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31.
32.
Guo Xiaoya Zhu Jian Maehara Akiko Monoly David Samady Habib Wang Liang Billiar Kristen L. Zheng Jie Yang Chun Mintz Gary S. Giddens Don P. Tang Dalin 《Biomechanics and modeling in mechanobiology》2017,16(1):333-344
Biomechanics and Modeling in Mechanobiology - Computational models have been used to calculate plaque stress and strain for plaque progression and rupture investigations. An intravascular... 相似文献
33.
Heng Zuo Dalin Tang Chun Yang Glenn Gaudette Kristen L. Billiar Pedro J. del Nidok 《Molecular & cellular biomechanics : MCB》2015,12(2):67-85
Right ventricular (RV) dysfunction is a common cause of heart failure in patients with congenital heart defects and often leads to impaired functional capacity and premature death. Myocardial tissue regeneration techniques are being developed for the potential that viable myocardium may be regenerated to replace scar tissues in the heart or used as patch material in heart surgery. 3D computational RV/LV/Patch models with fluid-structure interactions (FSI) were constructed based on data from a healthy dog heart to obtain local fluid dynamics and structural stress/strain information and identify optimal conditions under which tissue regeneration techniques could achieve best outcome. RV/LV/Patch geometry and blood pressure data were obtained from a dog following established procedures. Four FSI models were used to quantify the influence of different patch materials (Dacron scaffold, treated pericardium) on local environment around the patch area, especially focusing on the thickness and stiffness of the patch. Our results indicated that changes in patch stiffness had little impact on the ejection fraction of the right ventricle because the total patch area was small. However, patch stiffness had huge impact on local RV maximum principal stress (Stress-P1) and strain (Strain-P1) around the patch area. Compared to the no-patch model, patch models had increased Stress-P1 and decreased Strain-P1 values in the patch area. Softer patches were associated with greater stress/strain variations. Thinner patch led to complex local flow environment which may have impact on myocytes seeding and RV remodeling. Our multi-physics RV/LV/Patch FSI model can serve as a useful tool to investigate cellular biology and tissue regeneration under localized flow and structural stress environment. 相似文献
34.
HMGB1: endogenous danger signaling 总被引:12,自引:0,他引:12
Klune JR Dhupar R Cardinal J Billiar TR Tsung A 《Molecular medicine (Cambridge, Mass.)》2008,14(7-8):476-484
While foreign pathogens and their products have long been known to activate the innate immune system, the recent recognition of a group of endogenous molecules that serve a similar function has provided a framework for understanding the overlap between the inflammatory responses activated by pathogens and injury. These endogenous molecules, termed alarmins, are normal cell constituents that can be released into the extracellular milieu during states of cellular stress or damage and subsequently activate the immune system. One nuclear protein, High mobility group box-1 (HMGB1), has received particular attention as fulfilling the functions of an alarmin by being involved in both infectious and non-infectious inflammatory conditions. Once released, HMGB1 signals through various receptors to activate immune cells involved in the immune process. Although initial studies demonstrated HMGB1 as a late mediator of sepsis, recent findings indicate HMGB1 to have an important role in models of non-infectious inflammation, such as autoimmunity, cancer, trauma, and ischemia reperfusion injury. Furthermore, in contrast to its pro-inflammatory functions, there is evidence that HMGB1 also has restorative effects leading to tissue repair and regeneration. The complex functions of HMGB1 as an archetypical alarmin are outlined here to review our current understanding of a molecule that holds the potential for treatment in many important human conditions. 相似文献
35.
Peter Chung Tracy Cook Kaihong Liu Yoram Vodovotz Ruben Zamora Sydney Finkelstein Timothy Billiar David Blumberg 《Nitric oxide》2003,8(2):119-126
Nitric oxide (NO) has been reported to sensitize cancer cells to radiation. Since delivery of NO to tumors is limited in vivo by systemic toxicity of NO, we examined the potential of gene delivery of the human inducible nitric oxide synthase (iNOS) gene as a means of achieving high output NO production. We successfully transduced two colorectal cancer cell lines as evidenced by increased iNOS protein accumulation and nitrite production. We found that overexpression of iNOS enhanced the effects of radiation on apoptosis in both cell lines in a caspase-dependent fashion. Gene transfer of iNOS holds much promise as a potential radiosensitizer of cancer cells since it increases apoptosis in an additive manner with radiation. 相似文献
36.
