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Fungi are a diverse group of eukaryotic organisms that infect humans, animals, and plants. To successfully colonize their hosts, pathogenic fungi must continuously adapt to the host’s unique environment, e.g., changes in temperature, pH, and nutrient availability. Appropriate protein folding, assembly, and degradation are essential for maintaining cellular homeostasis and survival under stressful conditions. Therefore, the regulation of proteostasis is crucial for fungal pathogenesis. The heat shock response (HSR) is one of the most important cellular mechanisms for maintaining proteostasis. It is activated by various stresses and regulates the activity of heat shock proteins (HSPs). As molecular chaperones, HSPs participate in the proteostatic network to control cellular protein levels by affecting their conformation, location, and degradation. In recent years, a growing body of evidence has highlighted the crucial yet understudied role of stress response circuits in fungal infections. This review explores the role of protein homeostasis and HSPs in fungal pathogenicity, including their contributions to virulence and host–pathogen interactions, as well as the concerted effects between HSPs and the main proteostasis circuits in the cell. Furthermore, we discuss perspectives in the field and the potential for targeting the components of these circuits to develop novel antifungal therapies.

Treating fungal infections is challenging and frequently requires long-term courses of antifungal drugs. Considering the limited number of existing antifungal drugs, it is crucial to evaluate the possibility of repositioning drugs with antifungal properties and to revisit older antifungals for applications in combined therapy, which could widen the range of therapeutic possibilities. Undecanoic acid is a saturated medium-chain fatty acid with known antifungal effects; however, its antifungal properties have not been extensively explored. Recent advances indicate that the toxic effect of undecanoic acid involves modulation of fungal metabolism through its effects on the expression of fungal genes that are critical for virulence. Additionally, undecanoic acid is suitable for chemical modification and might be useful in synergic therapies. This review highlights the use of undecanoic acid in antifungal treatments, reinforcing its known activity against dermatophytes. Specifically, in Trichophyton rubrum , against which the activity of undecanoic acid has been most widely studied, undecanoic acid elicits profound effects on pivotal processes in the cell wall, membrane assembly, lipid metabolism, pathogenesis, and even mRNA processing. Considering the known antifungal activities and associated mechanisms of undecanoic acid, its potential use in combination therapy, and the ability to modify the parent compound structure, undecanoic acid shows promise as a novel therapeutic against fungal infections.

Dermatophytes are challenging to treat because they have developed many strategies to neutralize the stress triggered by antifungals. Drug tolerance is achieved by mechanisms such as drug efflux and biofilm formation, and cellular efflux is a consequence of the synergistic and compensatory regulation of efflux pumps. Alternative splicing (AS) has also been considered as a mechanism that enhances fungal adaptive responses. We used RNA-seq data from the dermatophyte Trichophyton rubrum exposed to undecanoic acid (UDA) to search for and validate AS in genes encoding efflux pumps. The magnitude of this phenomenon was evaluated using UDA and other antifungals (caspofungin, itraconazole, and terbinafine) in planktonic and biofilm cultures. In addition to the conventional isoforms, the efflux pump encoded by TERG_04309 presented two intron-retained isoforms. Biofilms trigger the simultaneous production of at least two isoforms. The intron-retained isoforms showed short lengths and topologically different organization. Furthermore, we identified the putative interaction of efflux pumps (TERG_04309 and TERG_04224). Co-expression of these genes suggests a synergistic action in antifungal resistance. Our data provide new insights into drug tolerance related to differential isoform usage and the co-expression of stress-responsive genes, which may lead to higher antifungal resistance, mainly in biofilms.

Alternative splicing (AS), a common process in pathogenic fungal species, is not fully understood. We hypothesized that AS is a critical regulatory mechanism that enables species to undergo continuous adaptations during interactions with challenging host environments. We utilized the model species to contextualize the role of AS in fungal physiology and virulence. We performed transcriptome-wide splicing analysis to search for AS events in RNA-sequencing data of grown in keratin. This scenario mimicked infection and allowed us to map biologically relevant splicing events. Overall, the results showed that AS is recruited to regulate approximately 12.6% of the genome under an infection-like scenario. We extended this analysis to infection models of grown on human nails and cocultured them with human HaCaT keratinocytes. We found that AS affects a wide range of cellular processes, including amino acid and carbohydrate metabolism, cell signaling, protein folding and transport, transcription, and translation. We showed that transcription factors such as PacC and Ap1 govern the major features of fungal virulence and metabolism and are controlled by the spliceosome machinery under different infection-like conditions. Our data indicate that mRNA isoforms originating from AS contribute to the adaptation of , demonstrating that AS of transcription factor genes plays a central role in fungal pathogenesis. The transcription and splicing machinery tune fungal physiology to achieve an optimal metabolic balance in virulence traits during infection.

