Measurement of specific absorption rate (SAR) of magnetic nanoparticles is crucial to assert their potential for magnetic hyperthermia. To perform this task, calorimetric methods are widely used. ...However, those methods are not very accurate and are difficult to standardize. In this paper, we present AC magnetometry results performed with a lab-made magnetometer that is able to obtain dynamic hysteresis-loops in the AC magnetic field frequency range from 50kHz to 1MHz and intensities up to 24kAm−1. In this work, SAR values of maghemite nanoparticles dispersed in water are measured by AC magnetometry. The so-obtained values are compared with the SAR measured by calorimetric methods. Both measurements, by calorimetry and magnetometry, are in good agreement. Therefore, the presented AC magnetometer is a suitable way to obtain SAR values of magnetic nanoparticles.
•We propose AC magnetometry as a method to measure the specific absorption rate (SAR) of magnetic nanoparticles suitable for magnetic hyperthermia therapy.•We have built a lab-made AC magnetometer, which is able to measure magnetic dynamic hysteresis-loops of nanoparticle dispersions.•The device works with AC magnetic field intensities up to 24kAm−1 in a frequency range from 75kHz to 1MHz.•The SAR values of maghemite nanoparticles around 12nm in magnetic diameter dispersed in water are measured by the lab-made magnetometer and different calorimetric methods.•Although all methods are in good agreement, several factors (probe location, thermal inertia, losses, etc.) make calorimetric method less accurate than AC magnetometry.
The HSV-1 (VC2) live-attenuated vaccine strain was engineered with specific deletions in the amino termini of glycoprotein K (gK) and membrane protein UL20, rendering the virus unable to enter ...neurons and establish latency. VC2 replicates efficiently in epithelial cell culture but produces lower viral titers and smaller viral plaques than its parental HSV-1 (F) wild-type virus. VC2 is an effective live-attenuated vaccine against HSV-1 and HSV-2 infections in mice and guinea pigs and an anti-tumor immunotherapeutic and oncolytic virus against melanoma and breast cancer in mouse models. Previously, we reported that the gK/UL20 complex interacts with the UL37 tegument protein, and this interaction is essential for virion intracellular envelopment and egress. To investigate the potential role of the UL37 deamidase functions, the recombinant virus FC819S and VC2C819S were constructed with a C819S substitution to inactivate the UL37 predicted deamidase active site on an HSV-1(F) and HSV-1(VC2) genetic background, respectively. FC819S replicated to similar levels with HSV-1(F) and produced similar size viral plaques. In contrast, VC2C819S replication was enhanced, and viral plaques increased in size, approaching those of the wild-type HSV-1(F) virus. FC819S infection of cell cultures caused enhanced GM-CSF secretion in comparison to HSV-1(F) across several cell lines, including HEp2 cells and cancer cell lines, DU145 (prostate) and Panc 04.03 (pancreas), and primary mouse peritoneal cells. VC2 infection of these cell lines caused GM-CSF secretion at similar levels to FC819S infection. However, the VC2C819S virus did not exhibit any further enhancement of GM-CSF secretion compared to the VC2 virus. These results suggest that the UL37 deamidation functions in conjunction with the gK/UL20 complex to facilitate virus replication and GM-CSF secretion.
Este artículo analiza 107 poemas paratextuales impresos en las obras de Lope de Vega entre 1598 y 1634, compuestos por poetas cercanos al autor, con el objetivo de discernir los mecanismos de ...figuración autorial que se emplean. Se identifican a 75 poetas diferentes que, a través de poemas laudatorios, presentan a Lope de Vega ante los lectores, y destacan determinados rasgos socio-literarios de una forma coral.
Para el desarrollo de esta investigación se ha empleado como herramienta metodológica la base de datos del proyecto PRESOLO, en la que se encuentran editados todos los poemas, y el análisis de los mismos se ha llevado a cabo a través de etiquetas codificadas en lenguaje TEI (Text Encoding Initiative). El trabajo se acompaña con un anexo en el que se identifican todos los poemas paratextuales y sus autores.
Plant invasions can affect key ecosystem processes regulating carbon and nutrient balances, i.e., litter decomposition. Exotic herb Hieracium pilosella (hawkweed, Asteraceae) recently invaded steppes ...of Tierra del Fuego island, Southern Patagonia, Argentina, where plant communities exhibit different vulnerabilities to invasion. To investigate H. pilosella invasion’s effects on litter decomposition, we conducted a field experiment in two plant communities, a tussock grassland and a grazing lawn, having contrasting environmental conditions and different vulnerabilities of being invaded by H. pilosella. At each community, we decomposed litter of dominant native species and of the exotic herb during 24 months. In addition, we characterized the litter qualities of the different species, and the microclimates of the communities. Exotic litter decomposition was remarkably faster and showed a higher association to microenvironmental variability compared to native litter decomposition. H. pilosella decomposed three-times faster than native litter in the moister, and more susceptible to invasion by H. pilosella plant community, the tussock grassland. By contrast, decomposition of native litter was not associated to the contrasting environmental conditions of the studied communities. Results suggest that introduced species may exhibit different ecosystem process rates and controls compared to resident species, affecting ecosystem nutrient and carbon cycles.
