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Coffee professionals have long known that the roast profile, i.e., the temperature versus time inside the roaster, strongly affects the flavor and quality of the coffee. A particularly important attribute of brewed coffee is the perceived sourness, which is known to be strongly correlated to the total titratable acidity (TA). Most prior work has focused on laboratory-scale roasters with little control over the roast profile, so the relationship between roast profile in a commercial-scale roaster and the corresponding development of TA to date remains unclear. Here we investigate roast profiles of the same total duration but very different dynamics inside a 5-kg commercial drum roaster, and we show that the TA invariably peaks during first crack and then decays to its original value by second crack. Although the dynamics of the TA development varied with roast profile, the peak TA surprisingly exhibited almost no statistically significant differences among roast profiles. Our results provide insight on how to manipulate and achieve desired sourness during roasting.

Abstract The oleaginous yeast species Rhodotorula toruloides is a promising candidate for applications in circular bioeconomy due to its ability to efficiently utilize diverse carbon sources being tolerant to cellular stress in bioprocessing. Previous studies including genome-wide analyses of the multi-stress tolerant strain IST536 MM15, derived through adaptive laboratory evolution from a promising IST536 strain for lipid production from sugar beet hydrolysates, suggested the occurrence of significant modifications in the cell wall. In this study, the cell wall integrity and carbohydrate composition of those strains was characterized to gain insights into the physicochemical changes associated to the remarkable multi-stress tolerance phenotype of the evolved strain. Compared to the original strain, the evolved strain exhibited a higher proportion of glucomannans, fucogalactomannans, and chitin relative to (1→4)-linked glucans, and an increased presence of glycoproteins with short glucosamine derived oligosaccharides, which have been found to be associated to ethanol stress tolerance and physical strength of the cell wall. Furthermore, the evolved strain cells were found to be significantly smaller than the original strain and more resistant to thermal and mechanical disruption, consistent with higher proportion of beta-linked polymers instead of glycogen, conferring a more rigid and robust cell wall. These findings provide further insights into the cell wall composition of this basidiomycetous red yeast species and into the alterations occurring in a multi-stress tolerant evolved strain. This new information can guide yeast genome engineering towards more robust strains of biotechnological relevance.

Abstract Brain death (BD) provides most of the donor organs destined for lung transplantation (LTx). However, the organs may be affected by inflammatory and oxidative processes. Based on this, we hypothesize that the angiotensin-converting enzyme 2 (ACE2) activation can reduce the lung injury associated with LTx. 3 h after BD induction, rats were injected with saline (BD group) or an ACE2 activator (ACE2a group; 15 mg/kg-1) and kept on mechanical ventilation for additional 3 h. A third group included a control ventilation (Control group) prior to transplant. After BD protocol, left LTx were performed, followed by 2 h-reperfusion. ACE2 activation was associated with better oxygenation after BD management (p = 0.01), attenuating edema (p = 0.05) followed by the reduction in tissue resistance (p = 0.01) and increase of respiratory compliance (p = 0.02). Nrf2 expression was also upregulated in the ACE2a group (p = 0.03). After transplantation, ACE2a group showed lower levels of TNF-α (p = 0.02), IL-6 (p = 0.001), IL-1β (p = 0.01), ROS (p = 0.004) and MDA (p = 0.002), in addition to higher CAT activity (p = 0.04). In conclusion, our study suggests that ACE2 activation improves anti-inflammatory and antioxidant activity in a model of LTx.

Abstract Understanding breast cancer genetic risk relies on identifying causal variants and candidate target genes in risk loci identified by genome-wide association studies (GWAS), which remains challenging. Since most loci fall in active gene regulatory regions, we developed a novel approach facilitated by pinpointing the variants with greater regulatory potential in the disease’s tissue of origin. Through genome-wide differential allelic expression (DAE) analysis, using microarray data from 64 normal breast tissue samples, we mapped the variants associated with DAE (daeQTLs). Then, we intersected these with GWAS data to reveal candidate risk regulatory variants and analysed their cis-acting regulatory potential. Finally, we validated our approach by extensive functional analysis of the 5q14.1 breast cancer risk locus. We observed widespread gene expression regulation by cis-acting variants in breast tissue, with 65% of coding and noncoding expressed genes displaying DAE (daeGenes). We identified over 54 K daeQTLs for 6761 (26%) daeGenes, including 385 daeGenes harbouring variants previously associated with BC risk. We found 1431 daeQTLs mapped to 93 different loci in strong linkage disequilibrium with risk-associated variants (risk-daeQTLs), suggesting a link between risk-causing variants and cis-regulation. There were 122 risk-daeQTL with stronger cis-acting potential in active regulatory regions with protein binding evidence. These variants mapped to 41 risk loci, of which 29 had no previous report of target genes and were candidates for regulating the expression levels of 65 genes. As validation, we identified and functionally characterised five candidate causal variants at the 5q14.1 risk locus targeting the ATG10 and ATP6AP1L genes, likely acting via modulation of alternative transcription and transcription factor binding. Our study demonstrates the power of DAE analysis and daeQTL mapping to identify causal regulatory variants and target genes at breast cancer risk loci, including those with complex regulatory landscapes. It additionally provides a genome-wide resource of variants associated with DAE for future functional studies.

