Search results for: gene regulation

Authors: Zoe M. G. Skalkos, Sam N. Dowland, James U. Van Dyke, Camilla. M. Whittington

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Syngnathid fishes (seahorses, pipefishes, and seadragons) are unique because embryos develop on or in the male in a specialised brooding structure. Many seahorse species are endangered or vulnerable, while others are popular in the ornamental fish trade. Seahorses are capable of nutrient provisioning (patrotrophy) of lipids during pregnancy via their fully enclosed brood pouch. Protein is vital for gene regulation and tissue growth during embryogenesis. We tested the hypothesis that protein is paternally transported to developing embryos during pregnancy in the Australian Pot-bellied seahorse, Hippocampus abdominalis. We compared the dry masses and nitrogen content in recently fertilised H. abdominalis embryos and newborns. We calculated an updated patrotrophy index, 1.34, but without a significant difference in dry mass between the two developmental stages. There was, however, a significant increase in total protein content from recently fertilised embryos to neonates. This suggests paternal protein transport is essential for H. abdominalis embryogenesis because protein yolk reserves are depleted by embryonic metabolism, and supplementation is required. This study is the first to provide evidence for paternal protein transport during pregnancy in seahorses. It furthers our understanding of the paternal influence on embryonic development in male pregnancy and how a protein-deficient diet during pregnancy may limit the allocation of resources to embryos, reducing offspring fitness. This research contributes to a deeper understanding of the fundamental reproductive biology of seahorses, which can help improve conservation and farming production outcomes.

Keywords: brood pouch, embryonic provisioning, nitrogen, parentotrophy, paternal investment, reproduction

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Authors: I. Boroňová, J.Bernasovská, J. Kľoc, Z. Tomková, E. Petrejčíková, D. Gabriková, S. Mačeková

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Osteoporosis is a complex health disease characterized by low bone mineral density, which is determined by an interaction of genetics with metabolic and environmental factors. Current research in genetics of osteoporosis is focused on identification of responsible genes and polymorphisms. TNFRSF11B gene plays a key role in bone remodeling. The aim of this study was to investigate the genotype and allele distribution of A163G (rs3102735) osteoprotegerin gene promoter and G1181C (rs2073618) osteoprotegerin first exon polymorphisms in the group of 180 unrelated postmenopausal women with diagnosed osteoporosis and 180 normal controls. Genomic DNA was isolated from peripheral blood leukocytes using standard methodology. Genotyping for presence of different polymorphisms was performed using the Custom Taqman®SNP Genotyping assays. Hardy-Weinberg equilibrium was tested for each SNP in the groups of participants using the chi-square (χ2) test. The distribution of investigated genotypes in the group of patients with osteoporosis were as follows: AA (66.7%), AG (32.2%), GG (1.1%) for A163G polymorphism; GG (19.4%), CG (44.4%), CC (36.1%) for G1181C polymorphism. The distribution of genotypes in normal controls were follows: AA (71.1%), AG (26.1%), GG (2.8%) for A163G polymorphism; GG (22.2%), CG (48.9%), CC (28.9%) for G1181C polymorphism. In A163G polymorphism the variant G allele was more common among patients with osteoporosis: 17.2% versus 15.8% in normal controls. Also, in G1181C polymorphism the phenomenon of more frequent occurrence of C allele in the group of patients with osteoporosis was observed (58.3% versus 53.3%). Genotype and allele distributions showed no significant differences (A163G: χ2=0.270, p=0.605; χ2=0.250, p=0.616; G1181C: χ2= 1.730, p=0.188; χ2=1.820, p=0.177). Our results represents an initial study, further studies of more numerous file and associations studies will be carried out. Knowing the distribution of genotypes is important for assessing the impact of these polymorphisms on various parameters associated with osteoporosis. Screening for identification of “at-risk” women likely to develop osteoporosis and initiating subsequent early intervention appears to be most effective strategy to substantially reduce the risks of osteoporosis.

Keywords: osteoporosis, real-time PCR method, SNP polymorphisms

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Authors: Sheng-Fen Fan, Sung-Hui Tseng

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Attention deficit hyperactivity deficit (ADHD) child display diverse sensory processing difficulty behaviors. There is less evidence to figure out how the association between executive function and sensory deficit. To determine whether sensory deficit influence the executive functions, we examined sensory processing by SPM and try to indicate hot/cold executive function (EF) by BRIEF2, respectively. We found that the hot executive function deficit might associate with auditory processing in a variety of settings, and vestibular input to maintain balance and upright posture; the cold EF deficit might opposite to the hot EF deficit, the vestibular sensory modulation difficulty association with emotion shifting and emotional regulation. These results suggest that sensory processing might be another consideration factor to influence the higher cognitive control or emotional regulation of EF. Overall, this study indicates the distinction between hot and cold EF impairments with different sensory modulation problem. Moreover, for clinician, it needs more cautious consideration to conduct intervention with ADHD.

Keywords: hot executive function, cold executive function, sensory processing, ADHD

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Authors: András Farkas, István Molnár, Jan Vrána, Veronika Burešová, Petr Cápal, András Cseh, Márta Molnár-Láng, Jaroslav Doležel

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Species of Aegilops played a central role in the evolution of wheat and are sources of traits related to yield quality and tolerance against biotic and abiotic stresses. These wild genes and alleles are desirable to use in crop improvement programs via introgressive hybridization. However, the success of chromosome mediated gene transfer to wheat are hampered by the pour knowledge on the genome structure of Aegilops relative to wheat and by the low number of cost-effective molecular markers specific for Aegilops chromosomes. The COS markers specific for genes conserved throughout evolution in both sequence and copy number between Triticeae/Aegilops taxa and define orthologous regions, thus enabling the comparison of regions on the chromosomes of related species. The present study compared individual chromosomes of Aegilops umbellulata (UU), Ae. comosa (MM), Ae. speltoides (SS) and Ae. caudata (CC) purified by flourescent labelling with oligonucleotid SSR repeats and biparametric flow cytometry with wheat by identifying orthologous chromosomal regions by COS markers. The linear order of bin-mapped COS markers along the wheat D chromosomes was identified by the use of chromosome-specific sequence data and virtual gene order. Syntenic regions of wheat identifying genome rearrangements differentiating the U, M, S or C genomes from the D genome of wheat were detected. The conserved orthologous set markers assigned to Aegilops chromosomes promise to accelerate gene introgression by facilitating the identification of alien chromatin. The syntenic relationships between the Aegilops species and wheat will facilitate the targeted development of new markers specific for U, M, S and C genomic regions and will contribute to the understanding of molecular processes related to the evolution of Aegilops.

