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61.
62.
Accumulating evidence support the notion that acute myeloid leukemia(AML) is organized in a hierarchical system, originating from a special proportion of leukemia stem cells(LSC). Similar to their normal counterpart, hematopoietic stem cells(HSC), LSC possess selfrenewal capacity and are responsible for the continued growth and proliferation of the bulk of leukemia cells in the blood and bone marrow. It is believed that LSC are also the root cause for the treatment failure and relapse of AML because LSC are often resistant to chemotherapy. In the past decade, we have made significant advancement in identification and understanding the molecular biology of LSC, but it remains a daunting task to specifically targeting LSC, while sparing normalHSC. In this review, we will first provide a historical overview of the discovery of LSC, followed by a summary of identification and separation of LSC by either cell surface markers or functional assays. Next, the review will focus on the current, various strategies for eradicating LSC. Finally, we will highlight future directions and challenges ahead of our ultimate goal for the cure of AML by targeting LSC. 相似文献
63.
E Martinez-Jaramillo R Garza-Morales MJ Loera-Arias O Saucedo-Cardenas R Montes-de-Oca-Luna LR McNally 《Biotechnic & histochemistry》2017,92(3):167-174
Fluorescent proteins are useful reporter molecules for a variety of biological systems. We present an alternative strategy for cloning reporter genes that are regulated by the nisin-controlled gene expression (NICE) system. Lactoccocus lactis was genetically engineered to express green fluorescent protein (GFP), mCherry or near-infrared fluorescent protein (iRFP). The reporter gene sequences were optimized to be expressed by L. lactis using inducible promoter pNis within the pNZ8048 vector. Expression of constructions that carry mCherry or GFP was observed by fluorescence microscopy 2 h after induction with nisin. Expression of iRFP was evaluated at 700 nm using an infrared scanner; cultures induced for 6 h showed greater iRFP expression than non-induced cultures or those expressing GFP. We demonstrated that L. lactis can express efficiently GFP, mCherry and iRFP fluorescent proteins using an inducible expression system. These strains will be useful for live cell imaging studies in vitro or for imaging studies in vivo in the case of iRFP. 相似文献
64.
Alomá Moreno O y MJ Freuler 《Phyton》2015,84(2):466-472
The present study of the Orchidaceae family was carried out in Guamuahaya’s mountain range, from 2000 to March 2013. Fifteen districts were explored after 33 expeditions in the Province of Cienfuegos. Ninety two plant species were identified in the studied area, taking into account the ecological parameters of the mountainous areas of Cienfuegos and Cumanayagua municipalities. 相似文献
65.
Integrins are transmembrane (TM) proteins that mediate bidirectional mechanical signaling between the extracellular matrix and the cellular cytoskeletal network. Each integrin molecule consists of non-covalently associated α- and β-subunits, with each subunit consisting of a large ectodomain, a single-pass TM helix, and a short cytoplasmic tail. Previously we found evidence for a polar interaction (hydrogen bond) in the outer membrane clasp (OMC) of the leukocyte integrin αLβ2 TMs that is absent in the platelet integrin αIIβ3 OMC. Here, we compare the self-assembly dynamics of αLβ2 and αIIβ3 TM helices in a model membrane using coarse-grained molecular dynamics simulations. We found that although αIIβ3 TM helices associate more easily, packing is suboptimal. In contrast, αLβ2 TM helices achieve close-to-optimal packing. This suggests that αLβ2 TM packing is more specific, possibly due to the interhelix hydrogen bond. Theoretical association free energy profiles show a deeper minimum at a smaller helix-helix separation for αLβ2 compared with αIIβ3. The αIIβ3 profile is also more rugged with energetic barriers whereas that of αLβ2 is almost without barriers. Disruption of the interhelix hydrogen bond in αLβ2 via the β2T686G mutation results in poorer association and a similar profile as αIIβ3. The OMC polar interaction in αLβ2 thus plays a significant role in the packing of the TM helices. 相似文献
66.
