antigen-A alleles were genotyped using PCR-sequence specific oligonucleotides (PCR-SSOs). Results: The frequency of HLA-A alleles were HLA-A*11:01 (190 alleles, 27.14%), HLA-A*24:02 (82 alleles, 11.71%), HLA-A*02:03 (80 alleles, 11.43%), HLA-A*33:03 (76 alleles, 10.86%), HLA-A*02:07 (58 alleles, 8.29%), HLA-A*02:01 (35 alleles, 5.00%), HLA-A*24:07 (29 alleles, 4.14%), HLA-A*02:06 – HLA-A*30:01 (15 alleles, 2.14%), and HLA-A*01:01 (14 alleles, 2.00%). Particularly, the number of HLA-A*31:01 alleles was 6 of 700 (0.86%) in the healthy Thai population. Many research presented varying distributions of HLA-A*31:01 in Asians, including 2% of Han Chinese, 9% of Japanese and 5% of Koreans. In addition, this allele was found approximately 2-5% in the Caucasian population. Conclusions: Thus, the pharmacogenetics database is vital to support in many populations, especially in Thais, for screening HLA-A*31:01 allele to avoid CBZ-induced SCARs before initiating treatments in each population.

Keywords: Carbamazepine, HLA-A*31:01, Thai population, pharmacogenetics

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Authors: Rodrigo Antunes, Olga Borisevich, David Demange

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The Tritium Laboratory Karlsruhe (TLK) has identified zeolite membranes as most promising for tritium processes in the future fusion reactors. Tritium diluted in purge gases or gaseous effluents, and present in both molecular and oxidized forms, can be pre-concentrated by a stage of zeolite membranes followed by a main downstream recovery stage (e.g., catalytic membrane reactor). Since 2011 several membrane zeolite samples have been tested to measure the membrane performances in the separation of hydrogen and water vapor from helium streams. These experiments were carried out in the ZIMT (Zeolite Inorganic Membranes for Tritium) facility where mass spectrometry and cold traps were used to measure the membranes’ performances. The membranes were tested at temperatures ranging from 25 °C up to 130 °C, at feed pressures between 1 and 3 bar, and typical feed flows of 2 l/min. During this experimental campaign, several zeolite-type membranes were studied: a hollow-fiber MFI nanocomposite membrane purchased from IRCELYON (France), and tubular MFI-ZSM5, NaA and H-SOD membranes purchased from Institute for Ceramic Technologies and Systems (IKTS, Germany). Among these membranes, only the MFI-based showed relevant performances for the H2/He separation, with rather high permeances (~0.5 – 0.7 μmol/sm2Pa for H2 at 25 °C for MFI-ZSM5), however with a limited ideal selectivity of around 2 for H2/He regardless of the feed concentration. Both MFI and NaA showed higher separation performances when water vapor was used instead; for example, at 30 °C, the separation factor for MFI-ZSM5 is approximately 10 and 38 for 0.2% and 10% H2O/He, respectively. The H-SOD evidenced to be considerably defective and therefore not considered for further experiments. In this contribution, a comprehensive analysis of the experimental methods and results obtained for the separation performance of different zeolite membranes during the past four years in inactive environment is given. These results are encouraging for the experimental campaign with molecular and oxidized tritium that will follow in 2017.

Keywords: gas separation, nuclear fusion, tritium processes, zeolite membranes

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