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Li Liu

Publications and source records attributed to Li Liu.

At least 37 records · Page 2Linked to original sources
PubMed2025

Characterization of oncohistone H2B variants in Schizosaccharomyces pombe reveals a key role of H2B monoubiquitination deficiency in genomic instability by altering gene expression.

Various amino acid substitutions commonly occur at one residue of a histone in human cancers, but it remains unclear whether these histone variants have distinct oncogenic effects and mechanisms. Our previous modeling study in the fission yeast Schizosaccharomyces pombe demonstrated that the oncohistone mutants H2BG52D, H2BD67N, and H2BP102L cause the homologous recombination defects and genomic instability by compromising H2B monoubiquitination (H2Bub). However, it is unknown whether other amino acid changes at the H2B-Gly52/Asp67/Pro102 residues influence H2Bub levels and whether they cause genomic instability by altering H2Bub-regulated gene expression. Here, we construct diverse oncomutants at the sole H2B gene htb1-Gly52/Asp67/Pro102 sites in S. pombe and study their impacts on genotoxic response, H2Bub levels, and gene expression. Interestingly, the oncomutants htb1-G52D, htb1-D67N, and htb1-P102L exclusively exhibit significant genotoxic sensitivity, reduced H2Bub levels, and altered gene expression. These defects can be rescued by restoring H2Bub levels with the deletion of the H2B deubiquitinase ubp8+. These strong genetic correlations suggest that H2Bub deficiency plays a determinant role in the genomic instability of htb1-Gly52/Asp67/Pro102 oncomutants and that the alteration of gene expression due to reduced H2Bub levels is a novel mechanism underlying the genomic instability caused by htb1-G52D, htb1-D67N, and htb1-P102L oncomutations.

Schizosaccharomyces↗
PubMed2025

Systematic comparison of quantity and quality of RNA recovered with commercial FFPE tissue extraction kits.

BACKGROUND: FFPE tissue samples are commonly used in biomedical research and are a valuable source for next-generation sequencing in oncology, however, extracting RNA from these samples can be difficult the quantity and quality achieved can impact the downstream analysis. This study compared the effectiveness of seven different commercially available RNA extraction kits specifically designed for use with FFPE samples in terms of the quantity and quality of RNA recovered. METHODS: This study used 9 samples of FFPE tissue from three different types of tissue (Tonsil, Appendix and lymph node of B-cell lymphoma) to evaluate RNA extraction methods. Three sections of 20 µm of each sample were combined per sample. The slices were distributed in a systematic manner to prevent any biases. Each of the 7 commercially available RNA extraction kits were used according to manufacturer's instructions, with each sample being tested in triplicate resulting in a total of 189 extractions. The concentration, RNA quality score (RQS) and DV200 of each extraction was analysed using a nucleic acid analyser to determine the quantity and quality of the recovered RNA. RESULTS: This study found that despite processing the FFPE samples in the same standardized way, there were disparities in the quantity and quality of RNA recovered across the different tissue types. Additionally, the study found notable differences in the quantity of RNA recovered when using different extraction kits. In terms of quality, three of the kits performed better than the other four in terms of RQS and DV200 values. CONCLUSION: Though many laboratories have developed their own protocols for specific tissue types, using commercially available kits is still a popular option. Although these kits use similar processes and extraction procedures, the amount and quality of RNA obtained can vary greatly between kits. In this study, among the kits tested, while the Roche kit, provided a nearly systematic better-quality recovery than other kits, the ReliaPrep FFPE Total RNA miniprep from Promega yielded the best ratio of both quantity and quality on the tested tissue samples.

Paraffin Embedding↗
PubMed2024

Maternal COVID-19 infection associated with offspring neurodevelopmental disorders.

Maternal COVID-19 infection increases the incidence of neurodevelopmental disorders (NDDs) in offspring, although the underlying mechanisms have not been elucidated. This study demonstrated that COVID-19 infection during pregnancy disrupted the balance of maternal and fetal immune environments, driving alterations in astrocytes, endothelial cells, and excitatory neurons. A risk score was established using 47 unique genes in the single-cell transcriptome of gestational mothers. The high risk score in CD4 proliferating T cell level served as an indicator for increased risk of offspring NDDs. Summary-based Mendelian randomization and phenome-wide association study analyses were conducted to identify the causal association of the transcriptional changes with the increased risk of offspring NDDs. Additionally, 10 drugs were identified as potential therapeutic candidates. Our findings support a model where the maternal COVID-19 infection changed the levels of CD4 proliferating T cells, leading to the alterations of astrocytes, endothelial cells, and excitatory neurons in offspring, contributing to the increased risk of NDDs in these individuals.

