Sulfonamide functionalized amino acid‐based pH ‐ and temperature‐sensitive biodegradable injectable hydrogels: Synthesis, physicochemical characterization and in vivo degradation kinetics

2021 ◽  
Vol 138 (21) ◽  
pp. 50488
Author(s):  
Thai Minh Duy Le ◽  
Vu Viet Linh Nguyen ◽  
Thuy An Trinh ◽  
Ngoc Sinh Pham ◽  
Doo Sung Lee ◽  
...  
1997 ◽  
Vol 110 (7) ◽  
pp. 911-925 ◽  
Author(s):  
J.L. Emtage ◽  
M. Bucci ◽  
J.L. Watkins ◽  
S.R. Wente

Studies of the essential nucleoporin Nup145p have shown that its depletion is coincident with a block in RNA export and that deletion of its amino-terminal domain results in clustering of nuclear pore complexes. To further define the functional domains of Nup145p, we have characterized a panel of nup145 mutants. Deletions from both the amino terminus and the carboxy terminus resulted in temperature sensitive mutants that accumulated polyadenylated RNA in the nucleus at the non-permissive temperature. In addition, these mutants also displayed constitutive clustering of nuclear pore complexes in localized patches of the nuclear envelope. These results suggested that an internal region of Nup145p consisting of amino acids 593–893 is essential for function. Accordingly, when this region was deleted, growth was not supported at any temperature, whereas the region alone was able to complement a null mutation when expressed on a high copy plasmid. Previous studies have suggested that Nup145p is cleaved into two polypeptides of approximately 65 and 80 kDa. Interestingly, our experiments suggest that cleavage occurs in vivo. However, a small internal deletion of 17 amino acid residues that abolished cleavage had no effect on cell growth. Therefore, cleavage is not necessary for Nup145p function. When a sequence harboring the Nup145p cleavage site required for Nup145p cleavage was inserted in a chimeric protein, it was not sufficient for mediating cleavage. Cleavage likely requires a second region from amino acid residues 247–524 in addition to the cleavage site.


2011 ◽  
Vol 96 (2-3) ◽  
pp. 140-143
Author(s):  
Jun Wei ◽  
Zhong-Hua Cao ◽  
Yan Jing ◽  
Zhong-yue zhang

1979 ◽  
Vol 236 (5) ◽  
pp. E514
Author(s):  
W E Mitch ◽  
W Chan

We have reported that branched-chain amino acid transaminase (BATase) activity of isolated rat kidney is stimulated by perfusion with alpha-ketoisocaproate (KL). This study examines the mechanism of this effect in kidney and documents that stimulation occurs in intact skeletal muscle. Increased activity was not attributable to synthesis of enzyme because it occurred in the presence of cycloheximide. The in vivo degradation rate of BATase estimated from sequential measurements of activity following intravenous cycloheximide was longer than 90 min, whereas during in vitro perfusion stimulation could be detected within 5 min. Incubation of supernatant from kidney homogenate with KL stimulated BATase; incubation with alpha-keto-beta-methylvalerate (KI), alpha-ketoisovalerate (KV), leucine (leu), or isovaleryl CoA did not. Perfusion of rat hindquarter with KL increased muscle BATase activity; perfusion with acetoacetate, KI, KV, or leu did not. Again, cycloheximide studies indicated a direct effect of KL on muscle BATase. These findings suggest that alpha-ketoisocaproate can increase BATase activity and thus may be involved in regulation of its activity.


Author(s):  
Muhammad Imran Rahim ◽  
Peter P. Mueller ◽  
Manfred Rohde ◽  
Hansjörg Hauser

Blood ◽  
2008 ◽  
Vol 112 (11) ◽  
pp. 284-284
Author(s):  
Duncan Carradice ◽  
Judith E Layton ◽  
Joan K Heath ◽  
Graham J Lieschke

