146 research outputs found
Co-Immobilization of Proteins and DNA Origami Nanoplates to Produce High-Contrast Biomolecular Nanoarrays
The biofunctionalization of nanopatterned surfaces with DNA origami nanostructures is an important topic in nanobiotechnology. An unexplored challenge is, however, to co-immobilize proteins with DNA origami at pre-determined substrate sites in high contrast relative to the nontarget areas. The immobilization should, in addition, preferably be achieved on a transparent substrate to allow ultrasensitive optical detection. If successful, specific co-binding would be a step towards stoichiometrically defined arrays with few to individual protein molecules per site. Here, we successfully immobilize with high specificity positively charged avidin proteins and negatively charged DNA origami nanoplates on 100 nm-wide carbon nanoislands while suppressing undesired adsorption to surrounding nontarget areas. The arrays on glass slides achieve unprecedented selectivity factors of up to 4000 and allow ultrasensitive fluorescence read-out. The co-immobilization onto the nanoislands leads to layered biomolecular architectures, which are functional because bound DNA origami influences the number of capturing sites on the nanopatches for other proteins. The novel hybrid DNA origami-protein nanoarrays allow the fabrication of versatile research platforms for applications in biosensing, biophysics, and cell biology, and, in addition, represent an important step towards single-molecule protein arrays
Pharmacokinetics of Modified-Release Prednisone Tablets in Healthy Subjects and Patients With Rheumatoid Arthritis
The Yeast La Related Protein Slf1p Is a Key Activator of Translation during the Oxidative Stress Response
The mechanisms by which RNA-binding proteins control the translation of subsets of mRNAs are not yet clear. Slf1p and Sro9p are atypical-La motif containing proteins which are members of a superfamily of RNA-binding proteins conserved in eukaryotes. RIP-Seq analysis of these two yeast proteins identified overlapping and distinct sets of mRNA targets, including highly translated mRNAs such as those encoding ribosomal proteins. In paralell, transcriptome analysis of slf1Δ and sro9Δ mutant strains indicated altered gene expression in similar functional classes of mRNAs following loss of each factor. The loss of SLF1 had a greater impact on the transcriptome, and in particular, revealed changes in genes involved in the oxidative stress response. slf1Δ cells are more sensitive to oxidants and RIP-Seq analysis of oxidatively stressed cells enriched Slf1p targets encoding antioxidants and other proteins required for oxidant tolerance. To quantify these effects at the protein level, we used label-free mass spectrometry to compare the proteomes of wild-type and slf1Δ strains following oxidative stress. This analysis identified several proteins which are normally induced in response to hydrogen peroxide, but where this increase is attenuated in the slf1Δ mutant. Importantly, a significant number of the mRNAs encoding these targets were also identified as Slf1p-mRNA targets. We show that Slf1p remains associated with the few translating ribosomes following hydrogen peroxide stress and that Slf1p co-immunoprecipitates ribosomes and members of the eIF4E/eIF4G/Pab1p ‘closed loop’ complex suggesting that Slf1p interacts with actively translated mRNAs following stress. Finally, mutational analysis of SLF1 revealed a novel ribosome interacting domain in Slf1p, independent of its RNA binding La-motif. Together, our results indicate that Slf1p mediates a translational response to oxidative stress via mRNA-specific translational control
Living-donor parathyroid allotransplantation for therapy-refractory postsurgical persistent hypoparathyroidism in a nontransplant recipient – three year results: a case report
Stearoyl-CoA Desaturase-1 (SCD1) Augments Saturated Fatty Acid-Induced Lipid Accumulation and Inhibits Apoptosis in Cardiac Myocytes
Mismatch between the uptake and utilization of long-chain fatty acids in the myocardium leads to abnormally high intracellular fatty acid concentration, which ultimately induces myocardial dysfunction. Stearoyl-Coenzyme A desaturase-1 (SCD1) is a rate-limiting enzyme that converts saturated fatty acids (SFAs) to monounsaturated fatty acids. Previous studies have shown that SCD1-deficinent mice are protected from insulin resistance and diet-induced obesity; however, the role of SCD1 in the heart remains to be determined. We examined the expression of SCD1 in obese rat hearts induced by a sucrose-rich diet for 3 months. We also examined the effect of SCD1 on myocardial energy metabolism and apoptotic cell death in neonatal rat cardiac myocytes in the presence of SFAs. Here we showed that the expression of SCD1 increases 3.6-fold without measurable change in the expression of lipogenic genes in the heart of rats fed a high-sucrose diet. Forced SCD1 expression augmented palmitic acid-induced lipid accumulation, but attenuated excess fatty acid oxidation and restored reduced glucose oxidation. Of importance, SCD1 substantially inhibited SFA-induced caspase 3 activation, ceramide synthesis, diacylglycerol synthesis, apoptotic cell death, and mitochondrial reactive oxygen species (ROS) generation. Experiments using SCD1 siRNA confirmed these observations. Furthermore, we showed that exposure of cardiac myocytes to glucose and insulin induced SCD1 expression. Our results indicate that SCD1 is highly regulated by a metabolic syndrome component in the heart, and such induction of SCD1 serves to alleviate SFA-induced adverse fatty acid catabolism, and eventually to prevent SFAs-induced apoptosis
Cross-language differences in fundamental frequency range: a comparison of English and German
This paper presents a systematic comparison of various measures of f0 range in female
speakers of English and German. F0 range was analysed along two dimensions, level (i.e. overall f0
height) and span (extent of f0 modulation within a given speech sample). These were examined using
two types of measures, one based on 'long-term distributional' (LTD) methods, and the other based on
specific landmarks in speech that are linguistic in nature ('linguistic' measures). The various methods
were used to identify whether and on what basis or bases speakers of these two languages differ in f0
range. Findings yielded significant cross-language differences in both dimensions of f0 range, but
effect sizes were found to be larger for span than for level, and for linguistic than for LTD measures.
