127 research outputs found
Room temperature plasmon laser by total internal reflection
Plasmon lasers create and sustain intense and coherent optical fields below
light's diffraction limit with the unique ability to drastically enhance
light-matter interactions bringing fundamentally new capabilities to
bio-sensing, data storage, photolithography and optical communications.
However, these important applications require room temperature operation, which
remains a major hurdle. Here, we report a room temperature semiconductor
plasmon laser with both strong cavity feedback and optical confinement to
1/20th of the wavelength. The strong feedback arises from total internal
reflection of surface plasmons, while the confinement enhances the spontaneous
emission rate by up to 20 times.Comment: 8 Page, 2 Figure
Control of echolocation pulses by neurons of the nucleus ambiguus in the rufous horseshoe bat,Rhinolophus rouxi
Wnt and Hedgehog Are Critical Mediators of Cigarette Smoke-Induced Lung Cancer
BACKGROUND: Lung cancer is the leading cause of cancer death in the world, and greater than 90% of lung cancers are cigarette smoke-related. Current treatment options are inadequate, because the molecular basis of cigarette-induced lung cancer is poorly understood. METHODOLOGY/PRINCIPAL FINDINGS: Here, we show that human primary or immortalized bronchial epithelial cells exposed to cigarette smoke for eight days in culture rapidly proliferate, show anchorage-independent growth, and form tumors in nude mice. Using this model of the early stages of smoke-induced tumorigenesis, we examined the molecular changes leading to lung cancer. We observed that the embryonic signaling pathways mediated by Hedgehog and Wnt are activated by smoke. Pharmacological inhibition of these pathways blocked the transformed phenotype. CONCLUSIONS/SIGNIFICANCE: These experiments provide a model in which the early stages of smoke-induced tumorigenesis can be elicited, and should permit us to identify molecular changes driving this process. Results obtained so far indicate that smoke-induced lung tumors are driven by activation of two embryonic regulatory pathways, Hedgehog (Hh) and Wnt. Based on the current and emerging availability of drugs to inhibit Hh and Wnt signaling, it is possible that an understanding of the role of Hh and Wnt in lung cancer pathogenesis will lead to the development of new therapies
In Vivo Mechanical Loading Modulates Insulin-Like Growth Factor Binding Protein-2 Gene Expression in Rat Osteocytes
Mechanical stimulation is essential for maintaining skeletal integrity. Mechanosensitive osteocytes are important during the osteogenic response. The growth hormone-insulin-like growth factor (GH-IGF) axis plays a key role during regulation of bone formation and remodeling. Insulin-like growth factor binding proteins (IGFBPs) are able to modulate IGF activity. The aim of this study was to characterize the role of IGFBP-2 in the translation of mechanical stimuli into bone formation locally in rat tibiae. Female Wistar rats were assigned to three groups (n = 5): load, sham, and control. The four-point bending model was used to induce a single period of mechanical loading on the tibial shaft. The effect on IGFBP-2 mRNA expression 6 hours after stimulation was determined with nonradioactive in situ hybridization on decalcified tibial sections. Endogenous IGFBP-2 mRNA was expressed in trabecular and cortical osteoblasts, some trabecular and subendocortical osteocytes, intracortical endothelial cells of blood vessels, and periosteum. Megakaryocytes, macrophages, and myeloid cells also expressed IGFBP-2 mRNA. Loading and sham loading did not affect IGFBP-2 mRNA expression in osteoblasts, bone marrow cells, and chondrocytes. An increase of IGFBP-2 mRNA-positive osteocytes was shown in loaded (1.68-fold) and sham-loaded (1.35-fold) endocortical tibial shaft. In conclusion, 6 hours after a single loading session, the number of IGFBP-2 mRNA-expressing osteocytes at the endosteal side of the shaft and inner lamellae was increased in squeezed and bended tibiae. Mechanical stimulation modulates IGFBP-2 mRNA expression in endocortical osteocytes. We suggest that IGFBP-2 plays a role in the lamellar bone formation process