Keywords: Aegilops, cos-markers, flow-sorting, wheat

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Authors: Joohyun Park, Jin Baek

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The purpose of this study is to Analyze the role and effect arise from Diagonal Plane Control by Street Width (DPCSW) in Architecture in Seoul, and to predict the aspect of transition about the relationship among buildings and Urban morphology After the abolition. To find the tendency of building shape regulation, This study review Building Acts concerned with form making (the building to land Ratio, building designated line, wall designated line, building height limit (DPCSW) and etc.) and simulate the shape of urban blocks made by Acts in drawings. The review results show DPCSW is not only limitation about height, but also making the building setback from road and make the Road broader. And it makes the typical shape of the urban block that buildings are moving away from surrounding road After the Abolition of DPCSW; it is expected by the legislature that domestic real estate’s market would be promoted by increased total floor areas in each building. Some substitution from the legislature is announced, but it just deals with Building Maximum unit by Block unit except the regulation about arrangement in urban Figure and Ground. In conclusion, refrain from the uncontrolled development of city, It is important to make regulation about not only height factors but limitation line in land. Furthermore, through revising District Unit Plan, It is positively necessary to reset the relationship between buildings for the making the city space better.

Keywords: diagonal plane control by street width, building maximum height, district unit plan, building acts, urban block type, morphology, building shape

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Authors: Dalia G. Aseel

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The potato (Solanum tubersum, L.) has become one of the major vegetable crops in Egypt and all over the world. Potato leafroll virus(PLRV) was observed on potato plants collected from different governorates in Egypt. Three cultivars, Spunta, Diamont, and Cara, infected with PLRV were collected; RNA was extracted and subjected to Real-Time PCR using the coat protein gene primers. The results showed that the expression of the coat protein was 39.6-fold, 12.45-fold, and 47.43-fold, respectively, for Spunta, Diamont, and Cara cultivars. Differential Display Polymerase Chain Reaction (DD-PCR) using pathogenesis-related protein 1 (PR-1), β-1,3-glucanases (PR-2), chitinase (PR-3), peroxidase (POD), and polyphenol oxidase (PPO) forward primers for pathogenesis-related proteins (PR). The obtained data revealed different banding patterns depending on the viral type and the region of infection. Regarding PLRV, 58 up-regulated and 19 down-regulated genes were detected. Sequence analysis of the up-and down-regulated genes revealed that infected plants were observed in comparison with the healthy control. Sequence analysis of the up-regulated gene was performed, and the encoding sequence analysis showed that the obtained genes include: induced stolen tip protein. On the other hand, two down-regulated genes were identified: disease resistance RPP-like protein and non-specific lipid-transfer protein. In this study, the expressions of PR-1, PR-2, PR-3, POD, and PPO genes in the infected leaves of three potato cultivars were estimated by quantitative real-time PCR. We can conclude that the PLRV-infection of potato plants inhibited the expression of the five PR genes. On the contrary, infected leaves by PLRV elevated the expression of some defense genes. This interaction may also induce and/or suppress the expression of some genes responsible for the plant's defense mechanisms.

Keywords: PLRV, pathogenesis-related proteins (PRs), DD-PCR, sequence, real-time PCR

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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: Amr A. El Hanafy, Muhammad I. Qureshi, Jamal Sabir, Mohamed Mutawakil, Mohamed M. Ahmed, Hassan El Ashmaoui, Hassan Ramadan, Mohamed Abou-Alsoud, Mahmoud Abdel Sadek

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β-Lactoglobulin (β-LG) is the dominant non-casein whey protein found in bovine milk and of most ruminants. The amino acid sequence of β-LG along with its 3-dimensional structure illustrates linkage with the lipocalin superfamily. Preliminary studies in goats indicated that milk yield can be influenced by polymorphism in genes coding for whey proteins. The aim of this study is to identify and evaluate the incidence of functional polymorphisms in the exonic and intronic portions of β-LG gene in native Saudi goat breeds (Ardi, Habsi, and Harri). Blood samples were collected from 300 animals (100 for each breed) and genomic DNA was extracted using QIAamp DNA extraction Kit. A fragment of the β-LG gene from exon 7 to 3’ flanking region was amplified with pairs of specific primers. Subsequent digestion with Sac II restriction endonuclease revealed two alleles (A and B) and three different banding patterns or genotypes i.e. AA, AB and BB. The statistical analysis showed that β-LG AA genotype had higher milk yield than β-LG AB and β-LG BB genotypes. Nucleotide sequencing of the selected β-LG fragments was done and submitted to GenBank NCBI (Accession No. KJ544248, KJ588275, KJ588276, KJ783455, KJ783456 and KJ874959). Two already established SNPs in exon 7 (+4601 and +4603) and one fresh SNP in the 3’ UTR region were detected in the β-LG fragments with designated AA genotype. The polymorphisms in exon 7 did not produce any amino acid change. Phylogenetic analysis on the basis of nucleotide sequences of native Saudi goats indicated evolutional similarity with the GenBank reference sequences of goat, Bubalus bubalis and Bos taurus.

