Search

Locally produced fish hydrolysate and oil from the agrifood sector comprises a sustainable solution both to the problem of fish waste disposal and to the petfood sector with potential benefits for the animal’s health. This study evaluated the effects of the dietary replacement of mainly imported shrimp hydrolysate (5%) and salmon oil (3%; control diet) with locally produced fish hydrolysate (5%) and oil (3.2%) obtained from fish waste (experimental diet) on systemic inflammation markers, adipokines levels, cardiac function and fecal microbiota of adult dogs. Samples and measurements were taken from a feeding trial conducted according to a crossover design with two diets (control and experimental diets), six adult Beagle dogs per diet and two periods of 6 weeks each. The experimental diet, with higher docosahexaenoic (DHA) and eicosapentaenoic (EPA) acids contents, decreased plasmatic triglycerides and the activity of angiotensin converting enzyme, also tending to decrease total cholesterol. No effects of diet were observed on serum levels of the pro-inflammatory cytokines interleukin (IL)-1β, IL-8, and IL-12/IL-23 p40, and of the serum levels of the anti-inflammatory adipokine adiponectin. Blood pressure, heart rate and echocardiographic measurements were similar between diets with the only exception of left atrial to aorta diameter ratio that was higher in dogs fed the experimental diet, but without clinical relevance. Diet did not significantly affect fecal immunoglobulin A concentration. Regarding fecal microbiome, Megasphaera was the most abundant genus, followed by Bifidobacterium, Fusobacterium, and Prevotella, being the relative abundances of Fusobacterium and Ileibacterium genera positively affected by the experimental diet. Overall, results from the performed short term trial suggest that shrimp hydrolysate and salmon oil can be replaced by protein hydrolysate and oil from fish by-products without affecting systemic inflammatory markers, cardiac structure and function, but potentially benefiting bacterial genera associated with healthy microbiome. Considering the high DHA and EPA contents and the antioxidant properties of fish oil and hydrolysate, it would be worthwhile in the future to assess their long-term effects on inflammatory markers and their role in spontaneous canine cardiac diseases and to perform metabolomic and metagenomics analysis to elucidate the relevance of microbiota changes in the gut.

Abstract In bovines few studies addressed the contribution of adipose tissue to the host immune response to infection. Here we evaluated the in vitro response of bovine adipose tissue stromal vascular fraction (SVF) cells to the protozoan parasite Neospora caninum, using live and freeze-killed tachyzoites. Live N. caninum induced the production of IL-6, IL-1β and IL-10 by SVF cells isolated from subcutaneous adipose tissue (SAT), while in mesenteric adipose tissue (MAT) SVF cell cultures only IL-1β and IL-10 production was increased, showing slight distinct responses between adipose tissue depots. Whereas a clear IL-8 increase was detected in peripheral blood leucocytes (PBL) culture supernatants in response to live N. caninum, no such increase was observed in SAT or MAT SVF cell cultures. Nevertheless, in response to LPS, increased IL-8 levels were detected in all cell cultures. IL-10 levels were always increased in response to stimulation (live, freeze-killed N. caninum and LPS). Overall, our results show that bovine adipose tissue SVF cells produce cytokines in response to N. caninum and can therefore be putative contributors to the host immune response against this parasite.

Abstract Background Students of color disproportionately experience racial discrimination and food insecurity, which both lead to poor academic and health outcomes. This study explores the extent to which the location of racial discrimination experienced is associated with food insecurity, stress, physical health and grade point average among college students Methods A cross sectional study design was implemented to survey 143 students from a racially diverse public university. Logistic regression models assessed if discrimination at various locations was associated with food insecurity and linear models assessed how racial discrimination was associated with physical health, stress and grade point average Results Student’s experiencing food security had an average discrimination score of 2.3 (1.23, 3.37), while those experiencing food insecurity had a statistically significant (P

