The world population is getting older and studies aiming to enhance our comprehension of the underlying mechanisms responsible for health span are of utmost interest for longevity and as a measure ...for health care. In this review, we summarized previous genetic association studies (GWAS) and next-generation sequencing (NGS) of elderly cohorts. We also present the updated hypothesis for the aging process, together with the factors associated with healthy aging. We discuss the relevance of studying older individuals and build databanks to characterize the presence and resistance against late-onset disorders. The identification of about 2 million novel variants in our cohort of more than 1000 elderly Brazilians illustrates the importance of studying highly admixed populations of non-European ancestry. Finally, the ascertainment of nonagenarians and particularly of centenarians who were recovered from COVID-19 or remained asymptomatic opens new avenues of research aiming to enhance our comprehension of biological mechanisms associated with resistance against pathogens.
Despite the high number of individuals infected by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) who develop coronavirus disease 2019 (COVID-19) symptoms worldwide, many exposed ...individuals remain asymptomatic and/or uninfected and seronegative. This could be explained by a combination of environmental (exposure), immunological (previous infection), epigenetic, and genetic factors. Aiming to identify genetic factors involved in immune response in symptomatic COVID-19 as compared to asymptomatic exposed individuals, we analyzed 83 Brazilian couples where one individual was infected and symptomatic while the partner remained asymptomatic and serum-negative for at least 6 months despite sharing the same bedroom during the infection. We refer to these as "discordant couples". We performed whole-exome sequencing followed by a state-of-the-art method to call genotypes and haplotypes across the highly polymorphic major histocompatibility complex (MHC) region. The discordant partners had comparable ages and genetic ancestry, but women were overrepresented (65%) in the asymptomatic group. In the antigen-presentation pathway, we observed an association between
alleles encoding Lys at residue 71 (mostly DRB1*03:01 and DRB1*04:01) and DOB*01:02 with symptomatic infections and
alleles encoding 144Q/151R with asymptomatic seronegative women. Among the genes related to immune modulation, we detected variants in
and
associated with symptomatic infections. These variants are related to higher expression of soluble MICA and low expression of MICB. Thus, quantitative differences in these molecules that modulate natural killer (NK) activity could contribute to susceptibility to COVID-19 by downregulating NK cell cytotoxic activity in infected individuals but not in the asymptomatic partners.
This study investigated the kinetic and thermodynamic parameters of the synthesis of 2-ethylhexyl oleate catalyzed by
Candida antarctica
lipase (CALB) immobilized on magnetic poly(styrene-
co
...-divinylbenzene) (STY-DVB-M). The influence of acid/alcohol molar ratio and temperature on oleic acid conversion, ester concentration, and productivity was also assessed. Excess of one of the reagents resulted in high conversions, but the highest productivities were obtained at the stoichiometric ratio. Thus, a 1:1 molar ratio was considered optimal. Thermodynamic parameters calculated from the van’t Hoff equation (Δ
S
= + 850.64 J mol
−1
K
−1
, Δ
H
= + 273.78 kJ mol
−1
) revealed that the reaction is endothermic with a positive entropy change. Temperatures below 45 °C negatively affected reaction kinetics, explained by the positive Δ
G
values. CALB-STY-DVB-M showed a hydrolytic activity of 522.97 ± 19.14 U g
−1
and was about 1.7 times more thermally stable at 60 °C than the free enzyme. In an operational stability test, conducted for 7 consecutive cycles of 24 h, the biocatalyst had a half-life of 739 h. CALB-STY-DVB-M showed satisfactory performance in the synthesis of 2-ethylhexyl oleate, providing oleic acid conversions close to 100%, ester concentration of 450 g L
−1
, and productivity of 0.5 mmol g
−1
h
−1
. The biocatalyst holds promise for industrial applications.