Keywords: β-Lactoglobulin, Saudi goats, PCR-RFLP, functional polymorphism, nucleotide sequencing, phylogenetic analysis

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Authors: Jung-En Kuan, Whei-Fen Wu

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In this study, a symbiotic bacteria from yellow mealworm's (Tenebrio molitor) mid-gut was isolated with characteristics of growth on minimal-tributyrin medium. After a PCR-amplification of its 16s rDNA, the resultant nucleotide sequences were then analyzed by schemes of the phylogeny trees. Accordingly, it was designated as Pseudomonas nitroreducens D-01. Next, by searching the lipolytic enzymes in its protein data bank, one of those potential lipolytic α/β hydrolases was identified, again using PCR-amplification and nucleotide-sequencing methods. To construct an expression of this lipolytic gene in plasmids, the target-gene primers were then designed, carrying the C-terminal his-tag sequences. Using the vector pET21a, a recombinant lipolytic hydrolase D gene with his-tag nucleotides was successfully cloned into it, of which the lipolytic D gene is under a control of the T7 promoter. After transformation of the resultant plasmids into Eescherichia coli BL21 (DE3), an IPTG inducer was used for the induction of the recombinant proteins. The protein products were then purified by metal-ion affinity column, and the purified proteins were found capable of forming a clear zone on tributyrin agar plate. Shortly, its enzyme activities were determined by degradation of p-nitrophenyl ester(s), and the substantial yellow end-product, p-nitrophenol, was measured at O.D.405 nm. Specifically, this lipolytic enzyme efficiently targets p-nitrophenyl butyrate. As well, it shows the most reactive activities at 40°C, pH 8 in potassium phosphate buffer. In thermal stability assays, the activities of this enzyme dramatically drop when the temperature is above 50°C. In metal ion assays, MgCl₂ and NH₄Cl induce the enzyme activities while MnSO₄, NiSO₄, CaCl₂, ZnSO₄, CoCl₂, CuSO₄, FeSO₄, and FeCl₃ reduce its activities. Besides, NaCl has no effects on its enzyme activities. Most organic solvents decrease the activities of this enzyme, such as hexane, methanol, ethanol, acetone, isopropanol, chloroform, and ethyl acetate. However, its enzyme activities increase when DMSO exists. All the surfactants like Triton X-100, Tween 80, Tween 20, and Brij35 decrease its lipolytic activities. Using Lineweaver-Burk double reciprocal methods, the function of the enzyme kinetics were determined such as Km = 0.488 (mM), Vmax = 0.0644 (mM/min), and kcat = 3.01x10³ (s⁻¹), as well the total efficiency of kcat/Km is 6.17 x10³ (mM⁻¹/s⁻¹). Afterwards, based on the phylogenetic analyses, this lipolytic protein is classified to type IV lipase by its homologous conserved region in this lipase family.

Keywords: enzyme, esterase, lipotic hydrolase, type IV

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Authors: Hanno Schmidt, Assaf Malik, Anne Bicker, Gesa Poetzsch, Aaron Avivi, Imad Shams, Thomas Hankeln

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The blind subterranean mole rat Spalax shows a remarkable tolerance to hypoxia, cancer-resistance and longevity. Unravelling the genomic basis of these adaptations will be important for biomedical applications. RNA-Seq gene expression data were obtained from normoxic and hypoxic Spalax and rat liver tissue. Hypoxic Spalax broadly downregulates genes from major liver function pathways. This energy-saving response is likely a crucial adaptation to low oxygen levels. In contrast, the hypoxiasensitive rat shows massive upregulation of energy metabolism genes. Candidate genes with plausible connections to the mole rat’s phenotype, such as important key genes related to hypoxia-tolerance, DNA damage repair, tumourigenesis and ageing, are substantially higher expressed in Spalax than in rat. Comparative liver transcriptomics highlights the importance of molecular adaptations at the gene regulatory level in Spalax and pinpoints a variety of starting points for subsequent functional studies.

Keywords: cancer, hypoxia, longevity, transcriptomics

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Authors: Oluwabiyi Adeola Ayodele

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This study analysed the Policy and general issues that have arisen over time in Nigeria’ Cashless banking environment as a result of the lack of a Legal framework on Electronic banking in Nigeria. It undertook an in-depth study of the cashless banking system. It discussed the evolution, growth and development of cashless banking in Nigeria; It revealed the expected benefits of the cashless banking system; It appraised regulatory issues and other prevalent problems on cashless banking in Nigeria; and made appropriate recommendations where necessary. The study relied on primary and secondary sources of information. The primary sources included the Constitution of the Federal Republic of Nigeria, Statutes, Conventions and Judicial decisions, while the secondary sources included Books, Journals Articles, Newspapers and Internet Materials. The study revealed that cashless banking has been adopted in Nigeria but still at the developing stage. It revealed that there is no law for the regulation of cashless banking in Nigeria, what Nigeria relies on for regulation is the Central Bank of Nigeria’s Cashless Policy, 2014. The Banks and Other Financial Institutions Act Chapter B3, LFN, 2004 of Nigeria lack provision to accommodate issues on Internet banking. However, under the general principles of legality in criminal law, and by the provisions of the Nigerian Constitution, a person can only be punished for conducts that have been defined to be criminal by written laws with the penalties specifically stated in the law. Although Nigeria has potent laws for the regulation of paper banking, these laws cannot be substituted for paperless transactions. This is because the issues involved in both transactions vary. The study also revealed that the absence of law in the cashless banking environment in Nigeria will subject consumers to endless risks. This study revealed that the creation of banking markets via the Internet relies on both available technologies and appropriate laws and regulations. It revealed however that Law of some of the countries considered on cashless banking has taken care of most of the legal issues and other problems prevalent in the cashless banking environment. The study also revealed some other problems prevalent in the Nigerian cashless banking environment. The study concluded that for Nigeria to find solutions to the legal issues raised in its cashless banking environment and other problems of cashless banking, it should have a viable legal Frame work for internet banking. The study concluded that the Central Bank of Nigeria’s Policy on Cashless banking is not potent enough to tackle the challenges posed to cashless banking in Nigeria because policies only have a persuasive effect and not a binding effect. There is, therefore, a need for appropriate Laws for the regulation of cashless Banking in Nigeria. The study also concluded that there is a need to create more awareness of the system among Nigerians and solve infrastructural problems like prevalent power outage which often have been creating internet network problem.

