70 research outputs found
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Identification of an avian polyomavirus associated with Adélie penguins (Pygoscelis adeliae)
Little is known about viruses associated with Antarctic animals, although they are probably widespread. We recovered a novel polyomavirus from Adélie penguin (Pygoscelis adeliae) faecal matter sampled in a subcolony at Cape Royds, Ross Island, Antarctica. The 4988 nt Adélie penguin polyomavirus (AdPyV) has a typical polyomavirus genome organization with three ORFs that encoded capsid proteins on the one strand and two non-structural protein-coding ORFs on the complementary strand. The genome of AdPyV shared ~60% pairwise identity with all avipolyomaviruses. Maximum-likelihood phylogenetic analysis of the large T-antigen (T-Ag) amino acid sequences showed that the T-Ag of AdPyV clustered with those of avipolyomaviruses, sharing between 48 and 52% identities. Only three viruses associated with Adélie penguins have been identified at a genomic level, avian influenza virus subtype H11N2 from the Antarctic Peninsula and, respectively, Pygoscelis adeliae papillomavirus and AdPyV from capes Crozier and Royds on Ross Island
Modeling the drug release from hydrogel-based matrices
In this work the behavior of hydrogel-based matrices, the most widespread systems for oral controlled release of pharmaceuticals, has been mathematically described. In addition, the calculations of the model have been validated against a rich set of experimental data obtained working with tablets made of hydroxypropyl methylcellulose (a hydrogel) and theophylline (a model drug). The model takes into account water uptake, hydrogel swelling, drug release, and polymer erosion. The model was obtained as an improvement of a previous code, describing the diffusion in concentrated systems, and obtaining the erosion front (which is a moving boundary) from the polymer mass balance (in this way, the number of fitting parameters was also reduced by one). The proposed model was found able to describe all the observed phenomena, and then it can be considered a tool with predictive capabilities, useful in design and testing of new dosage systems based on hydrogels
Diffusion in Model Networks as Studied by NMR and Fluorescence Correlation Spectroscopy
We have studied the diffusion of small solvent molecules (octane) and larger hydrophobic dye probes in octane-swollen poly(dimethyl siloxane) linear-chain solutions and end-linked model networks, using pulsed-gradient nuclear magnetic resonance (NMR) and fluorescence correlation spectroscopy (FCS), respectively, focusing on diffusion in the bulk polymer up to the equilibrium degree of swelling of the networks, that is, 4.8 at most. The combination of these results allows for new conclusions on the feasibility of different theories describing probe diffusion in concentrated polymer systems. While octane diffusion shows no cross-link dependence, the larger dyes are increasingly restricted by fixed chemical meshes. The simple Fujita free-volume theory proved most feasible to describe probe diffusion in linear long-chain solutions with realistic parameters, while better fits were obtained assuming a stretched exponential dependence on concentration. Importantly, we have analyzed the cross-link specific effect on probe diffusion independently of any specific model by comparing the best-fit interpolation of the solution data with the diffusion in the networks. The most reasonable description is obtained by assuming that the cross-link effect is additive in the effective friction coefficient of the probes. The concentration dependences as well as the data compared at the equilibrium degrees of swelling indicate that swelling heterogeneities and diffusant shape have a substantial influence on small-molecule diffusion in networks.
Substrate cycling between de novo lipogenesis and lipid oxidation: a thermogenic mechanism against skeletal muscle lipotoxicity and glucolipotoxicity
Life is a combustion, but how the major fuel substrates that sustain human life compete and interact with each other for combustion has been at the epicenter of research into the pathogenesis of insulin resistance ever since Randle proposed a 'glucose-fatty acid cycle' in 1963. Since then, several features of a mutual interaction that is characterized by both reciprocality and dependency between glucose and lipid metabolism have been unravelled, namely: 1. the inhibitory effects of elevated concentrations of fatty acids on glucose oxidation (via inactivation of mitochondrial pyruvate dehydrogenase or via desensitization of insulin-mediated glucose transport), 2. the inhibitory effects of elevated concentrations of glucose on fatty acid oxidation (via malonyl-CoA regulation of fatty acid entry into the mitochondria), and more recently 3. the stimulatory effects of elevated concentrations of glucose on de novo lipogenesis, that is, synthesis of lipids from glucose (via SREBP1c regulation of glycolytic and lipogenic enzymes). This paper first revisits the physiological significance of these mutual interactions between glucose and lipids in skeletal muscle pertaining to both blood glucose and intramyocellular lipid homeostasis. It then concentrates upon emerging evidence, from calorimetric studies investigating the direct effect of leptin on thermogenesis in intact skeletal muscle, of yet another feature of the mutual interaction between glucose and lipid oxidation: that of substrate cycling between de novo lipogenesis and lipid oxidation. It is proposed that this energy-dissipating substrate cycling that links glucose and lipid metabolism to thermogenesis could function as a 'fine-tuning' mechanism that regulates intramyocellular lipid homeostasis, and hence contributes to the protection of skeletal muscle against lipotoxicity