Opportunistic fungi cause lethal systemic infections and impose high medical costs to health systems. The World Health Organization has recognized the importance of fungal infections, including them in its global priority list guiding research, development, and discovery of new therapeutic approaches. Fungal vaccine development has been proposed as one of the treatment and prevention strategies in the last decade. In this study, we present the design of a lipid antigen delivery system based on Dioctadecyldimethylammonium bromide: Monoolein (DODAB: MO) containing recombinant Candida albicans Chitinase 3 (Cht3) for modulation the immune response against fungal infections. Several DODAB:MO liposomes containing Cht3 were prepared and those prepared by the incubation method and containing 5 µg/mL Cht3 were selected due to their favorable size, ζ-potential and stability, suited for antigen delivery applications. The encapsulation of Cht3 in these liposomes resulted in a significant increase in cellular uptake compared to empty liposomes, demonstrating their efficacy in delivering the antigen. Moreover, the liposomes proved to be safe for use in immunization procedures. Subcutaneous administration of Cht3 liposomes elicited a Th1/Th17 immune response profile, associated with the production of high levels of antibodies against Cht3. These antibodies recognized both the native and the recombinant forms of the protein, opsonizing mother-yeast at the cell scars, which has the potential to disrupt cell separation and hinder yeast growth. The findings suggest that the designed lipid antigen delivery system shows promise as a potential candidate for enhancing immune responses against fungal infections, offering a valuable strategy for future fungal vaccine development.

This research aimed to segment the market of visitors who practise outdoor activities in the North region of Portugal based on their motivations. An online survey was conducted between June to September of 2021, with a sample of 200 tourists who realised the region's outdoor activities during this period. The data collected allowed determining factor analysis and the clusters. Two factors: services/hospitality and nature experiences, and three clusters: soft practitioners, radicals, and enthusiasts were delimited. The results show that these groups differ in motivations and practised activities. Segmentation of outdoor tourism demand in North of Portugal should set out marketing and promotion strategies in different destinations, attracting demand from outside the region, and according to their preferences.

PurposeThe growing incidence and lethality of pancreatic cancer urges the development of new therapeutic approaches. Anti-tumoral vaccines can potentiate the immune response against the tumor, targeting specific antigens expressed only on tumor cells. In this work, we designed new vaccines for pancreatic cancer, composed by chitosan nanocapsules (CS NCs) containing imiquimod (IMQ) as adjuvant, and targeting the K-Ras mutation G12V.Experimental designWe tested the immunogenicity of our vaccines in mice, carrying different combinations of K-Ras mutated peptides. Then, we analyzed their prophylactic and therapeutic efficacy in mice bearing heterotopic pancreatic cancer.ResultsUnexpectedly, although good results were observed at short time points, the different combinations of our CS NCs vaccines seemed to potentiate tumor growth and reduce survival rate. We propose that this effect could be due to an inadequate immune response, partially because of the induction of a regulatory tolerogenic response.ConclusionOur results call for caution in the use of some NCs containing IMQ in the immunotherapy against pancreatic cancer.

The amount of biological data available in online repositories is increasing at an exponential rate. However, data on marine invertebrate biodiversity resources from Mozambique and São Tomé and Príncipe are still sparse and scattered. Online repositories are useful instruments for biodiversity research, as they provide a fast access to data from different sources. The use of interactive platforms comprising web mapping are becoming more important, not only for the scientific community, but also for conservation managers, decision-makers and the general public as they allow data presentation in simple and understandable visual schemes. The main goal of this study was to create an interactive online digital map (hosted and available at MARINBIODIV Atlas), through the collection of data from various sources, to visualise marine invertebrate occurrences and distribution across different habitats, namely mangroves, seagrasses, corals and other coastal areas, in Mozambique and São Tomé and Príncipe. The acquired biodiversity data were managed and structured to be displayed as spatial data and to be disseminated using the geographic information system ArcGIS, where data can be accessed, filtered and mapped. The ArcGIS web mapping design tools were used to produce interactive maps to visualise marine invertebrate diversity information along the coasts of Mozambique and São Tomé and Príncipe, through different habitats, offering the foundation for analysing species incidence and allocation information. Understanding the spatial occurrences and distribution of marine invertebrates in both countries can provide a valuable baseline, regarding information and trends on their coastal marine biodiversity.