Convulxin (CVX), a C-type lectin-like protein isolated from the venom of the snake species, Crotalus durissus terrificus , stimulates platelet aggregation by acting as a collagen receptor agonist for glycoprotein VI found in the platelets. The effect of CVX on platelets has been studied, but its effect on human peripheral blood mononuclear cells (PBMCs) remains unclear. Given the significance of PBMCs in inflammation, this study explored the effect of CVX on PBMCs, specifically regarding NLRP3 inflammasome activation by assessing cell viability, ability to induce cell proliferation, reactive oxygen species (ROS) and nitric oxide production, interleukin (IL)-2 and IL-10 secretion, NLRP3 complex activation, and the role of C-type lectin-like receptors (CTLRs) in these. CVX was not toxic to PBMCs at the investigated concentrations and did not increase PBMC growth or IL-2 release; however, CVX induced IL-10 release and ROS generation via monocyte activation. It also activated the NLRP3 complex, resulting in IL-1β induction. Furthermore, the interaction between CVX and Dectin-2, a CTLR, induced IL-10 production. CVX interaction with CTLR has been demonstrated by laminarin therapy. Because of the involvement of residues near the Dectin-2 carbohydrate-recognition site, the generation of ROS resulted in inflammasome activation and IL-1β secretion. Overall, this work helps elucidate the function of CVX in immune system cells.

Breeding programs of the species Coffea canephora rely heavily on the significant genetic variability between and within its two varietal groups (conilon and robusta). The use of hybrid families and individuals has been less common. The objectives of this study were to evaluate parents and families from the populations of conilon, robusta, and its hybrids and to define the best breeding and selection strategies for productivity and disease resistance traits. As such, 71 conilon clones, 56 robusta clones, and 20 hybrid families were evaluated over several years for the following traits: vegetative vigor, incidence of rust and cercosporiosis, fruit ripening time, fruit size, plant height, canopy diameter, and yield per plant. Components of variance and genetic parameters were estimated via residual maximum likelihood (REML) and genotypic values were predicted via best linear unbiased prediction (BLUP). Genetic variability among parents (clones) and hybrid families was detected for most of the evaluated traits. The Mulamba-Rank index suggests potential gains up to 17% for the genotypic aggregate of traits in the hybrid population. An intrapopulation recurrent selection within the hybrid population would be the best breeding strategy because the genetic variability, narrow and broad senses heritabilities and selective accuracies for important traits were maximized in the crossed population. Besides, such strategy is simple, low cost and quicker than the concurrent reciprocal recurrent selection in the two parental populations, and this maximizes the genetic gain for unit of time.

Stockyard–port planning is a complex combinatorial problem that has been studied primarily through simulation or optimization techniques. However, due to its classification as non-deterministic polynomial-time hard (NP-hard), the generation of optimal or near-optimal solutions in real time requires optimization techniques based on heuristics or metaheuristics. This paper proposes a deterministic simulation and a meta-heuristic algorithm to address the stockyard–port planning problem, with the aim of reducing the time that ships spend in berths. The proposed algorithm is based on the ore handling operations in a real stockyard–port terminal, considering the interaction of large physical equipment and information about the production processes. The stockyard–port system is represented by a graph in order to define ship priorities for planning and generation of an initial solution through a deterministic simulation. Subsequently, the Variable Neighborhood Descent (VND) meta-heuristic is used to improve the initial solution. The convergence time of VND ranged from 1 to 190 s, with the total number of ships served in the berths varying from 10 to 1000 units, and the number of stockyards and berths varying from 11 to 15 and 3 to 5, respectively. Simulation results demonstrate the efficiency of the proposed algorithm in determining the best allocation of stockpiles, berths, car-dumpers, and conveyor belts. The results also show that increasing the number of conveyor belts is an important strategy that decreases environmental impacts due to exposure of the raw material to the atmosphere, while also increasing the stockyard–port productivity. This positive impact is greater when the number yards and ship berths increases. The proposed algorithm enables real-time decision-making from small and large instances, and its implementation in an iron ore stockyard–port that uses Industry 4.0 principles is suitable.

The purpose this study was to examine the effects of caffeine ingestion on performance and energy expenditure (anaerobic and aerobic contribution) during a 4-km cycling time trial (TT) performed after a carbohydrate (CHO) availability-lowering exercise protocol. After preliminary and familiarization trials, seven amateur cyclists performed three 4-km cycling TT in a double-blind, randomized and crossover design. The trials were performed either after no previous exercise (CON), or after a CHO availability-lowering exercise protocol (DEP) performed in the previous evening, followed by either placebo (DEP-PLA) or 5 mg.kg(-1) of caffeine intake (DEP-CAF) 1 hour before the trial. Performance was reduced (-2.1%) in DEP-PLA vs CON (421.0±12.3 vs 412.4±9.7 s). However, performance was restored in DEP-CAF (404.6±17.1 s) compared with DEP-PLA, while no differences were found between DEP-CAF and CON. The anaerobic contribution was increased in DEP-CAF compared with both DEP-PLA and CON (67.4±14.91, 47. 3±14.6 and 55.3±14.0 W, respectively), and this was more pronounced in the first 3 km of the trial. Similarly, total anaerobic work was higher in DEP-CAF than in the other conditions. The integrated electromyographic activity, plasma lactate concentration, oxygen uptake, aerobic contribution and total aerobic work were not different between the conditions. The reduction in performance associated with low CHO availability is reversed with caffeine ingestion due to a higher anaerobic contribution, suggesting that caffeine could access an anaerobic \"reserve\" that is not used under normal conditions.

