Carbonic anhydrases in metazoan model organisms : molecules, mechanisms, and physiology

During the past three decades, mice, zebrafish, fruit flies, and Caenorhabditis elegans have been the primary model organisms used for the study of various biological phenomena. These models have also been adopted and developed to investigate the physiological roles of carbonic anhydrases (CAs) and carbonic anhydrase-related proteins (CARPs). These proteins belong to eight CA families and are identified by Greek letters: α, β, γ, δ, ζ, η, θ, and ι. Studies using model organisms have focused on two CA families, α-CAs and β-CAs, which are expressed in both prokaryotic and eukaryotic organisms with species-specific distribution patterns and unique functions. This review covers the biological roles of CAs and CARPs in light of investigations performed in model organisms. Functional studies demonstrate that CAs are not only linked to the regulation of pH homeostasis, the classical role of CAs, but also contribute to a plethora of previously undescribed functions.acceptedVersionPeer reviewe

Coordinate up-regulation of TMEM97 and cholesterol biosynthesis genes in normal ovarian surface epithelial cells treated with progesterone: implications for pathogenesis of ovarian cancer

<p>Abstract</p> <p>Background</p> <p>Ovarian cancer (OvCa) most often derives from ovarian surface epithelial (OSE) cells. Several lines of evidence strongly suggest that increased exposure to progesterone (P4) protects women against developing OvCa. However, the underlying mechanisms of this protection are incompletely understood.</p> <p>Methods</p> <p>To determine downstream gene targets of P4, we established short term <it>in vitro </it>cultures of non-neoplastic OSE cells from six subjects, exposed the cells to P4 (10^-6M) for five days and performed transcriptional profiling with oligonucleotide microarrays containing over 22,000 transcripts.</p> <p>Results</p> <p>We identified concordant but modest gene expression changes in cholesterol/lipid homeostasis genes in three of six samples (responders), whereas the other three samples (non-responders) showed no expressional response to P4. The most up-regulated gene was <it>TMEM97 </it>which encodes a transmembrane protein of unknown function (MAC30). Analyses of outlier transcripts, whose expression levels changed most significantly upon P4 exposure, uncovered coordinate up-regulation of 14 cholesterol biosynthesis enzymes, insulin-induced gene 1, low density lipoprotein receptor, <it>ABCG1</it>, endothelial lipase, stearoyl- CoA and fatty acid desaturases, long-chain fatty-acyl elongase, and down-regulation of steroidogenic acute regulatory protein and <it>ABCC6</it>. Highly correlated tissue-specific expression patterns of <it>TMEM97 </it>and the cholesterol biosynthesis genes were confirmed by analysis of the GNF Atlas 2 universal gene expression database. Real-time quantitative RT-PCR analyses revealed 2.4-fold suppression of the <it>TMEM97 </it>gene expression in short-term cultures of OvCa relative to the normal OSE cells.</p> <p>Conclusion</p> <p>These findings suggest that a co-regulated transcript network of cholesterol/lipid homeostasis genes and <it>TMEM97 </it>are downstream targets of P4 in normal OSE cells and that <it>TMEM97 </it>plays a role in cholesterol and lipid metabolism. The P4-induced alterations in cholesterol and lipid metabolism in OSE cells might play a role in conferring protection against OvCa.</p

Electric impedance assisted micropipette aspiration

Micropipette aspiration is a technique to selectively isolate cells from cell cultures using suction pressure. Cells can selectively be isolated one by one from neighboring cells into the micropipette. This paper presents a novel micropipette aspiration system assisted by an impedance measurement system. Furthermore, a method to reduce the adhesion force at a single cell level for a gentler detachment of the cell from a cultivation surface and surrounding cell connections is proposed.Peer reviewe

Cost-effectiveness analysis of breast cancer control interventions in peru

Contains fulltext : 125263.pdf (publisher's version ) (Open Access)OBJECTIVES: In Peru, a country with constrained health resources, breast cancer control is characterized by late stage treatment and poor survival. To support breast cancer control in Peru, this study aims to determine the cost-effectiveness of different breast cancer control interventions relevant for the Peruvian context. METHODS: We performed a cost-effectiveness analysis (CEA) according to WHO-CHOICE guidelines, from a healthcare perspective. Different screening, early detection, palliative, and treatment interventions were evaluated using mathematical modeling. Effectiveness estimates were based on observational studies, modeling, and on information from Instituto Nacional de Enfermedades Neoplasicas (INEN). Resource utilizations and unit costs were based on estimates from INEN and observational studies. Cost-effectiveness estimates are in 2012 United States dollars (US$) per disability adjusted life year (DALY) averted. RESULTS: The current breast cancer program in Peru ($8,426 per DALY averted) could be improved through implementing triennial or biennial screening strategies. These strategies seem the most cost-effective in Peru, particularly when mobile mammography is applied (from $4,125 per DALY averted), or when both CBE screening and mammography screening are combined (from$4,239 per DALY averted). Triennially, these interventions costs between $63 million and$72 million per year. Late stage treatment, trastuzumab therapy and annual screening strategies are the least cost-effective. CONCLUSIONS: Our analysis suggests that breast cancer control in Peru should be oriented towards early detection through combining fixed and mobile mammography screening (age 45-69) triennially. However, a phased introduction of triennial CBE screening (age 40-69) with upfront FNA in non-urban settings, and both CBE (age 40-49) and fixed mammography screening (age 50-69) in urban settings, seems a more feasible option and is also cost-effective. The implementation of this intervention is only meaningful if awareness raising, diagnostic, referral, treatment and basic palliative services are simultaneously improved, and if financial and organizational barriers to these services are reduced