Humans↗
PubMed2024

Genome-wide screening and functional validation of methylation barriers near promoters.

CpG islands near promoters are normally unmethylated despite being surrounded by densely methylated regions. Aberrant hypermethylation of these CpG islands has been associated with the development of various human diseases. Although local genetic elements have been speculated to play a role in protecting promoters from methylation, only a limited number of methylation barriers have been identified. In this study, we conducted an integrated computational and experimental investigation of colorectal cancer methylomes. Our study revealed 610 genes with disrupted methylation barriers. Genomic sequences of these barriers shared a common 41-bp sequence motif (MB-41) that displayed homology to the chicken HS4 methylation barrier. Using the CDKN2A (P16) tumor suppressor gene promoter, we validated the protective function of MB-41 and showed that loss of such protection led to aberrant hypermethylation. Our findings highlight a novel sequence signature of cis-acting methylation barriers in the human genome that safeguard promoters from silencing.

Animals↗
PubMed2024

Metagenome reveals the possible mechanism that microbial strains promote methanogenesis during anaerobic digestion of food waste.

For better understanding the mechanism of microbial strains promoting methane production, four strains Hungatella xylanolytica A5, Bacillus licheniformis B1, Paraclostridium benzoelyticum C2 and Advenella faeciporci E1 were inoculated into anaerobic digestion systems. After bioaugmentation, the cumulative methane production of A5, B1, C2 and E1 groups elevated by 11.68%, 8.20%, 18.21% and 15.67% compared to CK group, respectively. The metagenomic analysis revealed that the species diversity and uniformity of the experimental groups was improved, and hydrolytic acidifying bacteria, represented by Clostridiaceae, Anaerolineaceae and Oscillospiraceae, and methanogens, such as Methanotrichaceae and Methanobacteriaceae, were enriched. Meanwhile, the abundance of key genes in carbohydrate, pyruvate and methane metabolism was increased in the inoculated groups, providing reasonable reasons for more methane production. The strengthening mechanism of microbial strains in this study offered a theoretical foundation for selecting a suitable bioaugmentation strategy to solve the problems of slow start-up and low methane production in anaerobic digestion.

Methane↗
PubMed2007

Plants and people from the Early Neolithic to Shang periods in North China.

An assemblage of charred plant remains collected from 26 sites in the Yiluo valley of North China as part of an archaeological survey spans the period from the sixth millennium to 1300 calibrated calendrical years (cal) B.C. The plant remains document a long sequence of crops, weeds, and other plants in the country. The results also demonstrate the effectiveness of sediment sampling as part of an archaeological survey. Ten accelerator mass spectrometer (AMS) radiocarbon dates on crop remains inform an assessment of the sequence of agricultural development in the region. Foxtail millet (Setaria italica subsp. italica) was grown during the Early Neolithic period and was the principal crop for at least four millennia. Broomcorn millet (Panicum miliaceum) was significantly less important throughout the sequence. Rice (Oryza sativa) was introduced by 3000 cal B.C. but apparently was not an important local crop. Wheat became a significant crop between 1600 and 1300 cal B.C. The weed flora diversified through time and were dominated by annual grasses, some of which were probably fodder for domesticated animals. The North China farming tradition that emphasized dry crops (millets, wheat, and legumes) with some rice appears to have been established at the latest by the Early Shang (Erligang; 1600-1300 B.C.) period.

Agriculture↗
PubMed2007

Prostaglandin F2alpha inhibits adipocyte differentiation via a G alpha q-calcium-calcineurin-dependent signaling pathway.