Adr1 and Cat8 Mediate Coactivator Recruitment and Chromatin Remodeling at Glucose-Regulated Genes
Adr1 and Cat8 co-regulate numerous glucose-repressed genes in S. cerevisiae, presenting a unique opportunity to explore their individual roles in coactivator recruitment, chromatin remodeling, and transcription.We determined the individual contributions of Cat8 and Adr1 on the expression of a cohort of glucose-repressed genes and found three broad categories: genes that need both activators for full derepression, genes that rely mostly on Cat8 and genes that require only Adr1. Through combined expression and recruitment data, along with analysis of chromatin remodeling at two of these genes, ADH2 and FBP1, we clarified how these activators achieve this wide range of co-regulation. We find that Adr1 and Cat8 are not intrinsically different in their abilities to recruit coactivators but rather, promoter context appears to dictate which activator is responsible for recruitment to specific genes. These promoter-specific contributions are also apparent in the chromatin remodeling that accompanies derepression: ADH2 requires both Adr1 and Cat8, whereas, at FBP1, significant remodeling occurs with Cat8 alone. Although over-expression of Adr1 can compensate for loss of Cat8 at many genes in terms of both activation and chromatin remodeling, this over-expression cannot complement all of the cat8Delta phenotypes.Thus, at many of the glucose-repressed genes, Cat8 and Adr1 appear to have interchangeable roles and promoter architecture may dictate the roles of these activators
The Features of the Synovium in Early Rheumatoid Arthritis According to the 2010 ACR/EULAR Classification Criteria
OBJECTIVES: It has been shown in early arthritis cohorts that the 2010 ACR/EULAR criteria for rheumatoid arthritis (RA) enable an earlier diagnosis, perhaps at the cost of a somewhat more heterogeneous patient population. We describe the features of synovial inflammation in RA patients classified according to these new criteria. METHODS: At baseline, synovial tissue biopsy samples were obtained from disease-modifying antirheumatic drug (DMARD)-naïve early RA patients (clinical signs and symptoms <1 year). Synovial tissue was analyzed for cell infiltration, vascularity, and expression of adhesion molecules. Stained sections were evaluated by digital image analysis. Patients were classified according to the two different sets of classification criteria, autoantibody status, and outcome. FINDINGS: Synovial tissue of 69 RA patients according to 2010 ACR/EULAR criteria was analyzed: 56 patients who fulfilled the criteria for RA at baseline and 13 who were initially diagnosed as undifferentiated arthritis but fulfilled criteria for RA upon follow up. The synovium at baseline was infiltrated by plasma cells, macrophages, and T cells as well as other cells, and findings were comparable to those when patients were selected based on the 1987 ACR criteria for RA. There was no clear cut difference in the characteristics of the synovium between RA patients initially diagnosed as undifferentiated arthritis and those who already fulfilled classification criteria at baseline. CONCLUSION: The features of synovial inflammation are similar when the 2010 ACR/EULAR classification criteria are used compared to the 1987 ACR criteria
Proteomic Identification of Protein Targets for 15-Deoxy-Δ12,14-Prostaglandin J2 in Neuronal Plasma Membrane