Graphic Abstract
This study investigated the synthesis of 2-ethylhexyl oleate catalyzed by
Candida antarctica
lipase immobilized on magnetic poly(styrene-
co
-divinylbenzene) particles in a continuous packed-bed ...bioreactor. Runs were carried out in a solvent-free system at 50 °C. The performance of the reactor was evaluated for substrates composed by oleic acid and 2-ethylhexanol at five molar ratios (1:4–4:1), determining its operation limits in terms of substrate flow rate. The system performance was quantified for three different flow rates corresponding to space-time between 3 and 12 h. For each condition, the influence of the space-time in the ester formation, esterification yield and productivity was determined. The molar ratio of acid-to-alcohol interfered, in a remarkable way, in the formation of 2-ethylhexyl oleate and the best performance was attained for substrate at equimolar ratio running at 12 h space-time. Under this condition, average 2-ethylhexyl oleate concentration was 471.65 ± 2.98 g L
−1
which corresponded to ester productivity of 23.16 ± 0.49 mmol g
−1
L
−1
h
−1
. This strategy also gave high biocatalyst operational stability, revealing a half-life time of 2063 h. A model based on the ping-pong Bi–Bi mechanism was developed to describe the kinetics of the esterification reaction and validated using experimental data. The goodness of fit of the model was satisfactory (
R
2
= 0.9310–0.9952).
This study investigated the glycerolysis of babassu oil by
Burkholderia cepacia
lipase immobilized on SiO
2
–PVA particles in a continuous packed bed reactor. Experiments were conducted in a ...solvent-free system at 273.15 K either in an inert atmosphere or in the presence of cocoa butter to prevent lipid oxidation. The reactor (15 × 55 mm) was run at a fixed space time of 9.8 h using different molar ratios of babassu oil to glycerol (1:3, 1:6, 1:9, 1:12, and 1:15) to assess the effects of reactant molar ratio on monoacylglycerol productivity and selectivity. Nitrogen atmosphere and cocoa butter were equally effective in inhibiting lipid oxidation, indicating that addition of cocoa butter to glycerolysis reactions may be an interesting cost-reduction strategy. An oil/glycerol molar ratio of 1:9 resulted in the highest productivity (52.3 ± 2.9 mg g
−1
h
−1
) and selectivity (31.5 ± 1.8%). Residence time distribution data were fitted to an axial dispersion model for closed-vessel boundary conditions, giving a mass transfer coefficient (
k
c
) of 3.4229 × 10
−6
m s
−1
. A kinetic model based on elementary steps of the studied reaction was written in Scilab and compared with experimental data, providing standard deviations in the range of 5.5–7.5%.
•Delayed or insufficient humoral immune response to SARS-CoV-2 in patients with Turner syndrome (TS).•Lower interferon-γ production in volunteers with TS after stimulation with toll-like receptors ...7/8 agonists.•Higher cytotoxic activity by cluster of differentiation 8+ and natural killer cells after phorbol myristate acetate (PMA)/ionomycin stimuli in TS.
The X-chromosome contains the largest number of immune-related genes, which play a major role in COVID-19 symptomatology and susceptibility. Here, we had a unique opportunity to investigate, for the first time, COVID-19 outcomes in six unvaccinated young Brazilian patients with Turner syndrome (TS; 45, X0), including one case of critical illness in a child aged 10 years, to evaluate their immune response according to their genetic profile.
A serological analysis of humoral immune response against SARS-CoV-2, phenotypic characterization of antiviral responses in peripheral blood mononuclear cells after stimuli, and the production of cytotoxic cytokines of T lymphocytes and natural killer cells were performed in blood samples collected from the patients with TS during the convalescence period. Whole exome sequencing was also performed.
Our volunteers with TS showed a delayed or insufficient humoral immune response to SARS-CoV-2 (particularly immunoglobulin G) and a decrease in interferon-γ production by cluster of differentiation (CD)4+ and CD8+ T lymphocytes after stimulation with toll-like receptors 7/8 agonists. In contrast, we observed a higher cytotoxic activity in the volunteers with TS than the volunteers without TS after phorbol myristate acetate/ionomycin stimulation, particularly granzyme B and perforin by CD8+ and natural killer cells. Interestingly, two volunteers with TS carry rare genetic variants in genes that regulate type I and III interferon immunity.
Following previous reports in the literature for other conditions, our data showed that patients with TS may have an impaired immune response against SARS-CoV-2. Furthermore, other medical conditions associated with TS could make them more vulnerable to COVID-19.