Keywords: cashless-banking, Nigeria, policies, laws

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Authors: Arfan Ali, Muhammad Shahzad Iqbal, Idrees Ahmad Nasir

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Potato (Solanum tuberosum L.) is ranked among the top leading staple foods in the world. Salinity adversely affects potato crop yield and quality. Therefore, increased level of salt tolerance is a key factor to ensure high yield. The present study focused on the Agrobacterium-mediated transformation of Atriplex canescens betaine aldehyde dehydrogenase (BADH) gene, using single, double and triple CAMV35s promoter to improve salt tolerance in potato. Detection of seven potato lines harboring BADH gene, followed by identification of T-DNA insertions, determination of transgenes copies no through Southern Hybridization and quantification of BADH protein through Enzyme Linked Immunosorbent Assay were considered in this study. The results clearly depict that the salt tolerance of potato was found to be promoter-dependent, as the potato transgenic lines with triple promoter showed 4.4 times more glycine betaine production which consequently leads towards high resistance to salt stress as compared to transgenic potato lines with single and double promoters having least production of glycine betaine. Moreover, triple promoter transgenic potato lines have also shown lower levels of H2O2, malondialdehyde (MDA), relative electrical conductivity, high proline and chlorophyll content as compared other two lines having a single and double promoter. Insilco analysis also confirmed that Atriplex canescens BADH has the tendency to interact with sodium ions and water molecules. Taken together these facts it can be concluded that over-expression of BADH under triple CAMV35s promoter with more glycine betaine, chlorophyll & MDA contents, high relative quantities of other metabolites results in an enhanced level of salt tolerance in potato.

Keywords: Atriplex canescens, BADH, CAMV35s promotor, potato, Solanum tubersum

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Authors: Savitha Janakiraman, Shivakumar M. C

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Anidulafungin, an advanced class of antifungal agent used for the treatment of chronic fungal infections, is derived from Echinocandin B nucleus, an intermediate metabolite of Echinocandin B produced by Aspergillus nidulans. The enzyme acylase derived from the fermentation broth of Actinoplanes utahensis (NRRL 12052) plays a key role in the bioconversion of echinocandin B to echinocandin B nucleus. The membrane-bound nature of acylase and low levels of expression contributes to the rate-limiting process of enzymatic deacylation, hence low yields of ECB nucleus and anidulafungin. In the present study, this is addressed through novel genetic engineering approaches of overexpression and heterologous expression studies, immobilization of whole cells of Actinoplanes utahensis (NRRL 12052) and Co-cultivation studies. Overexpression of the acylase gene in Actinoplanes utahensis (NRRL 12052) was done by increasing the gene copy number to increase the echinocandin B nucleus production. Echinocandin B acylase gene, under the control of a PermE* promoter, was cloned in pSET152 vector and introduced into Actinoplanes utahensis (NRRL12052) by a ɸC31-directed site-specific recombination method. The resultant recombinant strain (C2-18) showed a 3-fold increase in acylase expression, which was confirmed by HPLC analysis. Pichia pastoris is one of the most effective and versatile host systems for the production of heterologous proteins. The ECB acylase gene was cloned into pPIC9K vector with AOX1 promoter and was transformed into Pichia pastoris (GS115). The acylase expression was confirmed by protein expression and bioconversion studies. The heterologous expression of acylase in Pichia pastoris, is a milestone in the development of antifungals. Actively growing cells of Actinoplanes utahensis (NRRL 12052) were immobilized and tested for bioconversion ability which showed >90% conversion in each cycle. The stability of immobilized cell beads retained the deacylation ability up to 60 days and reusability was confirmed up to 4 cycles. The significant findings from the study have revealed that immobilization of whole cells of Actinoplanes utahensis (NRRL 12052) could be an alternative option for bioconversion of echinocandin B to echinocandin B nucleus, which has not been reported to date. The concept of co-cultivation of Aspergillus nidulans and Actinoplanes utahensis strains for the production of the echinocandin B nucleus was also carried out in order to produce echinocandin B nucleus. The process completely reduced the ECB purification step and, therefore, could be recommended as an ingenious method to improve the yield of the ECB nucleus.

Keywords: acylase, anidulafungin, antifungals, Aspergillus nidulans

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Authors: V. Petkova, V. Valchanova, D. Grekova, K. Andreevska, S. T. Geurguiev, V. Madgarov, D. Grekov

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Introduction: Production, distribution and sale of cosmetics is a global industry, which played a key role in the European Union (EU), the US and Japan. A major participant EU whose market cosmetics is greater than in the US and 2 times greater than that in Japan. The output value of the cosmetics industry in the EU is estimated at about € 35 billion in 2001. Nearly 5 billion cosmetic products (number of packages) are sold annually in the EU, and the main markets are France, Germany, Italy, Spain and the UK. The aim of the study is legal and marketing analysis of cosmetic products dispensed in a pharmacy. Materials and methodology: Historical legislative analysis - the method is applied in the analysis of changes in the legislative regulation of the activities of cosmetic products in Japan and Bulgaria Comparative legislative analysis - the method is applied when comparing the legislative requirements for cosmetic products in the already mentioned countries. Both methods are applied to the following regulations: 1) Japanese Pharmaceuticals Affairs Law, Tokyo, Japan, Ministry of Health, Labour and Welfare; 2) Law on Medicinal Products for Human Use; effective from 3.01.2014. Results: The legislative framework for cosmetic products in Bulgaria and Japan is close and generally includes general guidelines: Definition of a medicinal product; Categorization of drugs (with differences in sub-categories); Pre-registration and marketing approval of the competent authorities; Compulsory compliance with gmp (unlike cosmetics); Regulatory focus on product quality, efficacy and safety; Obligations for labeling of such products; Created systems Pharmacovigilance and commitment of all parties - industry and health professionals; The main similarities in the regulation of products classified as cosmetics are in the following segments: Full producer responsibility for product safety; Surveillance of market regulatory authorities; No need for pre-registration or pre-marketing approval (a basic requirement for notification); Without restrictions on sales channels; GMP manuals for cosmetics; Regulatory focus on product safety (than over efficiency); General requirements in labeling: The main differences in the regulation of products classified as cosmetics are in the following segments: Details in the regulation of cosmetic products; Future convergence of regulatory frameworks can contribute to the removal of barriers to trade, to encourage innovation, while simultaneously ensuring a high level of protection of consumer safety.

Keywords: cosmetics, legislation, comparative analysis, Bulgaria, Japan

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Authors: S. J. Taylor, S. Chowdhury, T. A. Pychyl

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Attention Deficit Hyperactivity Disorder (ADHD) and procrastination are often discussed in relation to problems with self-regulation and executive functioning (EF). The small body of extant research that has explored the relations between these variables has many limitations particularly in terms of the samples used and the measurement of procrastination. In this study, we recruited a sample of undergraduate students with a confirmed clinical diagnosis of ADHD (n = 48, 66.7% females) as well as a sample of student volunteers without ADHD (n = 68, 75.8% females) to investigate the relations between ADHD subtypes, EF, procrastination and other forms of delay. We used the newly developed Multidimensional Measure of Academic Procrastination and Delay Questionnaire. As hypothesized, the results revealed that individuals with ADHD displayed significantly more irrational delay, general procrastination and academic procrastination compared to individuals without ADHD. This study contributed to the research literature indicating that individuals with ADHD struggle with procrastination as a result of symptoms of ADHD and EF deficits. Theses results provide support for adopting a new language when describing procrastination problems among individuals with ADHD, and they have implications for the nature of academic accommodations and interventions for individuals with ADHD.