15-deoxy-Δ12,14-prostaglandin J2 (15d-PGJ2) is one of factors contributed to the neurotoxicity of amyloid β (Aβ), a causative protein of Alzheimer's disease. Type 2 receptor for prostaglandin D2 (DP2) and peroxysome-proliferator activated receptorγ (PPARγ) are identified as the membrane receptor and the nuclear receptor for 15d-PGJ2, respectively. Previously, we reported that the cytotoxicity of 15d-PGJ2 was independent of DP2 and PPARγ, and suggested that 15d-PGJ2 induced apoptosis through the novel specific binding sites of 15d-PGJ2 different from DP2 and PPARγ. To relate the cytotoxicity of 15d-PGJ2 to amyloidoses, we performed binding assay [3H]15d-PGJ2 and specified targets for 15d-PGJ2 associated with cytotoxicity. In the various cell lines, there was a close correlation between the susceptibilities to 15d-PGJ2 and fibrillar Aβ. Specific binding sites of [3H]15d-PGJ2 were detected in rat cortical neurons and human bronchial smooth muscle cells. When the binding assay was performed in subcellular fractions of neurons, the specific binding sites of [3H]15d-PGJ2 were detected in plasma membrane, nuclear and cytosol, but not in microsome. A proteomic approach was used to identify protein targets for 15d-PGJ2 in the plasma membrane. By using biotinylated 15d-PGJ2, eleven proteins were identified as biotin-positive spots and classified into three different functional proteins: glycolytic enzymes (Enolase2, pyruvate kinase M1 (PKM1) and glyceraldehyde 3-phosphate dehydrogenase (GAPDH)), molecular chaperones (heat shock protein 8 and T-complex protein 1 subunit α), cytoskeletal proteins (Actin β, F-actin-capping protein, Tubulin β and Internexin α). GAPDH, PKM1 and Tubulin β are Aβ-interacting proteins. Thus, the present study suggested that 15d-PGJ2 plays an important role in amyloidoses not only in the central nervous system but also in the peripheral tissues
The epidemiology of mild cognitive impairment (MCI) and Alzheimer’s disease (AD) in community-living seniors: protocol of the MemoVie cohort study, Luxembourg
BACKGROUND: Cognitive impairment and Alzheimer’s disease (AD) are increasingly considered a major public health problem. The MemoVie cohort study aims to investigate the living conditions or risk factors under which the normal cognitive capacities of the senior population in Luxembourg (≥ 65 year-old) evolve (1) to mild cognitive impairment (MCI) – transitory non-clinical stage – and (2) to AD. Identifying MCI and AD predictors undeniably constitutes a challenge in public health in that it would allow interventions which could protect or delay the occurrence of cognitive disorders in elderly people. In addition, the MemoVie study sets out to generate hitherto unavailable data, and a comprehensive view of the elderly population in the country. METHODS/DESIGN: The study has been designed with a view to highlighting the prevalence in Luxembourg of MCI and AD in the first step of the survey, conducted among participants selected from a random sample of the general population. A prospective cohort is consequently set up in the second step, and appropriate follow-up of the non-demented participants allows improving the knowledge of the preclinical stage of MCI. Case-control designs are used for cross-sectional or retrospective comparisons between outcomes and biological or clinical factors. To ensure maximal reliability of the information collected, we decided to opt for structured face to face interviews. Besides health status, medical and family history, demographic and socio-cultural information are explored, as well as education, habitat network, social behavior, leisure and physical activities. As multilingualism is expected to challenge the cognitive alterations associated with pathological ageing, it is additionally investigated. Data relative to motor function, including balance, walk, limits of stability, history of falls and accidents are further detailed. Finally, biological examinations, including ApoE genetic polymorphism are carried out. In addition to standard blood parameters, the lipid status of the participants is subsequently determined from the fatty acid profiles in their red blood cells. The study obtained the legal and ethical authorizations. DISCUSSION: By means of the multidisciplinary MemoVie study, new insights into the onset of cognitive impairment during aging should be put forward, much to the benefit of intervention strategies as a whole
Cholinergic receptor pathways involved in apoptosis, cell proliferation and neuronal differentiation
