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181.
Salomon Kuizon Kathleen DiMaiuta Marius Walus Edmund C. Jenkins Jr Marisol Kuizon Elizabeth Kida Adam A. Golabek Daniel O. Espinoza Raju K. Pullarkat Mohammed A. Junaid 《PloS one》2010,5(8)
Background
Tripeptidyl aminopeptidase I (TPPI) is a crucial lysosomal enzyme that is deficient in the fatal neurodegenerative disorder called classic late-infantile neuronal ceroid lipofuscinosis (LINCL). It is involved in the catabolism of proteins in the lysosomes. Recent X-ray crystallographic studies have provided insights into the structural/functional aspects of TPPI catalysis, and indicated presence of an octahedrally coordinated Ca2+.Methodology
Purified precursor and mature TPPI were used to study inhibition by NBS and EDTA using biochemical and immunological approaches. Site-directed mutagenesis with confocal imaging technique identified a critical W residue in TPPI activity, and the processing of precursor into mature enzyme.Principal Findings
NBS is a potent inhibitor of the purified TPPI. In mammalian TPPI, W542 is critical for tripeptidyl peptidase activity as well as autocatalysis. Transfection studies have indicated that mutants of the TPPI that harbor residues other than W at position 542 have delayed processing, and are retained in the ER rather than transported to lysosomes. EDTA inhibits the autocatalytic processing of the precursor TPPI.Conclusions/Significance
We propose that W542 and Ca2+ are critical for maintaining the proper tertiary structure of the precursor proprotein as well as the mature TPPI. Additionally, Ca2+ is necessary for the autocatalytic processing of the precursor protein into the mature TPPI. We have identified NBS as a potent TPPI inhibitor, which led in delineating a critical role for W542 residue. Studies with such compounds will prove valuable in identifying the critical residues in the TPPI catalysis and its structure-function analysis. 相似文献182.
A chromosome rearrangement in Neurospora that produces segmental aneuploid progeny containing only part of the nucleolus organizer 总被引:1,自引:0,他引:1
In translocation T(ILVL)OY321 of Neurospora crassa a distal portion of the nucleolus organizer chromosome, including ribosomal DNA sequences and the nucleolus satellite, is interchanged with a long terminal segment of IL. When OY321 is crossed by Normal sequence, one-fourth of the meiotic products are segmental aneuploids that contain two copies of the long IL segment and that are deficient for the distal portion of the organizer. Each such product forms a nucleolus and is viable. The complementary aneuploid products are deficient for the IL segment and are therefore inviable. — In crosses of OY321xOY321, each product is capable of making two nucleoli; nucleoli formed by the separated nucleolus organizer parts usually fuse, but most 8-spored asci contain some nuclei in which two separate nucleoli can be seen. One nucleolus is then terminal on its chromosome while the second is interstitial and somewhat smaller. — In crosses of OY321 x Normal, half of the meiotic products are capable of making two nucleoli. However, only about 15% of 8-spored asci have one or more nuclei containing separate nucleoli. At pachytene and later in prophase I, the single fusion nucleolus is associated with three bivalent chromosome segments. Each nucleus of every ascus contains at least one nucleolus, even in asci where some nuclei display two nucleoli. — Crosses of Aneuploid x Normal are usually semibarren, producing a reduced number of ascospores, some of which are inviable. Some aneuploid cultures become fully fertile by reverting to a quasinormal sequence lacking a satellite. In some crosses of Aneuploid x Normal, individual asci may show at prophase I either complete loss, partial loss, or pycnosis of the translocated IL segment. This observation of pycnosis suggests chromosome inactivation. — Growth from aneuploid ascospores is initially slow, but can accelerate to the wild-type rate. 相似文献
183.