The linguistic measures also uncovered some differences between the two languages in how f0 range
varies through an intonation contour. This helps shed light on the relation between intonational
structure and f0 range.caslAltenberg, E. P., and Ferrand, C. T. (2006). Fundamental frequency in
monolingual English, bilingual English=Russian, and bilingual English-
Cantonese young adult women,- J. Voice 20(1), 89-96.
Awan, S. N., and Mueller, P. B. (1996). Speaking fundamental frequency
characteristics of white, African American, and Hispanic kindergartners,-
J. Speech. Hear. Res. 39(3), 573-577.
Baken, R. J., and Orlikoff, R. F. (2000). Clinical Measurement of Speech
and Voice, 2nd ed. (Singular Publishing Group, San Diego, CA).
Banse, R., and Scherer, K. R. (1996). Acoustic profiles in vocal emotion
expression,- J. Pers. Soc. Psychol. 70(3), 614-636.
Beckman, M., and Ayers Elam, G. (1997). Guidelines for ToBI Labeling,
version 3 (Ohio State University, Ohio).
Benjamini, Y., and Hochberg, Y. (1995). Controlling the false discovery
rate-a practical and powerful approach to multiple testing,- J. R. Statist.
Soc. B 57(1), 289-300.
Boersma, P., and Weenink, D. (2007). Praat: Doing phonetics by computer
(version 4.6) [computer program],- http:==www.praat.org= (Last viewed
May 14, 2007).
Breen, M., Dilley, L. C., Kraemer, J., and Gibson, E. (2012). Inter-transcriber
agreement for two systems of prosodic annotation: ToBI (Tones
and Break Indices) and RaP (Rhythm and Pitch),- Corpus Linguist. Linguist.
Theory (in press).
Brown, A., and Docherty, G. J. (1995). Phonetic variation in dysarthric
speech as a function of sampling task,- Eur. J. Disord. Commun. 30(1),
17-35.
Chen, S. H. (2005). The effects of tones on speaking frequency and intensity
ranges in Mandarin and Min dialects,- J. Acoust. Soc. Am. 117(5),
3225-3230.
Clark-Carter, D. (1997). Doing Quantitative Psychological Research: From
Design to Report (Psychology Press, Hove, East Sussex).
Cohen, J. (1960). A coefficient for agreement for nominal scales,- Educ.
Psychol. Meas. 20, 37-46.
Deutsch, D., Le, J., Shen, J., and Henthorn, T. (2009). The pitch levels of
female speech in two Chinese villages,- J. Acoust. Soc. Am. 125(5),
EL208-EL213.
Diehl, J. J., Watson, D., Bennetto, L., Mcdonough, J., and Gunlogson, C.
(2009). An acoustic analysis of prosody in high-functioning autism,-
Appl. Psycholinguist. 30(3), 385-404.
Dilley, L. C., and Brown, M. (2007). Effects of pitch range variation on f0
extrema in an imitation task,- J. Phonetics 35(4), 523-551.
Dolson, M. (1994). The pitch of speech as a function of linguistic
community,- Music. Percept. 11(3), 321-331.
Eady, S. J. (1982). Differences in the F0 patterns of speech: Tone language
versus stress language,- Lang. Speech 25, 29-42.
Eckert, H., and Laver, J. (1994). Menschen und ihre Stimmen: Aspekte der
vokalen Kommunikation (Humans and their Voices: Aspects of Vocal
Communication) (Psychologie Verlags Union, Weinheim).
