101 research outputs found
Network Clustering Revealed the Systemic Alterations of Mitochondrial Protein Expression
The mitochondrial protein repertoire varies depending on the cellular state. Protein component modifications caused by mitochondrial DNA (mtDNA) depletion are related to a wide range of human diseases; however, little is known about how nuclear-encoded mitochondrial proteins (mt proteome) changes under such dysfunctional states. In this study, we investigated the systemic alterations of mtDNA-depleted (ρ0) mitochondria by using network analysis of gene expression data. By modularizing the quantified proteomics data into protein functional networks, systemic properties of mitochondrial dysfunction were analyzed. We discovered that up-regulated and down-regulated proteins were organized into two predominant subnetworks that exhibited distinct biological processes. The down-regulated network modules are involved in typical mitochondrial functions, while up-regulated proteins are responsible for mtDNA repair and regulation of mt protein expression and transport. Furthermore, comparisons of proteome and transcriptome data revealed that ρ0 cells attempted to compensate for mtDNA depletion by modulating the coordinated expression/transport of mt proteins. Our results demonstrate that mt protein composition changed to remodel the functional organization of mitochondrial protein networks in response to dysfunctional cellular states. Human mt protein functional networks provide a framework for understanding how cells respond to mitochondrial dysfunctions
Soluble TNF Mediates the Transition from Pulmonary Inflammation to Fibrosis
BACKGROUND: Fibrosis, the replacement of functional tissue with excessive fibrous tissue, can occur in all the main tissues and organ systems, resulting in various pathological disorders. Idiopathic Pulmonary Fibrosis is a prototype fibrotic disease involving abnormal wound healing in response to multiple sites of ongoing alveolar epithelial injury. METHODOLOGY/PRINCIPAL FINDINGS: To decipher the role of TNF and TNF-mediated inflammation in the development of fibrosis, we have utilized the bleomycin-induced animal model of Pulmonary Fibrosis and a series of genetically modified mice lacking components of TNF signaling. Transmembrane TNF expression is shown to be sufficient to elicit an inflammatory response, but inadequate for the transition to the fibrotic phase of the disease. Soluble TNF expression is shown to be crucial for lymphocyte recruitment, a prerequisite for TGF-b1 expression and the development of fibrotic lesions. Moreover, through a series of bone marrow transfers, the necessary TNF expression is shown to originate from the non-hematopoietic compartment further localized in apoptosing epithelial cells. CONCLUSIONS: These results suggest a primary detrimental role of soluble TNF in the pathologic cascade, separating it from the beneficial role of transmembrane TNF, and indicate the importance of assessing the efficacy of soluble TNF antagonists in the treatment of Idiopathic Pulmonary Fibrosis
Inventory of current EU paediatric vision and hearing screening programmes
Background: We examined the diversity in paediatric vision and hearing screening
programmes in Europe.
Methods: Themes relevant for comparison of screening programmes were derived from
literature and used to compile three questionnaires on vision, hearing and public-health
screening. Tests used, professions involved, age and frequency of testing seem to influence
sensitivity, specificity and costs most. Questionnaires were sent to ophthalmologists,
orthoptists, otolaryngologists and audiologists involved in paediatric screening in all EU fullmember,
candidate and associate states. Answers were cross-checked.
Results: Thirty-nine countries participated; 35 have a vision screening programme, 33 a
nation-wide neonatal hearing screening programme. Visual acuity (VA) is measured in 35
countries, in 71% more than once. First measurement of VA varies from three to seven years
of age, but is usually before the age of five. At age three and four picture charts, including Lea
Hyvarinen are used most, in children over four Tumbling-E and Snellen. As first hearing
screening test otoacoustic emission (OAE) is used most in healthy neonates, and auditory
brainstem response (ABR) in premature newborns. The majority of hearing testing
programmes are staged; children are referred after one to four abnormal tests. Vision
screening is performed mostly by paediatricians, ophthalmologists or nurses. Funding is
mostly by health insurance or state. Coverage was reported as >95% in half of countries, but
reporting was often not first-hand.
Conclusion: Largest differences were found in VA charts used (12), professions involved in
vision screening (10), number of hearing screening tests before referral (1-4) and funding
sources (8)
Immunocytochemical localization on β-hexosaminidase and electron-microscopic characterization of human fibroblasts following treatment with monensin and nigericin
Association between maternal obesity and group B streptococcus (GBS) colonization in a national US cohort
Is group B streptococcus colonization associated with chorioamnionitis in an era of intrapartum antibiotic prophylaxis?
Mutation and biochemical analysis in carnitine palmitoyltransferase type II (CPT II) deficiency
Labour management of a woman with carnitine palmitoyl transferase type 2 deficiency
Carnitine palmitoyl transferase (CPT) type 2 deficiency is a disorder of mitochondrial fatty acid oxidation. In situations where energy stores are inadequate, such as may occur during labour women with CPT type 2 deficiency are at risk of rhabdomyolysis. There is limited experience in the management of women with this condition in labour. We report a case of successful labour management of a woman with CPT type 2 deficiency, together with a brief review of the published case reports and a discussion of the issues surrounding anaesthetic management.E.M. Slater, R. Grivell and A.M. Cyn
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