Triple-negative breast cancer (TNBC) represents an aggressive subtype of breast cancer (BC) with a typically poorer prognosis than other subtypes of BC and limited therapeutic options. Therefore, new drugs would be particularly welcome to help treat TNBC. Preussin, isolated from the marine sponge-associated fungus, Aspergillus candidus, has shown the potential to reduce cell viability and proliferation as well as to induce cell death and cell cycle arrest in 2D cell culture models. However, studies that better mimic the tumors in vivo, such as 3D cell cultures, are needed. Here, we studied the effects of preussin in the MDA-MB-231 cell line, comparing 2D and 3D cell cultures, using ultrastructural analysis and the MTT, BrdU, annexin V-PI, comet (alkaline and FPG modified versions), and wound healing assays. Preussin was found to decrease cell viability, both in 2D and 3D cell cultures, in a dose-dependent manner, impair cell proliferation, and induce cell death, therefore excluding the hypothesis of genotoxic properties. The cellular impacts were reflected by ultrastructural alterations in both cell culture models. Preussin also significantly inhibited the migration of MDA-MB-231 cells. The new data expanded the knowledge on preussin actions while supporting other studies, highlighting its potential as a molecule or scaffold for the development of new anticancer drugs against TNBC.

Brown macroalgae are an important source of polysaccharides, mainly fucose-containing sulphated polysaccharides (FCSPs), associated with several biological activities. However, the structural diversity and structure–function relationships for their bioactivities are still undisclosed. Thus, the aim of this work was to characterize the chemical structure of water-soluble Saccharina latissima polysaccharides and evaluate their immunostimulatory and hypocholesterolemic activities, helping to pinpoint a structure–activity relationship. Alginate, laminarans (F1, neutral glucose-rich polysaccharides), and two fractions (F2 and F3) of FCSPs (negatively charged) were studied. Whereas F2 is rich in uronic acids (45 mol%) and fucose (29 mol%), F3 is rich in fucose (59 mol%) and galactose (21 mol%). These two fractions of FCSPs showed immunostimulatory activity on B lymphocytes, which could be associated with the presence of sulphate groups. Only F2 exhibited a significant effect in reductions in in vitro cholesterol’s bioaccessibility attributed to the sequestration of bile salts. Therefore, S. latissima FCSPs were shown to have potential as immunostimulatory and hypocholesterolemic functional ingredients, where their content in uronic acids and sulphation seem to be relevant for the bioactive and healthy properties.

ABSTRACT Staphylococcus epidermidis is a major nosocomial pathogen with a remarkable ability to persist on indwelling medical devices through biofilm formation. Nevertheless, it remains intriguing how this process is efficiently achieved under the host’s harsh conditions, where the availability of nutrients, such as essential metals, is scarce. Following our previous identification of two iron-regulated loci putatively involved in iron transport, hts and fhuC, we assessed here their individual contribution to both bacterial physiology and interaction with host immune cells. Single deletions of the hts and fhuC loci led to marked changes in the cell iron content, which were partly detrimental for planktonic growth and strongly affected biofilm formation under iron-restricted conditions. Deletion of each of these two loci did not lead to major changes in S. epidermidis survival within human macrophages or in an ex vivo human blood model of bloodstream infection. However, the lack of either hts or fhuC loci significantly impaired bacterial survival in vivo in a murine model of bacteremia. Collectively, this study establishes, for the first time, the pivotal role of the iron-regulated loci hts and fhuC in S. epidermidis biofilm formation and survival within the host, providing relevant information for the development of new targeted therapeutics against this pathogen. IMPORTANCE Staphylococcus epidermidis is one of the most important nosocomial pathogens and a major cause of central line-associated bloodstream infections. Once in the bloodstream, this bacterium must surpass severe iron restriction in order to survive and establish infection. Surprisingly, very little is known about the iron acquisition mechanisms in this species. This study represents the first report on the involvement of the S. epidermidis iron-regulated loci hts and fhuC in biofilm formation under host relevant conditions and, most importantly, in survival within the host. Ultimately, these findings highlight iron acquisition and these loci in particular, as potential targets for future therapeutic strategies against biofilm-associated S. epidermidis infections.

