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Biomedical subjects

Yong Lu

Publications and source records attributed to Yong Lu.

At least 19 recordsLinked to original sources
PubMed2025

A complete and near-perfect rhesus macaque reference genome: lessons from subtelomeric repeats and sequencing bias.

A truly complete, telomere-to-telomere (T2T), and error-free reference genome remains a foundational resource-and long-standing goal-for unbiased comparative and functional genomics. While recent T2T assemblies of humans and other primates have made substantial progress, most still contain thousands of base-level errors, particularly within highly repetitive regions. Here, we present T2T-MMU8v2.0, a near-perfect T2T assembly of the rhesus macaque (Macaca mulatta), representing the highest base-level accuracy reported in a primate genome to date. By employing an optimized ONT-only assembly strategy, we identify subtelomeric satellite-rich regions as the principal bottleneck to improving assembly quality, owing to technological biases in long-read platforms and limitations in current hybrid assembly frameworks. We discover 268 previously unannotated repeat families and resolve ~8 Mbp of SATR satellite arrays, with over 99-fold enrichment in historically misassembled subtelomeric regions. These satellites form four distinct genomic architectures, each with unique SATR satellite composition, segmental duplication organization, and epigenetic signatures, distinct from the subtelomeric architectures observed in hominid genomes. Notably, in contrast to the largely gene-poor subtelomeric regions in African hominids, the SATR architectures in macaques harbor 58 actively transcribed genes, supported by open chromatin and expression data, suggesting gene innovation within these repetitive regions. Functionally, T2T-MMU8v2.0 improves read mappability and accuracy across sequencing platforms, and results in a 19% improvement of transcription start site enrichment scores and 5,821 additional chromatin accessibility peaks on average, thereby enhancing variant detection, regulatory annotation, and transcriptomic resolution in population genetics or single-nucleus studies. Together, this work establishes a new benchmark for genomics, offers a roadmap for resolving complex repetitive regions, and reveals previously unrecognized features of subtelomeric genome structure and evolution.

Journal Article↗
PubMed2007

Anionic four-electron donor-based palladacycles as catalysts for addition reactions of arylboronic acids with alpha,beta-unsaturated ketones, aldehydes, and alpha-ketoesters.

Anionic four-electron donor-based palladacycle-catalyzed 1,4-additions of arylboronic acids with alpha,beta-unsaturated ketones and 1,2-additions of arylboronic acids with aldehydes and alpha-ketoesters are described. Our study demonstrated that palladacycles were highly efficient, practical catalysts for these addition reactions. The work described here not only opened a new paradigm for the application of palladacycles, but may also pave the road for other metalacycles as practically useful catalysts for such addition reactions including asymmetric ones. [reaction: see text].

Alcohols↗
PubMed2006

Total synthesis of indole alkaloid (+/-)-subincanadine F via SmI2)-mediated ring opening and bridge-forming Mannich reaction.

The first total synthesis of (+/-)-subincanadine F, a bioactive indole alkaloid structurally featuring a 1-azabicyclo[4.3.1]decane unit, has been realized from 1-(para-methoxybenzyl)tryptamine in six steps. The bridge-containing tetracyclic framework of subincanadine F was efficiently assembled by a SmI2-mediated ring opening followed by an acid-mediated Mannich reaction. In addition, the tetracyclic ketoester 6, a key intermediate potentially useful for synthesizing structurally related indole alkaloids as well, was obtained in one step from alpha,beta-diketoester 5.

Cyclization↗
PubMed2006

Endogenous mGluR activity suppresses GABAergic transmission in avian cochlear nucleus magnocellularis neurons.

