60 research outputs found
A Beckwith–Wiedemann-associated CDKN1C mutation allows the identification of a novel nuclear localization signal in human p57Kip2
No full textp57Kip2 protein is a member of the CIP/Kip family, mainly localized in the nucleus where it exerts its Cyclin/CDKs inhibitory function. In addition, the protein plays key roles in embryogenesis, differentiation, and carcinogenesis depending on its cellular localization and interactors. Mutations of CDKN1C, the gene encoding human p57Kip2, result in the development of different genetic diseases, including Beckwith–Wiedemann, IMAGe and Silver–Russell syndromes. We investigated a specific Beckwith–Wiedemann associated CDKN1C change (c.946 C>T) that results in the substitution of the C-terminal amino acid (arginine 316) with a tryptophan (R316W-p57Kip2). We found a clear redistribution of R316W-p57Kip2, in that while the wild-type p57Kip2 mostly occurs in the nucleus, the mutant form is also distributed in the cytoplasm. Transfection of two expression constructs encoding the p57Kip2 N-and C-terminal domain, respectively, allows the mapping of the nuclear localization signal(s) (NLSs) between residues 220–316. Moreover, by removing the basic RKRLR sequence at the protein C-terminus (from 312 to 316 residue), p57Kip2 was confined in the cytosol, implying that this sequence is absolutely required for nuclear entry. In conclusion, we identified an unreported p57Kip2 NLS and suggest that its absence or mutation might be of relevance in CDKN1C-associated human diseases determining significant changes of p57Kip2 localization/regulatory roles
Iron overload, a metabolic syndrome related condition, affects mesenchymal stromal cells phenotype
No full text
Antarctic sea-ice thickness and volume estimates from ice charts between 1995 and 1998
No full textPublisher's PDFThis work evaluates two distinct calculations of central tendency for sea-ice thickness and
quantifies the impact such calculations have on ice volume for the Southern Ocean. The first
calculation, area-weighted average thickness, is computed from polygonal ice features and then
upscaled to regions. The second calculation, integrated thickness, is a measure of the central value of
thickness categories tracked across different scales and subsequently summed to chosen regions. Both
methods yield the same result from one scale to the next, but subsequent scales develop diverging
solutions when distributions are strongly non-Gaussian. Data for this evaluation are sea-ice stage-ofdevelopment
records from US National Ice Center ice charts from 1995 to 1998, as proxy records of ice
thickness. Results show regionally integrated thickness exceeds area-weighted average thickness by as
much as 60% in summer with as few as five bins in thickness distribution. Year-round, the difference
between the two calculations yields volume differences consistently >10%. The largest discrepancies
arise due to bimodal distributions which are common in ice charts based on current subjective-analysis
protocols. We recommend that integrated distribution be used for regional-scale sea-ice thickness and
volume estimates from ice charts and encourage similar testing of other large-scale thickness data
archives.University of Delaware. Department of Geography
p57Kip2 Phosphorylation Modulates Its Localization, Stability, and Interactions
No full textp57Kip2 is a member of the cyclin-dependent kinase (CDK) Interacting Protein/Kinase Inhibitory Protein (CIP/Kip) family that also includes p21Cip1/WAF1 and p27Kip1. Different from its siblings, few data are available about the p57Kip2 protein, especially in humans. Structurally, p57Kip2 is an intrinsically unstructured protein, a characteristic that confers functional flexibility with multiple transient interactions influencing the metabolism and roles of the protein. Being an IUP, its localization, stability, and binding to functional partners might be strongly modulated by post-translational modifications, especially phosphorylation. In this work, we investigated by two-dimensional analysis the phosphorylation pattern of p57Kip2 in different cellular models, revealing how the human protein appears to be extensively phosphorylated, compared to p21Cip1/WAF1 and p27Kip1. We further observed clear differences in the phosphoisoforms distributed in the cytosolic and nuclear compartments in asynchronous and synchronized cells. Particularly, the unmodified form is detectable only in the nucleus, while the more acidic forms are present in the cytoplasm. Most importantly, we found that the phosphorylation state of p57Kip2 influences the binding with some p57Kip2 partners, such as CDKs, LIMK1 and CRM1. Thus, it is necessary to completely identify the phosphorylated residues of the protein to fully unravel the roles of this CIP/Kip protein, which are still partially identified
Proposta di protocollo per la determinazione dei valori normali di riferimento per i comuni test di routine nella popolazione anziana
No full textEFFECTS OF CONJUGATED LINOLEIC ACID AND RESISTANCE TRAINING IN RECREATIONAL ATHLETES
