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| 2. |
- El-Sayed, Ashraf S. A., et al.
(författare)
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Aspergillus nidulans thermostable arginine deiminase-Dextran conjugates with enhanced molecular stability, proteolytic resistance, pharmacokinetic properties and anticancer activity
- 2019
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Ingår i: Enzyme and microbial technology. - : Elsevier. - 0141-0229 .- 1879-0909. ; 131
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Tidskriftsartikel (refereegranskat)abstract
- The potential anticancer activity of arginine deiminase (ADI) via deimination of L-arginine into citrulline has been extensively verified against various arginine-auxotrophic tumors, however, the higher antigenicity, structural instability and in vivo proteolysis are the major challenges that limit this enzyme from further clinical implementation. Since, this clinically applied enzyme was derived from Mycobacterium spp, thus, searching for ADI from eukaryotic microbes "especially thermophilic fungi" could have a novel biochemical conformational and catalytic properties. Aspergillus nidulans ADI was purified with 5.3 folds, with molecular subunit structure 48 kDa and entire molecular mass 120 kDa, ensuring its homotrimeric identity. The peptide fingerprinting analysis revealing the domain Glu(95)-Gly(96)-Gly(97) as the conserved active site of A. nidulans ADI, with higher proximity to Mycobacterium ADI Glade IV. In an endeavor to fortify the structural stability and anticancer activity of A. nidulans ADI, the enzyme was chemically modified with dextran. The optimal activity of Dextran-ADI conjugates was determined at 0.08:20 M ratio of ADI: Dextran, with an overall increase to ADI molecular subunit mass to (similar to)100 kDa. ADI was conjugated with dextran via the a-amino groups interaction of surface lysine residues of ADI. The resistance of Dextran-ADI conjugate to proteolysis had been increased by 2.5 folds to proteinase K and trypsin, suggesting the shielding of > 50% of ADI surface proteolytic recognition sites. The native and Dextran-ADI conjugates have the same optimum reaction temperature (37 degrees C), reaction pH and pH stability (7.0-8.0) with dependency on K+ ions as a cofactor. Dextran-ADI conjugates exhibited a higher thermal stability by (similar to) 2 folds for all the tested temperatures, ensuring the acquired structural and catalytic stability upon dextran conjugation. Dextran conjugation slightly protect the reactive amino and thiols groups of surface amino acids of ADI from amino acids suicide inhibitors. The affinity of ADI was increased by 5.3 folds to free L-arginine with a dramatic reduction in citrullination of peptidylarginine residues upon dextran conjugation. The anticancer activity of ADI to breast (MCF-7), liver (HepG-2) and colon (HCTB, HT29, DLD1 and LS174 T) cancer cell lines was increased by 1.7 folds with dextran conjugation in vitro. Pharmacokinetically, the half-life time of ADI was increased by 1.7 folds upon dextran conjugation, in vivo. From the biochemical and hematological parameters, ADIs had no signs of toxicity to the experimental animals. In addition to the dramatic reduction of L-arginine in serum, citrulline level was increased by 2.5 folds upon dextran conjugation of ADI. This is first report exploring thermostable ADI from thermophilic A. nidulans with robust structural stability, catalytic efficiency and proteolytic resistance.
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- Eltom, Mohamed A., et al.
(författare)
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Increasing prevalence of type 2 diabetes mellitus and impact of ethnicity in north Sudan
- 2018
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Ingår i: Diabetes Research and Clinical Practice. - : ELSEVIER IRELAND LTD. - 0168-8227 .- 1872-8227. ; 136, s. 93-99
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Tidskriftsartikel (refereegranskat)abstract
- Background: Diabetes mellitus constitutes a global health threat, with increasing burden of disease in low and middle-income countries witnessing ongoing epidemiological transition including Sudan.Aims: To study the prevalence of type 2 diabetes mellitus (T2DM) and prediabetes and determine the relationship to gender, age, waist circumference, body mass index, residence and ethnicity among the adult population in north Sudan.Methods: A cross-sectional, population-based study in Northern State and River Nile State using random multi-stage cluster sampling targeting 5376 participants from 14 localities divided into 60 urban and 40 rural clusters. In each cluster, 60 households were studied. Blood glucose level and anthropometric measurements were recorded and a questionnaire containing demographic data was obtained from each participant.Results: The prevalence of T2DM among participants was 18.7% and prediabetes was 12.9%. Among people living with T2DM, 694(71.0%) were known cases of T2DM, whereas 284 (29.0%) were newly diagnosed cases. The significant associated risk factors for T2DM included urban residence (AOR 1.23, 95% CI 1.09-1.41), age above 60 years (AOR 4.77, 95% CI 4.04-5.63), obese BMI (AOR 1.26, 95% CI 1.03-1.55) and central obesity (AOR 1.39, 95% CI 1.14-1.68). Compared to indigenous population, individuals of Egyptian descents (AOR 1.28, 95% CI 1.04-1.57) and mixed origin (AOR 1.24, 95% CI 1.04-1.48) had increased risk of T2DM.Conclusion: The prevalence of T2DM and prediabetes in north Sudan have increased significantly since 1996 with variations between ethnicities which showed to be an independent risk factor for T2DM. Health authorities are recommended to set plans to meet the health needs of these communities.
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| 4. |
- Meyer, Heather M, et al.
(författare)
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Fluctuations of the transcription factor ATML1 generate the pattern of giant cells in the Arabidopsis sepal
- 2017
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Ingår i: eLife. - 2050-084X.