Keywords: ADHD, delay, executive functioning, procrastination, self-regulation

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Authors: Muhammad Nur Haniff Mohd Noor, Rokiah Kadir, Suriyani Muhamad

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The National Forestry Act (NFA) 1984 is the primary forest law that regulates forest-related activities in Peninsular Malaysia. In the 1990s, abundance of illegal logging cases have called for legislative reform of the NFA 1984. As a result, NFA 1984 was amended in 1993 with the principal goal of controlling illegal forest encroachment in the forms of illegal logging, unauthorized harvesting, unlicensed forest settlement and other forms of unlawful activities. At a conceptual level, this paper discusses the policies and strategies implemented under the NFA 1984 (Amendment 1993) that are dedicated to overcome illegal logging. Then, the policies and strategies employed are reviewed and evaluated. Next, this paper conceptually discusses the loopholes of NFA 1984 (Amendment 1993) in relation to aspects where the regulation is considered insufficient to curb illegal logging. In the final section, vital actions and suggested improvements to improve the overall effectiveness of NFA 1984 (Amendment 1993) are examined.

Keywords: forest law and regulation, illegal logging, National Forestry Act 1984, NFA 1984, Amendment 1993, Peninsular Malaysia

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Authors: Catherine McWhorter

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Robotics is a fast-evolving field lacking comprehensive and harm-mitigating regulation; it also lacks critical data on how human-robot interaction (HRI) may affect human psychology. As most anthropomorphic robots are intended as substitutes for humans, this paper asserts that the commercial robotics industry should be preemptively regulated at the federal level such that robots capable of embodying a victim role in criminal scenarios (“vicbots”) are prohibited until clinical studies determine their effects on the user and society. The results of these studies should then inform more permanent legislation that strives to mitigate risks of harm without infringing upon fundamental rights or stifling innovation. This paper explores these concepts through the lens of the sex robot industry. The sexbot industry offers some of the most realistic, interactive, and customizable robots for sale today. From approximately 2010 until 2017, some sex robot producers, such as True Companion, actively promoted ‘vicbot’ culture with personalities like “Frigid Farrah” and “Young Yoko” but received significant public backlash for fetishizing rape and pedophilia. Today, “Frigid Farrah” and “Young Yoko” appear to have vanished. Sexbot producers have replaced preprogrammed vicbot personalities in favor of one generic, customizable personality. According to the manufacturer ainidoll.com, when asked, there is only one thing the user won’t be able to program the sexbot to do – “…give you drama”. The ability to customize vicbot personas is possible with today’s generic personality sexbots and may undermine the intent of some current legislative efforts. Current debate on the effects of vicbots indicates a lack of consensus. Some scholars suggest vicbots may reduce the rate of actual sex crimes, and some suggest that vicbots will, in fact, create sex criminals, while others cite their potential for rehabilitation. Vicbots may have value in some instances when prescribed by medical professionals, but the overall uncertainty and lack of data further underscore the need for preemptive regulation and clinical research. Existing literature on exposure to media violence and its effects on prosocial behavior, human aggression, and addiction may serve as launch points for specific studies into the hyperrealism of vicbots. Of course, the customization, anthropomorphism and artificial intelligence of sexbots, and therefore more mainstream robots, will continue to evolve. The existing sexbot industry offers an opportunity to preemptively regulate and to research answers to these and many more questions before this type of technology becomes even more advanced and mainstream. Robots pose complicated moral, ethical, and legal challenges, most of which are beyond the scope of this paper. By examining the possibility for custom vicbots via the sexbots industry, reviewing existing literature on regulation, media violence, and vicbot user effects, this paper strives to underscore the need for preemptive federal regulation prohibiting vicbot capabilities in robots while advocating for further research into the potential for the user and societal harm by the same.

Keywords: human-robot interaction effects, regulation, research, robots

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Authors: Rostika Flora, Muhammad Zulkarnain, Syokumawena

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Background: Aerobic physical exercises are recommended to keep body fit and healthy although physical exercises themselves can increase body metabolism and oxygen and can lead into tissue hypoxia. Oxygen pressure can serve as Vascular Endhothelial Growth Factor (VEGF) regulator. Hypoxia increases gene expression of VEGF through ascendant regulation of HIF-1. VEGF is involved in regulating angiogenesis process. Aerobic physical exercises can increase the concentration of VEGF in brain and enables angiogenesis process. We have investigated the influence of aerobic physical exercise to the VGEF concentration of wistar rat’s brain. Methods: This was experimental study using post test only control group design. Independent t-test was used as statistical test. The samples were twenty four wistar rat (Rattus Norvegicus) which were divided into four groups: group P1 (control group), group P2 (treatment group with once-a-week exercise), group P3 (treatment group with three time-a-week exercise), and group P4 (treatment group with seven time-a-week exercise). Group P2, P3, and P4 were treated with treadmil with speed of 20 m/minute for 30 minutes. The concentration of VEGF was determined by ELISA. Results: There was a significant increase of VEGF in treatment group compared with control one (<0.05). The maximum increase was found in group P2 (129.02±64.49) and the minimum increase was in group P4 (96.98±11.20). Conclusion: The frequency of aerobic physical exercises influenced the concentration of Vascular Endhothelial Growth Factor (VEGF) of brain tissue of Rattus Norvegicus.