Abstract To verify if data obtained in the prehospital evaluation of patients with severe acute respiratory syndrome (SARS) during the initial response to the COVID-19 pandemic is associated with clinical outcomes: mechanical ventilation, hospital discharge, and death. This is a retrospective analysis involving secondary data from the Emergency Medical Service (EMS) records and the Health Surveillance Information System of patients assisted by the EMS in Manaus, from January to June 2020, the period of the first peak of COVID-19 cases. The combination of the two databases yielded a total of 1.190 patients, who received a first EMS response and were later admitted to hospital with SARS and had data on clinical outcomes of interest available. Patients were predominantly male (754, 63.4%), with a median age of 66 (IQR: 54.0–78.0) years. SARS illness before medical assistance was associated to need for invasive mechanical ventilation (IMV, p

Abstract The global concern over water pollution caused by contaminants of emerging concern has been the subject of several studies due to the complexity of treatment. Here, the synthesis of a graphene oxide-based magnetic material (GO@Fe3O4) produced according to a modified Hummers’ method followed by a hydrothermal reaction was proposed; then, its application as a photocatalyst in clonazepam photo-Fenton degradation was investigated. Several characterization analyses were performed to analyze the structure, functionalization and magnetic properties of the composite. A 23 factorial design was used for the optimization procedure to investigate the effect of [H2O2], GO@Fe3O4 dose and pH on clonazepam degradation. Adsorption experiments demonstrated that GO@Fe3O4 could not adsorb clonazepam. Photo-Fenton kinetics showed that total degradation of clonazepam was achieved within 5 min, and the experimental data were better fitted to the PFO model. A comparative study of clonazepam degradation by different processes highlighted that the heterogeneous photo-Fenton process was more efficient than homogeneous processes. The radical scavenging test showed that $${O}_{2}^{\cdot -}$$ O 2 · - was the main active free radical in the degradation reaction, followed by hydroxyl radicals (•OH) and holes (h+) in the valence layer; accordingly, a mechanism of degradation was proposed to describe the process.

Abstract Humans exhibit consistent color preferences that are often described as a curvilinear pattern across hues. The recent literature posits that color preference is linked to the preference for objects or other entities associated with those colors. However, many studies examine this preference using isoluminant colors, which don’t reflect the natural viewing experience typically influenced by different light intensities. The inclusion of random luminance levels (luminance noise) in chromatic stimuli may provide an initial step towards assessing color preference as it is presented in the real world. Employing mosaic stimuli, this study aimed to evaluate the influence of luminance noise on human color preference. Thirty normal trichromats engaged in a two-alternative forced-choice paradigm, indicating their color preferences between presented pairs. The chromatic stimuli included saturated versions of 8 standard hues, presented in mosaics with varying diameters under different luminance noise conditions. Results indicated that the inclusion of luminance noise increased color preference across all hues, specifically under the high luminance noise range, while the curvilinear pattern remained unchanged. Finally, women exhibit a greater sensitivity to the presence of luminance noise than men, potentially due to differences between men and women in aesthetic evaluation strategies.

Abstract Cryptococcus neoformans (Cn) is an opportunistic yeast that causes meningoencephalitis in immunocompromised individuals. Calorie restriction (CR) prolongs Cn replicative lifespan (RLS) and mimics low-glucose environments in which Cn resides during infection. The effects of CR-mediated stress can differ among strains and have only been studied in MATα cells. Cn replicates sexually, generating two mating types, MATα and MATa. MATα strains are more dominant in clinical and environmental isolates. We sought to compare the effects of CR stress and longevity regulation between congenic MATα and MATa. Although MATα and MATa cells extended their RLS in response to CR, they engaged different pathways. The sirtuins were upregulated in MATα cells under CR, but not in MATa cells. RLS extension was SIR2-dependent in KN99α, but not in KN99a. The TOR nutrient-sensing pathway was downregulated in MATa strains under CR, while MATα strains demonstrated no difference. Lower oxidative stress and higher ATP production were observed in KN99α cells, possibly due to higher SOD expression. SIR2 was important for mitochondrial morphology and function in both mating types. Increased ATP production during CR powered the upregulated ABC transporters, increasing efflux in MATα cells. This led to enhanced fluconazole tolerance, while MATa cells remained sensitive to fluconazole. Our investigation highlights differences in the response of the mating types to CR.