Abstract Zinc finger and BTB domain containing proteins (BTB-ZF) are transcriptional repressors from a family including members with critical roles in hematopoiesis and oncogenesis (BCL6, PLZF, HIC). In an N-ethyl-N-nitrosourea (ENU) mutagenesis screen for defects in myeloid development, we identified a neutropenic zebrafish mutant with a mutation in zbtb11, a novel BTB-ZF transcription factor, suggesting that zbtb11 is critical for normal neutrophil development. The mutant was found in a gynogenetic haploid ENU screen for defective expression of genes along the developmental pathway from mesoderm to mature neutrophil (deltaC, spi1 and myeloperoxidase/mpx), undertaken to search for novel genetic regulators of myelopoiesis in an unbiased fashion. Since zebrafish are poikilothermic, embryos were screened at 33°C to maximise recovery of temperature dependant alleles; marsanne (man) was one mutant pedigree recovered. man is an early embryonic lethal mutant with normal scl and spi1 expression but markedly reduced numbers of mpx expressing cells. Erythropoiesis is unaffected. Reduced numbers of Sudan Black stained cells demonstrate that man is deficient in neutrophils themselves, not just mpx transcripts. man mutants also develop brain and spinal cord degeneration with hydrocephalus due to apoptosis. man is a temperature sensitive allele i.e. numbers of mpx expressing cells per embryo decrease at higher (restrictive) temperatures and are partially restored at lower (permissive) temperatures: Water temperature Number of mpx expressing cells/embryo (mean ± SD, 48hpf) man/man +/? 22°C 75±15 89±14 28°C 42±10 81±12 33°C 27±11 81±22 Hence man serves as a conditional allele, allowing manipulation of protein function via manipulation of water temperature. man was mapped to a 40kb region on chromosome 6 containing a single gene, zbtb11. Sequencing of man and WT zbtb11 cDNA revealed a missense mutation (346T->A, 116Cys->Ser) affecting a cysteine residue conserved throughout vertebrate evolution. Pedigree analysis proved this substitution was introduced by ENU mutagenesis and segregated absolutely with the man phenotype in 3863 mutant embryos. Genetic tests implicated this zbtb11 mutation as causing the man phenotype, zbtb11 knockdown with an antisense morpholino oligonucleotide recapitulated the mpx deficiency and other features of the man phenotype. Injection of WT but not mutant zbtb11 mRNA into man embryos completely rescued mpx expression (125 +/−38 mpx positive cells per embryo vs. 67+/−35, p<0.001; uninjected WT 109 +/19, mean +/− SD, 48hpf) and all other aspects of the man phenotype. Since the mutant Zbtb11 protein is inactive in this assay, we hypothesise the amino acid substitution in the N-terminus of the protein compromises function. In view of the temperature sensitive nature of man, this may result from an effect on weak bonding, differentially affecting protein structure at permissive vs. restrictive temperatures. Zebrafish zbtb11 encodes a 1146 amino acid protein with a predicted N-terminal BTB (also known as POZ) domain and 12 C-terminal C2H2 (Kruppel-type) zinc fingers. The BTB domain is a highly conserved, approximately 100 amino acid domain, mediating protein-protein interaction and dimerization. The zebrafish protein is approximately 75% identical to mouse and human ZBTB11 across its BTB domain and zinc fingers. ZBTB11 is expressed physiologically in human hematopoietic cells (Ferrari F et al. BMC Genomics. 2007) and mouse embryonic brain (Gray PA et al. Science. 2004). It appears to be over-expressed in K562 CML cells compared to other acute leukemia and lymphoma lines (Su AI et al. PNAS 2002), suggesting a possible role in oncogenesis. The function of mammalian ZBTB11 is unknown and there are no mammalian models of ZBTB11 dysfunction. The rescue of man by WT zbtb11 forms the basis of a bioassay to test modified Zbtb11 proteins, and a whole animal assay for chemical modifiers of Zbtb11 function. Rescue of man with human ZBTB11 is being attempted to assess functional conservation and to provide a heterologous mammalian bioassay. Temperature-shift experiments exploiting the temperature sensitivity of man should define the time-dependant requirement for Zbtb11 during development. man provides a unique reagent with which to advance understanding of Zbtb11 biochemistry and biology in vivo.


2010 ◽  
Vol 9 (2) ◽  
Author(s):  
Tian-Ming Hu ◽  
Zhong-Hua Cao ◽  
Jun Wei ◽  
She-Hui Cao ◽  
Yan Jing ◽  
...  

1984 ◽  
Vol 21 (5) ◽  
pp. 561-582 ◽  
Author(s):  
Masaharu Asano ◽  
Masaru Yoshida ◽  
Isao Kaetsu ◽  
Hidetoshi Yamanaka ◽  
Katsuyuki Nakai ◽  
...  

2016 ◽  
Vol 42 (11) ◽  
pp. 1732-1741 ◽  
Author(s):  
Zhen Li ◽  
Jinxu Cao ◽  
Beibei Hu ◽  
Heran Li ◽  
Hongzhuo Liu ◽  
...  

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