The Novel HLA-A*02:1229 Allele Was Identified by Next-Generation Sequencing.
HLA-A*02:1229 differs from HLA-A*02:07:01:01 by a single nucleotide substitution at position 1014 T>A.
Humans↗
Biomedical subjects
Ying Li
Publications and source records attributed to Ying Li.
Alternative spliceosomal protein Eftud2 mediated Kif3a exon skipping promotes SHH-subgroup medulloblastoma progression.
Alternative splicing plays a pivotal role in various facets of organogenesis, immune response, and tumorigenesis. Medulloblastoma represents a prevalent childhood brain tumor, with approximately one-third classified as the Sonic Hedgehog (SHH) subgroup. Nevertheless, the contribution of alternative splicing to medulloblastoma oncogenesis remains elusive. This investigation delineated an upregulation of the spliceosomal protein Eftud2 in the SHH-subgroup medulloblastoma mouse model and human medulloblastoma patients. Targeted ablation of Eftud2 in granule precursor cells (GNPs) within the cerebellum prolonged the survival of SHH-subgroup medulloblastoma mice, indicating a putative association between Eftud2 expression and medulloblastoma prognosis. Functional assays unveiled that EFTUD2 depletion in human medulloblastoma cells significantly curtailed cellular proliferation by impeding the activation of the SHH signaling pathway. Through multi-omics sequencing analysis, it was discerned that Eftud2 influences exons 10-11 skipping of Kif3a, a kinesin motor critical for primary cilia formation. Notably, exons 10-11 skipping in Kif3a augmented human medulloblastoma cell proliferation by potentiating the transcriptional activity of Gli2. These findings underscore a robust correlation between Eftud2 and SHH-subgroup medulloblastoma, emphasizing its regulatory role in modulating downstream transcription factors through the alternative splicing of pivotal genes within the SHH signaling pathway, thereby propelling the aggressive proliferation of SHH-subgroup medulloblastoma.
Medulloblastoma↗
Identification of the Novel HLA-C*01:257N Allele by Next-Generation Sequencing.
HLA-C*01:257N differs from the HLA-C*01:02:01:01 allele by one nucleotide substitution in exon 4.
Humans↗
Characterisation of the Novel HLA-DQA1*05:06:02 Allele by Next-Generation Sequencing.
HLA-DQA1*05:06:02 shows one single nucleotide substitution at position 6 C > T in exon 1 compared with HLA-DQA1*05:06:01:01.
Humans↗
The Novel HLA-DQA1*03:63 Allele Was Identified by Next-Generation Sequencing.
HLA-DQA1*03:63 differs from HLA-DQA1*03:02:01:01 by a single nucleotide substitution at position 722 G>A.
Humans↗
Characterisation of the Novel HLA-C*08:01:37 Allele by Next-Generation Sequencing.
HLA-C*08:01:37 differs from HLA-C*08:01:01:01 by one single nucleotide substitution at position 927 G>A in exon 5.
Humans↗
Phase Transition of Wax Enabling CRISPR Diagnostics for Automatic At-Home Testing of Multiple Sexually Transmitted Infection Pathogens.
Sexually transmitted infections (STIs) significantly impact women's reproductive health. Rapid, sensitive, and affordable detection of these pathogens is essential, especially for home-based self-testing, which is crucial for individuals who prioritize privacy or live in areas with limited access to healthcare services. Herein, an automated diagnostic system called Wax-CRISPR has been designed specifically for at-home testing of multiple STIs. This system employs a unique strategy by using the solid-to-liquid phase transition of wax to sequentially isolate and mix recombinase polymerase amplification (RPA) and CRISPR assays in a microfluidic chip. By incorporating a home-built controlling system, Wax-CRISPR achieves true one-pot multiplexed detection. The system can simultaneously detect six common critical gynecological pathogens (CT, MG, UU, NG, HPV 16, and HPV 18) within 30 min, with a detection limit reaching 10-18 M. Clinical evaluation demonstrates that the system achieves a sensitivity of 96.8% and a specificity of 97.3% across 100 clinical samples. Importantly, eight randomly recruited untrained operators performe a double-blinded test and successfully identified the STI targets in 33 clinical samples. This wax-transition-based one-pot CRISPR assay offers advantages such as low-cost, high-stability, and user-friendliness, making it a useful platform for at-home or field-based testing of multiple pathogen infections.
Sexually Transmitted Diseases↗
Abundant mRNA m1A modification in dinoflagellates: a new layer of gene regulation.