Iron acquisition through siderophores, a class of small, potent iron-chelating organic molecules, is a widely spread strategy among pathogens to survive in the iron-restricted environment found in the host. Although these molecules have been implicated in the pathogenesis of several species, there is currently no comprehensive study addressing siderophore production in Staphylococcus epidermidis. Staphylococcus epidermidis is an innocuous skin commensal bacterium. The species, though, has emerged as a leading cause of implant-associated infections, significantly supported by an inherent ability to form biofilms. The process of adaptation from skin niche environments to the hostile conditions during invasion is yet not fully understood. Herein, we addressed the possible role of siderophore production in S. epidermidis virulence. We first identified and deleted a siderophore homolog locus, sfaABCD, and provided evidence for its involvement in iron acquisition. Our findings further suggested the involvement of siderophores in the protection against oxidative stress-induced damage and demonstrated the in vivo relevance of a siderophore-mediated iron acquisition during S. epidermidis infections. Conclusively, this study addressed, for the first time in this species, the underlying mechanisms of siderophore production, highlighting the importance of a siderophore-mediated iron acquisition under host relevant conditions and, most importantly, its contribution to survival within the host.

Systemic fungal infections are associated with significant morbidity and mortality, and Candida albicans is the most common causative agent. Recognition of yeast cells by immune cell surface receptors can trigger phagocytosis of fungal pathogens and a pro-inflammatory response that may contribute to fungal elimination. Nevertheless, the elicited inflammatory response may be deleterious to the host by causing excessive tissue damage. We developed a nanoparticle-based approach to modulate the host deleterious inflammatory consequences of fungal infection by using β1,3-glucan-functionalized polystyrene (β-Glc-PS) nanoparticles. β-Glc-PS nanoparticles decreased the levels of the proinflammatory cytokines TNF-α, IL-6, IL-1β and IL-12p40 detected in in vitro culture supernatants of bone marrow-derived dendritic cells and macrophage challenged with C. albicans cells. Moreover, β-Glc-PS nanoparticles impaired the production of reactive oxygen species by bone marrow-derived dendritic cells incubated with C. albicans. This immunomodulatory effect was dependent on the nanoparticle size. Overall, β-Glc-PS nanoparticles reduced the proinflammatory response elicited by fungal cells in mononuclear phagocytes, setting the basis for a targeted therapy aimed at protecting the host by lowering the inflammatory cost of infection.

Neospora caninum is an obligate intracellular protozoan responsible for abortion and stillbirths in cattle. We previously developed a mucosal vaccination approach using N. caninum membrane proteins and CpG adjuvant that conferred long-term protection against neosporosis in mice. Here, we have extended this approach by alternatively using the carbomer-based adjuvant Carbigen™ in the immunizing preparation. Immunized mice presented higher proportions and numbers of memory CD4+ and CD8+ T cells. Stimulation of spleen, lungs and liver leukocytes with parasite antigens induced a marked production of IFN-γ and IL-17A and, less markedly, IL-4. This balanced response was also evident in that both parasite-specific IgG1 and IgG2c were raised by immunization, together with specific intestinal IgA. Upon intraperitoneal infection with N. caninum, immunized mice presented lower parasitic burdens than sham-immunized controls. In the infected immunized mice, memory CD4+ T cells predominantly expressed T-bet and RORγt, and CD8+ T cells expressing T-bet were found increased. While spleen, lungs and liver leukocytes of both immunized and sham-immunized infected animals produced high amounts of IFN-γ, only the cells from immunized mice responded with high IL-17A production. Since in cattle both IFN-γ and IL-17A have been associated with protective mechanisms against N. caninum infection, the elicited cytokine profile obtained using CarbigenTM as adjuvant indicates that it could be worth exploring for bovine neosporosis vaccination.

Yeast-derived products containing β-glucans have long been used as feed supplements in domesticated animals in an attempt to increase immunity. β-glucans are mainly recognized by the cell surface receptor CLEC7A, also designated Dectin-1. Although the immune mechanisms elicited through Dectin-1 activation have been studied in detail in mice and humans, they are poorly understood in other species. Here, we evaluated the response of bovine monocytes to soluble and particulate purified β-glucans, and also to Zymosan. Our results show that particulate, but not soluble β-glucans, can upregulate the surface expression of costimulatory molecules CD80 and CD86 on bovine monocytes. In addition, stimulated cells increased production of IL-8 and of TNF, IL1B, and IL6 mRNA expression, in a dose-dependent manner, which correlated positively with CLEC7A gene expression. Production of IL-8 and TNF expression decreased significantly after CLEC7A knockdown using two different pairs of siRNAs. Overall, we demonstrated here that bovine monocytes respond to particulate β-glucans, through Dectin-1, by increasing the expression of pro-inflammatory cytokines. Our data support further studies in cattle on the induction of trained immunity using dietary β-glucans.

