Biomedical subjects

Ling Huang

Publications and source records attributed to Ling Huang.

At least 19 recordsLinked to original sources

PubMed2025

Mitochondrial DNA homeostasis: A novel therapeutic target for neurodegenerative diseases.

The mitochondrial genomic homeostasis is essential for the function of the oxidative phosphorylation system and cellular homeostasis. Mitochondrial DNA is particularly susceptible to aging-related oxidative stress due to the lack of a histone coat. Disturbances in mitochondrial DNA may contribute to functional decline during the aging process and in neurodegenerative diseases, leading to further impairment of mitochondrial DNA and initiating a vicious cycle. To date, it remains unclear how disturbed mitochondrial DNA is involved in the etiology of pathological aging and neurodegenerative diseases. The purpose of this review is to clarify the crucial roles of mitochondrial DNA homeostasis in the pathogenesis of neurodegenerative diseases. Mitochondrial DNA is distributed within nucleoids and is then transcribed into polycistronic mitochondrial DNA molecules within the mitochondrial granule region. Within the ultrastructure of the mitochondrial nucleoid and granule, a group of essential mitochondrial proteins involved in DNA replication, DNA transcription, RNA translation, RNA surveillance, and RNA degradation plays a crucial role in maintaining mitochondrial structure, genome integrity, and mitochondrial DNA processing. The uniparentally inherited mitochondrial DNA undergoes heritable polyploid variations, which include homoplasmy and heteroplasmy. Accumulating mitochondrial DNA alterations, such as deletions, point mutations, and methylations, occur during the pathogenic processes of neurodegenerative diseases. The increased mitochondrial DNA alterations can be propagated by the rise of deleterious heteroplasmy in neurodegenerative diseases, ultimately resulting in impairment to the oxidative phosphorylation system, biogenesis defects, and cellular metabolic dysfunction. Therefore, developing appropriate gene editing tools to rectify aberrant alterations in mitochondrial DNA and targeting the key proteins involved in maintaining mitochondrial DNA homeostasis can be considered promising therapeutic strategies for neurodegenerative diseases. Although therapeutic strategies targeting mitochondrial DNA in diseases show great potential, challenges related to efficacy and safety require a better understanding of the mechanisms underlying mitochondrial DNA alterations in aging and neurodegenerative diseases.

Alzheimer’s disease↗

PubMed2006

Dip-pen nanolithography of high-melting-temperature molecules.

Direct nanopatterning of a number of high-melting-temperature molecules has been systematically investigated by dip-pen nanolithography (DPN). By tuning DPN experimental conditions, all of the high-melting-temperature molecules transported smoothly from the atomic force microscope (AFM) tip to the surface at room temperature without tip preheating. Water meniscus formation between the tip and substrate is found to play a critical role in patterning high-melting-temperature molecules. These results show that heating an AFM probe to a temperature above the ink's melting temperature is not a prerequisite for ink delivery, which extends the current "ink-substrate" combinations available to DPN users.

Ink↗

PubMed2006

Selective assembly and alignment of actin filaments with desired polarity on solid substrates.

We report a new strategy to selectively assemble and align filamentous actin (F-actin) onto desired locations on a solid substrate with a specific structural polarity. In this strategy, biotinylated gelsolin caps the structural minus end of F-actin so that the F-actin binds onto a streptavidin pattern with a specific structural polarity. We also demonstrate that an electric field can be utilized to align bound F-actin along a desired direction. This can be one of the major technical breakthroughs toward the assembly of nanomechanical systems based on myosin biomotors.

Actin Cytoskeleton↗

PubMed2006

Comparative genomic analysis links karyotypic evolution with genomic evolution in the Indian muntjac (Muntiacus muntjak vaginalis).

The karyotype of Indian muntjacs (Muntiacus muntjak vaginalis) has been greatly shaped by chromosomal fusion, which leads to its lowest diploid number among the extant known mammals. We present, here, comparative results based on draft sequences of 37 bacterial artificial clones (BAC) clones selected by chromosome painting for this special muntjac species. Sequence comparison on these BAC clones uncovered sequence syntenic relationships between the muntjac genome and those of other mammals. We found that the muntjac genome has peculiar features with respect to intron size and evolutionary rates of genes. Inspection of more than 80 pairs of orthologous introns from 15 genes reveals a significant reduction in intron size in the Indian muntjac compared to that of human, mouse, and dog. Evolutionary analysis using 19 genes indicates that the muntjac genes have evolved rapidly compared to other mammals. In addition, we identified and characterized sequence composition of the first BAC clone containing a chromosomal fusion site. Our results shed new light on the genome architecture of the Indian muntjac and suggest that chromosomal rearrangements have been accompanied by other salient genomic changes.