Escudero, D., Aguilar, L., Vanrell, M. M., and Prieto, P. (2012). Analysis
of inter-transcriber consistency in the Cat_ToBI prosodic labelling system,-
Speech Communications, retrieved from http:==prosodia.upf.
edu=home=arxiu=publicacions=escudero-et-al_analysis-intertranscriberconsistency-
cattobi.pdf (Last viewed December 21, 2011).
Field, A. (2005). Discovering Statistics using SPSS, 2nd ed. (SAGE Publications,
London).
Gibbon, D. (1998). German Intonation,- in Intonation Systems: A Survey of
Twenty Languages, edited by D. J. Hirst and A. Di Christo (Cambridge
University Press, Cambridge, MA), pp. 78-95.
Grabe, E. (1998). Comparative intonational phonology: English and
German,- Ph.D. thesis, Max Planck Institute for Psycholinguistics Nijmegen,
Max Planck Institute Series in Psycholinguistics No. 7, Wageningen,
Ponsen en Looien.
Gussenhoven, C., Repp, B. H., Rietveld, A., Rump, H. H., and Terken, J.
(1997). The perceptual prominence of fundamental frequency peaks,- J.
Acoust. Soc. Am. 102(5), 3009-3022.
Hanley, T. D., Snidecor, J. C., and Ringel, R. L. (1967). Some acoustic
differences among languages,- Phonetica 14, 97-107.
Hirschberg, J., and Ward, G. (1992). The influence of pitch range, duration,
amplitude, and spectral features on the interpretation of the rise fall rise
intonation contour in English,- J. Phonetics 20(2), 241-251.
Hollien, H., Hollien, P. A., and de Jong, G. (1997). Effects of three parameters
on speaking fundamental frequency,- J. Acoust. Soc. Am. 102(5),
2984-2992.
Hubbard, K., and Trauner, D. A. (2007). Intonation and emotion in autistic
spectrum disorders,- J. Psycholinguist. Res. 36(2), 159-173.
Keating, P., and Kuo, G. (2010). Comparison of speaking fundamental
frequency in English and Mandarin,- UCLA Work. Papers Phonetics 108,
164-187.
Kreiman, J., and Van Lancker Sidtis, D. (2011). Foundations of Voice Studies:
An Interdisciplinary Approach to Voice Production and Perception
(John Wiley and Sons, Chichester).
Ladd, D. R. (2008). Intonational Phonology, 2nd ed. (Cambridge University
Press, Cambridge).
Ladd, D. R., Silverman, K. E. A., Tolkmitt, F., Bergmann, G., and Scherer,
K. R. (1985). Evidence for the independent function of intonation contour
type, voice quality, and F0 range in signaling speaker affect,- J. Acoust.
Soc. Am. 78(2), 435-444.
Landis, J., and Koch, G. (1977). The measurement of observer agreement
for categorical data,- Biometrics 33(1), 159-174.
Liberman, M., and Pierrehumbert, J. (1984). Intonational invariance under
changes in pitch range and length,- in Language Sound Structure, edited
by M. Aronoff, R. Oehrle, F. Kelley, and B. W. Stephens (MIT Press,
Cambridge, MA), pp. 157-233.
Majewski, W., Hollien, H., and Zalewski, J. (1972). Speaking fundamental
frequency of Polish adult males,- Phonetica 25(2), 119-125.
Mangold, M., and Grebe, P. (2005). Duden Ausspracheworterbuch (Duden
Pronunciation Dictionary), 6th ed. (Dudenverlag, Mannheim).
Nishio, M., and Niimi, S. (2008). Changes in speaking fundamental
frequency characteristics with aging,- Folia Phoniatr. Logo. 60(3), 120-127.
NIST=SEMATECH e-Handbook of Statistical Methods, (2010).
http:==www.itl.nist.gov=div898=handbook= (Last viewed October 26, 2010).
Patterson, D. (2000). A linguistic approach to pitch range modelling,-
Ph.D. thesis, University of Edinburgh, Edinburgh.
Pierrehumbert, J. (1979). Perception of fundamental-frequency
declination,- J. Acoust. Soc. Am. 66(2), 363-369.
Pierrehumbert, J. (1980). The phonology and phonetics of English intonation,-
Ph.D. thesis, MIT, Cambridge, MA.
Rendall, D., Vokey, J. R., and Nemeth, C. (2007). Lifting the curtain on
the Wizard of Oz: Biased voice-based impressions of speaker size,- J.
Exp. Psychol. Hum. Percept. Perform. 33(5), 1208-1219.
Sobin, C., and Alpert, M. (1999). Emotion in speech: The acoustic attributes
of fear, anger, sadness, and joy,- J. Psycholinguist. Res. 28(4), 347-365.
