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101.
Lim NS Kozlov G Chang TC Groover O Siddiqui N Volpon L De Crescenzo G Shyu AB Gehring K 《The Journal of biological chemistry》2006,281(20):14376-14382
The PABC domain is a peptide-binding domain that is specifically found in poly(A)-binding protein (PABP) and a HECT ubiquitin-protein isopeptide ligase (E3) known as HYD (hyperplastic discs), EDD (E3 isolated by differential display), or Rat100. The PABC domain of PABP recruits various regulatory proteins and translation factors to poly(A) mRNAs through binding of a conserved 12-amino acid peptide motif, PAM2 (PABP-interacting motif 2). In contrast, little is known about the specificity or function of the domain from HYD. Here, we used isothermal calorimetry and surface plasmon resonance titrations to show that the PABC domain of HYD binds PAM2 peptides with micromolar affinity. NMR chemical shift perturbations were used to map the peptide-binding site in the PABC domain of HYD. The structural features of binding are very similar to those of the interactions with the domain of PABP, which explains the overlapping peptide specificity and binding affinity. We identified the anti-proliferative Tob proteins as potential binding partners of HYD. This was confirmed by glutathione S-transferase pulldown and immunoprecipitation experiments demonstrating the interaction with full-length Tob2. Altogether, our results point to a role of the PABC domain as a protein-protein interaction domain that brings together the processes of translation, ubiquitin-mediated protein degradation, and cell cycle control. 相似文献
102.
Regulation of immune response is marked by complex interactions among the cells that recognize and present antigens. Antigen presenting cells (APCs), the antigen presenting cell component of the innate immune response plays an important role in effector CD4+ T cell response. Thermal injury and/or superimposed sepsis in rats' leads to suppressed CD4+ T cell functions. We investigated modulations of CD4+ T cell function by APCs (purified non-T cells) from thermally injured and/or septic rats. Rats were subjected to 30% total body surface area scald burn or exposed to 37 degrees C water (Sham burn) and sepsis was induced by cecal-ligation and puncture (CLP) method. At day 3 post-injury animals were sacrificed and CD4+ T cells and APCs from mesenteric lymph nodes (MLN) were obtained using magnetic microbead isolation procedure. APCs from injured rats were co-cultured with sham rat MLN CD4+ T cells and proliferative responses (thymidine incorporation), phenotypic changes (Flow cytometry), IL-2 production (ELISA) and CTLA-4 mRNA (RT-PCR) were determined in naive rat CD4+ T cells. The data indicate that APCs from thermally injured and/or septic rats when co-cultured with CD4+ T cells suppressed CD4+ T cell effector functions. This lack of CD4+ T cell activation was accompanied with altered co-stimulatory molecules, i.e., CD28 and/or CTLA-4 (CD152). In conclusion, our studies indicated that defective APCs from thermally injured and/or septic rats modulate CD4+ T cell functions via changes in co-stimulatory molecules expressed on naive CD4+ T cells. This altered APC: CD4+ T cell interaction leads to suppressed CD4+ T cell activation of healthy animals. 相似文献
103.
Prion protein gene polymorphisms in four goat breeds of Pakistan 总被引:1,自引:0,他引:1
Four different goat breeds (Pak-Angora, Dera Din Panah, Naachi and Teddy) of Pakistan were selected to investigate polymorphism
in the prion protein gene (PrP gene) responsible for scrapie disease resistance in goats. Initially, genotyping of 187 animals
of these four breeds by restriction fragment length polymorphism (RFLP) was done to see the genotype for codon 136 and 154.
All the animals were monomorphic with a genotype of AARR except one animal of Teddy breed having the genotype of AARH. Sequencing
of PrP gene of twenty animals representing these four goat breeds revealed two genotypes PPSSSS and PPSSPS with haplotypes
PSS and PSP of PrP gene at the codon numbers 42, 138, and 240. All four breeds showed both wild type monomorphic sequence
and mutant polymorphic sequences of these codons. The mutants of 42 and 138 codons translate the same amino acids as with
the wild type sequences, while the mutant of codon 240 is responsible for a different amino acid translation i.e., serine
to proline. In short, this study provides preliminary information about alleles and genotypes of PrP gene in four goat breeds
of Pakistan. 相似文献
104.