Abstract The state of Maternal Protein Malnutrition (MPM) is associated with several deleterious effects, including inflammatory processes and dysregulation in oxidative balance, which can promote neurodegeneration. On the other hand, it is known that aerobic exercise can promote systemic health benefits, combating numerous chronic diseases. Therefore, we evaluate the effect of aerobic exercise training (AET) on indicators of mitochondrial bioenergetics, oxidative balance, endoplasmic reticulum stress, and neurotrophic factor in the prefrontal cortex of malnourished juvenile Wistar rats. Pregnant Wistar rats were fed with a diet containing 17% or 8% casein during pregnancy and lactation. At 30 days of life, male offspring were divided into 4 groups: Low-Protein Control (LS), Low-Protein Trained (LT), Normoprotein Control (NS), and Normoprotein Trained (NT). The trained groups performed an AET for 4 weeks, 5 days a week, 1 h a day per session. At 60 days of life, the animals were sacrificed and the skeletal muscle, and prefrontal cortex (PFC) were removed to evaluate the oxidative metabolism markers and gene expression of ATF-6, GRP78, PERK and BDNF. Our results showed that MPM impairs oxidative metabolism associated with higher oxidative and reticulum stress. However, AET restored the levels of indicators of mitochondrial bioenergetics, in addition to promoting resilience to cellular stress. AET at moderate intensity for 4 weeks in young Wistar rats can act as a non-pharmacological intervention in fighting against the deleterious effects of a protein-restricted maternal diet.

Abstract Fatty acids are precursors of inflammatory oxylipins. In the context of COVID-19, an excessive production of pro-inflammatory cytokines is associated with disease severity. The objective was to investigate whether the baseline omega 3/omega 6 fatty acids ratio and the oxylipins were associated with inflammation and oxidative stress in unvaccinated patients with COVID-19, classified according to the severity of the disease during hospitalization. This Prospective population-based cohort study included 180 hospitalized patients with COVID-19. The patients were classified into five groups according to the severity of their disease. Group 1 was the least severe and Group 5 was the most severe. Three specific types of fatty acids—eicosapentaenoic acid (EPA), docosahexaenoic acid (DHA), and arachidonic acid (AA)—as well as their enzymatic and non-enzymatic oxylipins were determined using chromatography coupled mass spectrometry. There was no difference in the ratio of omega-3 to omega-6 fatty acids between the groups (p = 0.276). However, the EPA/AA ratio was lower in Group 4 compared to Group 1 (p = 0.015). This finding was associated with an increase in both C-Reactive Protein (p

Abstract: The TIGIT+FOXP3+Treg subset (TIGIT+Tregs) exerts robust suppressive activity on cellular immunity and predisposes septic individuals to opportunistic infection. We hypothesized that TIGIT+Tregs could play an important role in intensifying the COVID-19 severity and hampering the defense against nosocomial infections during hospitalization. Herein we aimed to verify the association between the levels of the TIGIT+Tregs with the mechanical ventilation requirement, fatal outcome, and bacteremia during hospitalization. TIGIT+Tregs were immunophenotyped by flow cytometry from the peripheral blood of 72 unvaccinated hospitalized COVID-19 patients at admission from May 29th to August 6th, 2020. The patients were stratified during hospitalization according to their mechanical ventilation requirement and fatal outcome. COVID-19 resulted in a high prevalence of the TIGIT+Tregs at admission, which progressively increased in patients with mechanical ventilation needs and fatal outcomes. The prevalence of TIGIT+Tregs positively correlated with poor pulmonary function and higher plasma levels of LDH, HMGB1, FGL2, and TNF. The non-survivors presented higher plasma levels of IL-33, HMGB1, FGL2, IL-10, IL-6, and 5.54 times more bacteremia than survivors. Conclusions: The expansion of the TIGIT+Tregs in COVID-19 patients was associated with inflammation, lung dysfunction, bacteremia, and fatal outcome.