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101.
Monroe-Augustus M Ramón NM Ratzel SE Lingard MJ Christensen SE Murali C Bartel B 《Plant molecular biology》2011,77(1-2):1-15
Mutations in peroxisome biogenesis proteins (peroxins) can lead to developmental deficiencies in various eukaryotes. PEX14 and PEX13 are peroxins involved in docking cargo-receptor complexes at the peroxisomal membrane, thus aiding in the transport of the cargo into the peroxisomal matrix. Genetic screens have revealed numerous Arabidopsis thaliana peroxins acting in peroxisomal matrix protein import; the viable alleles isolated through these screens are generally partial loss-of-function alleles, whereas null mutations that disrupt delivery of matrix proteins to peroxisomes can confer embryonic lethality. In this study, we used forward and reverse genetics in Arabidopsis to isolate four pex14 alleles. We found that all four alleles conferred reduced PEX14 mRNA levels and displayed physiological and molecular defects suggesting reduced but not abolished peroxisomal matrix protein import. The least severe pex14 allele, pex14-3, accumulated low levels of a C-terminally truncated PEX14 product that retained partial function. Surprisingly, even the severe pex14-2 allele, which lacked detectable PEX14 mRNA and PEX14 protein, was viable, fertile, and displayed residual peroxisome matrix protein import. As pex14 plants matured, import improved. Together, our data indicate that PEX14 facilitates, but is not essential for peroxisomal matrix protein import in plants. 相似文献
102.
In vitro models based on embryonic stem cells (ESC) are highly promising for improvement of predictive toxicology screening in humans. After the successful validation of embryonic stem cell test (EST) in 2001; concerns have been raised on the usage of mouse ESC and also the morphological evaluation of beating cell clusters. This requires specialized skill-sets and is highly prone to misjudgement and false positive results. To overcome these limitations, we undertook the present study incorporating improvisations over the conventional EST. Here, we explored the potential of a human ESC (hESC)-based assay to evaluate the potential toxicity of penicillin-G, caffeine, and hydroxyurea. Drug treatment inhibited hESC adhesion and substantially altered the morphology and viability (~ 50%) of embryoid bodies (EBs). Flow cytometry analysis not only showed a significant increase of apoptotic cells in the highest doses but also induced a diverse pattern in DNA content and cell cycle distribution relative to control. Both semi-quantitative and quantitative RT-PCR studies revealed a selective down regulation of markers associated with stemness (Nanog, Rex1, SOX-2, and hTERT); cardiac mesoderm (Cripto1, MEF-2C, and Brachyury); hepatic endoderm (AFP, HNF-3β, HNF-4α, GATA-4, and SOX-17); and neuroectoderm (Nestin, SOX-1, NURR1, NEFH, Synaptophysin, TH, and Olig2) in a drug as well as dose dependent manner indicating abnormal differentiation. Furthermore, a decrease in the expression of AFP and GFAP proteins followed by a dose-dependent reduction in the levels of hCG-β, progesterone-II, and estradiol hormones was demonstrated by immunocytochemistry and ECLIA, respectively. This new and unique approach comprising of DNA cell cycle analysis, germ layer-specific marker expression and hormone levels as endpoints might offer a clinically relevant and commercially viable alternative for predicting in vivo developmental toxicity. 相似文献
103.
Pitts WJ Guo J Dhar TG Shen Z Gu HH Watterson SH Bednarz MS Chen BC Barrish JC Bassolino D Cheney D Fleener CA Rouleau KA Hollenbaugh DL Iwanowicz EJ 《Bioorganic & medicinal chemistry letters》2002,12(16):2137-2140
A series of novel triazine-based small molecule inhibitors (IV) of inosine monophosphate dehydrogenase was prepared. The synthesis and the structure-activity relationships (SAR) derived from in vitro studies are described. 相似文献
104.
Prabhu AD Karim RA Thazhkuni IE Rajendran S Thamaran RA Vellachamy KA Sridharan V Vettath MP 《Innovations (Philadelphia, Pa.)》2007,2(4):213-214
SUMMARY:: Suprahepatic inferior vena caval (IVC) injuries are rare but carry nearly a 100% mortality rate. The main problem with its surgical management is the technical difficulty in draining the IVC during cardiopulmonary bypass. In this report, an efficient method of IVC drainage for repair of the IVC on cardiopulmonary bypass is described. 相似文献
105.
R. Nagaraja Reddy R. Madhusudhana S. Murali Mohan D. V. N. Chakravarthi N. Seetharama 《Molecular breeding : new strategies in plant improvement》2012,29(3):543-564
Molecular variation within known genes controlling specific functions provide candidate gene-based markers which are tightly
linked with the trait of interest. Unigene-derived microsatellite markers, with their unique identity and positions, offer
the advantage of unraveling variation in the expressed component of the genome. We characterized ≥12-bp-long microsatellite
loci from 13,899 unique sequences of sorghum [Sorghum bicolor (L.) Moench] available in the NCBI unigene database for their abundance and possible use in sorghum breeding. Analysis of
12,464 unigenes (≥200-bp) using MISA software identified 14,082 simple sequence repeats (SSRs) in 7,370 unigenes, from which
1,519 unigene SSR markers were developed. The average frequency of SSR was 1 per1.6 kb and 1.0 per 1.1 unigene; hexamers followed
by trimers were found in abundance, of which 33.3% AT-rich and CCG repeats were the most abundant. Of the 302 unigene SSRs
tested, 60 (19.8%) were polymorphic between the two parents, M35-1 and B35 of a recombinant inbred line (RIL) mapping population.