Keywords: brain tissue, hypoxia, physical exercises, vascular endhothelial growth factor

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Authors: M. L. Mangena, N. Mokoena, K. Rashamuse, M. G. Tlou

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Tertiary alcohol ester (TAE) hydrolases are a group of esterases (EC 3.1.1.-) that catalyze the kinetic resolution of TAEs and as a result, they are sought-after for the production of optically pure tertiary alcohols (TAs) which are useful as building blocks for number biologically active compounds. What sets these enzymes apart is, the presence of a GGG(A)X-motif in the active site which appears to be the main reason behind their activity towards the sterically demanding TAEs. The genome of Pseudomonas syringae pv. maculicola (Psm) comprises a multitude of genes that encode esterases. We therefore, hypothesize that some of these genes encode TAE hydrolases. In this study, Psm was screened for TAE hydrolase activity using the linalyl acetate (LA) plate assay and a positive reaction was observed. As a result, the genome of Psm was screened for esterases with a GGG(A)X-motif using the motif search tool and two potential TAE hydrolase genes (PsmEST1 and 2, 1100 and 1000bp, respectively) were identified, PsmEST1 was amplified by PCR and the gene sequenced for confirmation. Analysis of the sequence data with the SingnalP 4.1 server revealed that the protein comprises a signal peptide (22 amino acid residues) on the N-terminus. Primers specific for the gene encoding the mature protein (without the signal peptide) were designed such that they contain NdeI and XhoI restriction sites for directional cloning of the PCR products into pET28a. The gene was expressed in E. coli JM109 (DE3) and the clones screened for TAE hydrolase activity using the LA plate assay. A positive clone was selected, overexpressed and the protein purified using nickel affinity chromatography. The activity of the esterase towards LA was confirmed using thin layer chromatography.

Keywords: hydrolases, tertiary alcohol esters, tertiary alcohols, screening, Pseudomonas syringae pv., maculicola genome, esterase activity, linalyl acetate

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Authors: Atul C. Mahajan, A. K. Chakravarty, V. Jamuna, C. S. Patil, Neeraj Kashyap, Bharti Deshmukh, Vijay Kumar

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The selection of Sahiwal bulls on the basis of dams best lactation milk yield under breeding programme in herd of the country neglecting fertility traits leads to deterioration in their performances and economy. The goal of this study was to explore polymorphism of CRISP2 gene and their association with semen traits (Post Thaw Motility, Hypo-osmotic Swelling Test, Acrosome Integrity, DNA Fragmentation and capacitation status), scrotal circumference, expected predicted difference (EPD) for milk yield and fertility. Sahiwal bulls included in present study were 60 bulls used in breeding programme as well as 50 young bulls yet to be included in breeding programme. All the Sahiwal bulls were found to be polymorphic for CRISP2 gene (AA, AG and GG) present within exon 7 to the position 589 of CRISP2 mRNA by using PCR-SSCP and Sequencing. Semen analysis were done on 60 breeding bulls frozen semen doses pertaining to four season (winter, summer, rainy and autumn). The scrotal circumference was measured from existing Sahiwal breeding bulls in the herd (n=47). The effect of non-genetic factors on reproduction traits were studied by least-squares technique and the significant difference of means between subclasses of season, period, parity and age group were tested. The data were adjusted for the significant non-genetic factors to remove the differential environmental effects. The adjusted data were used to generate traits like Waiting Period (WP), Pregnancy Rate (PR), Expected Predicted Difference (EPD) of fertility, respectively. Genetic and phenotypic parameters of reproduction traits were estimated. The overall least-squares means of Age at First Calving (AFC), Service Period (SP) and WP were estimated as 36.69 ± 0.18 months, 120.47 ± 8.98 days and 79.78 ± 3.09 days respectively. Season and period of birth had significant effect (p < 0.01) on AFC. AFC was highest during autumn season of birth followed by summer, winter and rainy. Season and period of calving had significant effect (p < 0.01) on SP and WP of sahiwal cows. The WP for Sahiwal cows was standardized based on four developed predicted model for pregnancy rate 42, 63, 84 and 105 days using all lactation records. The WP for Sahiwal cows were standardized as 42 days. A selection criterion was developed for Sahiwal breeding bulls and young Sahiwal bulls on the basis of EPD of fertility. The genotype has significant effect on expected predicted difference of fertility and some semen parameters like post thaw motility and HOST. AA Genotype of CRISP2 gene revealed better EPD for fertility than EPD of milk yield. AA genotype of CRISP2 gene has higher scrotal circumference than other genotype. For young Sahiwal bulls only AA genotypes were present with similar patterns. So on the basis of association of genotype with seminal traits, EPD of milk yield and EPD for fertility status, AA and AG genotype of CRISP2 gene was better for higher fertility in Sahiwal bulls.

Keywords: expected predicted difference, fertility, sahiwal, waiting period

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Authors: Edi Artono, Budi Tamtomo, Gema Wahyudi Purnama

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The world energy demand increasing extreamly high time by time, including domestic demand. That is impossible to avoid because energy a country demand proportional to surge in the number of residents, economic growth and addition of industrial sector. Domestic Oil and gas conventional reserves depleted naturally while production outcome from reservoir also depleted time to time. In the other hand, new reserve did not discover significantly to replace it all. Many people are investigating to looking for new alternative energy to answer the challenge. There are several option to solve energy fossil needed problem using Unconventional Hydrocarbon. There are four aspects to consider as a management reference in order that Unconventional Hydrocarbon business can work properly, divided to: 1. Legal aspect, 2. Environmental aspect, 3. Technical aspect and 4. Economy aspect. The economic aspect as the key to whether or not a project can be implemented or not in Oil and Gas business scheme, so do Unconventional Hydorcarbon business scheme. The support of regulation are needed to buttress Unconventional Hydorcarbon business grow up and make benefits contribute to Government.