Dinoflagellates, a class of unicellular eukaryotic phytoplankton, exhibit minimal transcriptional regulation, representing a unique model for exploring gene expression. The biosynthesis, distribution, regulation, and function of mRNA N1-methyladenosine (m1A) remain controversial due to its limited presence in typical eukaryotic mRNA. This study provides a comprehensive map of m1A in dinoflagellate mRNA and shows that m1A, rather than N6-methyladenosine (m6A), is the most prevalent internal mRNA modification in various dinoflagellate species, with an asymmetric distribution along mature transcripts. In Amphidinium carterae, we identify 6549 m1A sites characterized by a non-tRNA T-loop-like sequence motif within the transcripts of 3196 genes, many of which are involved in regulating carbon and nitrogen metabolism. Enriched within 3'UTRs, dinoflagellate mRNA m1A levels negatively correlate with translation efficiency. Nitrogen depletion further decreases mRNA m1A levels. Our data suggest that distinctive patterns of m1A modification might influence the expression of metabolism-related genes through translational control.
Dinoflagellida↗
Organ-delimited gene regulatory networks provide high accuracy in candidate transcription factor selection across diverse processes.
Organ-specific gene expression datasets that include hundreds to thousands of experiments allow the reconstruction of organ-level gene regulatory networks (GRNs). However, creating such datasets is greatly hampered by the requirements of extensive and tedious manual curation. Here, we trained a supervised classification model that can accurately classify the organ-of-origin for a plant transcriptome. This K-Nearest Neighbor-based multiclass classifier was used to create organ-specific gene expression datasets for the leaf, root, shoot, flower, and seed in Arabidopsis thaliana. A GRN inference approach was used to determine the: i. influential transcription factors (TFs) in each organ and, ii. most influential TFs for specific biological processes in that organ. These genome-wide, organ-delimited GRNs (OD-GRNs), recalled many known regulators of organ development and processes operating in those organs. Importantly, many previously unknown TF regulators were uncovered as potential regulators of these processes. As a proof-of-concept, we focused on experimentally validating the predicted TF regulators of lipid biosynthesis in seeds, an important food and biofuel trait. Of the top 20 predicted TFs, eight are known regulators of seed oil content, e.g., WRI1, LEC1, FUS3. Importantly, we validated our prediction of MybS2, TGA4, SPL12, AGL18, and DiV2 as regulators of seed lipid biosynthesis. We elucidated the molecular mechanism of MybS2 and show that it induces purple acid phosphatase family genes and lipid synthesis genes to enhance seed lipid content. This general approach has the potential to be extended to any species with sufficiently large gene expression datasets to find unique regulators of any trait-of-interest.
Arabidopsis↗
Pediatric T-cell post-transplant lymphoproliferative disorder after solid organ transplantation.
Post-transplant lymphoproliferative disorder (PTLD) is the most common treatment related malignancy that occurs after solid organ transplantation (SOT). PTLD has extended from its initial description as an Epstein-Barr virus (EBV)-driven B-cell proliferation to include EBV-negative and non B-lineage cases. T-cell PTLD (T-PTLD) is rare in both adults and children. We report two cases of pediatric T-PTLD after SOT (liver and lungs) and review cases reported in the literature. Both patients had a bimodal response to therapy with initial eradication of bulky nodal disease with regimens typically used to treat leukemia, but persistence of low-level clonal T-cells in marrow, CSF and lung in one case.
Child, Preschool↗
The whisking rhythm generator: a novel mammalian network for the generation of movement.
Using the rat vibrissa system, we provide evidence for a novel mechanism for the generation of movement. Like other central pattern generators (CPGs) that underlie many movements, the rhythm generator for whisking can operate without cortical inputs or sensory feedback. However, unlike conventional mammalian CPGs, vibrissa motoneurons (vMNs) actively participate in the rhythmogenesis by converting tonic serotonergic inputs into the patterned motor output responsible for movement of the vibrissae. We find that, in vitro, a serotonin receptor agonist, alpha-Me-5HT, facilitates a persistent inward current (PIC) and evokes rhythmic firing in vMNs. Within each motoneuron, increasing the concentration of alpha-Me-5HT significantly increases the both the magnitude of the PIC and the motoneuron's firing rate. Riluzole, which selectively suppresses the Na(+) component of PICs at low concentrations, causes a reduction in both of these phenomena. The magnitude of this reduction is directly correlated with the concentration of riluzole. The joint effects of riluzole on PIC magnitude and firing rate in vMNs suggest that the two are causally related. In vivo we find that the tonic activity of putative serotonergic premotoneurons is positively correlated with the frequency of whisking evoked by cortical stimulation. Taken together, these results support the hypothesized novel mammalian mechanism for movement generation in the vibrissa motor system where vMNs actively participate in the rhythmogenesis in response to tonic drive from serotonergic premotoneurons.