Although older adults are at a high risk of severe or critical Covid-19, there are many cases of unvaccinated centenarians who had a silent infection or recovered from mild or moderate Covid-19. We ...studied three Brazilian supercentenarians, older than 110 years, who survived Covid-19 in 2020 before being vaccinated.
Despite their advanced age, humoral immune response analysis showed that these individuals displayed robust levels of IgG and neutralizing antibodies (NAbs) against SARS-CoV-2. Enrichment of plasma proteins and metabolites related to innate immune response and host defense was also observed. None presented autoantibodies (auto-Abs) to type I interferon (IFN). Furthermore, these supercentenarians do not carry rare variants in genes underlying the known inborn errors of immunity, including particular inborn errors of type I IFN.
These observations suggest that their Covid-19 resilience might be a combination of their genetic background and their innate and adaptive immunity.
Penicillium camemberti lipase immobilized on a magnetized poly(styrene‐co‐divinylbenzene) was used as a biocatalyst for isopropyl palmitate synthesis. The reaction conditions were determined by 22 ...factorial central composite design. A mathematical model based on a simplified kinetic approach was developed to describe the system and validated with the experimental data. An assay carried out in a stirred‐tank reactor confirmed the proposed model. The ester was purified and the properties such as density and water content were similar to those found in commercially available isopropyl palmitate.
Biocatalyst concentration and substrate molar ratio were statistically significant factors for the synthesis of isopropyl palmitate catalyzed by lipase G immobilized on poly(styrene‐co‐divinylbenzene). Optimum reaction conditions were determined by 22 factorial central composite design. An advantageous process design from an economic, environmental, and technological point of view was obtained.
The parameters that effect the synthesis of poly(styrene-co-divinylbenzene) magnetized with magnetite (STY-DVB-M) by polymerization emulsion were assessed in order to obtain magnetic beads to be used ...as matrix for lipase immobilization. The combined effect of polyvinyl alcohol (PVA) concentration and agitation was studied using response surface methodology. A 2
2
full-factorial design was employed for experimental design and analysis of the results. The optimum PVA concentration and agitation were found to be 1 wt% and 400 rpm, respectively. These conditions allow attaining the best particle size distribution of the synthesized particles (80% between 80 and 24 mesh). The performance of the magnetic beads was tested as a matrix for immobilizing two microbial lipases (Lipases from
Burkholderia cepacia-
BCL and
Pseudomonas fluorescens-
AKL) by physical adsorption and high immobilization yields (> 70%) and hydrolytic activities (≅ 1850 U g
−1
) were attained. The properties of free and immobilized lipases were searched and compared. Similar performance regarding the analyzed parameters (biochemical properties, kinetic constants and thermal stability) were obtained. Moreover, both immobilized lipases were found to be able to catalyze the transesterification of coconut oil with ethanol to produce fatty acid ethyl esters (FAEE). Further study showed that the
B. cepacia
immobilized lipase could be used seven times without significant decrease of activity, revealing half-life time of 970 h.
Graphical abstract
Summary
Zika virus (ZIKV) is an enveloped, positive single‐stranded sense RNA virus transmitted by Aedes species. Many efforts have been conducted to find a good, reliable and cost‐effective test for ...ZIKV diagnosis. Diagnosis is still imprecise, expensive and there is not a standard model. We investigated the publications on ZIKV diagnostics and analyzed varieties of diagnostic methods, sensibility, specificity, and the evolution of new methodologies. Conducted in accordance with the PRISMA‐P statement, three blocks of MeSH terms were assembled: group I: virus infection; group II: diagnostic methodologies; group III: characteristics and varieties on diagnostic methods. Search was performed on PubMed, Web of Science and SCOPUS databases. Eighteen articles were retrieved, reporting serological and molecular diagnostic techniques. Serum was used as the main biological material in the serological diagnosis, but urine and sperm were presented as an alternative. Molecular methods used structural and nonstructural regions of ZIKV genome. Experimental methodologies were more efficient, faster, and cheaper. Serological tests are faster and less expensive than molecular assays, but molecular assays are more specific. The use of both methodologies would be the most appropriate and reliable way to obtain correct diagnostic results.
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