Context. The spiral galaxy NGC 6946 hosts magnetic spiral arms, highly aligned magnetic fields between the gas/optical arms. Aims. The origin of the magnetic phenomena and their relation to the ...interstellar gas are investigated. Methods. NGC 6946 was observed in total intensity and linear polarization in five radio bands between 3 cm and 21 cm. Maps of spectral index, Faraday rotation and depolarization were derived. Results. At the inner edge of the inner gas spiral arm the ordered magnetic field is only mildly compressed and turns smoothly, to become aligned along the gas arm. Hence the field is not shocked and is probably connected to the warm, diffuse gas. At larger radii, two bright magnetic arms between the optical arms are visible in polarized intensity. The field in the northern magnetic arm is almost totally aligned. Faraday rotation measures ( RM) in these arms are consistent with the superposition of two low azimuthal dynamo modes. Three more magnetic arms are discovered in the outer galaxy, located between {\rm H\,\scriptstyle I} arms. The RM structure function confirms large-scale coherent fields. The observed anti-correlation between the fields pitch angles and the RM values is a possible signature of helical fields.-Due to strong Faraday depolarization the galaxy is not transparent to polarized waves at \lambda18\,{\rm cm} and \lambda20\,{\rm cm}. The large-scale asymmetry in depolarization with respect to the major axis may be another indication of large-scale helical fields. Three depolarization rings of almost zero polarization seen at \lambda20\,{\rm cm} are probably generated by differential Faraday rotation in {\rm H\,\scriptstyle II} complexes in NGC 6946 of 300-500 pc size.-In the gas/optical spiral arms, the total (mostly turbulent) magnetic field is amplified to \simeq20 \muG. Its energy density is \simeq10 times larger than that of the ionized gas and is similar to that of the turbulent gas motions in the inner galaxy. The magnetic energy exceeds that of the turbulent energy in the outer galaxy. All energy densities in NGC 6946 are about one order of magnitude larger than those in the Milky Way. Conclusions. Density waves in the inner gaseous spiral arms mildly compress the field. Dynamo action probably generates the magnetic spiral arms. The magnetic field is dynamically important, interacts with the gas flow and possibly determines the properties of the gas spiral arms.
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The generation of multi-functional drug delivery systems, namely solid dosage forms loaded with nano-sized carriers, remains little explored and is still a challenge for formulators. ...For the first time, the coupling of two important technologies, 3D printing and nanotechnology, to produce innovative solid dosage forms containing drug-loaded nanocapsules was evaluated here. Drug delivery devices were prepared by fused deposition modelling (FDM) from poly(ε-caprolactone) (PCL) and Eudragit® RL100 (ERL) filaments with or without a channelling agent (mannitol). They were soaked in deflazacort-loaded nanocapsules (particle size: 138nm) to produce 3D printed tablets (printlets) loaded with them, as observed by SEM. Drug loading was improved by the presence of the channelling agent and a linear correlation was obtained between the soaking time and the drug loading (r2=0.9739). Moreover, drug release profiles were dependent on the polymeric material of tablets and the presence of the channelling agent. In particular, tablets prepared with a partially hollow core (50% infill) had a higher drug loading (0.27% w/w) and faster drug release rate. This study represents an original approach to convert nanocapsules suspensions into solid dosage forms as well as an efficient 3D printing method to produce novel drug delivery systems, as personalised nanomedicines.
Accurate obesity classification is important so that appropriate intervention can be instituted to modify metabolic risk factors. Commonly utilized body mass index (BMI) and percentage body fat (PBF) ...are influenced by lean mass whereas fat mass index (FMI) measures only body fat. This study compares the prevalence of obesity and metabolic risk factors with FMI, BMI and PBF using DXA (dual-energy x-ray absorptiometry).
489 women randomly recruited from the electoral roll were stratified into 4 age groups; 40-49, 50-59, 60-69 and 70-79 years from 2000 to 2001. Clinical data and DXA body composition were obtained. Statistical analyses were performed using Medcalc v15 (Ostend, Belgium) with significance level at p = 0.05 (two-tailed).
