• Title/Summary/Keyword: transmembrane

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The proteasome inhibition enhances apoptosis by P53 expression and the dissipation of mitochondrial transmembrane potential in TRAIL-resistant lung cancer cells (Proteasome 억제에 의한 P53의 발현과 미토콘드리아 막 전압의 소실로 TRAIL에 저항하는 폐암세포의 사멸 강화)

  • Seol, Jae-Won;Park, Sang-Youel
    • Korean Journal of Veterinary Research
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    • v.49 no.1
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    • pp.1-8
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    • 2009
  • The ubiquitin-proteasome mediated protein degradation pathway plays an important role in regulating both cell proliferation and cell death. Proteasome inhibitors are well known to induce apoptosis in various human cancer cell lines. We investigated the effect of combined treatment with proteasome inhibitor and TRAIL, and a possible mechanism of the enhancing apoptosis by the both treatment, on TRAIL-resistant non-small cell lung cancer. A549 cells were exposed to the N-Acetyl-Leu-Leu-Norleu-al (ALLN) as a proteasome inhibitor and then treated with recombinant TRAIL protein. In A549 cells under proteasome inhibition conditions by pretreatment with ALLN, TRAIL treatment significantly decreased cell viability compared to that ALLN and TRAIL alone treatment. Also, the both treatment induced cell damage through DNA fragmentation and p53 expression. In addition, the combined treatment of both markedly increased caspase-8 activation, especially the exposure for 2 h, and Bax expression and induced the dissipation of mitochondrial transmembrane potential in A549 cells. Taken together, these findings showed that proteasome inhibition by ALLN enhanced TRAIL-induced apoptosis via DNA degradation by activated P53 and mitochondrial transmembrane potential loss by caspase-8 activation and bax expression. Therefore, our results suggest that proteasome inhibitor may be used a very effectively chemotherapeutic agent for the tumor treatment, especially TRAIL-resistant tumor cell.

Ultrafiltration membranes for drinking-water production from low-quality surface water: A case study in Spain

  • Rojas-Serrano, Fatima;Alvarez-Arroyo, Rocio;Perez, Jorge I.;Plaza, Fidel;Garralon, Gloria;Gomez, Miguel A.
    • Membrane and Water Treatment
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    • v.6 no.1
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    • pp.77-94
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    • 2015
  • Ultrafiltration membranes have several advantages over conventional drinking-water treatment. However, this technology presents major limitations, such as irreversible fouling and low removal of natural organic matter. Fouling depends heavily on the raw-water quality as well as on the operating conditions of the process, including flux, permeate recovery, pre-treatment, chemical cleaning, and backwashing. Starting with the premise that the optimisation of operating variables can improve membrane performance, different experiments were conducted in a pilot plant located in Granada (Spain). Several combinations of permeate and backwashing flow rates, backwashing frequencies, and aeration flow rates were tested for low-quality water coming from Genil River with the following results: the effluent quality did not depend on the combination of operating conditions chosen; and the membrane was effective for the removal of microorganisms, turbidity and suspended solids but the yields for the removal of dissolved organic carbon were extremely low. In addition, the threshold transmembrane pressure (-0.7 bar) was reached within a few hours and it was difficult to recover due to the low efficiency of the chemical cleanings. Moreover, greater transmembrane pressure due to fouling also increased the energy consumption, and it was not possible to lower it without compromising the permeate recovery. Finally, the intensification of aeration contributed positively to lengthening the operation times but again raised energy consumption. In light of these findings, the feasibility of ultrafiltration as a single treatment is questioned for low-quality influents.

Ultrafiltration of oil-in-water emulsion: Analysis of fouling mechanism

  • Chakrabarty, B.;Ghoshal, A.K.;Purkait, M.K.
    • Membrane and Water Treatment
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    • v.1 no.4
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    • pp.297-316
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    • 2010
  • Membrane fouling is one of the major operational concerns of membrane processes which results in loss of productivity. This paper investigates the ultrafiltration (UF) results of synthetic oil-in-water (o/w) emulsion using flat sheets of polysulfone (PSf) membrane synthesized with four different compositions. The aim is to identify the mechanisms responsible for the observed permeate flux reduction with time for different PSf membranes. The experiments were carried out at four transmembrane pressures i.e., 68.9 kPa, 103.4 kPa, 137.9 kPa and 172.4 kPa. Three initial oil concentrations i.e., 75 $mgL^{-1}$, 100 $mgL^{-1}$ and 200 $mgL^{-1}$ were considered. The resistance-in-series (RIS) model was applied to interpret the data and on that basis, the individual resistances were evaluated. The significances of these resistances were studied in relation to parameters, namely, transmembrane pressure and initial oil concentration. The total resistance to permeate flow is found to increase with increase in both transmembrane pressure and initial oil concentration while for higher oil concentration, resistance due to concentration polarization is found to be the prevailing resistance. The applicability of the constant pressure filtration models to the experimental data was also tested to explain the blocking process. The study shows that intermediate pore blocking is the dominant mechanism at the initial period of UF while in the later period, the fouling process is found to approach cake filtration like mechanism. However, the duration of pore blocking mechanism is different for different membranes depending on their morphological and permeation properties.

