1,613 research outputs found
How students use social media for information searching?
This article deals with a research in progress conducted with private universities, located in SĂŁo Paulo - SP - Brazil, in which were analyzed some aspects of the use of social media selected: WhatsApp, Facebook, LinkedIn, YouTube, Instagram and Twitter.The application used was SurveyMonkey for the preparation of a questionnaire to be answered by students of the universities. The primary research question is How social media are most used by studentsâ. This research is in progress, but at the conclusion of the article are presented some preliminary results that can contribute to the clarify the primary research question
Production of Zika virus-like particles (VLPs) by perfusion processes
Zika virus (ZIKV) emerged as a major international public health concern in 2015 and rapidly spread to more than 80 countries in Africa, Asia and the Americas. ZIKV infection has been shown to cause Guillain-Barré syndrome in adults, as well as severe congenital malformations in fetuses from as much as 42% of infected mothers (Brasil et al., 2016, doi:10.1056/NEJMoa1602412). While no ZIKV vaccine becomes approved for human use, periodic outbreaks will continue to occur in endemic regions and the risk of spreading to non-endemic regions will continue to exist, especially because ZIKV persists in body fluids for very long time after infection and can be transmitted via the sexual route.
Among many different vaccine platforms currently under study, virus-like particles (VLPs) are a promising alternative for the development of vaccines, since three-dimensional structures, constituted by recombinant structural proteins of the virus but lacking the viral genome, are able to display the antigen in a repetitive pattern, triggering a robust immune response.
In this work, we investigated the production of Zika virus-like particles by both intermittent and continuous perfusion processes, using a recombinant HEK293 cell pool previously generated in our laboratory, which constitutively expresses the VLPs. In order to improve production levels, we first enriched the recombinant cell pool for high producers by means of fluorescence-activated cell sorting (FACS). Using this FACS-enriched cell pool, small-scale shake flask studies showed that intermittent perfusion (also known as pseudoperfusion) with daily medium exchange enhanced viable cell density by 3.5 fold and VLP titer by 4 fold when compared to batch cultures. Continuous perfusion in a controlled stirred-tank bioreactor was carried out using an ATF-2 unit as cell retention device. A steady-state viable cell concentration of 25-30 Ă 106 cells/mL was maintained at a cell-specific perfusion rate (CSPR) of 50-60 pL/cell/day. VLP titers inside the bioreactor were higher than in the harvest, evidencing product retention by the ATF hollow fiber, especially from day 14 of cultivation on.
Our results show that the use of cell lines constitutively expressing zika VLPs, cultured in stirred-tank perfusion bioreactors, represents a promising system for the production of a VLP-based Zika vaccine candidate. This process could potentially be more cost-effective than traditional viral vaccine platforms based on batch production of whole viruses, especially considering that VLPs can be produced in lower biosafety level plants, and that perfusion systems are characterized by higher volumetric productivities, reduced bioreactor sizes, smaller plant footprint and lower investment costs when compared to batch processes
Association or Causation? Exploring the Oral Microbiome and Cancer Links
Several epidemiological investigations have found associations between poor oral health and different types of cancer, including colorectal, lung, pancreatic, and oral malignancies. The oral health parameters underlying these relationships include deficient oral hygiene, gingival bleeding, and bone and tooth loss. These parameters are related to periodontal diseases, which are directly and indirectly mediated by oral bacteria. Given the increased accessibility of microbial sequencing platforms, many recent studies have investigated the link between the oral microbiome and these cancers. Overall, it seems that oral dysbiotic states can contribute to tumorigenesis in the oral cavity as well as in distant body sites. Further, it appears that certain oral bacterial species can contribute to carcinogenesis, in particular, Fusobacterium nucleatum and Porphyromonas gingivalis, based on results from epidemiological as well as mechanistic studies. Yet, the strength of the findings from these investigations is hampered by the heterogeneity of the methods used to measure oral diseases, the treatment of confounding factors, the study design, the platforms employed for microbial analysis, and types of samples analyzed. Despite these limitations, there is an overall indication that the presence of oral dysbiosis that leads to oral diseases may directly and/or indirectly contribute to carcinogenesis. Proper methodological standardized approaches should be implemented in future epidemiological studies as well as in the mechanistic investigations carried out to explore these results. © International & American Associations for Dental Research 202
Models of Metal Poor Stars with Gravitational Settling and Radiative Accelerations: I. Evolution and Abundance Anomalies
Evolutionary models have been calculated for Pop II stars of 0.5 to
1.0 from the pre-main-sequence to the lower part of the giant branch.