Prostaglandin F2alpha (PGF2alpha) is a potent physiological inhibitor of adipocyte differentiation, however the specific signaling pathways and molecular mechanisms involved in mediating its anti-adipogenic effects are not well understood. In the current study, we now provide evidence that PGF2alpha inhibits adipocyte differentiation via a signaling pathway that requires heterotrimeric G-protein G alpha q subunits, the elevation of the intracellular calcium concentration ([Ca2+]i), and the activation of the Ca2+/calmodulin-regulated serine/threonine phosphatase calcineurin. We show that while this pathway acts to inhibit an early step in the adipogenic cascade, it does not interfere with the initial mitotic clonal expansion phase of adipogenesis, nor does it affect either the expression, DNA binding activity or differentiation-induced phosphorylation of the early transcription factor C/EBPbeta. Instead, we find that PGF2alpha inhibits adipocyte differentiation via a calcineurin-dependent mechanism that acts to prevent the expression of the critical pro-adipogenic transcription factors PPARgamma and C/EBPalpha. Furthermore, we demonstrate that the inhibitory effects of PGF2alpha on both the expression of PPARgamma and C/EBPalpha and subsequent adipogenesis can be attenuated by treatment of preadipocytes with the histone deacetylase (HDAC) inhibitor trichostatin A. Taken together, these results indicate that PGF2alpha inhibits adipocyte differentiation via a G alpha q-Ca2+-calcineurin-dependent signaling pathway that acts to block expression of PPARgamma and C/EBPalpha by a mechanism that appears to involves an HDAC-sensitive step.

3T3-L1 Cells↗
PubMed2007

Acquired ADAMTS-13 deficiency in pediatric patients with severe sepsis.

We studied the state of ultra-large von Willebrand factor (ULVWF) proteolysis in 21 pediatric patients with severe sepsis and found that the overall group of patients had moderately reduced ADAMTS-13 activity, but 31% had severe enzymatic deficiency. The severe deficiency correlated with greater adhesion activity of von Willebrand factor, severity of thrombocytopenia and plasma levels of interleukin-6. It also correlated clinically with severity of illness and organ dysfunction. These results suggest that ULVWF proteolysis is insufficient in septic patients and severely deficient in a subgroup of patients. The deficiency may contribute to the development of thrombocytopenia and ischemic organ failure associated with sepsis.

ADAM Proteins↗
PubMed2006

Neuronal transcriptome of Aplysia: neuronal compartments and circuitry.

Molecular analyses of Aplysia, a well-established model organism for cellular and systems neural science, have been seriously handicapped by a lack of adequate genomic information. By sequencing cDNA libraries from the central nervous system (CNS), we have identified over 175,000 expressed sequence tags (ESTs), of which 19,814 are unique neuronal gene products and represent 50%-70% of the total Aplysia neuronal transcriptome. We have characterized the transcriptome at three levels: (1) the central nervous system, (2) the elementary components of a simple behavior: the gill-withdrawal reflex-by analyzing sensory, motor, and serotonergic modulatory neurons, and (3) processes of individual neurons. In addition to increasing the amount of available gene sequences of Aplysia by two orders of magnitude, this collection represents the largest database available for any member of the Lophotrochozoa and therefore provides additional insights into evolutionary strategies used by this highly successful diversified lineage, one of the three proposed superclades of bilateral animals.

Animals↗
PubMed2006

Evidence of the existence of the low-density liquid phase in supercooled, confined water.

By confining water in a nanoporous structure so narrow that the liquid could not freeze, it is possible to study properties of this previously undescribed system well below its homogeneous nucleation temperature TH = 231 K. Using this trick, we were able to study, by means of a Fourier transform infrared spectroscopy, vibrational spectra (HOH bending and OH-stretching modes) of deeply supercooled water in the temperature range 183 < T < 273 K. We observed, upon decreasing temperature, the building up of a new population of hydrogen-bonded oscillators centered around 3,120 cm(-1), the contribution of which progressively dominates the spectra as one enters into the deeply supercooled regime. We determined that the fractional weight of this spectral component reaches 50% just at the temperature, TL approximately 225 K, where the confined water shows a fragile-to-strong dynamic cross-over phenomenon [Ito, K., Moynihan, C. T., Angell, C. A. (1999) Nature 398:492-494]. Furthermore, the fact that the corresponding OH stretching spectral peak position of the low-density-amorphous solid water occurs exactly at 3,120 cm(-1) [Sivakumar, T. C., Rice, S. A., Sceats, M. G. (1978) J. Chem. Phys. 69:3468-3476.] strongly suggests that these oscillators originate from existence of the low-density-liquid phase derived from the occurrence of the first-order liquid-liquid (LL) phase transition and the associated LL critical point in supercooled water proposed earlier by a computer molecular dynamics simulation [Poole, P. H., Sciortino, F., Essmann, U., Stanley, H. E. (1992) Nature 360:324-328].