Acetylcholine (ACh) has been shown to modulate neuronal differentiation during early development. Both muscarinic and nicotinic acetylcholine receptors (AChRs) regulate a wide variety of physiological responses, including apoptosis, cellular proliferation and neuronal differentiation. However, the intracellular mechanisms underlying these effects of AChR signaling are not fully understood. It is known that activation of AChRs increase cellular proliferation and neurogenesis and that regulation of intracellular calcium through AChRs may underlie the many functions of ACh. Intriguingly, activation of diverse signaling molecules such as Ras-mitogen-activated protein kinase, phosphatidylinositol 3-kinase-Akt, protein kinase C and c-Src is modulated by AChRs. Here we discuss the roles of ACh in neuronal differentiation, cell proliferation and apoptosis. We also discuss the pathways involved in these processes, as well as the effects of novel endogenous AChRs agonists and strategies to enhance neuronal-differentiation of stem and neural progenitor cells. Further understanding of the intracellular mechanisms underlying AChR signaling may provide insights for novel therapeutic strategies, as abnormal AChR activity is present in many diseases
Differential regulation of mitochondrial pyruvate carrier genes modulates respiratory capacity and stress tolerance in yeast
Mpc proteins are highly conserved from yeast to humans and are necessary for the uptake of pyruvate at the inner mitochondrial membrane, which is used for leucine and valine biosynthesis and as a fuel for respiration. Our analysis of the yeast MPC gene family suggests that amino acid biosynthesis, respiration rate and oxidative stress tolerance are regulated by changes in the Mpc protein composition of the mitochondria. Mpc2 and Mpc3 are highly similar but functionally different: Mpc2 is most abundant under fermentative non stress conditions and important for amino acid biosynthesis, while Mpc3 is the most abundant family member upon salt stress or when high respiration rates are required. Accordingly, expression of the MPC3 gene is highly activated upon NaCl stress or during the transition from fermentation to respiration, both types of regulation depend on the Hog1 MAP kinase. Overexpression experiments show that gain of Mpc2 function leads to a severe respiration defect and ROS accumulation, while Mpc3 stimulates respiration and enhances tolerance to oxidative stress. Our results identify the regulated mitochondrial pyruvate uptake as an important determinant of respiration rate and stress resistance.This work was supported by Ministerio de Economia y Competitividad grant BFU2011-23326 to M.P.; A.T.-G. was supported by a JAE predoctoral grant from Consejo Superior de Investigaciones Cientificas. The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript.Timón Gómez, A.; Proft ., MH.; Pascual-Ahuir Giner, MD. (2013). Differential regulation of mitochondrial pyruvate carrier genes modulates respiratory capacity and stress tolerance in yeast. PLoS ONE. 8(11):1-9. doi:10.1371/journal.pone.0079405S19811Murphy, M. P. (2008). How mitochondria produce reactive oxygen species. Biochemical Journal, 417(1), 1-13. doi:10.1042/bj20081386Pan, Y. (2011). Mitochondria, reactive oxygen species, and chronological aging: A message from yeast. Experimental Gerontology, 46(11), 847-852. doi:10.1016/j.exger.2011.08.007Perrone, G. G., Tan, S.-X., & Dawes, I. W. (2008). Reactive oxygen species and yeast apoptosis. Biochimica et Biophysica Acta (BBA) - Molecular Cell Research, 1783(7), 1354-1368. doi:10.1016/j.bbamcr.2008.01.023Galdieri, L., Mehrotra, S., Yu, S., & Vancura, A. (2010). Transcriptional Regulation in Yeast during Diauxic Shift and Stationary Phase. OMICS: A Journal of Integrative Biology, 14(6), 629-638. doi:10.1089/omi.2010.0069Broach, J. R. (2012). Nutritional Control of Growth and Development in Yeast. Genetics, 192(1), 73-105. doi:10.1534/genetics.111.135731Hedbacker, K. (2008). SNF1/AMPK pathways in yeast. Frontiers in Bioscience, 13(13), 2408. doi:10.2741/2854Martínez-Pastor, M., Proft, M., & Pascual-Ahuir, A. (2010). Adaptive Changes of the Yeast Mitochondrial Proteome in Response to Salt Stress. OMICS: A Journal of Integrative Biology, 14(5), 