No full textConjugated linoleic acid (CLA) is a mixture of positional and geometrical isomers of linoleic acid, that are known to posses several physiological effects such as enhancing immune response, reducing arteriosclerosis risk, and inhibiting carcinogenesis. Over the last decade, the use of CLA supplement has become widespread among elite and recreational athletes because it should increase training effects, improve fat oxidation, increase energy delivery, reduce body weight, improve lipid profile, and so on. The purpose of this project is to investigate whether CLA supplementation after a resistance training session affects general markers of muscle damage, total testosterone, cortisol and sex hormone binding globulin. In a double-blind and randomized manner 13 recreational athletes were randomly assigned to supplement their diet with 6 g per day of an sunflower oil placebo or 6 g per day of CLA for 21 days. After two weeks of wash-out, all subjects crossed over to the opposite group for an additional 21 days. The 3 weeks of supplementation were preceded and followed by a resistance training session involved 8 exercise, chosen to include all major muscle groups, consisting of 3 sets of 10 repetitions at approximately 75-80% of one-repetition maximum. Before and after the training session were drawn blood to measure the creatine phosphokinase, lactate dehydrogenase, creatine kinase mass, total testosterone, cortisol and sex hormone binding globulin concentrations. Measurements at baseline and after the 3 week of supplementation included body composition and stregth. The results indicate that CLA supplementation during resistance training should increase the anabolic effect and decrease the catabolic effects of training on muscle protein
A novel plasmonic optical-fiber-based point-of-care test for periodontal MIP-1α detection
No full textThe analysis of salivary biomarkers as expression of periodontal health conditions has been proposed as a useful aid to conventional diagnostic approaches. In this study, we present a point-of-care test (POCT) exploiting a surface plasmon resonance (SPR)-based optical biosensor to detect salivary macrophage inflammatory protein (MIP)-1α, a promising marker of periodontitis. A plastic optical fiber (POF) was suitably modified and functionalized by an antibody self-assembled monolayer against MIP-1α for plasmonic detection. The proposed SPR-POF biosensor showed high selectivity and very low limit of detection for MIP-1α of 129 fM (1.0 pg/mL) in phosphate-buffered saline and 346 fM (2.7 pg/mL) in saliva. As a proof of concept, this POCT was also able to discriminate between a periodontitis patient and a healthy subject. The obtained results support the future application of this technology for an on-site detection and real-time monitoring of periodontal health conditions for diagnostic and therapeutic purposes
Plasmon resonance biosensor for interleukin-1β point-of-care determination: A tool for early periodontitis diagnosis
No full textAmong pro-inflammatory cytokines, Interleukin-1β is crucially involved in several inflammatory-based diseases and even cancer. Increased Interleukin-1β levels in oral fluids have been proposed as an early marker of periodontitis, a broadly diffused chronic inflammatory condition of periodontal-supporting tissues, leading eventually to tooth loss. We describe the development of a portable surface-plasmon-resonance-based optical fiber probe suitably coated with an anti-Interleukin-1β antibody monolayer. A pico-nanomolar linear range of determination was obtained in both buffer solution and saliva with a rapid (3 min) incubation and high selectivity in presence of interferents. Higher Interleukin-1β concentration in the saliva of a periodontitis patient compared to a healthy control was determined. These measurements were validated by an automated ELISA system. Our results sustain the potential applicability of the proposed SPR-POF as diagnostic point-of-care device for real-time monitoring of salivary Interleukin-1β, that can support early detection of oral inflammatory-based pathologies and rapid and timely therapeutic decisions
Blowin\u27 in the wind: Short-term weather and belief in anthropogenic climate change.
No full textAbstract
A series of polls provides new tests for how weather influences public beliefs about climate change. Statewide data from 5000 random-sample telephone interviews conducted on 99 days over 2.5 yr (2010-12) are merged with temperature and precipitation indicators derived from U.S. Historical Climatology Network (USHCN) station records. The surveys carry a question designed around scientific consensus statements that climate change is happening now, caused mainly by human activities. Alternatively, respondents can state that climate change is not happening, or that it is happening but mainly for natural reasons. Belief that humans are changing the climate is predicted by temperature anomalies on the interview day and the previous day, controlling for season, survey, and individual characteristics. Temperature effects concentrate among one subgroup, however: individuals who identify themselves as independent, rather than aligned with a political party. Interviewed on unseasonably warm days, independents tend to agree with the scientific consensus regarding anthropogenic climate change. On unseasonably cool days, they tend not to agree. Although temperature effects are sharpest for just a 2-day window, positive effects are seen for longer windows as well. As future climate change shifts the distribution of anomalies and extremes, this will first affect beliefs among unaligned voters
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