Kainat Masood Humaira Yasmin Sidra Batool Noshin Ilyas Asia Nosheen Rabia Naz Naeem Khan Muhammad Nadeem Hassan Adil Aldhahrani Fayez Althobaiti 《Saudi Journal of Biological Sciences》2021,28(9):4957-4968
Avian colibacillosis caused by the zoonotic pathogen Escherichia coli is a common bacterial infection that causes major losses in the poultry sector. Extracts of different medicinal plants and antibiotics have been used against poultry bacterial pathogens. However, overuse of antibiotics and extracts against pathogenic strains leads to the proliferation of multi-drug resistant bacteria. Due to their environmentally friendly nature, nanotechnology and beneficial bacterial strains can be used as effective strategies against poultry infections. Green synthesis of zinc oxide nanoparticles (ZnO-NPs) from Eucalyptus globulus leaves was carried out in this study. Their characterization was done by UV–vis spectroscopy, X-ray diffraction (XRD), and Fourier transmission infrared spectroscopy (FT-IR) which confirmed their synthesis, structure, and size. In vitro, antimicrobial activities of plant leaf extract, ZnO-NPs, and plant growth-promoting rhizobacteria (PGPR) were checked against E. coli using well diffusion as well as disc diffusion method. Results proved that the antimicrobial activity of ZnO-NPs and PGPR strains was more enhanced when compared to eucalyptus leaf extract at 36 h. The maximum relative inhibition shown by ZnO-NPs, PGPR strains and eucalyptus leaf extracts was 88%, 67% and 58%, respectively. The effectiveness of ZnO-NPs was also increased with an increase in particle dose and treatment time. The 90 mg/ml of ZnO-NPs was more effective. PGPR strains from all over the tested strains, Pseudomonas sp. (HY8N) exhibited a strong antagonism against the E. coli strain as compared to other PGPR strains used in this study. However, combined application of PGPR (Pseudomonas sp. (HY8N)) and ZnO-NPs augment antagonistic effects and showed maximum 69% antagonism. The study intends to investigate the binding affinity of ZnO-NPs with the suitable receptor of the bacterial pathogen by in silico methods. The binding site conformations showed that the ligand ZnO binds with conserved binding site of penicillin-binding protein 6 (PBP 6) receptor. According to the interactions, ZnO-NPs form the same interaction pattern with respect to other reported ligands, hence it can play a significant role in the inhibition of PBP 6. This research also found that combining ZnO-NPs with Pseudomonas sp. (HY8N) was a novel and effective technique for treating pathogenic bacteria, including multidrug-resistant bacteria. 相似文献
105.
Salinity is one of the most important stresses that hamper agricultural productivity in nearly every part of the world. Enhanced biosynthesis of ethylene in plants under salinity stress is well established. Higher ethylene concentration inhibits root growth and ultimately affects the overall plant growth. Overcoming this ethylene-induced root inhibition is a prerequisite for successful crop production. Recent studies have shown that ethylene level in plants is regulated by a key enzyme 1-aminocyclopropane-1-carboxylicacid (ACC)-deaminase. This enzyme is present in plant growth-promoting bacteria (PGPR) and lowers the ethylene level by metabolizing its precursor ACC into α-ketobutyrate and ammonia (NH3). Inoculation of plants under salinity stress with PGPR having ACC-deaminase activity mitigates the inhibitory effects of salinity on root growth by lowering the ethylene concentration in the plant. This in turn results in prolific root growth, which is beneficial for the uptake of nutrients and maintenance of growth under stressful environment. The present review critically discusses the effects of salinity stress on plant growth with special reference to ethylene production and the effects of rhizobacteria containing ACC-deaminase on crop improvement under salinity stress. It also discusses how much progress has been made in producing transgenic lines of different crops over-expressing the gene encoding ACC-deaminase and how far such transformed lines can tolerate salinity stress. 相似文献
106.
Sadaf J. Gilani Suroor A. Khan Nadeem Siddiqui 《Bioorganic & medicinal chemistry letters》2010,20(16):4762-4765
The significance of this study was to prepare various isoniazid derivatives by introducing the isoniazid core into several molecules to explore the possibilities of some altered biological activities. Series of 6-substituted-1,2,4-triazolo-[3,4-b]-1,3,4-thiadiazole (3a–g) and 1,3,4-oxadiazole (4a–g and 5) derivatives of isoniazid were synthesized in satisfactory yield and pharmacologically evaluated for their anti-inflammatory, analgesic, ulcerogenic, and lipid peroxidation activities by known experimental models. 相似文献
107.