N6‐methyladenine is the most widespread mRNA modification. A subset of human box C/D snoRNA species have target GAC sequences that lead to formation of N6‐methyladenine at a key trans Hoogsteen‐sugar A·G base pair, of which half are methylated in vivo. The GAC target is conserved only in those that are methylated. Methylation prevents binding of the 15.5‐kDa protein and the induced folding of the RNA. Thus, the assembly of the box C/D snoRNP could in principle be regulated by RNA methylation at its critical first stage. Crystallography reveals that N6‐methylation of adenine prevents the formation of trans Hoogsteen‐sugar A·G base pairs, explaining why the box C/D RNA cannot adopt its kinked conformation. More generally, our data indicate that sheared A·G base pairs (but not Watson–Crick base pairs) are more susceptible to disruption by N6mA methylation and are therefore possible regulatory sites. The human signal recognition particle RNA and many related Alu retrotransposon RNA species are also methylated at N6 of an adenine that forms a sheared base pair with guanine and mediates a key tertiary interaction. 相似文献
67.
Mumtaz Begum Mustafa Siti Salwah Salim Noraini Mohamed Bassam Al-Qatab Chng Eng Siong 《PloS one》2014,9(1)
Automatic speech recognition (ASR) is currently used in many assistive technologies, such as helping individuals with speech impairment in their communication ability. One challenge in ASR for speech-impaired individuals is the difficulty in obtaining a good speech database of impaired speakers for building an effective speech acoustic model. Because there are very few existing databases of impaired speech, which are also limited in size, the obvious solution to build a speech acoustic model of impaired speech is by employing adaptation techniques. However, issues that have not been addressed in existing studies in the area of adaptation for speech impairment are as follows: (1) identifying the most effective adaptation technique for impaired speech; and (2) the use of suitable source models to build an effective impaired-speech acoustic model. This research investigates the above-mentioned two issues on dysarthria, a type of speech impairment affecting millions of people. We applied both unimpaired and impaired speech as the source model with well-known adaptation techniques like the maximum likelihood linear regression (MLLR) and the constrained-MLLR(C-MLLR). The recognition accuracy of each impaired speech acoustic model is measured in terms of word error rate (WER), with further assessments, including phoneme insertion, substitution and deletion rates. Unimpaired speech when combined with limited high-quality speech-impaired data improves performance of ASR systems in recognising severely impaired dysarthric speech. The C-MLLR adaptation technique was also found to be better than MLLR in recognising mildly and moderately impaired speech based on the statistical analysis of the WER. It was found that phoneme substitution was the biggest contributing factor in WER in dysarthric speech for all levels of severity. The results show that the speech acoustic models derived from suitable adaptation techniques improve the performance of ASR systems in recognising impaired speech with limited adaptation data. 相似文献
68.
Intraspecific DNA sequence variation of the mitochondrial control region of white sturgeon (Acipenser transmontanus) 总被引:3,自引:0,他引:3
Intraspecific sequence variation in the D-loop region of mtDNA in white
sturgeon (Acipenser transmontanus), a relict North American fish species,
was examined in 27 individuals from populations of the Columbia and Fraser
rivers. Thirty-three varied nucleotide positions were present in a
462-nucleotide D-loop sequence, amplified using the polymerase chain
reaction. Bootstrapped neighbor-joining and maximum- parsimony trees of
sequences from 19 haplotypes suggest that the two populations have recently
diverged. This is consistent with the hypothesis that the Columbia River, a
Pleistocene refugium habitat, was the source of founders for the Fraser
River after the last glacial recession. On the basis of a divergence time
of 10-12 thousand years ago, the estimated substitution rate of the white
sturgeon D-loop region is 1.1-1.3 x 10(-7) nucleotides/site/year, which is
comparable to rates for hypervariable sequences in the human D-loop region.