Animals↗

PubMed2006

"Sliding kinetics" of single-walled carbon nanotubes on self-assembled monolayer patterns: beyond random adsorption.

We present the experimental results and theoretical model describing new adsorption kinetics of single-walled carbon nanotubes (swCNTs) onto self-assembled monolayer (SAM) including their sliding motion. The adsorption behavior of swCNTs on large-size SAM patterns is similar to the Langmuir isotherm, while that on nanoscale patterns shows a significant deviation which can be explained by the sliding motion of adsorbed nanotubes. The "sliding chamber" experiment confirms that swCNTs can align along the SAM patterns by sliding motion right above the SAM surfaces. This result provides new scientific insights regarding the adsorption kinetics of one-dimensional nanostructures, and, from a practical point of view, it can be an important guideline to design SAM patterns to assemble carbon nanotubes and nanowires into desired device structures.

Journal Article↗

PubMed2006

CD32B, the human inhibitory Fc-gamma receptor IIB, as a target for monoclonal antibody therapy of B-cell lymphoma.

Human CD32B (FcgammaRIIB), the low-affinity inhibitory receptor for IgG, is the predominant Fc receptor (FcR) present on B cells. Immunohistochemical and expression studies have identified CD32B expression in a variety of B-cell malignancies, suggesting that CD32B is a potential immunotherapeutic target for B-cell malignancies. A high-affinity monoclonal antibody (mAb 2B6), from a novel panel of anti-human CD32B-specific mAbs, was chimerized (ch2B6) and humanized (hu2B6-3.5). Both ch2B6 and hu2B6-3.5 were capable of directing cytotoxicity by peripheral blood mononuclear cells and monocyte-derived macrophages against B-lymphoma lines in vitro. In a human B-cell lymphoma mouse xenograft model, administration of ch2B6 or hu2B6-3.5 reduced tumor growth rate and improved tumor-free survival. Both the in vitro and in vivo activities of 2B6 required an intact Fc, suggesting an FcR-mediated mechanism of action. These data support the hypothesis that CD32B is a viable target for mAb treatment of B-cell lymphoproliferative disorders.

Animals↗

PubMed2006

"Lens" effect in directed assembly of nanowires on gradient molecular patterns.

We report a new phenomenon, named here as the "lens" effect, in the directed-assembly process of nanowires (NWs) on self-assembled monolayer (SAM) patterns. In this process, the adsorption of NWs is focused in the nanoscale regions at the center of microscale SAM patterns with gradient surface molecular density just like an optical lens focuses light. As a proof of concepts, we successfully demonstrated the massive assembly of V2O5 NWs and single-walled carbon nanotubes (swCNTs) with a nanoscale resolution using only microscale molecular patterning methods. This work provides us with important insights about the directed-assembly process, and from a practical point of view, it allows us to generate nanoscale patterns of NWs over a large area for mass fabrication of NW-based devices.

Letter↗

PubMed2006

Field evaluation of a rapid point-of-care assay for targeting antibiotic treatment for trachoma control: a comparative study.

BACKGROUND: Trachoma results from repeated episodes of conjunctival infection with Chlamydia trachomatis and is the leading infectious cause of blindness. To eliminate trachoma, control programmes use the SAFE strategy (Surgery, Antibiotics, Face cleanliness, and Environmental improvement). The A component is designed to treat C trachomatis infection, and is initiated on the basis of the prevalence of the clinical sign trachomatous inflammation-follicular (TF). Unfortunately, TF correlates poorly with C trachomatis infection. We sought to assess a newly developed point-of-care (POC) assay compared with presence of TF for guiding the use of antibiotics for trachoma control. METHODS: We compared performance outcomes of the POC assay and presence of TF using commercial PCR as a comparator in 664 children aged 1-9 years in remote, trachoma-endemic villages in Tanzania. Signs of trachoma were graded according to the WHO simplified trachoma grading system. FINDINGS: Of 664 participants, 128 (19%) were positive for ocular C trachomatis infection by PCR. Presence of TF had a sensitivity of 64.1% (95% CI 55.8-72.4), specificity of 80.2% (76.8-83.6), and positive predictive value of 43.6% (36.5-50.7). By contrast, the POC assay had a sensitivity of 83.6% (77.2-90.0), specificity of 99.4% (98.8-100.0), and positive predictive value of 97.3% (94.2-100.3). Interagreements and intra-agreements between four novice operators were 0.988 (0.973-1.000) and 0.950 (0.894-1.000), respectively. INTERPRETATION: The POC assay is substantially more accurate than TF prevalence in identifying the presence or absence of infection. Additional studies should assess the use of the assay in the planning and monitoring of trachoma control activities.

