Elucidation of the cellular and molecular mechanisms that maintain mammary epithelial tissue integrity is of broad interest and paramount to the design of more effective treatments for breast cancer. ...Evidence from both in vitro and in vivo experiments suggests that mammary cell differentiation is a hierarchical process originating in an uncommitted stem cell with self-renewal potential. However, analysis of the properties and regulation of mammary stem cells has been limited by a lack of methods for their prospective isolation. Here we report the use of multi-parameter cell sorting and limiting dilution transplant analysis to demonstrate the purification of a rare subset of adult mouse mammary cells that are able individually to regenerate an entire mammary gland within 6 weeks in vivo while simultaneously executing up to ten symmetrical self-renewal divisions. These mammary stem cells are phenotypically distinct from and give rise to mammary epithelial progenitor cells that produce adherent colonies in vitro. The mammary stem cells are also a rapidly cycling population in the normal adult and have molecular features indicative of a basal position in the mammary epithelium.
Celotno besedilo
Dostopno za:
DOBA, IJS, IZUM, KILJ, NUK, PILJ, PNG, SAZU, SIK, UILJ, UKNU, UL, UM, UPUK
In alternative expression analysis by sequencing (ALEXA-seq), we developed a method to analyze massively parallel RNA sequence data to catalog transcripts and assess differential and alternative ...expression of known and predicted mRNA isoforms in cells and tissues. As proof of principle, we used the approach to compare fluorouracil-resistant and -nonresistant human colorectal cancer cell lines. We assessed the sensitivity and specificity of the approach by comparison to exon tiling and splicing microarrays and validated the results with reverse transcription-PCR, quantitative PCR and Sanger sequencing. We observed global disruption of splicing in fluorouracil-resistant cells characterized by expression of new mRNA isoforms resulting from exon skipping, alternative splice site usage and intron retention. Alternative expression annotation databases, source code, a data viewer and other resources to facilitate analysis are available at http://www.alexaplatform.org/alexa_seq/.
A continuous terrestrial succession was recovered from the Songke‐2 (SK‐2) borehole in the Songliao Basin, Northeastern China. This borehole provides a unique material for further research on the ...continental paleoclimate during Cretaceous greenhouse period, following a series of achievements of the Songke‐1 (SK‐1) core. In this study, thorium (Th) logging data were chosen as a paleoclimate proxy to conduct a detailed cyclostratigraphic analysis. The Th series varies quasi‐periodically; power spectra and evolutionary fast Fourier transformation (FFT) analysis reveal significant cycles in the Quantou (K2q), Qingshankou (K2qn), Yaojia (Ky and Nenjiang (K2n) formations. The ratio of cycle wavelengths in these stratigraphic units is approximately 20:5:2:1, corresponding to long orbital eccentricity (405 kyr), short orbital eccentricity (100 kyr), obliquity (37 kyr), and precession cycles (22.5 kyr and 18.4 kyr). The durations of the K2n, K2y, K2qn and K2q are estimated as 6.97, 1.83, 5.30 and 4.52 Myr, respectively, based on the constructed ∼18.62 Myr “floating” astronomical time scale (ATS). Comparison of the durations between the SK‐1 s and SK‐2 boreholes exhibits a slight difference of 0.06 Myr and 0.459 Myr for K2qn and K2y. Nevertheless, our ATS of K2n supports the chronostratigraphic frame constructed by the CA‐ID‐TIMS data of the SK‐1s borehole. This new “floating” ATS provides precise numerical ages for stratigraphic boundaries, biozones and geological events in the Songliao Basin, and can serve as a basis for correlation of strata and events between marine and terrestrial systems.
The cause of mental retardation in one-third to one-half of all affected individuals is unknown. Microscopically detectable chromosomal abnormalities are the most frequently recognized cause, but ...gain or loss of chromosomal segments that are too small to be seen by conventional cytogenetic analysis has been found to be another important cause. Array-based methods offer a practical means of performing a high-resolution survey of the entire genome for submicroscopic copy-number variants. We studied 100 children with idiopathic mental retardation and normal results of standard chromosomal analysis, by use of whole-genome sampling analysis with Affymetrix GeneChip Human Mapping 100K arrays. We found de novo deletions as small as 178 kb in eight cases, de novo duplications as small as 1.1 Mb in two cases, and unsuspected mosaic trisomy 9 in another case. This technology can detect at least twice as many potentially pathogenic de novo copy-number variants as conventional cytogenetic analysis can in people with mental retardation.
A detailed paleomagnetic and rock-magnetic investigation spanning loess L7 to paleosol S8 has been carried out at the Baoji and Xifeng sections. Results of anisotropy of magnetic susceptibility ...confirm that the studied loess-paleosol sediments retain primary sedimentary fabrics. Stepwise thermal demagnetization shows that two well-defined magnetization components can be isolated from both loess and paleosol specimens. A low-temperature component, isolated between 100°C and 200°C, is consistent with the present geomagnetic field direction, and a high-temperature component, isolated between 200-300°C and 620-680°C, includes clearly normal and reversed polarities. Isothermal remanent magnetization and thermomagnetic analyses indicate that characteristic remanent magnetization is mainly carried by magnetite and hematite. The Day plot, together with the stratigraphic variations of rock-magnetic parameters, shows that the uniformity of magnetic mineralogy and grain size fulfills the criteria for relative paleointensity （RPI） studies. RPI records have been constructed using natural remanent magnetization （NRM） intensity after thermal demagnetization at 300°C normalized by low-frequency magnetic susceptibility （NRM 300 /χ）. The results show that the RPI record from the Baoji section, where pedogenesis is quite weak, is compatible with the stacked PISO-1500 paleointensity record, suggesting that it might reflect the paleointensity variation of the geomagnetic field. The RPI record from the Xifeng section, where pedogenesis is rather strong, indicates a clear dissimilarity with the stacked PISO-1500 paleointensity record, implying that it does not reflect the paleointensity variation of the geomagnetic field. Our new results show that the NRM 300 /χ from the strongly pedogenetic paleosols does not completely eliminate the pedogenetic （climatic） influence, so it might be unsuitable for a reliable paleointensity study.