GABAergic transmission in the avian cochlear nucleus magnocellularis (NM) of the chick is subject to modulation by gamma-aminobutyric acid type B (GABA(B)) autoreceptors. Here, I investigated modulation of GABAergic transmission in NM by metabotropic glutamate receptors (mGluRs) with whole cell recordings in brain slice preparations. I found that tACPD, a nonspecific mGluR agonist, exerted dose-dependent suppression on evoked inhibitory postsynaptic currents (eIPSCs) in NM neurons. At concentrations of 100 or 200 microM, tACPD increased the failure rate of GABAergic transmission. Agonists for group I (3,5-DHPG, 200 microM), group II (DCG-IV, 2 microM), and group III (L-AP4, 10 microM) mGluRs produced a significant reduction in the amplitude of eIPSCs and a significant increase in failure rate, indicating the involvement of multiple mGluRs in this modulation. The frequency, but not the amplitude, of miniature IPSCs (mIPSCs) was decreased significantly by 3,5-DHPG or DCG-IV. Neither frequency nor amplitude of mIPSCs was affected by L-AP4. mGluR antagonists LY341495 (20 microM) plus CPPG (10 microM) significantly increased the amplitude of eIPSCs, indicating that endogenous mGluR activity suppresses GABA release to NM neurons. Furthermore, blockage of mGluRs increased GABA-evoked discharges recorded under physiological Cl(-) concentrations, whereas tACPD (100 microM) eliminated them. The results indicate that mGluRs play important roles in achieving balanced excitation and inhibition in NM and preserving fidelity of temporal information encoded by NM neurons.

2-Amino-5-phosphonovalerate↗
PubMed2006

Development of spontaneous miniature EPSCs in mouse AVCN neurons during a critical period of afferent-dependent neuron survival.

During a critical period prior to hearing onset, cochlea ablation leads to massive neuronal death in the mouse anteroventral cochlear nucleus (AVCN), where cell survival is believed to depend on glutamatergic input. We investigated the development of spontaneous miniature excitatory postsynaptic currents (mEPSCs) in AVCN neurons using whole cell patch-clamp techniques during [postnatal day 7 (P7)] and after (P14, P21) this critical period. We also examined the effects of unilateral cochlea ablation on mEPSC development. The two main AVCN neuron types, bushy and stellate cells, were distinguished electrophysiologically. Bushy cell mEPSCs became more frequent and faster between P7 and P14/P21 but with little change in amplitude. Dendritic filtering of mEPSCs was not detected as indicated by the lack of correlation between 10 and 90% rise times and decay time constants. Seven days after cochlea ablation at P7 or P14, mEPSCs in surviving bushy cells were similar to controls, except that rise and decay times were positively correlated (R = 0.31 and 0.14 for surgery at P7 and P14, respectively). Consistent with this evidence for a shift of synaptic activity from the somata to the dendrites, SV2 staining (a synaptic vesicle marker) forms a ring around somata of control but not experimental bushy cells. In contrast, mEPSCs of stellate cells showed few significant changes over these ages with or without cochlea ablation. Taken together, mEPSCs in mouse AVCN bushy cells show dramatic developmental changes across this critical period, and cochlea ablation may lead to the emergence of excitatory synaptic inputs impinging on bushy cell dendrites.

Action Potentials↗
PubMed2006

Novel microfibrous composite bed reactor: high efficiency H2 production from NH3 with potential for portable fuel cell power supplies.

A novel microfibrous composite bed reactor was developed and was demonstrated for high efficiency hydrogen production by the decomposition of ammonia at moderate temperatures in portable fuel cell power system applications. By using a high-speed and low-cost papermaking technology combined with a subsequent sintering process, sinter-locked three-dimensional microfibrous networks consisting of approximately 3 vol% 8 microm (dia.) nickel microfibers were utilized to entrap approximately 35 vol% 100-200 microm dia. porous Al(2)O(3) support particulates. A CeO(2) promoter and active Ni component were then dispersed onto the pore surface of the entrapped Al(2)O(3) support particulates by a stepwise incipient wetness impregnation method. The microfibrous structure took advantage of a large void volume, entirely open structure, high heat/mass transfer, high permeability, good thermal stability, and unique form factors. Addition of ceria significantly promoted the low-temperature activity of Ni/Al(2)O(3) catalyst particulates incorporated into the micorfibrous structure. The use of fine particles of catalyst significantly attenuated the intraparticle mass transport limitations. As a result, the present novel microfibrous composite bed reactor provided excellent activity and structure stability in ammonia decomposition, as well as low pressure drop and high efficiency reactor design. At a 90% conversion of a 145 sccm ammonia feed rate, the microfibrous entrapped Ni/CeO(2)-Al(2)O(3) catalyst composite bed could provide a 4-fold reduction of catalytic bed volume and a 5-fold reduction of catalytic bed weight (or 9-fold reduction of catalyst dosage), while leading to a reduction of reaction temperature of 100 degrees C, compared to a packed bed with 2 mm dia. Ni/CeO(2)-Al(2)O(3) catalyst pellets. This composite bed was capable of producing roughly 22 W of hydrogen power, with an ammonia conversion of 99% at 600 degrees C in a bed volume of 0.5 cm(3) throughout a 100 h continuous test. These initial and promising results established that the microfibrous nickel-based catalyst composites were effective for high efficiency production of hydrogen by ammonia decomposition, while achieving a significant reduction of overall catalytic bed weight and volume. We anticipate our assay to be a new point for small-scale hydrogen production, where the microfibrous catalytic reactors considered in isolation can satisfy several of the most fundamental criteria needed for useful operation.