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Re-activation of the healing process is a major challenge in the field of chronic wound treatment. For that purpose, lipid-nanoparticles, especially nanostructured lipid carriers ...(NLC), possess extremely useful characteristics such as biodegradability, biocompatibility and long-term stability, besides being suitable for drug delivery. Moreover, they maintain wound moisture due to their occlusive properties, which have been associated with increased healing rates. In the light of above, NLC have been extensively used topically for wound healing; but to date, there are no safety-preclinical studies concerning such type of application. Thus, in this work, biodistribution studies were performed in rats with the NLC previously developed by our research group, using technetium-99 m (99mTc-NLC) as radiomarker, topically administered on a wound. 99mTc-NLC remained on the wound for 24 h and systemic absorption was not observed after administration. In addition, toxicological studies were performed to assess NLC safety after topical administration. The results obtained demonstrated that NLC were non-cytotoxic, non-sensitizing and non-irritant/corrosive. Overall, it might be concluded that developed NLC remained at the administration area, potentially exerting a local effect, and were safe after topical administration on wounds.
Stroke remains the leading cause of disability and death in the Philippines. Evaluating the current state of stroke care, the needed resources, and the gaps in health policies and programs is crucial ...to decrease stroke-related mortality and morbidity effectively. This paper aims to characterize the Philippines' stroke system of care and network using the World Health Organization health system building blocks framework. To integrate existing national laws and policies governing stroke and its risk factors dispersed across many general policies, the Philippine Department of Health (DOH) institutionalized a national policy framework for preventing and managing stroke. Despite policy reforms, government financing coverage remains limited. In terms of access to medicines, the government launched its stroke medicine access program (MAP) in 2016, providing more than 1,000 vials of recombinant tissue plasminogen activator (rTPA) or alteplase subsidized to selected government hospitals across the country. However, DOH discontinued the program due to the lack of neuroimaging machines and organized system of care to support the provision of the said medicine. Despite limited resources, stroke diagnostics and treatment facilities are more concentrated in urban settings, mostly in private hospitals, where out-of-pocket expenditures prevail. These barriers to access are also reflective of the current state of human resource on stroke where medical specialists (e.g., neurologists) serve in the few tertiary and training hospitals situated in urban settings. Meanwhile, there is no established unified national stroke registry thus, determining the local burden of stroke remains a challenge. The lack of centralization and fragmentation of the stroke cases reporting system leads to reliance on data from hospital records or community-based stroke surveys, which may inaccurately depict the country's actual stroke incidence and prevalence. Based on these gaps, specific recommendations geared toward systems approach - governance, financing, information system, human resources for health, and medicines were identified.
Herpes simplex virus type-1 (HSV-1) ocular infection is one of the leading causes of infectious blindness in developed countries. The resultant herpetic keratitis (HK) is caused by an exacerbated ...reaction of the adaptive immune response that persists beyond virus clearance causing substantial damage to the cornea. Intramuscular immunization of mice with the HSV-1(VC2) live-attenuated vaccine strain has been shown to protect mice against lethal ocular challenge. Herein, we show that following ocular challenge, VC2 vaccinated animals control ocular immunopathogenesis in the absence of neutralizing antibodies on ocular surfaces. Ocular protection is associated with enhanced intracorneal infiltration of γδ T cells compared to mock-vaccinated animals. The observed γδ T cellular infiltration was inversely proportional to the infiltration of neutrophils, the latter associated with exacerbated tissue damage. Inhibition of T cell migration into ocular tissues by the S1P receptors agonist FTY720 produced significant ocular disease in vaccinated mice and marked increase in neutrophil infiltration. These results indicate that ocular challenge of mice immunized with the VC2 vaccine induce a unique ocular mucosal response that leads into the infiltration of γδ T cells resulting in the amelioration of infection-associated immunopathogenesis.