Journal Article↗
PubMed2006

Catalytic and highly enantioselective Friedel-Crafts alkylation of aromatic ethers with trifluoropyruvate under solvent-free conditions.

[Structure: see text] Highly enantioselective Friedel-Crafts alkylation of simple and aromatic ethers (4a-l) with 3,3,3-trifluoropyruvate (3) was accomplished by using chiral (4R,5S)-DiPh-BOX(1b)-Cu(OTf)2 complex (1 mol %) as a catalyst under solvent-free conditions. Excellent yields and enantioselectivities (90-93% ee, after recrystallization up to 99% ee) of the Friedel-Crafts alkylation products were obtained.

Journal Article↗
PubMed2006

Sorafenib blocks the RAF/MEK/ERK pathway, inhibits tumor angiogenesis, and induces tumor cell apoptosis in hepatocellular carcinoma model PLC/PRF/5.

Angiogenesis and signaling through the RAF/mitogen-activated protein/extracellular signal-regulated kinase (ERK) kinase (MEK)/ERK cascade have been reported to play important roles in the development of hepatocellular carcinomas (HCC). Sorafenib (BAY 43-9006, Nexavar) is a multikinase inhibitor with activity against Raf kinase and several receptor tyrosine kinases, including vascular endothelial growth factor receptor 2 (VEGFR2), platelet-derived growth factor receptor (PDGFR), FLT3, Ret, and c-Kit. In this study, we investigated the in vitro effects of sorafenib on PLC/PRF/5 and HepG2 HCC cells and the in vivo antitumor efficacy and mechanism of action on PLC/PRF/5 human tumor xenografts in severe combined immunodeficient mice. Sorafenib inhibited the phosphorylation of MEK and ERK and down-regulated cyclin D1 levels in these two cell lines. Sorafenib also reduced the phosphorylation level of eIF4E and down-regulated the antiapoptotic protein Mcl-1 in a MEK/ERK-independent manner. Consistent with the effects on both MEK/ERK-dependent and MEK/ERK-independent signaling pathways, sorafenib inhibited proliferation and induced apoptosis in both HCC cell lines. In the PLC/PRF/5 xenograft model, sorafenib tosylate dosed at 10 mg/kg inhibited tumor growth by 49%. At 30 mg/kg, sorafenib tosylate produced complete tumor growth inhibition. A dose of 100 mg/kg produced partial tumor regressions in 50% of the mice. In mechanism of action studies, sorafenib inhibited the phosphorylation of both ERK and eIF4E, reduced the microvessel area (assessed by CD34 immunohistochemistry), and induced tumor cell apoptosis (assessed by terminal deoxynucleotidyl transferase-mediated nick end labeling) in PLC/PRF/5 tumor xenografts. These results suggest that the antitumor activity of sorafenib in HCC models may be attributed to inhibition of tumor angiogenesis (VEGFR and PDGFR) and direct effects on tumor cell proliferation/survival (Raf kinase signaling-dependent and signaling-independent mechanisms).

Animals↗
PubMed2006

Cleaning verification assays for highly potent compounds by high performance liquid chromatography mass spectrometry: strategy, validation, and long-term performance.

A cleaning-verification assay was validated for a highly potent family of compounds utilizing a swab-sampling procedure and high performance liquid chromatography mass spectrometry (LC-MS) for separation and detection of the analytes. Due to the high potency of the compound, the LC-MS method was validated at a level of 50 ng/25 cm(2) and 50 ng/100 cm(2) (which equates to 10 ng/ml after extraction in 5 ml of sample solvent, and 3 ng/ml after correction for sampling losses). This validation exercise included recovery estimates from all drug product contact surfaces within the clinical trial manufacturing equipment, namely, stainless steel, anodized aluminum, Rilsan coated aluminum, bronze, polyvinylchloride, and Oilon. The limit of detection for the LC-MS method was determined to be less than 0.5 ng/ml, or less than 0.1 ng/cm(2), of the analyte. This method does not employ an internal standard. Long-term performance of the validated method is also reported. The precision on replicate injections of the standard prepared in the range of 3-6 ng/ml was typically better than 8.0% relative standard deviation (R.S.D.) over the course of 1 year, which resulted from 10 cleaning-verification submissions. Those results were consistent with the data obtained during method validation.