A mapping population consisting of 500 RILs was developed using the above two parents, and a subset of random 245 RILs was
used for genotyping with polymorphic SSRs. We developed a linkage map containing 231 markers, of which 228 (174 genomic and
54 genic) were microsatellites and three were morphological markers. Markers were distributed over 21 linkage groups, and
spanned a genetic distance of 1235.5 cM. This map includes 81 new SSRs, of which 35 (21 unigene and 14 genomic) were developed
in the present study and 46 from other studies. The order of the SSR markers mapped in the present study was confirmed physically
by BLAST search against the whole-genome shotgun sequence of sorghum. Many unigene sequences used for marker development in
this study include genes coding for important regulatory proteins and functional proteins that are involved in stress-related
metabolism. The unigene SSR markers used together with other SSR markers to construct the sorghum genetic map will have applications
in studies on comparative mapping, functional diversity analysis and association mapping, and for quantitative trait loci
detection for drought and other agronomically important traits in sorghum. 相似文献
106.
The causal link between disparate tropomyosin (Tm) functions and the structural instability in Tm is unknown. To test the hypothesis that the structural instability in the central region of Tm modulates the function of the overlapping ends of contiguous Tm dimers, we used transgenic mice (TmDM) that expressed a mutant α-Tm in the heart; S229E and H276N substitutions induce structural instability in the central region and the overlapping ends of Tm, respectively. In addition, two mouse cardiac troponin T mutants (TnT1–44Δ and TnT45–74Δ) that have a divergent effect on the overlapping ends of Tm were employed. The S229E-induced instability in the central region of TmDM altered the overlapping ends of TmDM, thereby it negated the attenuating effect of H276N on Ca2+-activated maximal tension. The rate of cross-bridge detachment (g) decreased in TmDM+TnTWT and TmH276N+TnTWT fibers but increased in TmDM+TnT45–74Δ fibers; however, TnT45–74Δ did not alter g, demonstrating that S229E in TmDM had divergent effects on g. The S229E substitution in TmDM ablated the H276N-induced desensitization of myofilament Ca2+ sensitivity in TmDM+TnT1–44Δ fibers. To our knowledge, novel findings from this study show that the structural instability in the central region of Tm modifies cardiac contractile function via its effect on the overlapping ends of contiguous Tm. 相似文献
107.
108.
Bacillus cereus, Bacillus thuringiensis and Bacillus anthracis are the major concerns for the food safety in terms of frequency and/or seriousness of the disease. Being members of the
same group and sharing DNA homology to a larger extent, they do create problems when their specific detection/identification
is attempted from different food and environmental sources. Numerous individual polymerase chain reaction (PCR) and few multiplex
PCR (mPCR) methods have been employed to detect these organisms by targeting toxin genes but with lack of internal amplification
control (IAC). Therefore, we attempted a mPCR with IAC for the detection of enterotoxic B. cereus group strains by selecting hbl A, nhe A and cyt K genes from B. cereus, indicative of the diarrheal potential and cry I A and pag genes, the plasmid borne phenotypic markers specific to B. thuringiensis and B. anthracis strains, respectively. Multiplex PCR assay validation was performed by simultaneous comparison with the results of single-target
PCR assays and correlated to the classical conventional and biochemical identification of the organisms. The mPCR was able
to detect as low as 101–102 organisms per ml following overnight enrichment of spiked food samples (vegetable biriyani and milk) in buffered peptone
water (BPW). The presence of these organisms could also be detected by mPCR in naturally contaminated samples of rice based
dishes and milk. The high throughput and cost-effective mPCR method described could provide a powerful tool for simultaneous,
rapid and reliable detection of enterotoxic B. cereus group organisms. 相似文献
109.
Murali K. Ravoori Masato Nishimura Sheela P. Singh Chunhua Lu Lin Han Brian P. Hobbs Sunila Pradeep Hyun J. Choi James A. Bankson Anil K. Sood Vikas Kundra 《PloS one》2015,10(6)
Purpose
To assess whether T1 relaxation time of tumors may be used to assess response to bevacizumab anti-angiogenic therapy. Procedures: 12 female nude mice bearing subcutaneous SKOV3ip1-LC ovarian tumors were administered bevacizumab (6.25ug/g, n=6) or PBS (control, n=6) therapy twice a week for two weeks. T1 maps of tumors were generated before, two days, and 2 weeks after initiating therapy. Tumor weight was assessed by MR and at necropsy. Histology for microvessel density, proliferation, and apoptosis was performed.Results
Bevacizumab treatment resulted in tumor growth inhibition (p<0.04, n=6), confirming therapeutic efficacy. Tumor T1 relaxation times increased in bevacizumab treated mice 2 days and 2 weeks after initiating therapy (p<.05, n=6). Microvessel density decreased 59% and cell proliferation (Ki67+) decreased 50% in the bevacizumab treatment group (p<.001, n=6), but not apoptosis.Conclusions
Findings suggest that increased tumor T1 relaxation time is associated with response to bevacizumab therapy in ovarian cancer model and might serve as an early indicator of response. 相似文献110.