Huang CS Kawamura T Peng X Tochigi N Shigemura N Billiar TR Nakao A Toyoda Y 《Biochemical and biophysical research communications》2011,(2):253-258
Entry of enveloped viruses into cells is initiated by binding of their envelope glycoproteins (Envs) to cell surface-associated receptors. The Crimean-Congo hemorrhagic fever virus (CCHFV) has two Envs, Gn and Gc, with poorly understood role in binding to susceptible cells. We expressed codon optimized Gn and Gc, and identified independently folded soluble Env fragments, one of which (Gc residues 180–300) bound CCHFV susceptible cells supposedly by interacting with a putative receptor. This receptor binding domain (RBD) was used to identify its interacting partner by coimmunoprecipitation and mass spectrometry. Thus we identified the human cell surface nucleolin as a putative CCHFV entry factor. Nucleolin was expressed on all susceptible cells tested but not on the surface of cells resistant to CCHFV infection. Further studies are needed to explore the nucleolin function as a plausible CCHFV receptor and the molecular mechanisms of the Gc-nucleolin interactions. The identification of the CCHFV RBD and its binding partner could provide novel targets for therapy and tools for prevention as well as more complete understanding of the mechanisms of CCHFV entry and pathogenesis. 相似文献
37.
Evolution of eutherian cytochrome c oxidase subunit II: heterogeneous rates of protein evolution and altered interaction with cytochrome c 总被引:3,自引:1,他引:2
Cytochrome c oxidase subunit II (COII), encoded by the mitochondrial
genome, exhibits one of the most heterogeneous rates of amino acid
replacement among placental mammals. Moreover, it has been demonstrated
that cytochrome c oxidase has undergone a structural change in higher
primates which has altered its physical interaction with cytochrome c. We
collected a large data set of COII sequences from several orders of mammals
with emphasis on primates, rodents, and artiodactyls. Using phylogenetic
hypotheses based on data independent of the COII gene, we demonstrated that
an increased number of amino acid replacements are concentrated among
higher primates. Incorporating approximate divergence dates derived from
the fossil record, we find that most of the change occurred independently
along the New World monkey lineage and in a rapid burst before apes and Old
World monkeys diverged. There is some evidence that Old World monkeys have
undergone a faster rate of nonsynonymous substitution than have apes. Rates
of substitution at four-fold degenerate sites in primates are relatively
homogeneous, indicating that the rate heterogeneity is restricted to
nondegenerate sites. Excluding the rate acceleration mentioned above,
primates, rodents, and artiodactyls have remarkably similar nonsynonymous
replacement rates. A different pattern is observed for transversions at
four-fold degenerate sites, for which rodents exhibit a higher rate of
replacement than do primates and artiodactyls. Finally, we hypothesize
specific amino acid replacements which may account for much of the
structural difference in cytochrome c oxidase between higher primates and
other mammals.
相似文献
38.
Molecular evolution of cytochrome c oxidase: rate variation among subunit VIa isoforms 总被引:3,自引:1,他引:2
Schmidt TR; Jaradat SA; Goodman M; Lomax MI; Grossman LI 《Molecular biology and evolution》1997,14(6):595-601
Cytochrome c oxidase (COX) consists of 13 subunits, 3 encoded in the
mitochondrial genome and 10 in the nucleus. Little is known of the role of
the nuclear-encoded subunits, some of which exhibit tissue-specific
isoforms. Subunit VIa is unique in having tissue-specific isoforms in all
mammalian species examined. We examined relative evolutionary rates for the
COX6A heart (H) and liver (L) isoform genes along the length of the
molecule, specifically in relation to the tissue-specific function(s) of
the two isoforms. Nonsynonymous (amino acid replacement) substitutions in
the COX6AH gene occurred more frequently than in the ubiquitously expressed
COX6AL gene. Maximum-parsimony analysis and sequence divergences from
reconstructed ancestral sequences revealed that after the ancestral COX6A
gene duplicated to yield the genes for the H and L isoforms, the sequences
encoding the mitochondrial matrix region of the COX VIa protein experienced
an elevated rate of nonsynonymous substitutions relative to synonymous
substitutions. This is expected for relaxed selective constraints after
gene duplication followed by purifying selection to preserve the
replacements with tissue-specific functions.
相似文献
39.
Summary The distribution of (125I) alpha bungarotoxin (-BTX) binding sites in the suprachiasmatic nucleus (SCN) of the adult female rat was examined by electron-microscopic autoradiography. The ultrastructural distribution of silver grains was analysed by line source, direct point count, and 50% probability circle methods. Real grain distribution was significantly different from that of randomly generated hypothetical grains. Line source analysis demonstrated two populations of sources: one associated with membranes, and one inside neuronal structures. Probability circle analysis of shared grains indicated that membrane-bound-radioactive sources were mainly asssociated with axo-dendritic appositions. Only a small proportion of labeled neuronal interfaces exhibited synaptic differentiations in the plane of section. However, the compartment containing synaptic terminals was the most enriched when comparing real to hypothetical grains. Probability circle analysis of exclusive grains demonstrated that sources that were not associated with neuronal plasma membranes were likely to be within nerve cell bodies and dendrites. It is concluded that the majority of specifically labeled -BTX binding sites in the SCN is membrane bound, and may be associated with axodendritic synaptic transmission. The presence of a significant proportion of the label in the soma and dendrites of suprachiasmatic neurons 24 h after ventricular infusion suggests that some of the labeled binding sites (junctional or nonjunctional) may be internalized within these two compartments. 相似文献
40.