Anti-Bacterial Agents↗

PubMed2006

Cross-species chromosome painting unveils cytogenetic signatures for the Eulipotyphla and evidence for the polyphyly of Insectivora.

Insectivore-like animals are traditionally believed among the first eutherian mammals that have appeared on the earth. The modern insectivores are thus crucial for understanding the systematics and phylogeny of eutherian mammals as a whole. Here cross-species chromosome painting, with probes derived from flow-sorted chromosomes of human, was used to delimit the homologous chromosomal segments in two Soricidae species, the common shrew (Sorex araneus, 2n = 20/21), and Asiatic short-tailed shrew (Blarinella griselda, 2n = 44), and one Erinaceidae species, the shrew-hedgehog (Neotetracus sinensis, 2n = 32), and human. We report herewith the first comparative maps for the Asiatic short-tailed shrew and the shrew-hedgehog, in addition to a refined comparative map for the common shrew. In total, the 22 human autosomal paints detected 40, 51 and 58 evolutionarily conserved segments in the genomes of common shrew, Asiatic short-tailed shrew, and shrew-hedgehog, respectively, demonstrating that the common shrew has retained a conserved genome organization while the Asiatic short-tailed shrew and shrew-hedgehog have relatively rearranged genomes. In addition to confirming the existence of such ancestral human segmental combinations as HSA 3/21, 12/22, 14/15 and 7/16 that are shared by most eutherian mammals, our study reveals a shared human segmental combination, HSA 4/20, that could phylogenetically unite the Eulipotyphlan (i.e., the core insectivores) species. Our results provide cytogenetic evidence for the polyphyly of the order Insectivora and additional data for the eventual reconstruction of the ancestral eutherian karyotype.

Animals↗

PubMed2006

High-density comparative BAC mapping in the black muntjac (Muntiacus crinifrons): molecular cytogenetic dissection of the origin of MCR 1p+4 in the X1X2Y1Y2Y3 sex chromosome system.

The black muntjac (Muntiacus crinifrons, 2n = 8[female symbol]/9[male symbol]) is a critically endangered mammalian species that is confined to a narrow region of southeastern China. Male black muntjacs have an astonishing X1X2Y1Y2Y3 sex chromosome system, unparalleled in eutherian mammals, involving approximately half of the entire genome. A high-resolution comparative map between the black muntjac (M. crinifrons) and the Chinese muntjac (M. reevesi, 2n = 46) has been constructed based on the chromosomal localization of 304 clones from a genomic BAC (bacterial artificial chromosome) library of the Indian muntjac (M. muntjak vaginalis, 2n = 6[female symbol]/7[male symbol]). In addition to validating the chromosomal homologies between M. reevesi and M. crinifrons defined previously by chromosome painting, the comparative BAC map demonstrates that all tandem fusions that have occurred in the karyotypic evolution of M. crinifrons are centromere-telomere fusions. The map also allows for a more detailed reconstruction of the chromosomal rearrangements leading to this unique and complex sex chromosome system. Furthermore, we have identified 46 BAC clones that could be used to study the molecular evolution of the unique sex chromosomes of the male black muntjacs.

Animals↗

PubMed2006

76-space analysis of grey matter diffusivity: methods and applications.

Diffusion-weighted imaging (DWI) and diffusion tensor imaging (DTI) allow in vivo investigation of molecular motion of tissue water at a microscopic level in cerebral gray matter (GM) and white matter (WM). DWI/DTI measure of water diffusion has been proven to be invaluable for the study of many neurodegenerative diseases (e.g., Alzheimer's disease and Creutzfeldt-Jakob disease) that predominantly involve GM. Thus, quantitative analysis of GM diffusivity is of scientific interest and is promised to have a clinical impact on the investigation of normal brain aging and neuropathology. In this paper, we propose an automated framework for analysis of GM diffusivity in 76 standard anatomic subdivisions of gray matter to facilitate studies of neurodegenerative and other gray matter neurological diseases. The computational framework includes three enabling technologies: (1) automatic parcellation of structural MRI GM into 76 precisely defined neuroanatomic subregions ("76-space"), (2) automated segmentation of GM, WM and CSF based on DTI data, and (3) automatic measurement of the average apparent diffusion coefficient (ADC) in each segmented GM subregion. We evaluate and validate this computational framework for 76-space GM diffusivity analysis using data from normal volunteers and from patients with Creutzfeldt-Jakob disease.