Journal Article↗
PubMed2006

Decreased expression of thyroid receptor-associated protein 220 in temporal lobe tissue of patients with refractory epilepsy.

PURPOSE: TRAP220 (thyroid hormone receptor-associated protein) functions as a coactivator for nuclear receptors and stimulates transcription by recruiting the TRAP mediator complex to hormone responsive promoter regions. Thus, TRAP220 enhances the function of thyroid/steroid hormone receptors such as thyroid hormone and oestrogen receptors. This study investigated the expression of TRAP220 mRNA and protein level in epileptic brains comparing with human control. METHODS: We examined the expression of TRAP220 mRNA and protein levels in temporal lobes from patients with chronic pharmacoresistant epilepsy who have undergone surgery. RESULTS: Expression of TRAP220 mRNA and protein was shown to be decreased significantly in the temporal cortex of the patients with epilepsy. CONCLUSIONS: Our work showed that a decrease in TRAP220 mRNA and protein levels may be involved in the pathophysiology of epilepsy and may be associated with impairment of the brain caused by frequent seizures.

Adolescent↗
PubMed2006

Identifying cycling genes by combining sequence homology and expression data.

MOTIVATION: The expression of genes during the cell division process has now been studied in many different species. An important goal of these studies is to identify the set of cycling genes. To date, this was done independently for each of the species studied. Due to noise and other data analysis problems, accurately deriving a set of cycling genes from expression data is a hard problem. This is especially true for some of the multicellular organisms, including humans. RESULTS: Here we present the first algorithm that combines microarray expression data from multiple species for identifying cycling genes. Our algorithm represents genes from multiple species as nodes in a graph. Edges between genes represent sequence similarity. Starting with the measured expression values for each species we use Belief Propagation to determine a posterior score for genes. This posterior is used to determine a new set of cycling genes for each species. We applied our algorithm to improve the identification of the set of cell cycle genes in budding yeast and humans. As we show, by incorporating sequence similarity information we were able to obtain a more accurate set of genes compared to methods that rely on expression data alone. Our method was especially successful for the human dataset indicating that it can use a high quality dataset from one species to overcome noise problems in another. AVAILABILITY: C implementation is available from the supporting website: http://www.cs.cmu.edu/~lyongu/pub/cellcycle/.

Algorithms↗
PubMed2006

Analysis of velopharyngeal morphology in adults with velopharyngeal incompetence after surgery of a cleft palate.

This study analyzed the relationship of velopharyngeal morphology and velopharyngeal function among 13 adults with velopharyngeal incompetence (VPI), 14 adults with velopharyngeal competence (VPC) after primary surgical treatment of cleft palate, and 20 noncleft adults. The measurements included velar length, pharyngeal depth, pharyngeal height, and the need ratio of pharyngeal depth to velar length. In addition, the cranial base, cervical vertebrae, posterior nasal spine, and also the position of the posterior pharyngeal wall (PPW) in the pharyngeal triangle were analyzed. All data were subjected to the Student t test of statistical significance. The results showed that the VPI group had normal pharyngeal depth and a significantly shorter velar length, resulting in a greater depth/length ratio than those of the VPC group and normal control subjects. The position of PPW in the pharyngeal triangle was located significantly more superior in the VPI group compared with the VPC group and normal control subjects. Measurements of the anteroposterior and the vertical dimensions in the regions of the cranial base and cervical vertebrae revealed no significant difference among the 3 groups. According to this study, the velopharyngeal morphology of adults with VPI is characterized by a shorter palate, greater need ratio, slightly counterclockwise-rotated pharyngeal triangle, and superiorly positioned PPW.