Introduction Depression is one of the most disabling diseases globally, with a high disease burden that generates high direct and indirect costs. The incidence of depression is twofold higher in adult women than in men. Biological and psychosocial factors constitute the pathophysiological bases of the condition and due to the complexity of the condition, current understanding is that the “treatment strategy must be multimodal”. The objective of this study was to measure the effect of introducing the frequent use of makeup on improving depressive symptoms in adult women of medium–low purchasing power Methods Participants with the targeted profile who did not frequently use makeup were selected and randomised to receive (test group) or not (control group) stimuli and makeup products intended for encouraging the frequent use of makeup. The Zung Depression Self-Assessment Scale was used to assess depressive symptoms, with additional assessments on self-image perception using the mirror test and salivary cortisol level. Results The results demonstrated a sustained reduction in depressive symptoms (8.3 percentage points reduction in the Average Zung Index; P  < 0.05), with a significant improvement in self-image perception (25% increase in the average score obtained in the mirror test; P  < 0.05) and a specific influence on salivary cortisol levels (55% reduction in salivary cortisol concentration; P  < 0.05) after the first makeup application. Conclusion The results show that encouraging the frequent use of makeup, a practice that can be achieved by most people and which is simple and inexpensive to implement, can contribute to effective and sustainable improvement in the well-being and mental health of a significant portion of the population.

Continued unsustainable exploitation of natural resources promotes environmental degradation and threatens the preservation of dry forests around the world. This situation exposes the fragility and the necessity to study landscape transformations. In addition, it is necessary to consider the biomass quantity and to establish strategies to monitor natural and anthropic disturbances. Thus, this research analyzed the relationship between vegetation index and the estimated biomass using allometric equations in different Brazilian caatinga forest areas from satellite images. This procedure is performed by estimating the biomass from 9 dry tropical forest fragments using allometric equations. Area delimitations were obtained from the Embrapa collection of dendrometric data collected in the period between 2011 and 2012. Spectral variables were obtained from the orthorectified images of the RapidEye satellite. The aboveground biomass ranged from 6.88 to 123.82 Mg.ha-1. SAVI values were L = 1 and L = 0.5, while NDVI and EVI ranged from 0.1835 to 0.4294, 0.2197 to 0.5019, 0.3622 to 0.7584, and 0.0987 to 0.3169, respectively. Relationships among the estimated biomass and the vegetation indexes were moderate, with correlation coefficients (Rs) varying between 0.64 and 0.58. The best adjusted equation was the SAVI equation, for which the coefficient of determination was R² = 0.50, R2aj = 0.49, RMSE = 17.18 Mg.ha-1 and mean absolute error of prediction (MAE) = 14.07 Mg.ha-1, confirming the importance of the Savi index in estimating the caatinga aboveground biomass. RESUMO: A exploração contínua e insustentável dos recursos naturais promove a degradação ambiental e ameaça a conservação das florestas secas no mundo. Essa situação expõe a fragilidade e a necessidade de estudar as transformações da paisagem. É necessário considerar o quantitativo de biomassa e o estabelecimento de estratégias para monitorar distúrbios naturais e antrópicos. Assim, este trabalho teve como objetivo analisar a relação entre o índice de vegetação e a biomassa estimada por meio de equações alométricas em diferentes áreas da caatinga brasileira a partir de imagens de satélite. Este procedimento é realizado estimando-se a biomassa de nove fragmentos de floresta tropical seca com o uso em equações alométricas. As delimitações das áreas foram obtidas da coleção da Empresa Brasileira de Pesquisa Agropecuária, a partir dos dados dendrométricos coletados no período entre 2011 e 2012. As variáveis espectrais foram obtidas a partir das imagens ortorretificadas do satélite RapidEye. A biomassa acima do solo variou de 6,88 a 123,82 Mg.ha-1. Os valores de SAVI para os coeficientes L = 1 e L = 0,5, NDVI e EVI variaram de 0,1835 a 0,4294, 0,2197 a 0,5019, 0,3622 a 0,7584 e 0,0987 a 0,3169, respectivamente. As relações entre a biomassa estimada e os índices de vegetação foram moderadas, com coeficiente de correlação (rs) variando entre 0,64 e 0,58. A equação mais bem ajustada foi a Equação do SAVI, com coeficiente de determinação foi R² = 0,50, R2aj = 0.49, RMSE = 17.18 Mg.ha-1 e erro médio absoluto de predição (MAE) = 14.07 Mg.ha-1, confirmando a importância do índice SAVI na estimativa da biomassa aérea da Caatinga.