Adult↗

PubMed2006

Phylogenomics of several deer species revealed by comparative chromosome painting with Chinese muntjac paints.

A set of Chinese muntjac (Muntiacus reevesi) chromosome-specific paints has been hybridized onto the metaphases of sika deer (Cervus nippon, CNI, 2n = 66), red deer (Cervus elaphus, CEL, 2n = 62) and tufted deer (Elaphodus cephalophus, ECE, 2n = 47). Thirty-three homologous autosomal segments were detected in genomes of sika deer and red deer, while 31 autosomal homologous segments were delineated in genome of tufted deer. The Chinese muntjac chromosome X probe painted to the whole X chromosome, and the chromosome Y probe gave signals on the Y chromosome as well as distal region of the X chromosome of each species. Our results confirmed that exclusive Robertsonian translocations have contributed to the karyotypic evolution of sika deer and red deer. In addition to Robertsonian translocation, tandem fusions have played a more important role in the karyotypic evolution of tufted deer. Different types of chromosomal rearrangements have led to great differences in the genome organization between cervinae and muntiacinae species. Our analysis testified that six chromosomal fissions in the proposed 2n = 58 ancestral pecoran karyotype led to the formation of 2n = 70 ancestral cervid karyotype and the deer karyotypes is more derived compare with those of bovid species. Combining previous cytogenetic and molecular systematic studies, we analyzed the genome phylogeny for 11 cervid species.

Animals↗

PubMed2006

[Clinical study of the setting of positive end expiratory pressure in patients with acute cardiogenic pulmonary edema during mechanical ventilation].

OBJECTIVE: To compare the effects on hemodynamics and lung mechanics when different positive end expiratory pressure (PEEP) levels were used in acute cardiac pulmonary edema. METHODS: Thirty-nine patients with respiratory failure and treated with mechanical ventilation were divided into two groups according to cardiac index (CI). The changes of hemodynamics [including cardiac output (CO), CI, pulmonary capillary blood flow (PCBF), central venous pressure (CVP), surround vascular resistance (SVR)], lung mechanical variables [intrinsic positive end expiratory pressure (PEEPi), peak inspiratory pressure (Ppeak), mean of airway pressure (Pmean), minute volume (MV), alveolar tidal volume (Vtalv)], percutaneous saturation of oxygen (SpO(2)) and blood pressure (BP) were determined with when selected different PEEP levels under the bi-level positive airway pressure (BIPAP) mode in normal cardiac function group (n=18, CI> or =2.0 L.min(-1).m(-2)) and poor cardiac function group (n=20, CI<2.0 L.min(-1)xm(-2)). RESULTS: In normal cardiac function group, PEEP has no effect on hemodynamics when varied from 0-13 cm H(2)O (1 cm H(2)O=0.098 kPa), and Ppeak and PEEPi increased with the elevation of PEEP. Resistance of airway (R) fell when PEEP was increased. However, in poor cardiac function group SVR, CO, CI showed curvilinear changes with an increase in PEEP, and CO, CI were high when PEEP changed from 0 to 7 cm H(2)O, but dropped markedly when PEEP was increased in 13 cm H(2)O, while the changes of SVR was the reverse of CO and CI. The effects on lung mechanics varied relatively smaller range when PEEP was set between 5-7 cm H(2)O, and the burden of breathing was slight. CONCLUSION: The mode of artificial ventilation should be adjusted according to the changes in hemodynamics and lung mechanics. PEEP should be individualized, and 5-7 cm H(2)O (normally below 10 cm H(2)O) is suitable.

Acute Disease↗

PubMed2006

[The use of CAD/CAM system with zirconia in modern prosthodontics].

Computer assisted design/computer assisted machining (CAD/CAM) technology has received considerable clinical and research interest from modern dental practices as a means of delivering all-ceramic restorations. Up to now the CAD/CAM system with zirconia has the highest fracture strength in all all-ceramic materials, and consistently enabled the most esthetic, lifelike reproduction of natural dentition. They have been widely received by both dentists and patients. The CAD/CAM system with zirconia is indicated for crowns and bridges in natural teeth or implants and telescope dentures, the CAD/CAM with zirconia can be placed anywhere in the mouth, and can replace the porcelain crowns and bridges for single crown and bridges less than 6 units. This paper described the techniques of CAD/CAM system with zirconia in fabrication of crowns, bridges, telescope dentures and implant dentures with colored illustrations.