Keywords: alternative energy, unconventional hydrocarbon, regulation support, management strategy

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Authors: Edison Bicudo

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Cell and gene therapies (CGTs) result from the intense manipulation of cells or the use of techniques such as gene editing. They have been increasingly used to tackle rare diseases or conditions of genetic origin, such as cancer. One might expect such a complex scientific field to be dominated by scientific findings and evidence-based explanations. However, people engaged in scientific argumentation also mobilize a range of cognitive operations of which they are not fully aware, in addition to drawing on widely available oral traditions. This paper analyses how experts discussing the potentialities and challenges of CGTs have recourse to a particular kind of prototypical myth. This sociology study, conducted at the University of Sussex (UK), involved interviews with scientists, regulators, and entrepreneurs involved in the development or governance of CGTs. It was observed that these professionals, when voicing their views, sometimes have recourse to narratives where CGTs appear as promising tools for alleviating or curing diseases. This is said to involve much personal, scientific, and financial sacrifice. In his study of traditional narratives, Hogan identified three prototypes: the romantic narrative, moved by the ideal of romantic union; the heroic narrative, moved by the desire for political power; and the sacrificial narrative, where the ideal is plenty, well-being, and health. It is argued here that discourses around CGTs often involve some narratives – or myths – that have a sacrificial nature. In this sense, the development of innovative therapies is depicted as a huge sacrificial endeavor involving biomedical scientists, biotech and pharma companies, and decision-makers. These sacrificial accounts draw on oral traditions and benefit from an emotional intensification that can be easily achieved in stories of serious diseases and physical suffering. Furthermore, these accounts draw on metaphorical understandings where diseases and vectors of diseases are considered enemies or invaders while therapies are framed as shields or protections. In this way, this paper aims to unravel the cognitive underpinnings of contemporary science – and, more specifically, biomedicine – revealing how myths, prototypes, and metaphors are highly operative even when complex reasoning is at stake. At the same time, this paper demonstrates how such hidden cognitive operations underpin the construction of powerful ideological discourses aimed at defending certain ways of developing, disseminating, and governing technologies and therapies.

Keywords: cell and gene therapies, myths, prototypes, metaphors

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Authors: Weaam Aldeeban, Majd Aljamali, Lama A. Youssef

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Background & Objective: Warfarin is considered a problematic drug due to its narrow therapeutic window and wide inter-individual response variations, which are attributed to demographic, environmental, and genetic factors, particularly single nucleotide polymorphism (SNPs) in the genes encoding VKORC1 and CYP2C9 involved in warfarin's mechanism of action and metabolism, respectively. CYP2C9*2rs1799853 and CYP2C9*3rs1057910 alleles are linked to reduced enzyme activity, as carriers of either or both alleles are classified as moderate or slow metabolizers, and therefore exhibit higher sensitivity of warfarin compared with wild type (CYP2C9*1*1). Our study aimed to assess the frequency of *1, *2, and *3 alleles in the CYP2C9 gene in a cohort of Syrian patients receiving a maintenance dose of warfarin for different indications, the impact of genotypes on warfarin dosing, and the frequency of adverse effects (i.e., bleedings). Subjects & Methods: This retrospective cohort study encompassed 94 patients treated with warfarin. Patients’ genotypes were identified by sequencing the polymerase chain reaction (PCR) specific products of the gene encoding CYP2C9, and the effects on warfarin therapeutic outcomes were investigated. Results: Sequencing revealed that 43.6% of the study population has the *2 and/or *3 SNPs. The mean weekly maintenance dose of warfarin was 37.42 ± 15.5 mg for patients with the wild-type allele (CYP2C9*1*1), whereas patients with one or both variants (*2 and/or *3) demanded a significantly lower dose (28.59 ±11.58 mg) of warfarin, (P= 0.015). A higher percentage (40.7%) of patients with allele *2 and/or *3 experienced hemorrhagic accidents compared with only 17.9% of patients with the wild type *1*1, (P = 0.04). Conclusions: Our study proves an association between *2 and *3 genotypes and higher sensitivity to warfarin and a tendency to bleed, which necessitates lowering the dose. These findings emphasize the significance of CYP2C9 genotyping prior to commencing warfarin therapy in order to achieve optimal and faster dose control and to ensure effectiveness and safety.

Keywords: warfarin, CYP2C9, polymorphisms, Syrian, hemorrhage

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Authors: Jae Woong Sull

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Lipid levels are related to the risk of cardiovascular diseases. Cholesterol ester transfer protein (CETP) gene is one of the candidate genes of cardiovascular diseases. A total of 2,304 persons were chosen from a Hospital (N=4,294) in South Korea. Female subjects with the CG/GG genotype had a 2.03 -fold (p=0.0001) higher risk of having abnormal HDL cholesterol levels (<40 mg/dL) than subjects with the CC genotype. Male subjects with the CG/GG genotype had a 1.34 -fold (p=0.0019) higher risk than subjects with the CC genotype. When analyzed by body mass index, the association with CETP was much stronger in male subjects with BMI>=25.69 (OR=1.55, 95% CI: 1.15-2.07, P=0.0037) than in male lean subjects. When analyzed by family history of diabetes, the association with CETP was much stronger in male subjects with positive family history of low physical activity (OR=4.82, 95% CI: 1.86-12.5, P=0.0012) than in male subjects with negative family history of diabetes. This study clearly demonstrates that genetic variants in CETP influence HDL cholesterol levels in Korean adults.

Keywords: CETP, diabetes, obesity, polymorphisms

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Authors: Maryam Zafar, Sajida Rasheed, Imran Hashmi

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Water as an environmental reservoir is reported to act as a habitat and transmission route to microaerophilic bacteria such as Heliobacter pylori. It has been studied that in biofilms are the predominant dwellings for the bacteria to grow in water and protective reservoir for numerous pathogens by protecting them against harsh conditions, such as shear stress, low carbon concentration and less than optimal temperature. In this study, influence of these and many other parameters was studied on H. pylori in stagnant and moving water biofilms both in surface and underground aquatic reservoirs. H. pylori were recovered from pipe of different materials such as Polyvinyl Chloride, Polypropylene and Galvanized iron pipe cross sections from an urban water distribution network. Biofilm swabbed from inner cross section was examined by molecular biology methods coupled with gene sequencing and H. pylori 16S rRNA peptide nucleic acid probe showing positive results for H. pylori presence. Studies showed that pipe material affect growth of biofilm which in turn provide additional survival mechanism for pathogens like H. pylori causing public health concerns.