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Tidskriftsartikel (refereegranskat)abstract
- Multicellular development produces patterns of specialized cell types. Yet, it is often unclear how individual cells within a field of identical cells initiate the patterning process. Using live imaging, quantitative image analyses and modeling, we show that during Arabidopsis thaliana sepal development, fluctuations in the concentration of the transcription factor ATML1 pattern a field of identical epidermal cells to differentiate into giant cells interspersed between smaller cells. We find that ATML1 is expressed in all epidermal cells. However, its level fluctuates in each of these cells. If ATML1 levels surpass a threshold during the G2 phase of the cell cycle, the cell will likely enter a state of endoreduplication and become giant. Otherwise, the cell divides. Our results demonstrate a fluctuation-driven patterning mechanism for how cell fate decisions can be initiated through a random yet tightly regulated process.
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| 5. |
- Tan, B. K., et al.
(författare)
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Investigation of the performance of an SIS mixer with Nb-AlN-NBN tunnel junctions in the 780-950 GHz frequency band
- 2018
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Ingår i: 2018 29th IEEE International Symposium on Space Terahertz Technology, ISSTT 2018. ; , s. 139-142
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Konferensbidrag (refereegranskat)abstract
- In this paper, we present preliminary measured performance of an SIS mixer employing a Nb/AIN/NbN tunnel junction in the frequency range of 780-950 GHz range. The mixer design is an upgrade of the Carbon Heterodyne Array of the Max-Planck-Institute Plus (CHAMP+) mixer, coupled with an easy to fabricate smooth-walled horn. The noise temperature of the mixer is measured using the standard Y-factor method, but all the RF optics is enclosed in the cryostat. We use a rotating mirror in the cryostat to switch between a room temperature load and a 4 K blackbody load. With this method, we have measured a noise temperature of 330 K around 850 GHz, corrected for a mismatch between a reduced height rectangular waveguide at the input of the mixer block and a full height waveguide at the output of the horn. To remove this mismatch we now plan to redesign a new mixer chip with a full-height waveguide back-piece. The expected performance of the new mixer chip is also reported.
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| 6. |
- Willis, Lisa, et al.
(författare)
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Cell size and growth regulation in the Arabidopsis thaliana apical stem cell niche
- 2016
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Ingår i: Proceedings of the National Academy of Sciences of the United States of America. - : Proceedings of the National Academy of Sciences. - 0027-8424. ; 113:51, s. 8238-8246
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Tidskriftsartikel (refereegranskat)abstract
- Cell size and growth kinetics are fundamental cellular properties with important physiological implications. Classical studies on yeast, and recently on bacteria, have identified rules for cell size regulation in single cells, but in the more complex environment of multicellular tissues, data have been lacking. In this study, to characterize cell size and growth regulation in a multicellular context, we developed a 4D imaging pipeline and applied it to track and quantify epidermal cells over 3-4 d in Arabidopsis thaliana shoot apical meristems. We found that a cell size checkpoint is not the trigger for G2/M or cytokinesis, refuting the unexamined assumption that meristematic cells trigger cell cycle phases upon reaching a critical size. Our data also rule out models in which cells undergo G2/M at a fixed time after birth, or by adding a critical size increment between G2/M transitions. Rather, cell size regulation was intermediate between the critical size and critical increment paradigms, meaning that cell size fluctuations decay by ∼75% in one generation compared with 100% (critical size) and 50% (critical increment). Notably, this behavior was independent of local cell-cell contact topologies and of position within the tissue. Cells grew exponentially throughout the first >80% of the cell cycle, but following an asymmetrical division, the small daughter grew at a faster exponential rate than the large daughter, an observation that potentially challenges present models of growth regulation. These growth and division behaviors place strong constraints on quantitative mechanistic descriptions of the cell cycle and growth control.
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| 7. |
- Yassin, M. A., et al.
(författare)
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Surfactant tuning of hydrophilicity of porous degradable copolymer scaffolds promotes cellular proliferation and enhances bone formation
- 2016
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Ingår i: Journal of Biomedical Materials Research. Part A. - : John Wiley & Sons. - 1549-3296 .- 1552-4965.
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Tidskriftsartikel (refereegranskat)abstract
- Poly(l-lactide-co-e(open)-caprolactone) (poly(LLA-co-CL)) has been blended with Tween 80 to tune the material properties and optimize cell-material interactions. Accordingly, the aims of this study were fourfold: to evaluate the effect of low concentrations of Tween 80 on the surface microstructure of 3D poly(LLA-co-CL) porous scaffolds: to determine the effect of different concentrations of Tween 80 on proliferation of bone marrow stromal cells (BMSCs) in vitro under dynamic cell culture at 7 and 21 days; to assess the influence of Tween 80 on the degradation rate of poly(LLA-co-CL) at 7 and 21 days; and in a subcutaneous rat model, to evaluate the effect on bone formation of porous scaffolds modified with 3% Tween 80 at 2 and 8 weeks. Blending 3% (w/w) Tween 80 with poly(LLA-co-CL) improves the surface wettability (p<0.001). Poly(LLA-co-CL)/3% Tween 80 shows significantly increased cellular proliferation at days 7 and 21 (p<0.001). Moreover, the presence of Tween 80 facilitates the degradation of poly(LLA-co-CL). Two weeks post-implantation, the poly(LLA-co-CL)/3% Tween 80 scaffolds exhibit significant mRNA expression of Runx2 (p=0.004). After 8 weeks, poly(LLA-co-CL)/3% Tween 80 scaffolds show significantly increased de novo bone formation, demonstrated by μ-CT (p=0.0133) and confirmed histologically. It can be concluded that blending 3% (w/w) Tween 80 with poly (LLA-co-CL) improves the hydrophilicity and osteogenic potential of the scaffolds.
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