Rosseland opacities and radiative accelerations were calculated taking into
account the concentration variations of 28 chemical species, including all
species contributing to Rosseland opacities in the OPAL tables. The effects of
radiative accelerations, thermal diffusion and gravitational settling are
included. While models were calculated both for Z=0.00017 and 0.0017, we
concentrate on models with Z=0.00017 in this paper. These are the first Pop II
models calculated taking radiative acceleration into account. It is shown that,
at least in a 0.8 star, it is a better approximation not to let Fe
diffuse than to calculate its gravitational settling without including the
effects of . In the absence of any turbulence outside of
convection zones, the effects of atomic diffusion are large mainly for stars
more massive than 0.7. Overabundances are expected in some stars with
\teff \ge 6000K. Most chemical species heavier than CNO are affected. At 12
Gyr, overabundance factors may reach 10 in some cases (e.g. for Al or Ni) while
others are limited to 3 (e.g. for Fe). The calculated surface abundances are
compared to recent observations of abundances in globular clusters as well as
to observations of Li in halo stars. It is shown that, as in the case of Pop I
stars, additional turbulence appears to be present.Comment: 40 pages, 17 color figures, to appear in The Astrophysical Journal,
April 2002 (paper with original high resolution figures can be found at
http://www.cerca.umontreal.ca/~richer/Fichiersps/popII_1.ps
High Susceptibility Of Activated Lymphocytes To Oxidative Stress-induced Cell Death.
The present study provides evidence that activated spleen lymphocytes from Walker 256 tumor bearing rats are more susceptible than controls to tert-butyl hydroperoxide (t-BOOH)-induced necrotic cell death in vitro. The iron chelator and antioxidant deferoxamine, the intracellular Ca2+ chelator BAPTA, the L-type Ca2+ channel antagonist nifedipine or the mitochondrial permeability transition inhibitor cyclosporin A, but not the calcineurin inhibitor FK-506, render control and activated lymphocytes equally resistant to the toxic effects of t-BOOH. Incubation of activated lymphocytes in the presence of t-BOOH resulted in a cyclosporin A-sensitive decrease in mitochondrial membrane potential. These results indicate that the higher cytosolic Ca2+ level in activated lymphocytes increases their susceptibility to oxidative stress-induced cell death in a mechanism involving the participation of mitochondrial permeability transition.80137-4
Detailed Analysis of Nearby Bulgelike Dwarf Stars II. Lithium Abundances
Li abundances are derived for a sample of bulgelike stars with isochronal
ages of 10-11 Gyr. These stars have orbits with pericentric distances, Rp, as
small as 2-3 kpc and Zmax < 1 kpc. The sample comprises G and K dwarf stars in
the metallicity range -0.80<[Fe/H]< +0.40. Few data of Li abundances in old
turn-off stars (> 4.5 Gyr) within the present metallicity range are available.
M67 (4.7 Gyr) and NGC 188 (6 Gyr) are the oldest studied metal-rich open
clusters with late-type stars. Li abundances have also been studied for few
samples of old metal-rich field stars. In the present work a high dispersion in
Li abundances is found for bulgelike stars for all the metallicity range,
comparable with values in M67. The role of metallicity and age on a Li
depletion pattern is discussed. The possible connection between Li depletion
and oxygen abundance due to atmospheric opacity effects is investigated.Comment: 9 pages, 7 figure
In vitro screening and chemometrics analysis on a series of azole derivatives with fungicide activity against moniliophthora perniciosa
Moniliophthora perniciosa, the causal agent of witches' broom disease in Theobroma cacao, significantly decreased cacao production, especially in Bahia State, the largest cocoa producing of the American continent. Control programs developed so far have low efficiency. Azole derivatives are active both in vitro and in loco against M. perniciosa, however there is no comprehensive study on the activity of azoles against this phytopatogen. Standardized in vitro biological data were employed to develop supervised and unsupervised chemometric models that highlight physicochemical and structural features that are crucial for azole's fungicidal activity against M. perniciosa. Thus, PCA and SIMCA models suggest that electronegativity (BEHe3) and dipolar moment (JGI4), as well as H-bonding to M. pernciosa's lanosterol 14α-desmethylase active site and lack of Cl atoms 6 to 8 bonds from the azole's nitrogen atoms play a major role to azoles' fungicide activity
Perfusion process for the production of a new, VLP-based yellow fever vaccine candidate
Yellow fever (YF) is an acute viral hemorrhagic disease endemic in tropical areas of Africa, Central and South America, which is transmitted by the bite of infected mosquitoes. It is a âhistorically devastating diseaseâ (Paules and Fauci, 2017) that killed during outbreaks in past centuries, before the introduction of the current vaccine, approximately 10% of the population of cities like Philadelphia (USA) and Barcelona (Spain). According to Garske et al. (2014), YF caused in 2013 78,000 deaths worldwide, which is a disease burden comparable to influenza. In the past few years, outbreaks in Angola (2016) and in Brazil (2017-2018) led to the depletion of the WHO vaccine stockpile and to the introduction of the emergency use of a fractional dose (1/5). Furthermore, the Angola outbreak in 2016 caused the first cases of YF ever to occur in Asia (11 imported cases to China), rising the concern about approximately 2 billion immunologically naĂŻve people who would be at high risk in Asia in case local transmission of the virus starts to occur (Wilder-Smith et al., 2019).