Keywords: biofilm, gene sequencing, heliobacter pylori, pipe materials

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Authors: Mesfin Angaw Tesfay

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L-xylose is an important intermediate in the pharmaceutical industry, playing a key role in the production of various antiviral and anticancer drugs. Despite its significance, L-xylose is a rare and costly sugar with limited availability in nature. In recent years, enzymatic production methods have garnered considerable attention due to their benefits over conventional chemical synthesis. In this research, a dual enzyme cascade system was developed to synthesize L-xylose from an inexpensive substrate, xylitol. The study involved cloning and co-expressing two key genes: the L-fucose isomerase (L-fucI) gene from Escherichia coli K-12 and the xylitol-4-dehydrogenase (xdh) gene from Pantoea ananatis ATCC 43072 in Escherichia coli. The resulting recombinant cells, engineered with the PET28a-xdh/L-fucI vector, were able to effectively convert xylitol to L-xylose. The system showed optimal performance at 40°C and a pH of 10.0. Moreover, Zn²⁺ (7.5 mM) enhanced the catalytic activity by 1.34 times. This approach yielded 52.2 g/L of L-xylose from an initial 80 g/L xylitol concentration, with a 65% conversion efficiency and a productivity rate of 1.86. The study highlights a practical method for producing L-xylose from xylitol through a co-expression system carrying the L-fucI and xdh genes.

Keywords: l-fucose isomerase, xylitol-4-dehydrogenase, l-xylose, xylitol, co-expression

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Authors: Peter Oyelere, Fernando Zanella

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Corporate governance is one of the most discussed and researched issues in recent times in countries around the world, with different countries developing and adopting different governance structures, models and mechanisms. While the Codes of corporate governance have been weaved into the regulatory fabrics of most countries, it is equally critically important that their mechanisms, procedures and practices be transparent, and be transparently communicated to all stakeholders. The Internet can be a very useful and cost-effective tool for the timely and voluntary communication of corporate governance matters to stakeholders. The current paper details the results of an investigation on the extent of which companies listed in the UAE are using the Internet for communicating corporate governance issues, matters and procedures. We surveyed the websites of companies listed on the two UAE Stock Exchanges – the Abu Dhabi Stock Exchange (ADX) and the Dubai Financial Market (DFM) – to find out their level and nature of usage of the Internet for corporate governance disclosures. Regulatory and policy implications of the results of our investigation, as well as other areas for further studies, are also presented in the paper.

Keywords: corporate governance, internet financial reporting, regulation, transparency, United Arab Emirates

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Authors: Jade Edey, Andrew Bennett, Gareth Hathway

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Nuclear receptor-related 1 protein (also known as Nurr1 or NR4A2) is an orphan nuclear receptor which plays a vital role in the development, survival and maintenance of dopaminergic (DA) neurons particularly in the substantia nigra (SN). Increasing research has investigated Nurr1’s additional role within microglia and astrocytes where it has been suggested to act as a negative regulator of inflammation; potentially offering neuroprotection. Considering both DA neurodegeneration and neuroinflammation are commonly accepted constituents of Parkinson’s Disease (PD), understanding the mechanisms by which Nurr1 regulates inflammatory processes could provide an attractive therapeutic target. Nurr1 regulates inflammation via a transrepressive mechanism possibly dependent upon SUMOylation. In addition, Nurr1 can transactivate numerous genes involved in DA synthesis, such as Tyrosine Hydroxylase (TH). A C-terminal splice variant of Nurr1, Nurr-1a, has been reported in both neuronal and glial cells. However, research into its transcriptional activity is minimal. We employed in vitro methods such as SUMO-Pulldown experiments alongside Luciferase reporter assays to investigate the SUMOylation status and transactivation capabilities of Nurr1 and Nurr-1a respectively. The SUMO-Pulldown assay demonstrated Nurr-1a undergoes significantly more SUMO modification than its full-length variant. Consequently, despite having less transcriptional activation than Nurr1, Nurr1a may play a more prominent role in repression of microglial inflammation. Contrary to published literature we also identified that SUMOylation enhances transcriptional activation by Nurr1 and Nurr1a. SUMOylation-dependent increases in Nurr1 and Nurr1a transcriptional activation were only evident in neuronal SHSY5Y cells but not in HEK293 cells. This research provides novel insight into the regulation of Nurr-1a and indicates differential effects of SUMOylation dependent regulation in neuronal and inflammatory cells.

Keywords: nuclear receptors, Parkinson’s disease, inflammation, transcriptional regulation

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Authors: Yao Huang, Hongjie Yu, Fangrong Xu, Longbiao Cai, Qiqiang He

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The Klotho gene has been found to be involved in cardiovascular health, and epigenetic mechanism has risen as good candidates to understand the role of lifestyle factors in obesity. The aim of this study was to investigate the effect of exercise intervention on the expression and DNA methylation of Klotho gene in high-fat diet induced obese mice. C57BL/6 male mice were fed a normal diet (ND) or a high-fat diet (HFD) for 12 weeks. HFD induced obese mice were divided into secondary group (SED) and exercise group (EX) randomly. The treadmill exercise was performed in EX group for 8 weeks. The expression and DNA methylation of Klotho were evaluated by Western blot, RT-PCR, and Methylation-specific PCR. Results indicated that Klotho protein and mRNA expression were significantly lower in the SED group than those in the ND and EX groups (P<0.01), whereas no significant difference, was found between ND group and EX group (P>0.05). Furthermore, mice in the ND group and SED group showed significantly lower levels of completely methylated Klotho DNA in ND group (0%) and SED group (50%) compared with the EX group (90%), and unmethylated Klotho DNA level in ND group (80%) was significantly higher than those in the SED (0%) and EX (0%) groups. These results suggested that exercise leads to increased Klotho expression and reduced Klotho DNA methylation level in HFD induced obese mice.

Keywords: DNA methylation, exercise intervention, klotho, obese mice

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Authors: Peter Fedichev

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We studied fundamental aspects of aging to develop a mathematical model of gene regulatory network. We show that aging manifests itself as an inherent instability of gene network leading to exponential accumulation of regulatory errors with age. To validate our approach we studied age-dependent omic data such as transcriptomes, metabolomes etc. of different model organisms and humans. We build a computational platform based on our model to identify the targets and biomarkers of aging to design new drugs against aging and age-related diseases. As biomarkers of aging, we choose the rate of aging and the biological age since they completely determine the state of the organism. Since rate of aging rapidly changes in response to an external stress, this kind of biomarker can be useful as a tool for quantitative efficacy assessment of drugs, their combinations, dose optimization, chronic toxicity estimate, personalized therapies selection, clinical endpoints achievement (within clinical research), and death risk assessments. According to our model, we propose a method for targets identification for further interventions against aging and age-related diseases. Being a biotech company, we offer a complete pipeline to develop an anti-aging drug-candidate.

Keywords: aging, longevity, biomarkers, senescence

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