There was higher prevalence of obesity using PBF compared to BMI and FMI (p<0.001). This difference was greater from age 50-59 (p<0.05) which may be explained by age-related lean mass loss. PBF over-classified obesity in over 35% of normal and 95% of overweight categories compared to FMI and BMI. BMI has a sensitivity of 78.9% and specificity of 98.3% for obesity using FMI as the standard. BMI under-classified obesity in the overweight category by 14.9% compared to FMI. There was no difference in diabetes, dyslipidemia, hypertension and metabolic syndrome prevalence within the BMI-obesity and FMI-obesity categories (p>0.05).
PBF classified more obesity than BMI and FMI because of its low pre-determined threshold. The greater difference with PBF compared to BMI and FMI from the 50-59 decade onwards can be attributed to age-related lean mass loss. BMI had the lowest sensitivity for obesity diagnosis. BMI under-classified obesity in the overweight category compared to FMI due to its inability to differentiate lean mass. However, there was no significant difference in the prevalence of metabolic risk factors between BMI and FMI-obesity categories indicating that fat location may influence metabolic dysregulation.
Celotno besedilo
Dostopno za:
DOBA, IZUM, KILJ, NUK, PILJ, PNG, SAZU, SIK, UILJ, UKNU, UL, UM, UPUK
Abstract Hydroxyapatite (HA) is the primary structural component of the skeleton and dentition. Under biological conditions, HA does not occur spontaneously and therefore must be actively synthesized ...by mineralizing cells such as osteoblasts. The mechanism(s) by which HA is actively synthesized by cells and deposited to create a mineralized matrix are not fully understood and the consequences of mineralization on cell function are even less well understood. HA can be chemically synthesized (HAp) and is therefore currently being investigated as a promising therapeutic biomaterial for use as a functional scaffold and implant coating for skeletal repair and dental applications. Here we investigated the biological effects of nano-HAp (10 × 100 nm) on the lineage commitment and differentiation of bone forming osteoblasts. Exposure of early stage differentiating osteoblasts resulted in dramatic and sustained changes in gene expression, both increased and decreased, whereas later stage osteoblasts were much less responsive. Analysis of the promoter region one of the most responsive genes, alkaline phosphatase, identified the stimulation of DNA methylation following cell exposure to nano-HAp. Collectively, the results reveal the novel epigenetic regulation of cell function by nano-HAp which has significant implication on lineage determination as well as identifying a novel potential therapeutic use of nanomaterials.
Obligate intracellular malaria parasites reside within a vacuolar compartment generated during invasion which is the principal interface between pathogen and host. To subvert their host cell and ...support their metabolism, these parasites coordinate a range of transport activities at this membrane interface that are critically important to parasite survival and virulence, including nutrient import, waste efflux, effector protein export, and uptake of host cell cytosol. Here, we review our current understanding of the transport mechanisms acting at the malaria parasite vacuole during the blood and liver-stages of development with a particular focus on recent advances in our understanding of effector protein translocation into the host cell by the Plasmodium Translocon of EXported proteins (PTEX) and small molecule transport by the PTEX membrane-spanning pore EXP2. Comparison to Toxoplasma gondii and other related apicomplexans is provided to highlight how similar and divergent mechanisms are employed to fulfill analogous transport activities.
Celotno besedilo
Dostopno za:
DOBA, IZUM, KILJ, NUK, PILJ, PNG, SAZU, SIK, UILJ, UKNU, UL, UM, UPUK
Transport of material within cells is mediated by trafficking vesicles that bud from one cellular compartment and fuse with another. Formation of a trafficking vesicle is driven by membrane coats ...that localize cargo and polymerize into cages to bend the membrane. Although extensive structural information is available for components of these coats, the heterogeneity of trafficking vesicles has prevented an understanding of how complete membrane coats assemble on the membrane. We combined cryo–electron tomography, subtomogram averaging, and cross-linking mass spectrometry to derive a complete model of the assembled coat protein complex I (COPI) coat involved in traffic between the Golgi and the endoplasmic reticulum. The highly interconnected COPI coat structure contradicted the current "adaptor-and-cage" understanding of coated vesicle formation.
The pathology of malaria is caused by infection of red blood cells with unicellular Plasmodium parasites. During blood-stage development, the parasite replicates within a membrane-bound ...parasitophorous vacuole. A central nexus for host-parasite interactions, this unique parasite shelter functions in nutrient acquisition, subcompartmentalization and the export of virulence factors, making its functional molecules attractive targets for the development of novel intervention strategies to combat the devastating impact of malaria. In this Review, we explore the origin, development, molecular composition and functions of the parasitophorous vacuole of Plasmodium blood stages. We also discuss the relevance of the malaria parasite's intravacuolar lifestyle for successful erythrocyte infection and provide perspectives for future research directions in parasitophorous vacuole biology.