Association of kidney disease measures with risk of renal function worsening in patients with type 1 diabetes
Background: Albuminuria has been classically considered a marker of kidney damage progression in diabetic patients and it is routinely assessed to monitor kidney function. However, the role of a mild GFR reduction on the development of stage 653 CKD has been less explored in type 1 diabetes mellitus (T1DM) patients. Aim of the present study was to evaluate the prognostic role of kidney disease measures, namely albuminuria and reduced GFR, on the development of stage 653 CKD in a large cohort of patients affected by T1DM. Methods: A total of 4284 patients affected by T1DM followed-up at 76 diabetes centers participating to the Italian Association of Clinical Diabetologists (Associazione Medici Diabetologi, AMD) initiative constitutes the study population. Urinary albumin excretion (ACR) and estimated GFR (eGFR) were retrieved and analyzed. The incidence of stage 653 CKD (eGFR < 60 mL/min/1.73 m2) or eGFR reduction > 30% from baseline was evaluated. Results: The mean estimated GFR was 98 \ub1 17 mL/min/1.73m2 and the proportion of patients with albuminuria was 15.3% (n = 654) at baseline. About 8% (n = 337) of patients developed one of the two renal endpoints during the 4-year follow-up period. Age, albuminuria (micro or macro) and baseline eGFR < 90 ml/min/m2 were independent risk factors for stage 653 CKD and renal function worsening. When compared to patients with eGFR > 90 ml/min/1.73m2 and normoalbuminuria, those with albuminuria at baseline had a 1.69 greater risk of reaching stage 3 CKD, while patients with mild eGFR reduction (i.e. eGFR between 90 and 60 mL/min/1.73 m2) show a 3.81 greater risk that rose to 8.24 for those patients with albuminuria and mild eGFR reduction at baseline. Conclusions: Albuminuria and eGFR reduction represent independent risk factors for incident stage 653 CKD in T1DM patients. The simultaneous occurrence of reduced eGFR and albuminuria have a synergistic effect on renal function worsening
Combining self-assembling peptide gels with three-dimensional elastomer scaffolds
[EN] Some of the problems raised by the combination of porous scaffolds and self-assembling peptide (SAP)
gels as constructs for tissue engineering applications are addressed for the first time. Scaffolds of poly(-
ethyl acrylate) and the SAP gel RAD16-I were employed. The in situ gelation of the SAP gel inside the
pores of the scaffolds was studied. The scaffold-cum-gel constructs were characterized morphologically,
physicochemically and mechanically. The possibility of incorporating an active molecule (bovine serum
albumin, taken here as a model molecule for others) in the gel within the scaffold’s pores was assessed,
and the kinetics of its release in phosphate-buffered saline was followed. Cell seeding and colonization of
these constructs were preliminarily studied with L929 fibroblasts and subsequently checked with sheep
adipose-tissue-derived stem cells intended for further preclinical studies. Static (conventional) and
dynamically assisted seedings were compared for bare scaffolds and the scaffold-cum-gel constructs.
The SAP gel inside the pores of the scaffold significantly improved the uniformity and density of cell colonization
of the three-dimensional (3-D) structure. These constructs could be of use in different advanced
tissue engineering applications, where, apart from a cell-friendly extracellular matrix -like aqueous environment,
a larger-scale 3-D structure able to keep the cells in a specific place, give mechanical support
and/or conduct spatially the tissue growth could be required.The authors acknowledge funding through the European Commission FP7 project RECATABI (NMP3-SL-2009-229239), and from the Spanish Ministerio de Ciencia e Innovacion through projects MAT2011-28791-C03-02 and -03. Dr. J.C. Chachques (Hopital Europeen Georges Pompidou, Paris) is thanked for providing the ASCs employed in this study. MMP acknowledges support of CIBER-BBN initiative, financed by Institut de Salud Carlos III (Spain) with the assistance of the European Regional Development Fund.VallĂ©s Lluch, A.; Arnal Pastor, MP.; MartĂnez Ramos, C.; Vilariño Feltrer, G.; Vikingsson, L.; Castells Sala, C.; Semino, CE.... (2013). Combining self-assembling peptide gels with three-dimensional elastomer scaffolds. Acta Biomaterialia. 9(12):9451-9460. https://doi.org/10.1016/j.actbio.2013.07.038S9451946091
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JenningsScottFisheriesWildlifeIdentificationAvianPolyomavirus_FigureS1.pdf
Little is known about viruses associated with Antarctic animals, although they are probably
widespread. We recovered a novel polyomavirus from Adélie penguin (Pygoscelis adeliae) faecal
matter sampled in a subcolony at Cape Royds, Ross Island, Antarctica. The 4988 nt Adélie
penguin polyomavirus (AdPyV) has a typical polyomavirus genome organization with three ORFs
that encoded capsid proteins on the one strand and two non-structural protein-coding ORFs on
the complementary strand. The genome of AdPyV shared ~60% pairwise identity with all
avipolyomaviruses. Maximum-likelihood phylogenetic analysis of the large T-antigen (T-Ag) amino
acid sequences showed that the T-Ag of AdPyV clustered with those of avipolyomaviruses,
sharing between 48 and 52% identities. Only three viruses associated with Adélie penguins have
been identified at a genomic level, avian influenza virus subtype H11N2 from the Antarctic
Peninsula and, respectively, Pygoscelis adeliae papillomavirus and AdPyV from capes Crozier and
Royds on Ross Island
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