Age structure of dominant plant populations is vital to forecast community dynamics during vegetation restoration. Pennisetum flaccidum, a perennial grass with long rhizomes, is widely distributed in ...the northeast and western regions as well as the Inner Mongolian Plateau of China. In the Kerqin grassland region, P. flaccidum is one of several native plant species that are used to restore coal ash storage pools generated by Coal Power Plants. In 2003, we located three ash storage pools (from here on referred to as 'plots') that differed in age (12, 8, and 5 years old) and contained P. flaccidum. We found that natural colonization had successfully restored these plots, with the average herbaceous cover for all three plots reaching 85%-90%. Sustaining fence to coal ash storage pools of Coal Power Plant is an effective way to vegetation restoration in the arid Kerqin grassland region.
Granulocyte colony-stimulating factor (G-CSF) mediates “emergency” granulopoiesis during infection, a process that is mimicked by clinical G-CSF use, yet we understand little about the intracellular ...signaling cascades that control demand-driven neutrophil production. Using a murine model with conditional deletion of signal transducer and activator of transcription 3 (STAT3) in bone marrow, we investigated the cellular and molecular mechanisms of STAT3 function in the emergency granulopoiesis response to G-CSF administration or infection with Listeria monocytogenes, a pathogen that is restrained by G-CSF signaling in vivo. Our results show that STAT3 deficiency renders hematopoietic progenitor cells and myeloid precursors refractory to the growth-promoting functions of G-CSF or L monocytogenes infection. STAT3 is necessary for accelerating granulocyte cell-cycle progression and maturation in response to G-CSF. STAT3 directly controls G-CSF–dependent expression of CCAAT-enhancer-binding protein β (C/EBPβ), a crucial factor in the emergency granulopoiesis response. Moreover, STAT3 and C/EBPβ coregulate c-Myc through interactions with the c-myc promoter that control the duration of C/EBPα occupancy during demand-driven granulopoiesis. These results place STAT3 as an essential mediator of emergency granulopoiesis by its regulation of transcription factors that direct G-CSF–responsive myeloid progenitor expansion.
DNA methylation is one of the essential epigenetic mechanisms that are closely correlated with the mechanisms underlying cell growth, differentiation and transformation in eukaryotes. Global changes ...in the epigenetic landscape are considered to be a hallmark of cancer. The initiation and progression of cancer are mediated through epigenetic modifications along with genetic alterations. Aberrant methylation of promoter regions is an epigenetic abnormality of the human genome that is highly characteristic of cancer. In this review, we aimed to summarize our current understanding of the alterations in the epigenetic landscape and investigate the potential use of DNA and RNA methylation in effective molecular treatment strategies.
Jatropha curcas L. has attracted worldwide recognitions in recent years, because its seed oil is suitable to substitute for fossil fuels, and it can grow in semi-arid lands. It has been traditionally ...planted in tropical and subtropical regions, but recent mass cultivation as a biofuel crop is still severally restricted by its low seed production, showing that it is necessary to develop high-yielding varieties. In this paper, to reveal genes or genomic regions underlying yield-related traits, the maker-trait association analysis was conducted in a wide collection of Mexican J. curcas accessions, on the basis of 67 simple sequence repeat (SSR) markers and eight retrotransposon-based insertion polymorphisms (RBIP) markers, by using mixed linear model method (MLM). As a result, eight significant marker-trait associations (MTAs) were found within six traits and six markers. Mean phenotypic variation explained by the markers was 0.24, as indicated by R2 value. Among them, the marker JCG0061, that showed significant associations with fruit weight (R2 = 0.4391) and seed yield per plant (R2 = 0.3151), was identified in a previously-reported interspecific quantitative trait loci (QTL) for the female flower number. This suggests that the genomic region linked to JCG0061 is critical for yield-related traits. Our study would contribute to breeding program for biofuel production and development of J. curcas in tropical and subtropical areas with the semi-arid climate.
More than 25% of patients with AML carry no mutations in genes known to be associated with leukemia. Analyses of genomes, transcriptomes, and methylomes of AML samples implicate mutations in ...cytogenetically normal AML and provide insight into the relationships among causative genes.
The molecular pathogenesis of acute myeloid leukemia (AML) has been studied with the use of cytogenetic analysis for more than three decades. Recurrent chromosomal structural variations are well established as diagnostic and prognostic markers, suggesting that acquired genetic abnormalities (i.e., somatic mutations) have an essential role in pathogenesis.
1
,
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However, nearly 50% of AML samples have a normal karyotype, and many of these genomes lack structural abnormalities, even when assessed with high-density comparative genomic hybridization or single-nucleotide polymorphism (SNP) arrays
3
–
5
(see Glossary). Targeted sequencing has identified recurrent mutations in
FLT3, NPM1, KIT, CEBPA,
and
TET2
.
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–
8
Massively parallel . . .
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