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•Lipid-core nanocapsules were used to co-encapsulate resveratrol and curcumin.•Nanoencapsulation increased resveratrol and curcumin photostability.•Co-encapsulation enhanced ...antioxidant activity of polyphenols.
Resveratrol and curcumin are natural antioxidants found in the human diet that have been used in the prevention and treatment of different diseases associated with oxidative stress. Aiming to improve the antioxidant effects of resveratrol and curcumin, lipid-core nanocapsules containing the combination of both polyphenols were developed. Physicochemical characteristics were evaluated and compared to the formulations containing each polyphenol individually. Co-encapsulation did not influence nanotechnological characteristics, and all formulations presented mean diameter around 200nm, low polydispersity index, and encapsulation efficiency close to 100%. Nanoencapsulation increases the photostability of resveratrol and curcumin, and co-encapsulation improves resveratrol photostability. The in vitro antioxidant activity of polyphenols against HO radicals was enhanced by nanoencapsulation, and a better effect was observed after their co-nanoencapsulation. Also, nanocapsules exhibited controlled release profile, for both polyphenols. The results showed that the strategy to co-encapsulate resveratrol and curcumin is a promising approach to improve the performance of medicines used to prevent and treat diseases associated with oxidative stress.
Abstract Objectives Osteoporotic fractures are associated with substantial morbidity and mortality. Although exercise has long been recommended for the prevention and management of osteoporosis, ...existing guidelines are often non-specific and do not account for individual differences in bone health, fracture risk and functional capacity. The aim of the current position statement is to provide health practitioners with specific, evidence-based guidelines for safe and effective exercise prescription for the prevention or management of osteoporosis, accommodating a range of potential comorbidities. Design Position statement. Methods Interpretation and application of research reports describing the effects of exercise interventions for the prevention and management of low bone mass, osteoporosis and osteoporotic fracture. Results Evidence from animal and human trials indicates that bone responds positively to impact activities and high intensity progressive resistance training. Furthermore, the optimisation of muscle strength, balance and mobility minimises the risk of falls (and thereby fracture), which is particularly relevant for individuals with limited functional capacity and/or a very high risk of osteoporotic fracture. It is important that all exercise programs be accompanied by sufficient calcium and vitamin D, and address issues of comorbidity and safety. For example, loaded spine flexion is not recommended, and impact activities may require modification in the presence of osteoarthritis or frailty. Conclusions Specific guidelines for safe and effective exercise for bone health are presented. Individual exercise prescription must take into account existing bone health status, co-morbidities, and functional or clinical risk factors for falls and fracture.
Spherical 50 nm silica-based nanoparticles (SiNPs) promote healthy bone homeostasis and maintenance by supporting bone forming osteoblast lineage cells while simultaneously inhibiting the ...differentiation of bone resorbing osteoclasts. Previous work demonstrated that an intraperitoneal injection of SiNPs in healthy mice - both young and old - increased bone density and quality, suggesting the possibility that SiNPs represent a dual action therapeutic. However, the underlying mechanisms governing the osteoclast response to SiNPs have yet to be fully explored and defined. Therefore, the goals of this study were to investigate the cellular and molecular mechanisms by which SiNPs inhibit osteoclastogenesis. SiNPs strongly inhibited RANKL-induced osteoclast differentiation within the first hours and concomitantly inhibited early transcriptional regulators such as Nfatc1. SiNPs simultaneously stimulated expression of autophagy related genes p62 and LC3β dependent on ERK1/2 signaling pathway. Intriguingly, SiNPs were found to stimulate autophagosome formation while inhibiting the autophagic flux necessary for RANKL-stimulated osteoclast differentiation, resulting in the inhibition of both the canonical and non-canonical NF-κB signaling pathways and stabilizing TRAF3. These results suggest a model in which SiNPs inhibit osteoclastogenesis by inhibiting the autophagic machinery and RANKL-dependent functionality. This mechanism of action defines a novel therapeutic strategy for inhibiting osteoclastogenesis.
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