Animals↗
The high incidence of varicella herpes zoster with the use of bortezomib in 10 patients.
Bortezomib, a proteasome inhibitor, has been used for patients with refractory and relapsed multiple myeloma, lymphoma and leukemia. We used bortezomib in ten refractory or relapsed patients (seven of multiple myeloma, two of lymphoma and one of acute myeloblastic leukemia). Six out of ten (60%) patients developed varicella herpes zoster after the complete of one cycle of bortezomib. The incidence of varicella herpes zoster was higher than reported in the literature. It may be due to immunosuppression caused by the combination of high-dose dexamethasone or other drugs. We considered that prophylactic antiviral medication could be used in predisposed patients to reduce the incidence of varicella herpes zoster.
Adult↗
Transplanted Schwann cells, not olfactory ensheathing cells, myelinate optic nerve fibres.
In a previous study we found that olfactory ensheathing cells transplanted into complete retrobulbar transections of the rat optic nerve mediated regeneration of severed retinal ganglion cell axons through the graft region. Although the regenerating axons were ensheathed by the transplanted cells, none of the regenerating axons became myelinated by either central or peripheral type myelin. In the present study we used the same operative procedure but transplanted Schwann cells instead of olfactory ensheathing cells. As with the olfactory ensheathing cell transplants the Schwann cells transplants also induced regeneration of the severed retinal ganglion cell axons into the graft region. In contrast to the situation with the olfactory ensheathing cell transplants, however, a considerable number of the regenerating axons became myelinated by peripheral type myelin produced by the transplanted Schwann cells. This observation identifies a further distinction between these two cell types which are phenotypically similar in many ways, but which have been shown to have major functional differences with regard to regeneration in spinal cord lesions.
Animals↗
Non-invasive prenatal detection of achondroplasia in size-fractionated cell-free DNA by MALDI-TOF MS assay.
Achondroplasia is the most common form of short-limbed dwarfism in humans and is caused by mutations in the FGFR3 gene. Currently, prenatal diagnosis of this disorder relies on invasive procedures. Recent studies have shown that fetal single gene point mutations could be detected in cell-free DNA (cf-DNA) from maternal plasma by either the matrix-assisted laser desorption/ionization time-of-flight mass spectrometry (MALDI-TOF MS) assay with single allele base extension reaction (SABER) approach or the size fractionation of cf-DNA in maternal plasma. Here, we combined the two approaches to non-invasively examine the fetal G1138A mutation in maternal plasma. cf-DNA was extracted from maternal plasma samples obtained from two pregnant women at risk for achondroplasia. The fetal G1138A mutation was determined by the analysis of size-fractionated cf-DNA in maternal plasma using MALDI-TOF MS with SABER approach and homogenous MassEXTEND (hME) assay, respectively. The fetal G1138A mutation was detectable in the two achondroplasia-affected pregnancies by the analysis of cf-DNA in maternal plasma using MALDI-TOF MS. However, the size-fractionation approach led to a more precise detection of the fetal mutation in both analyses. This analysis would be suitable for non-invasive prenatal diagnosis of diseases caused by fetal single gene point mutations.
Achondroplasia↗
Effect of aluminum on the nature of the iron species in Fe-SBA-15.
We report the preparation of highly ordered mesoporous Fe-Al-SBA-15 with isolated extraframework Fe species under acidic conditions. The materials were characterized by means of UV resonance Raman spectroscopy, in conjunction with BET, XRD, TEM, UV-vis, H2-TPR, FT-IR, and 27Al MAS NMR spectroscopy. The addition of both Fe and Al to the synthesis gel of SBA-15 results in the formation of isolated extraframework Fe species located close to the framework Al ions and the Fe content an order of magnitude higher than that in Fe-SBA-15 synthesized without Al. The existence of anchored extraframework Fe species was confirmed by the presence of a strong absorption band at 270 nm, hydrogen reduction at relatively low temperature, and the presence of a resonance Raman band at 1140 cm(-1). The location of Fe in close proximity to framework Al nuclei is further supported by 27Al MAS NMR measurements. Two characteristic UV Raman bands at 510 cm(-1) and 1090 cm(-1) excited by 244-nm laser are assigned to Fe-O-Si symmetric and asymmetric stretching modes of isolated tetrahedral Fe ions in the silica framework for Fe-SBA-15. The resonance Raman band at 1140 cm(-1) excited by 325-nm laser is attributed to the asymmetric stretching mode of the isolated extraframework iron species in Fe-Al-SBA-15. The isolated Fe species close to framework Al species are stable in acidic HCl solution, whereas the majority of Fe species in Fe-SBA-15 can be easily removed.