Saket?Chandra Dharmendra?Singh Jyoti?Pathak Supriya?Kumari Manish?Kumar Raju?Poddar Harindra?Singh?Balyan Kumble?Vinod?Prabhu Pushpendra?Kumar?Gupta Kunal?MukhopadhyayEmail authorView authors OrcID profile 《Molecular breeding : new strategies in plant improvement》2017,37(7):92
Single nucleotide polymorphisms (SNPs) are becoming the most amenable form of DNA-based molecular markers for genetic analysis. In hexaploid bread wheat (Triticum aestivum L.), it is difficult to discern true polymorphic SNPs due to homoeologous and paralogous genes. Two serial analysis of gene expression (SAGE) libraries were developed utilizing leaves from resistant plants carrying leaf rust resistance gene Lr28; one library was derived from leaves that were mock inoculated and the other was derived from leaves inoculated with the urediniospores of the leaf rust pathogen Puccinia triticina. Next-generation sequencing reads, after quality trimming and removal of fungal sequences, were mapped to wheat reference sequences at Ensembl Plants. CLC Genomics Workbench and Freebayes softwares were employed for SNP calling. A total of 611 SNPs were predicted to be common by both softwares, of which 207 varietal SNPs were identified by ConservedPrimer software. A subset of 100 SNPs was used for validation across 47 wheat genotypes using Kompetitive Allele Specific PCR (KASP) assay; 83 SNPs could be successfully validated. These SNPs were positioned on wheat subgenomes and chromosome arms. When functionally annotated, many sequences harboring SNPs showed homology to resistance and resistance-like genes listed in Plant Resistance Gene database (PRGdb) as well as pathogenesis-related (PR) and stress-responsive genes. The results of the present study involving discovery of SNPs associated with resistance to leaf rust, a major threat to wheat production worldwide, will be valuable for molecular breeding for rust resistance. 相似文献
184.
An efficient orange–red‐emitting LiNa3P2O7:Sm3+ pyrophosphate: Structural and optical analysis for solid‐state lighting 下载免费PDF全文
G.R. Dillip K. Munirathnam B. Deva Prasad Raju N. John Sushma S.W. Joo 《Luminescence》2017,32(5):772-778
A trivalent rare‐earth ion (Sm3+)‐doped LiNa3P2O7 (LNPO) phosphor was synthesized using a conventional high‐temperature solid‐state reaction route. A predominant orthorhombic phase of LNPO was observed in all X‐ray diffraction patterns. The surface states of the LNPO:Sm phosphor were confirmed by X‐ray photoelectron spectroscopy. Under 401 nm excitation, the Sm‐doped LNPO phosphors showed sharp emission peaks at 563, 600 and 647 nm that are related to the f–f transition of Sm3+ ions. The optimum concentration of Sm3+ (9 mol%) produced Commission Internationale de l'Eclairage chromaticity coordinates, color rendering index and correlated color temperature of (0.564, 0.434), 42 and 1843 K, respectively. 相似文献
185.
Lasing transition at 1.06 μm emission in Nd3+‐doped borate‐based tellurium calcium zinc niobium oxide glasses for high‐power solid‐state lasers 下载免费PDF全文
O. Ravi K. Prasad Rajiv Jain M. Venkataswamy Shivanand Chaurasia B. Deva Prasad Raju 《Luminescence》2017,32(5):688-694
The spectroscopic properties of Tellurium Calcium Zinc Niobium oxide Borate (TCZNB) glasses of composition (in mol%) 10TeO2 + 15CaO + 5ZnO + 10 Nb2O5 + (60 – x)B2O3 + Nd2O3 (x = 0.1, 0.5, 1.0 or 1.5 mol%) have been investigated experimentally. The three phenomenological intensity parameters Ω2, Ω4, Ω6 have been calculated using the Judd–Ofelt theory and in turn radiative properties such as radiative transition probabilities, emission cross‐sections, branching ratios and radiative lifetimes have been estimated. The trend found in the JO intensity parameter is Ω2 > Ω6 > Ω4 If Ω6 > Ω4, the glass system is favourable for the laser emission 4F3/2 → 4I11/2 in the infrared (IR) wavelength. The experimental values of branching ratio of 4F3/2 → 4I11/2 transition indicate favourable lasing action with low threshold power. The evaluated total radiative transition probabilities (AT), stimulated emission cross‐section (σe) and gain bandwidth parameters (σe × Δλp) were compared with earlier reports. An energy level analysis has been carried out considering the experimental energy positions of the absorption and emission bands. 相似文献
186.