Computer-Aided Design↗

PubMed2005

Computerized image analysis for quantitative neuronal phenotyping in zebrafish.

An integrated microscope image analysis pipeline is developed for automatic analysis and quantification of phenotypes in zebrafish with altered expression of Alzheimer's disease (AD)-linked genes. We hypothesize that a slight impairment of neuronal integrity in a large number of zebrafish carrying the mutant genotype can be detected through the computerized image analysis method. Key functionalities of our zebrafish image processing pipeline include quantification of neuron loss in zebrafish embryos due to knockdown of AD-linked genes, automatic detection of defective somites, and quantitative measurement of gene expression levels in zebrafish with altered expression of AD-linked genes or treatment with a chemical compound. These quantitative measurements enable the archival of analyzed results and relevant meta-data. The structured database is organized for statistical analysis and data modeling to better understand neuronal integrity and phenotypic changes of zebrafish under different perturbations. Our results show that the computerized analysis is comparable to manual counting with equivalent accuracy and improved efficacy and consistency. Development of such an automated data analysis pipeline represents a significant step forward to achieve accurate and reproducible quantification of neuronal phenotypes in large scale or high-throughput zebrafish imaging studies.

Animals↗

PubMed2005

A novel strategy to identify the regulatory DNA-organized cooperations among transcription factors.

To identify the functional contributions of cooperations among transcription factors on regulatory DNA is critical for understanding transcription activation. But so far there is a great lack of effective identifying methods. Here we describe a novel strategy, based on comprehensively perturbed experiments and a computational model, to identify the cooperations among NF-kappaB (p65), CREB, and AP-1 in transcription activation of human cytomegalovirus major IE1 promoter/enhancer (MIEP). In this strategy, functional profiles of protein-MIEP association and RNA synthesis are achieved through comprehensively perturbing the association of p65, CREB or AP-1 with MIEP and then subjected to the computational model. Consequently, the 'real' cooperations contributing to MIEP activation are found to comprise five but not seven types of potential cooperations. Thus, our research provides a facile systematic approach to identifying the DNA-organized cooperations among transcription factors and understanding transcription activation.

Cyclic AMP Response Element-Binding Protein↗

PubMed2005

Severe maternal morbidity in Canada, 1991-2001.

BACKGROUND: Although death rates are often used to monitor the quality of health care, in industrialized countries maternal deaths have become rare. Severe maternal morbidity has therefore been proposed as a supplementary indicator for surveillance of the quality of maternity care. Our purpose in this study was to describe severe maternal morbidity in Canada over a 10-year period, among women with or without major pre-existing conditions. METHODS: We carried out a retrospective cohort study of severe maternal morbidity involving 2,548,824 women who gave birth in Canadian hospitals between 1991 and 2000. Thirteen conditions that may threaten the life of the mother (e.g., eclampsia) and 11 major pre-existing chronic conditions (e.g., diabetes) that could be identified from diagnostic codes were noted. RESULTS: The overall rate of severe maternal morbidity was 4.38 per 1000 deliveries. The fatality rate among these women was 158 times that of the entire sample. Rates of venous thromboembolism, uterine rupture, adult respiratory distress syndrome, pulmonary edema, myocardial infarction, severe postpartum hemorrhage requiring hysterectomy, and assisted ventilation increased substantially from 1991 to 2000. The presence of major pre-existing conditions increased the risk of severe maternal morbidity to 6-fold. INTERPRETATION: Severe maternal morbidity occurs in about 1 of 250 deliveries in Canada, with marked recent increases in certain morbid conditions such as pulmonary edema, myocardial infarction, hemorrhage requiring hysterectomy, and the use of assisted ventilation.

Adult↗

PubMed2005

On-wire lithography.

We report a high-throughput procedure for lithographically processing one-dimensional nanowires. This procedure, termed on-wire lithography, combines advances in template-directed synthesis of nanowires with electrochemical deposition and wet-chemical etching and allows routine fabrication of face-to-face disk arrays and gap structures in the range of five to several hundred nanometers. We studied the transport properties of 13-nanometer gaps with and without nanoscopic amounts of conducting polymers deposited within by dip-pen nanolithography.

Journal Article↗