Adolescent↗
PubMed2006

Pharmacokinetic study with N-Ile1-Thr2-63-desulfato-r-hirudin in rabbits by means of bioassay.

AIM: To study the pharmacokinetic (PK) properties in rabbits treated with N-Ile(1)-Thr(2)-63-desulfato-r-hirudin (rH) newly developed in China by means of bioassay in order to provide preclinical experiment basis for its development as a novel anticoagulant agent. METHODS: rH plasma concentration was determined using bioassay based on ex vivo antithrombin activity of rH. Normal rabbits received iv rH 4.0, 2.0 and 1.0 mg/kg or sc rH 2.0 mg/kg, respectively. The rabbits with acute severe renal failure were given iv rH 2.0 mg/kg. RESULTS: The bioassay described in this paper met requirements for study of PK in rabbits. The major PK parameters after iv dosing were as follows: t(1/2beta) 58.4-59 min. V(d) 0.09-0.12 L/kg, CL 0.0035-0.0040 L/(kg.min); AUC were proportional to the doses, t(1/2) and CL did not change significantly with the doses. The sc bioavailability reached 94%. The rabbits suffering from acute severe renal failure presented 11-fold longer t(1/2beta) and 13-fold greater AUC than normal healthy rabbits. CONCLUSION: rH exhibited rapid elimination, distribution was only limited to extracellular space and good absorption from sc site. The excretion of rH by kidneys played a very important role in the elimination of rH. The PK of rH could be described by the two- and one-compartment model after iv and sc dosing, respectively, and followed linear kinetics.

Algorithms↗
PubMed2006

[Separation and culture of mouse embryonic palatal mesenchymal cells in vitro].

OBJECTIVE: To modify the operation of dissecting embryonic palatal shelves and purify the mouse embryonic palatal mesenchymal (EPM) cells in primary culture. METHODS: The embryonic palatal shelves were dissected using a surgical microscope by modified operation. Then the embryonic palatal shelves were incubated with Dispase and the isolated EPM cells were cultured. Immunofluorescence technique was used to identify the characteristics of cells. RESULTS: Embryonic palatal shelves could be dissected accurately and easily with a modified operation. The purified EPM cells contained scarcely epithelial cells. EPM cells were anti-HNK-1, S-100, vimentin positive and anti-CK negative. CONCLUSION: A modified method for dissecting embryonic palatal shelves and purifying the EPM cells of primary culture was established.

Animals↗
PubMed2006

[Individual repair technique of microform cleft lip: state of art].

OBJECTIVE: To explore an technique to repair the microform cleft lip (MCL). METHODS: The individual method was used to repair the MCL, a contrastive research was carried to analyzed the result. RESULTS: It was found that the form of the cupid's bow was good, and the configure of the upper lip was reconstructed. The deficit of the orbicularis muscle was overcame and the function was satisfying by this procedure. Symmetry was recovered. CONCLUSIONS: Individual technique is an available method to repair the microform cleft lip. Furthermore, this technique is also promising to repair the other kinds of cleft lip.

Cleft Lip↗
PubMed2006

[Morphology of the soft palate in normal humans with digital cephalometry].

OBJECTIVE: To study the morphology of the soft palate in normal humans with digital radiography and to provide the references for therapy of the cleft. METHODS: 106 normal people were involved. The morphology of the soft palate was observed with digital cephalometry. RESULTS: All static images of soft palate could be divided into six types: Shuttle-shaped, crescent-shaped, strip-shaped, S-shaped, hamulus-shaped and anomalous shaped. The dynamic image was knee-shaped. CONCLUSION: The morphology of the soft palate is varied.