Krishnamoorthy Venkateskumar Subramani Parasuraman Raju Gunasunderi Krishnan Sureshkumar M. Muralidhar Nayak Syed Adnan Ali Shah Khassen Khoo Heng Wei Kai 《AAPS PharmSciTech》2017,18(6):2085-2094
The dissolution and subsequent oral bioavailability of acyclovir (ACY) is limited by its poor aqueous solubility. An attempt has been made in this work to provide mechanistic insights into the solubility enhancement and dissolution of ACY by using the water-soluble carrier polyethylene glycol 6000 (PEG6000). Solid dispersions with varying ratios of the drug (ACY) and carrier (PEG6000) were prepared and evaluated by phase solubility, in vitro release studies, kinetic analysis, in situ perfusion, and in vitro permeation studies. Solid state characterization was done by powder X-ray diffraction (XRD), differential scanning calorimetry (DSC), and Fourier transform infrared (FTIR) analysis, and surface morphology was assessed by polarizing microscopic image analysis, scanning electron microscopy, atomic force microscopy, and nuclear magnetic resonance analysis. Thermodynamic parameters indicated the solubilization effect of the carrier. The aqueous solubility and dissolution of ACY was found to be higher in all samples. The findings of XRD, DSC, FTIR and NMR analysis confirmed the formation of solid solution, crystallinity reduction, and the absence of interaction between the drug and carrier. SEM and AFM analysis reports ratified the particle size reduction and change in the surface morphology in samples. The permeation coefficient and amount of ACY diffused were higher in samples in comparison to pure ACY. Stability was found to be higher in dispersions. The results suggest that the study findings provided clear mechanical insights into the solubility and dissolution enhancement of ACY in PEG6000, and such findings could lay the platform for resolving the poor aqueous solubility issues in formulation development. 相似文献
187.
Mohankumar V Dhanushkodi NR Raju R 《Biochemical and biophysical research communications》2011,(2):262-267
Genetically engineered Sindbis viruses (SIN) are excellent oncolytic agents in preclinical models. Several human cancers have aberrant Akt signaling, and kinase inhibitors including rapamycin are currently tested in combination therapies with oncolytic viruses. Therefore, it was of interest to delineate possible cross-regulation between SIN replication and PI3K/Akt/mTOR signaling. Here, using HEK293T cells as host, we report the following key findings: (a) robust SIN replication occurs in the presence of mTOR specific inhibitors, rapamycin and torin1 or Ly294002 – a PI3K inhibitor, suggesting a lack of requirement for PI3K/Akt/mTOR signaling; (b) suppression of phosphorylation of Akt, mTOR and its effectors S6, and 4E-BP1 occurs late during SIN infection: a viral function that may be beneficial in counteracting cellular drug resistance to kinase inhibitors; (c) Ly294002 and SIN act additively to suppress PI3K/Akt/mTOR pathway with little effect on virus release; and (d) SIN replication induces host translational shut off, phosphorylation of eIF2α and apoptosis. This first report on the potent inhibition of Akt/mTOR signaling by SIN replication, bolsters further studies on the development and evaluation of engineered SIN genotypes in vitro and in vivo for unique cytolytic functions. 相似文献
188.
189.
Ternary Cu(II) complexes [Cu(II)(saltrp)(B)] (1,2), (saltrp = salicylidene tryptophan, B = 1,10 phenathroline (1) or 2,2′ bipyridine (2)) were synthesized and characterized. Complex 2 was structurally characterized by single crystal X-ray crystallography. The molecular structure shows a distorted square pyramidal coordination geometry (CuN3O2) in which the ONO donor Schiff base is bonded to the Cu(II) in the basal plane. The N,N donor heterocyclic base displays an axial-equatorial binding mode. CT-DNA binding studies revealed that the complexes show good binding propensity (Intrinsic binding constant, Kb = 3.32 × 105 M−1 for 1 and Kb = 3.10 × 105 M−1 for 2). The catalytic role of these complexes in the oxidative and hydrolytic cleavage of DNA was studied in detail. Complex 1 binds and cleaves DNA more efficiently as compared to 2. From the kinetic experiments, rate constants for the hydrolysis of phosphodiester bond of DNA backbone were determined as 1.94 h−1 and 1.05 h−1 for 1 and 2 respectively. It amounts to (2.93-5.41) × 107 fold rate enhancement compared to uncatalyzed double stranded DNA, which is impressive as compared to related Cu(II) Schiff base complexes. 相似文献
190.
Shah HN Rajakaruna L Ball G Misra R Al-Shahib A Fang M Gharbia SE 《Systematic and applied microbiology》2011,34(1):81-86
Strains (n = 99) of Staphylococcus aureus isolated from a large number of clinical sources and tested for methicillin sensitivity were analysed by MALDI-TOF-MS using the Weak Cation Exchange (CM10) ProteinChip Array (designated SELDI-TOF-MS). The profile data generated was analysed using Artificial Neural Network (ANN) Analysis modelling techniques. Seven key ions identified by the ANNs that were predictive of MRSA and MSSA were validated by incorporation into a model. This model exhibited an area under the ROC curve value of 0.9147 indicating the potential application of this approach for rapidly characterising MRSA and MSSA isolates. Nearly all strains (n = 97) were correctly assigned to the correct group, with only two aberrant MSSA strains being misclassified. However, approximately 21% of the strains appeared to be in a process of transition as resistance to methicillin was being acquired. 相似文献