Michael K. Dame Narasimharao Bhagavathula Cohra Mankey Marissa DaSilva Tejaswi Paruchuri Muhammad Nadeem Aslam James Varani 《In vitro cellular & developmental biology. Animal》2010,46(2):114-122
Normal and neoplastic human colon tissue obtained at surgery was used to establish conditions for organ culture. Optimal conditions
included an atmosphere of 5% CO2 and 95% O2; tissue partially submerged with mucosa at the gas interface; and serum-free medium with 1.5 mM Ca2+ and a number of growth supplements. Histological, histochemical, and immunohistochemical features that distinguish normal
and neoplastic tissue were preserved over a 2-d period. With normal tissue, this included the presence of elongated crypts
with small, densely packed cells at the crypt base and mucin-containing goblet cells in the upper portion. Ki67 staining,
for proliferating cells, was confined to the lower third of the crypt, while expression of extracellular calcium-sensing receptor
was seen in the upper third and surface epithelium. E-cadherin and β-catenin were expressed throughout the epithelium and
confined to the cell surface. In tumor tissue, the same disorganized, abnormal glandular structures seen at time zero were
present after 2 d. The majority of cells in these structures were mucin-poor, but occasional goblet cells were seen and mucin
staining was present. Ki67 staining was seen throughout the abnormal epithelium and calcium-sensing receptor expression was
weak and variable. E-cadherin was seen at the cell surface (similar to normal tissue), but in some places, there was diffuse
cytoplasmic staining. Finally, intense cytoplasmic and nuclear β-catenin staining was observed in cultured neoplastic tissue. 相似文献
108.
Modified-release multiple-unit tablets of loratadine and pseudoephedrine hydrochloride with different release profiles were
prepared from the immediate-release pellets comprising the above two drugs and prolonged-release pellets containing only pseudoephedrine
hydrochloride. The immediate-release pellets containing pseudoephedrine hydrochloride alone or in combination with loratadine
were prepared using extrusion–spheronization method. The pellets of pseudoephedrine hydrochloride were coated to prolong the
drug release up to 12 h. Both immediate- and prolonged-release pellets were filled into hard gelatin capsule and also compressed
into tablets using inert tabletting granules of microcrystalline cellulose Ceolus KG-801. The in vitro drug dissolution study conducted using high-performance liquid chromatography method showed that both multiple-unit capsules
and multiple-unit tablets released loratadine completely within a time period of 2 h, whereas the immediate-release portion
of pseudoephedrine hydrochloride was liberated completely within the first 10 min of dissolution study. On the other hand,
the release of pseudoephedrine hydrochloride from the prolonged release coated pellets was prolonged up to 12 hr and followed
zero-order release kinetic. The drug dissolution profiles of multiple-unit tablets and multiple-unit capsules were found to
be closely similar, indicating that the integrity of pellets remained unaffected during the compression process. Moreover,
the friability, hardness, and disintegration time of multiple-unit tablets were found to be within BP specifications. In conclusion,
modified-release pellet-based tablet system for the delivery of loratadine and pseudoephedrine hydrochloride was successfully
developed and evaluated. 相似文献
109.
Ajmal N Riordan CL Cardwell N Nanney LB Shack RB 《Plastic and reconstructive surgery》2003,112(5):1449-54; discussion 1462-3
Capsular contracture remains the most common adverse sequela of aesthetic and reconstructive breast surgery when breast implants are used. Capsulectomy may be technically difficult and can result in damage to the neighboring tissues. The aim of this study was to verify the efficacy of sodium 2-mercaptoethane sulfonate (mesna) as a facilitator of periprosthetic dissection when instilled locally at the time of capsulectomy. Two 40-cc textured saline implants were placed dorsally into each of 20 rabbits. After 5 months, capsulectomy was performed after the removal of the implants. Mesna was used to highlight the junction between scar and normal tissue and to help separate the tissues during the capsulectomy in one of the two capsules in each rabbit. Saline was used for the same purpose in the other. The blood loss, duration of operation, and difficulty of dissection as experienced by the surgeon were recorded during the course of the operation. The capsules were also examined histologically for their thickness and graded according to their degree of intactness at the conclusion of the procedure. The histological grading based on the intactness of the removed capsule (p = 0.005), the operating time (p = 0.003), and the subjective evaluation of the difficulty of the procedure (p = 0.003) were significantly better in the mesna group. There was no significant difference in the blood loss between the two groups. Because of its ability as a chemical dissector, mesna may be a useful aid in capsulectomy. Clinical studies to confirm this evidence are required. 相似文献
110.