Cephalometry↗
PubMed2005

[CT-guided percutaneous removal of osteoid osteoma].

OBJECTIVE: To evaluate the methods of CT-guided percutaneous removal of osteoid osteoma. METHODS: From February 2003 to December 2003, there were 11 patients, at a mean age of 19.3 years old (from 14 to 32 years old). Seven cases were male, and 4 cases were female. Diagnosis was supported by the complete clinical and imaging file. Eleven cases with osteoid osteomas were treated with CT-guided percutaneous excision. The location involved were femoral neck (6 cases), acetabulum (4 cases), humeral neck (1 case). At first, CT scanning was done in the whole nidus with thin slices (2 mm thick), and the CT scan slice passing through the center of the nidus was selected. Then the whole nidus was removed by trephine along the guidewire which was inserted into the bone up to the nidus and was protected by the trocar. Finally complete lesion resection was checked with CT. RESULTS: Nine cases had a final pathological diagnosis of osteoid osteomas. Complete pain relief was obtained in these patients after the day of operation. There were no complications, no recurrence and patients remained symptom free at follow-up of 8-18 months (mean, 15.2 months). CONCLUSION: The methods of CT guided percutaneous removal of osteoid osteoma is a minimally invasive technique that represents the efficacy and safety.

Adolescent↗
PubMed2005

Derivation and growing human embryonic stem cells on feeders derived from themselves.

Human embryonic stem cells (hESCs) are pluripotent. They have the potential to differentiate into every cell type of an organism. Since many human somatic cell types have the ability to support the growth of hESCs, cells differentiated from hESCs may also be able to support the growth of themselves. We tested this hypothesis by growing hESCs on feeders derived from themselves and demonstrated that such feeders did constitute an environment suitable for the derivation and long-term growth of hESCs. hESCs maintained in this system expressed all the markers indicative of the undifferentiated state and gave rise to cell types representative of all three primary germ layers upon differentiation. By modifying the genome of hESCs, feeders with special features can be derived and mass produced. The system will facilitate large-scale production of hESCs in a standardized animal pathogen-free environment.

Animals↗
PubMed2005

Status of intracellular and extracellular magnesium concentration in patients with cardiac syndrome X.

OBJECTIVES: This study sought to clarify the differences of intracellular and extracellular magnesium levels in patients with cardiac syndrome X. METHODS: We evaluated the intracellular and extracellular magnesium status of 22 patients with cardiac syndrome X (group A) and 22 age--and gender--matched disorder-free control subjects (group B). Levels of magnesium were determined in serum, urine, erythrocytes, and the 24-h magnesium retention rate was calculated by a magnesium loading test. RESULTS: Group A showed a higher 24-h magnesium retention rate (49.8 +/- 1.3% vs. 32.6 +/- 7.5%, p < 0.05) and a lower intracellular concentration of magnesium in erythrocytes than group B (3.7 +/- 1.4 vs. 5.6 +/- 1.3 fg/cell, p < 0.05), demonstrating the presence of magnesium deficiency in group A. There were no significant differences in the serum concentration of magnesium between groups A and B (0.87 +/- 0.23 vs. 0.83 +/- 0.15 mmol/l). CONCLUSIONS: This study demonstrated that the intracellular magnesium level decreased in patients with cardiac syndrome X.

Adult↗
PubMed2005

[Different histological changes of hard palates in rats with different areas of denudated bone].

PURPOSE: To explore the relationship between the histological changes of the denudated bone in the hard palate of rats and its sizes. METHODS: Sixteen three-week-old SD male rats were randomly divided into 4 groups (a control group and 3 experimental groups). In the three experimental groups, one and two and three quarters of the bilateral palatal mucoperiosteum were excised respectively. One animal in each group was sacrificed every two weeks and the histological differences were observed. RESULTS: Different histological changes were found among the groups. When the denuded part was over half of the palate, tight connections between scar tissues and both the palatal bone and the periodontal fibers were observed. Many necrotic bone tissues appeared in the mid-palate if more than three quarters of areas were exposed. CONCLUSION: Different sizes of denuded bone may lead to different histological appearances. Structures and tissues change more when denuded part of the bone is larger.

Animals↗