Furthermore, the ratio of mean percent nucleotide differences in the D-
loop (2.27%) to that in whole mtDNA (0.54%, as estimated from
restriction-enzyme data) is 4.3, which is similar to the fourfold-to-
fivefold-higher substitution rate estimated for the human D-loop. The high
nucleotide substitution rate of the hypervariable region indicates that the
vertebrate D-loop has potential as a genetic marker in molecular population
studies.
相似文献
69.
Ancient large-scale genome duplications: phylogenetic and linkage analyses shed light on chordate genome evolution 总被引:12,自引:4,他引:8
Pebusque MJ; Coulier F; Birnbaum D; Pontarotti P 《Molecular biology and evolution》1998,15(9):1145-1159
Paralogous genes from several families were found in four human chromosome
regions (4p16, 5q33-35, 8p12-21, and 10q24-26), suggesting that their
common ancestral region underwent several rounds of large- scale
duplication. Searches in the EMBL databases, followed by phylogenetic
analyses, showed that cognates (orthologs) of human duplicated genes can be
found in other vertebrates, including bony fishes. In contrast, within each
family, only one gene showing the same high degree of similarity with all
the duplicated mammalian genes was found in nonvertebrates (echinoderms,
insects, nematodes). This indicates that large-scale duplications occurred
after the echinoderms/chordates split and before the bony vertebrate
radiation. It has been suggested that two rounds of gene duplication
occurred in the vertebrate lineage after the separation of Amphioxus and
craniate (vertebrates + Myxini) ancestors. Before these duplications, the
genes that have led to the families of paralogous genes in vertebrates must
have been physically linked in the craniate ancestor. Linkage of some of
these genes can be found in the Drosophila melanogaster and Caenorhabditis
elegans genomes, suggesting that they were linked in the triploblast
Metazoa ancestor.
相似文献
70.
Endogenous chloride channels of insect sf9 cells. Evidence for coordinated activity of small elementary channel units 总被引:1,自引:0,他引:1
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EH Larsen SE Gabriei MJ Stutts J Fullton EM Price RC Boucher 《The Journal of general physiology》1996,107(6):695-714
The endogenous Cl- conductance of Spodoptera frugiperda (Sf9) cells was studied 20-35 h after plating out of either uninfected cells or cells infected by a baculovirus vector carrying the cloned beta-galactosidase gene (beta-Gal cells). With the cation Tris+ in the pipette and Na+ in the bath, the reversal potential of whole-cell currents was governed by the prevailing Cl- equilibrium potential and could be fitted by the Goldman-Hodgkin-Katz equation with similar permeabilities for uninfected and beta-Gal cells. In the frequency range 0.12 < f < 300 Hz, the power density spectrum of whole-cell Cl- currents could be fitted by three Lorentzians. Independent of membrane potential, >50% of the total variance of whole-cell current fluctuations was accounted for by the low frequency Lorentzian (fc = 0.40 +/- 0.03 Hz, n = 6). Single-Cl- channels showed complex gating kinetics with long lasting (seconds) openings interrupted by similar long closures. In the open state, channels exhibited fast burst-like closures. Since the patches normally contained more than a single channel, it was not possible to measure open and closed dwell-time distributions for comparing single-Cl- channel activity with the kinetic features of whole-cell currents. However, the power density spectrum of Cl- currents of cell-attached and excised outside-out patches contained both high and low frequency Lorentzian components, with the corner frequency of the slow component (fc = 0.40 +/- 0.02 Hz, n = 4) similar to that of whole-cell current fluctuations. Chloride channels exhibited multiple conductance states with similar Goldman-Hodgkin-Katz-type rectification. Single-channel permeabilities covered the range from approximately 0.6.10(-14) cm5/s to approximately 6.10(-14) cm3/s, corresponding to a limiting conductance (gamma 150/150) of approximately 3.5 pS and approximately 35 pS, respectively. All states reversed near the same membrane potential, and they exhibited similar halide ion selectivity, P1 > PCl approximately PBr. Accordingly, Cl- current amplitudes larger than current flow through the smallest channel unit resolved seem to result from simultaneous open/shut events of two or more channel units. 相似文献