Abstract Parkinson's disease (PD) is diagnosed when striatal dopamine (DA) loss exceeds a certain threshold and the cardinal motor features become apparent. The presymptomatic compensatory mechanisms ...underlying the lack of motor manifestations despite progressive striatal depletion are not well understood. Most animal models of PD involve the induction of a severe dopaminergic deficit in an acute manner, which departs from the typical, chronic evolution of PD in humans. We have used 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP) administered to monkeys via a slow intoxication protocol to produce a more gradual development of nigral lesion. Twelve control and 38 MPTP-intoxicated monkeys were divided into four groups. The latter included monkeys who were always asymptomatic, monkeys who recovered after showing mild parkinsonian signs, and monkeys with stable, moderate and severe parkinsonism. We found a close correlation between cell loss in the substantia nigra pars compacta (SNc) and striatal dopaminergic depletion and the four motor states. There was an overall negative correlation between the degree of parkinsonism (Kurlan scale) and in vivo PET (18 F-DOPA Ki and11 C-DTBZ binding potential), as well as with TH-immunoreactive cell counts in SNc, striatal dopaminergic markers (TH, DAT and VMAT2) and striatal DA concentration. This intoxication protocol permits to establish a critical threshold of SNc cell loss and dopaminergic innervation distinguishing between the asymptomatic and symptomatic parkinsonian stages. Compensatory changes in nigrostriatal dopaminergic activity occurred in the recovered and parkinsonian monkeys when DA depletion was at least 88% of control, and accordingly may be considered too late to explain compensatory mechanisms in the early asymptomatic period. Our findings suggest the need for further exploration of the role of non-striatal mechanisms in PD prior to the development of motor features.
The study of invasion patterns across multiple spatial scales brings insight about the spread of exotic species in novel habitats. We examined the spatial patterns of yellow mouse-ear hawkweed (
...Hieracium pilosella
L.), a recognized invader plant in Tierra del Fuego rangelands, at the scales of landscape and vegetation stand to assess the roles of disturbance, propagule pressure and biotic drivers. We surveyed twenty plots along two transects (ca. 20 km) across paddocks with different disturbance history (degraded pastures vs. natural communities) and at increasing distances from invasion hotspots. We analyzed the patterns of density, cover, and size structure of local
H. pilosella
populations across the landscape scale, and we conducted point- and mark-pattern analyses of distribution of patches of this species within vegetation stands. At landscape scale, the hawkweed density and cover decreased from west to east only in the transect including degraded pastures in the western portion. Plots located within 7 km or less from degraded pastures exhibited higher cover of
H. pilosella
(5–10%) than plots farther away (< 0.1%). Local populations inside or near the degraded pastures exhibited higher frequency of large patches than populations located farther away. At the scale of vegetation stand, point-pattern analysis detected aggregation of
H. pilosella
patches at short distances (0.5–3 m) in most plots; whereas, in highly infested plots, mark-correlation function analysis indicated a negative association between the sizes of patches located at short distances (0.5–1.5 m) from each other. Human disturbance, propagule pressure originating in invasion hotspots, and long-distance dispersal events appear as determinants of the spread of
H. pilosella
invasion at landscape scale. At patch scale, field patterns suggest that local encroachment is mostly determined by vegetative growth and somehow limited by interference from large established hawkweed patches. Our results strongly suggest that, unless effective management actions are taken, over the near future (30–50 years) the exotic forb
H. pilosella
will continue to invade displacing the native shrub steppe and grassland vegetation in the region.
Most organisms exhibit some kind of rhythmicity in their behaviour and/or physiology as an adaptation to the cyclical movements of the Earth. In addition to circadian rhythms, many organisms have an ...annual rhythmicity in certain activities, such as reproduction, migration or induction of diapause. Current knowledge of the molecular basis controlling seasonal rhythmicity, especially in insects, is scarce. One element that seems to play an essential role in the maintenance of both circadian and seasonal rhythms in vertebrates is the hormone melatonin. In vertebrates, the limiting enzyme in its synthesis is the arylalkylamine N‐acetyltransferase (AANAT). Melatonin is also present in insects but the precise biochemical pathway and the enzymes involved in its synthesis are unknown. Insects possess phylogenetically distant arylalkylamine N‐acetyltransferases but their involvement in melatonin synthesis still needs to be fully demonstrated. Aphids have a seasonally rhythmical life cycle, reproducing parthenogenetically by viviparity in favourable seasons but, in unfavourable seasons, they produce a single generation of sexual individuals. The length of the photoperiod is the main environmental factor that controls the mode of reproduction in aphids. Taking advantage of the availability of the genome of the aphid Acyrthosiphon pisum, we searched for genes encoding aphid arylalkylamine N‐acetyltransferase homologues that could be candidates for participation in seasonal rhythmicity. We identified four AANAT genes, of which at least two (Ap‐AANAT1 and Ap‐AANAT3) showed highly significant variation in transcription levels depending on the photoperiod conditions. These results are discussed in the context of how seasonality can be controlled in aphids.
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