Differentiation and Characterization of Cystic Fibrosis Transmembrane Conductance Regulator Knockout Human Pluripotent Stem Cells into Salivary Gland Epithelial Progenitors

  • Shuang Yan;Yifei Zhang;Siqi Zhang;Shicheng Wei
    • International Journal of Stem Cells
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    • v.16 no.4
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    • pp.394-405
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    • 2023
  • The differentiation of pluripotent stem cells has been used to study disease mechanisms and development. We previously described a method for differentiating human pluripotent stem cells (hPSCs) into salivary gland epithelial progenitors (SGEPs). Here, cystic fibrosis transmembrane conductance regulator (CFTR) knockout hPSCs were differentiated into SGEPs derived from CFTR knockout hESCs (CF-SGEPs) using the same protocol to investigate whether the hPSC-derived SGEPs can model the characteristics of CF. CF-a disease that affects salivary gland (SG) function-is caused by mutations of the CFTR gene. Firstly, we successfully generated CFTR knockout hPSCs with reduced CFTR protein expression using the CRISPR-Cas9 system. After 16 days of differentiation, the protein expression of CFTR decreased in SGEPs derived from CFTR knockout hESCs (CF-SGEPs). RNA-Seq revealed that multiple genes modulating SG development and function were down-regulated, and positive regulators of inflammation were up-regulated in CF-SGEPs, correlating with the salivary phenotype of CF patients. These results demonstrated that CFTR suppression disrupted the differentiation of hPSC-derived SGEPs, which modeled the SG development of CF patients. In summary, this study not only proved that the hPSC-derived SGEPs could serve as manipulable and readily accessible cell models for the study of SG developmental diseases but also opened up new avenues for the study of the CF mechanism.

Odorant Receptors Containing Conserved Amino Acid Sequences in Transmembrane Domain 7 Display Distinct Expression Patterns in Mammalian Tissues

  • Ryu, Sang Eun;Shim, Tammy;Yi, Ju-Yeon;Kim, So Yeun;Park, Sun Hwa;Kim, Sung Won;Ronnett, Gabriele V.;Moon, Cheil
    • Molecules and Cells
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    • v.40 no.12
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    • pp.954-965
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    • 2017
  • Mammalian genomes are well established, and highly conserved regions within odorant receptors that are unique from other G-protein coupled receptors have been identified. Numerous functional studies have focused on specific conserved amino acids motifs; however, not all conserved motifs have been sufficiently characterized. Here, we identified a highly conserved 18 amino acid sequence motif within transmembrane domain seven (CAS-TM7) which was identified by aligning odorant receptor sequences. Next, we investigated the expression pattern and distribution of this conserved amino acid motif among a broad range of odorant receptors. To examine the localization of odorant receptor proteins, we used a sequence-specific peptide antibody against CAS-TM7 which is specific to odorant receptors across species. The specificity of this peptide antibody in recognizing odorant receptors has been confirmed in a heterologous in vitro system and a rat-based in vivo system. The CAS-TM7 odorant receptors localized with distinct patterns at each region of the olfactory epithelium; septum, endoturbinate and ectoturbinate. To our great interests, we found that the CAS-TM7 odorant receptors are primarily localized to the dorsal region of the olfactory bulb, coinciding with olfactory epithelium-based patterns. Also, these odorant receptors were ectopically expressed in the various non-olfactory tissues in an evolutionary constrained manner between human and rats. This study has characterized the expression patterns of odorant receptors containing particular amino acid motif in transmembrane domain 7, and which led to an intriguing possibility that the conserved motif of odorant receptors can play critical roles in other physiological functions as well as olfaction.

Assesment of Powdered Activated Carbon Effect on PAC+MF Hybrid Membrane Process (분말활성탄(PAC)+막여과(MF) 조합공정에서 PAC의 영향 평가)

  • Kim, Byung S.;Wang, Chang K.;Lim, Jae L.;Kim, Chung H.
    • Journal of Korean Society of Water and Wastewater
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    • v.22 no.5
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    • pp.517-522
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    • 2008
  • This study aims at an assessment of the effectiveness of taste & odor removal and transmembrane pressure changes in a pilot membrane plant(500m3/day) by adding PAC to MF process, and at providing a basis for applying it to the advanced water treatment process. The transmembrane pressure showed, in low turbidity of raw water, a tendency to decrease when PAC was injected at the Flux of 1, $1.5m^3/m^2{\cdot}d$, while it increased in high Flux($1.5m^3/m^2{\cdot}d$) in high turbidity of raw water. in addtion, it is shown that the fouling could be reduced more when PAC is injected together with appropriate amount of coagulant, than when PAC is solely injected. Taste & Odor-causing 2-MIB may not be detected in membrane filtered water, if the amount of PAC injection is increased in accordance with the increasing concentration of 2-MIB. Hence, PAC injection, as a pre-treatment process in MF membrane filtering, is supposed to be a suitable process for reducing fouling as well as for improvement effectiveness of taste & odor treatment.