The urgent need for a new YF vaccine becomes evident from two major issues concerning the current vaccine, which consists of a live-attenuated virus propagated in chicken embryos: (i) vaccine shortage due to limitations in the manufacturing technology; (ii) rare, but fatal adverse effects. Therefore, this work focuses on the development of a safe, non-replicating YF vaccine, produced by a high-productivity perfusion process.
Stable recombinant HEK293 cell lines constitutively expressing the structural proteins prM (pre-membrane) and E (envelope) of YFV were generated, enabling long-term production and secretion of recombinant virus-like particles (VLPs). FACS (fluorescence activated cell sorting) was used to sort the transfected population for high producer cells and allowed obtaining an enriched cell pool producing significantly higher amounts of VLPs. Small scale kinetic studies under intermittent perfusion (pseudoperfusion) were performed in order to investigate possible feeding strategies and to evaluate the use of short-chain fatty acids as productivity enhancers. Subsequently, perfusion runs were carried out in stirred-tank bioreactors in order to investigate optimal conditions for VLP production, as well as to evaluate different cell retention devices (e.g. inclined lamella settler and ATF-2). Partial retention of the VLPs in the perfusion bioreactor system occurred when the ATF-2 was used. VLPs produced by perfusion were purified by a two-step chromatographic process, and transmission electron microscopy (TEM) images confirmed the expected size and morphology of the VLPs, enabling their use in mouse immunogenicity studies.
References:
Garske T, Van Kerkhove MD, Yactayo S, Ronveaux O, Lewis RF, Staples JE, Perea W, Ferguson NM, Yellow Fever Expert Committee (2014). Yellow fever in Africa: estimating the burden of disease and impact of mass vaccination from outbreak and serological data. PLoS Medicine 11:e1001638.
Paules CI, Fauci AS (2017), Yellow fever - once again on the radar screen in the Americas, N Engl J Med 376: 1397-1399.
Wilder-Smith A, Lee V, Gubler DJ (2019), Yellow fever: is Asia prepared for an epidemic? The Lancet 19:241-242
Disruption of a neural microcircuit in the rod pathway of the mammalian retina by diabetes mellitus
Diabetes leads to dysfunction of the neural retina before and independent of classical microvascular diabetic retinopathy, but previous studies have failed to demonstrate which neurons and circuits are affected at the earliest stages. Here, using patch-clamp recording and two-photon Ca2+ imaging in rat retinal slices, we investigated diabetes-evoked changes in a microcircuit consisting of rod bipolar cells and their dyad postsynaptic targets, AII and A17 amacrine cells, which play an essential role in processing scotopic visual signals. AII amacrines forward their signals to ON- and OFF-cone bipolar cells and A17 amacrines provide GABAergic feedback inhibition to rod bipolar cells. Whereas Ca2+-permeable AMPA receptors mediate input from rod bipolar cells to both AII and A17 amacrines, diabetes changes the synaptic receptors on A17, but not AII amacrine cells. This was expressed as a change in pharmacological properties and single-channel conductance of the synaptic receptors, consistent with an upregulation of the AMPA receptor GluA2 subunit and reduced Ca2+ permeability. In addition, two-photon imaging revealed reduced agonist-evoked influx of Ca2+ in dendritic varicosities of A17 amacrine cells from diabetic compared with normal animals. Because Ca2+-permeable receptors in A17 amacrine cells mediate synaptic release of GABA, the reduced Ca2+ permeability of these receptors in diabetic animals leads to reduced release of GABA, followed by disinhibition and increased release of glutamate from rod bipolar cells. This perturbation of neuron and microcircuit dynamics can explain the decreased dynamic range and sensitivity of scotopic vision that has been observed in diabetes.publishedVersio
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