Journal Article↗
Molecular behavior and synergistic effects between sodium dodecylbenzene sulfonate and Triton X-100 at oil/water interface.
Significant synergistic effects between sodium dodecylbenzene sulfonate (SDBS) and nonionic nonylphenol polyethylene oxyether, Triton X-100 (TX-100), at the oil/water interface have been investigated by experimental methods and computer simulation. The influences of surfactant concentration, salinity, and the ratio of the two surfactants on the interfacial tension were investigated by conventional interfacial tension methods. A dissipative particle dynamics (DPD) method was used to simulate the adsorption properties of SDBS and TX-100 at the oil/water interface. The experiment and simulation results indicate that ultralow (lower than 10(-3) mN m(-1)) interfacial tension can be obtained at high salinity and very low surfactant concentration. Different distributions of surfactants in the interface and the bulk solution corresponding to the change of salinity have been demonstrated by simulation. Also by computer simulation, we have observed that either SDBS or TX-100 is not distributed uniformly over the interface. Rather, the interfacial layer contains large cavities between SDBS clusters filled with TX-100 clusters. This inhomogeneous distribution helps to enhancing our understanding of the synergistic interaction of the different surfactants. The simulation conclusions are consistent with the experimental results.
Journal Article↗
Differential target-dependent actions of coexpressed inhibitory dynorphin and excitatory hypocretin/orexin neuropeptides.
The hypocretin/orexin arousal system plays a key role in maintaining an alert wake state. The hypocretin peptide is colocalized with an opioid peptide, dynorphin. As dynorphin may be coreleased with hypocretin, we asked what action simultaneous stimulation with the excitatory neuropeptide hypocretin and the inhibitory peptide dynorphin might exert on cells postsynaptic to hypocretin axons, including hypocretin neurons. Hypocretin neurons received direct synaptic contact from other hypocretin neurons but showed little direct response to hypocretin. Here, we show that mouse hypocretin neurons are acutely sensitive to dynorphin. Dynorphin inhibits the hypocretin system by direct postsynaptic actions (hyperpolarization, decreased spike frequency, increased GIRK (G-protein-gated inwardly rectifying K+ channel) current, and attenuated calcium current, and indirectly by reducing excitatory synaptic tone. Interestingly, a selective antagonist of kappa-opioid receptors enhanced activity of the hypocretin system, suggesting ongoing depression by endogenous hypothalamic opioids. Electrical stimulation of hypothalamic microslices that contained hypocretin cells and their axons evoked dynorphin release. Costimulation with dynorphin and hypocretin had three different effects on neurons postsynaptic to hypocretin axons: direct response to only one or the other of the two peptides [hypocretin cells respond to dynorphin, arcuate neuropeptide Y (NPY) cells respond to hypocretin], differential desensitization causing shift from inhibitory current to excitatory current with repeated coexposure (melanin-concentrating hormone neurons), synergistic direct excitation by hypocretin and presynaptic attenuation of inhibition by dynorphin (arcuate NPY neurons). These results suggest that hypocretin neurons may be able to exercise a high degree of modulatory control over postsynaptic targets using multiple neuropeptides with target-dependent actions.
Animals↗
Biosorption and biodegradation of pentachlorophenol (PCP) in an upflow anaerobic sludge blanket (UASB) reactor.
In order to understand the fate of PCP in upflow anaerobic sludge blanket reactor (UASB) more completely, the sorption and biodegradation of pentachlorophenol (PCP) by anaerobic sludge granules were investigated. The anaerobic granular sludge degrading PCP was formed in UASB reactor, which was seeded with anaerobic sludge acclimated by chlorophenols. At the hydraulic retention time (HRT) of 20-22 h, and PCP loading rate of 200-220 mg l(-1) d(-1), UASB reactor exhibited good performance in treating wastewater which containing 170-180 mg l(-1) PCP and the PCP removal rate of 99.5% was achieved. Sequential appearance of tetra-, tri-, di-, and mono-chlorophenol was observed in the reactor effluent after 20 mg l(-1) PCP introduction. Sorption and desorption of PCP on the anaerobic sludge granules were all fitted to the Freundlich isotherm equation. Sorption of PCP was partly irreversible. The Freundlich equation could describe the behavior of PCP amount sorbed by granular sludge in anaerobic reactor reasonably well. The results demonstrated that the main mechanism leading to removal of PCP on anaerobic granular sludge was biodegradation, not sorption or volatization.
Adsorption↗