Terken, J. (1994). Fundamental-frequency and perceived prominence of
accented syllables II: Nonfinal accents,- J. Acoust. Soc. Am. 95(6),
3662-3665.
't Hart, J., Collier, R., and Cohen, A. (1990). A Perceptual Study of Intonation
(Cambridge University Press, Cambridge).
Van Bezooijen, R. (1995). Sociocultural aspects of pitch differences
between Japanese and Dutch women,- Lang. Speech 38, 253-265.
Van Dommelen, W. A., and Moxness, B. H. (1995). Acoustic parameters
in speaker height and weight identification: Sex-specific behaviour,-
Lang. Speech 38, 267-287.
Wells, J. C. (1982). Accents of English (Cambridge University Press,
Cambridge), Vols. 1-3.
Yoon, T., Chavarria, S., Cole, J., and Hasegawa, M. (2004). Intertranscriber
reliability of prosodic labeling on telephone conversation using ToBI,-
Proc. Interspeech 2004, 2729-2732.131pub2622pub
Immunological and Cardiometabolic Risk Factors in the Prediction of Type 2 Diabetes and Coronary Events: MONICA/KORA Augsburg Case-Cohort Study
BACKGROUND: This study compares inflammation-related biomarkers with established cardiometabolic risk factors in the prediction of incident type 2 diabetes and incident coronary events in a prospective case-cohort study within the population-based MONICA/KORA Augsburg cohort. METHODS AND FINDINGS: Analyses for type 2 diabetes are based on 436 individuals with and 1410 individuals without incident diabetes. Analyses for coronary events are based on 314 individuals with and 1659 individuals without incident coronary events. Mean follow-up times were almost 11 years. Areas under the receiver-operating characteristic curve (AUC), changes in Akaike's information criterion (ΔAIC), integrated discrimination improvement (IDI) and net reclassification index (NRI) were calculated for different models. A basic model consisting of age, sex and survey predicted type 2 diabetes with an AUC of 0.690. Addition of 13 inflammation-related biomarkers (CRP, IL-6, IL-18, MIF, MCP-1/CCL2, IL-8/CXCL8, IP-10/CXCL10, adiponectin, leptin, RANTES/CCL5, TGF-β1, sE-selectin, sICAM-1; all measured in nonfasting serum) increased the AUC to 0.801, whereas addition of cardiometabolic risk factors (BMI, systolic blood pressure, ratio total/HDL-cholesterol, smoking, alcohol, physical activity, parental diabetes) increased the AUC to 0.803 (ΔAUC [95% CI] 0.111 [0.092-0.149] and 0.113 [0.093-0.149], respectively, compared to the basic model). The combination of all inflammation-related biomarkers and cardiometabolic risk factors yielded a further increase in AUC to 0.847 (ΔAUC [95% CI] 0.044 [0.028-0.066] compared to the cardiometabolic risk model). Corresponding AUCs for incident coronary events were 0.807, 0.825 (ΔAUC [95% CI] 0.018 [0.013-0.038] compared to the basic model), 0.845 (ΔAUC [95% CI] 0.038 [0.028-0.059] compared to the basic model) and 0.851 (ΔAUC [95% CI] 0.006 [0.003-0.021] compared to the cardiometabolic risk model), respectively. CONCLUSIONS: Inclusion of multiple inflammation-related biomarkers into a basic model and into a model including cardiometabolic risk factors significantly improved the prediction of type 2 diabetes and coronary events, although the improvement was less pronounced for the latter endpoint
CD14 Deficiency Impacts Glucose Homeostasis in Mice through Altered Adrenal Tone
The toll-like receptors comprise one of the most conserved components of the innate immune system, signaling the presence of molecules of microbial origin. It has been proposed that signaling through TLR4, which requires CD14 to recognize bacterial lipopolysaccharide (LPS), may generate low-grade inflammation and thereby affect insulin sensitivity and glucose metabolism. To examine the long-term influence of partial innate immune signaling disruption on glucose homeostasis, we analyzed knockout mice deficient in CD14 backcrossed into the diabetes-prone C57BL6 background at 6 or 12 months of age. CD14-ko mice, fed either normal or high-fat diets, displayed significant glucose intolerance compared to wild type controls. They also displayed elevated norepinephrine urinary excretion and increased adrenal medullary volume, as well as an enhanced norepinephrine secretory response to insulin-induced hypoglycemia. These results point out a previously unappreciated crosstalk between innate immune- and sympathoadrenal- systems, which exerts a major long-term effect on glucose homeostasis
Effects of low-stearate palm oil and high-stearate lard high-fat diets on rat liver lipid metabolism and glucose tolerance
- …