Acetates↗
PubMed2006

Improved breast cancer prognosis through the combination of clinical and genetic markers.

MOTIVATION: Accurate prognosis of breast cancer can spare a significant number of breast cancer patients from receiving unnecessary adjuvant systemic treatment and its related expensive medical costs. Recent studies have demonstrated the potential value of gene expression signatures in assessing the risk of post-surgical disease recurrence. However, these studies all attempt to develop genetic marker-based prognostic systems to replace the existing clinical criteria, while ignoring the rich information contained in established clinical markers. Given the complexity of breast cancer prognosis, a more practical strategy would be to utilize both clinical and genetic marker information that may be complementary. METHODS: A computational study is performed on publicly available microarray data, which has spawned a 70-gene prognostic signature. The recently proposed I-RELIEF algorithm is used to identify a hybrid signature through the combination of both genetic and clinical markers. A rigorous experimental protocol is used to estimate the prognostic performance of the hybrid signature and other prognostic approaches. Survival data analyses is performed to compare different prognostic approaches. RESULTS: The hybrid signature performs significantly better than other methods, including the 70-gene signature, clinical makers alone and the St. Gallen consensus criterion. At the 90% sensitivity level, the hybrid signature achieves 67% specificity, as compared to 47% for the 70-gene signature and 48% for the clinical makers. The odds ratio of the hybrid signature for developing distant metastases within five years between the patients with a good prognosis signature and the patients with a bad prognosis is 21.0 (95% CI:6.5-68.3), far higher than either genetic or clinical markers alone. AVAILABILITY: The breast cancer dataset is available at www.nature.com and Matlab codes are available upon request.

Algorithms↗
PubMed2006

Construction of equalized short hairpin RNA library from human brain cDNA.

Short hairpin RNA (shRNA) library is a powerful new tool for high-throughput loss-of-function genetic screens in mammalian cells. An shRNA library can be constructed from synthetic oligonucleotides or enzymatically cleaved natural cDNA. Here, we describe a new method for constructing equalized shRNA libraries from cDNA. First, enzymatically digested cDNA fragments are equalized by a suppression PCR-based method modified from suppression subtractive hybridization. The efficiency of equalization was confirmed by quantitative real-time PCR. The fragments are then converted into an shRNA library by a series of enzymatic treatments. With this new technology, we constructed a library from human brain cDNA. Sequence analysis showed that most of the randomly selected clones had inverted repeat sequences converted from different cDNA. After transfecting HEK 293T cells and detecting gene expression, three out of eight clones were demonstrated to significantly inhibit their target genes.

Base Sequence↗
PubMed2006

Silencing stathmin gene expression by survivin promoter-driven siRNA vector to reverse malignant phenotype of tumor cells.

Stathmin gene overexpression has been shown to play an important role in maintenance of malignant phenotype in tumor cells, and the blocking efficacy and tumor specificity of this target has been concerned in clinical trails. In this report, we designed survivin promoter-driven siRNA eukaryotic expression vector that expressed the small interfering RNA targeting stathmin gene to selectively knock down the stathmin gene expression in two different kinds of tumor cell lines while sparing normal cell lines. The therapeutic potential of this recombinant vector was tested in human cervical cancer Hela cells and osteosarcoma SSOP-9607 cells, and in human umbilical vein endothelial cell line ECV304 cells as control. The siRNA vector- transfected Hela cells and SSOP-9607 cells revealed marked inhibition of stathmin expression and a dramatic growth inhibition comparing with ECV304 cells, parental-vector transfected cells and untransfected cells. Cell cycle analysis of siRNA vector transfected tumor cells by Flow Cytometry showed G(2)/M phase block, while morphologic analysis by TURNEL staining method showed marked increase of apoptosis. Our study indicates that survivin gene promoter-driven stathmin siRNA expression vector may have potential use in tumor gene therapy with targeted tumor gene silencing effect.

Apoptosis↗