541-552. doi:10.1089/omi.2010.0020Pastor, M. M., Proft, M., & Pascual-Ahuir, A. (2009). Mitochondrial Function Is an Inducible Determinant of Osmotic Stress Adaptation in Yeast. Journal of Biological Chemistry, 284(44), 30307-30317. doi:10.1074/jbc.m109.050682Saito, H., & Posas, F. (2012). Response to Hyperosmotic Stress. Genetics, 192(2), 289-318. doi:10.1534/genetics.112.140863Ruiz-Roig, C., Noriega, N., Duch, A., Posas, F., & de Nadal, E. (2012). The Hog1 SAPK controls the Rtg1/Rtg3 transcriptional complex activity by multiple regulatory mechanisms. Molecular Biology of the Cell, 23(21), 4286-4296. doi:10.1091/mbc.e12-04-0289Bricker, D. K., Taylor, E. B., Schell, J. C., Orsak, T., Boutron, A., Chen, Y.-C., … Rutter, J. (2012). A Mitochondrial Pyruvate Carrier Required for Pyruvate Uptake in Yeast, Drosophila, and Humans. Science, 337(6090), 96-100. doi:10.1126/science.1218099Herzig, S., Raemy, E., Montessuit, S., Veuthey, J.-L., Zamboni, N., Westermann, B., … Martinou, J.-C. (2012). Identification and Functional Expression of the Mitochondrial Pyruvate Carrier. Science, 337(6090), 93-96. doi:10.1126/science.1218530Winzeler, E. A. (1999). Functional Characterization of the S. cerevisiae Genome by Gene Deletion and Parallel Analysis. Science, 285(5429), 901-906. doi:10.1126/science.285.5429.901Ghaemmaghami, S., Huh, W.-K., Bower, K., Howson, R. W., Belle, A., Dephoure, N., … Weissman, J. S. (2003). Global analysis of protein expression in yeast. Nature, 425(6959), 737-741. doi:10.1038/nature02046Alberti, S., Gitler, A. D., & Lindquist, S. (2007). A suite of Gateway®cloning vectors for high-throughput genetic analysis inSaccharomyces cerevisiae. Yeast, 24(10), 913-919. doi:10.1002/yea.1502Westermann, B., & Neupert, W. (2000). Mitochondria-targeted green fluorescent proteins: convenient tools for the study of organelle biogenesis inSaccharomyces cerevisiae. Yeast, 16(15), 1421-1427. doi:10.1002/1097-0061(200011)16:153.0.co;2-uHong, H.-Y., Yoo, G.-S., & Choi, J.-K. (2000). Direct Blue 71 staining of proteins bound to blotting membranes. Electrophoresis, 21(5), 841-845. doi:10.1002/(sici)1522-2683(20000301)21:53.0.co;2-4Nakai, T., Yasuhara, T., Fujiki, Y., & Ohashi, A. (1995). Multiple genes, including a member of the AAA family, are essential for degradation of unassembled subunit 2 of cytochrome c oxidase in yeast mitochondria. Molecular and Cellular Biology, 15(8), 4441-4452. doi:10.1128/mcb.15.8.4441Boubekeur, S., Bunoust, O., Camougrand, N., Castroviejo, M., Rigoulet, M., & Guérin, B. (1999). A Mitochondrial Pyruvate Dehydrogenase Bypass in the YeastSaccharomyces cerevisiae. Journal of Biological Chemistry, 274(30), 21044-21048. doi:10.1074/jbc.274.30.21044Palmieri, L., Lasorsa, F. M., Iacobazzi, V., Runswick, M. J., Palmieri, F., & Walker, J. E. (1999). Identification of the mitochondrial carnitine carrier in Saccharomyces cerevisiae. FEBS Letters, 462(3), 472-476. doi:10.1016/s0014-5793(99)01555-0Martínez-Montañés, F., Pascual-Ahuir, A., & Proft, M. (2010). Toward a Genomic View of the Gene Expression Program Regulated by Osmostress in Yeast. OMICS: A Journal of Integrative Biology, 14(6), 619-627. doi:10.1089/omi.2010.0046Proft, M., Gibbons, F. D., Copeland, M., Roth, F. P., & Struhl, K. (2005). Genomewide Identification of Sko1 Target Promoters Reveals a Regulatory Network That Operates in Response to Osmotic Stress inSaccharomyces cerevisiae. Eukaryotic Cell, 4(8), 1343-1352. doi:10.1128/ec.4.8.1343-1352.2005Divakaruni, A. S., & Murphy, A. N. (2012). A Mitochondrial Mystery, Solved. Science, 337(6090), 41-43. doi:10.1126/science.1225601Smith, R. A. J., Hartley, R. C., Cochemé, H. M., & Murphy, M. P. (2012). Mitochondrial pharmacology. Trends in Pharmacological Sciences, 33(6), 341-352. doi:10.1016/j.tips.2012.03.010Poteet, E., Choudhury, G. R., Winters, A., Li, W., Ryou, M.-G., Liu, R., … Yang, S.-H. (2013). Reversing the Warburg Effect as a Treatment for Glioblastoma. Journal of Biological Chemistry, 288(13), 9153-9164. doi:10.1074/jbc.m112.440354Soga, T. (2013). Cancer metabolism: Key players in metabolic reprogramming. Cancer Science, 104(3), 275-281. doi:10.1111/cas.1208
- …