Congenital toxoplasmosis has a high impact on human disease worldwide, inducing serious consequences from fetus to adulthood. Despite this, there are currently no human vaccines available to prevent this infection. Most vaccination studies against Toxoplasma gondii infection used animal models in which the infection was established by exogenous inoculation. Here, we review recent research on potential T. gondii vaccines using animal models in which infection was congenitally established. Endeavors in this field have so far revealed that live or subunit vaccines previously found to confer protection against extrinsically established infections can also protect, at least partially, from vertically transmitted infection. Nevertheless, there is no consensus on the more adequate immune response to protect the host and the fetus in congenital infection. Most of the vaccination studies rely on the assessment of maternal systemic immune responses, quantification of parasitic loads in the fetuses, and survival indexes and/or brain parasitic burden in the neonates. More research must be carried out not only to explore new vaccines but also to further study the nature of the elicited immune protection at the maternal-fetal interface. Particularly, the cellular and molecular effector mechanisms at the maternal-fetal interface induced by immunization remain poorly characterized. Deeper knowledge on the immune response at this specific location will certainly help to refine the vaccine-induced immunity and, consequently, to provide the most effective and safest protection against T. gondii vertical infection.

Pseudomonas aeruginosa is one of the leading causes of nosocomial pneumonia and its associated mortality. Moreover, extensively drug-resistant high-risk clones are globally widespread, presenting a major challenge to the healthcare systems. Despite this, no vaccine is available against this high-concerning pathogen. Here we tested immunogenicity and protective efficacy of an experimental live vaccine against P. aeruginosa pneumonia, consisting of an auxotrophic strain which lacks the key enzyme involved in D-glutamate biosynthesis, a structural component of the bacterial cell wall. As the amounts of free D-glutamate in vivo are trace substances in most cases, blockage of the cell wall synthesis occurs, compromising the growth of this strain, but not its immunogenic properties. Indeed, when delivered intranasally, this vaccine stimulated production of systemic and mucosal antibodies, induced effector memory, central memory and IL-17A-producing CD4+ T cells, and recruited neutrophils and mononuclear phagocytes into the airway mucosa. A significant improvement in mice survival after lung infection caused by ExoU-producing PAO1 and PA14 strains was observed. Nearly one third of the mice infected with the XDR high-risk clone ST235 were also protected. These findings highlight the potential of this vaccine for the control of acute pneumonia caused by this bacterial pathogen.

Neospora caninum is an apicomplexan parasite that in cattle assumes particular importance, as it is responsible for abortions reported worldwide. Leptin is an adipokine mainly secreted by adipocytes, which beside its role in maintaining metabolic homeostasis also has important effects in both innate and adaptive immunity. In previous work, we showed that mice chronically infected with N. caninum had elevated serum leptin levels. Here, we sought to assess whether acute infection with N. caninum infection influenced the production of this adipokine as well as leptin receptor mRNA levels. Our results show that acute infection with N. caninum led to decreased leptin serum levels and mRNA expression in adipose tissue. A decrease in leptin receptor transcript variant 1 mRNA (long isoform) and leptin receptor transcript variant 3 mRNA (one of the short isoforms) expression was also observed. An increase in the number of cells staining positive for leptin in the liver of infected mice was observed, although this increase was less marked in Interleukin (IL)-12/IL-23 p40-deficient mice. Overall, our results show that N. caninum infection also influences leptin production during acute infection.

Zinc is an essential element, a cofactor of many enzymes, and performs catalytic, structural and regulatory functions. Once in the gastrointestinal tract, zinc can interact with food constituents. Phytic acid, the major phosphorus storage in plants, limits zinc availability from animal feeds due to the formation of insoluble complexes with phytates. This study tested the effect of supplemental zinc source (zinc sulfate and a chelate zinc proteinate) and the addition of exogenous enzymes from a solid-state fermentation product of Aspergillus niger to a high phytate diet. The study was designed according to three Latin Squares 4 × 4 with a 2 × 2 factorial arrangement of treatments, with four periods, four diets, and 12 young adult Beagles. Periods lasted 5 weeks each. Diets were supplemented with 75 mg/kg of zinc sulfate (IZ) or zinc proteinate (OZ), and without or with 200 mg/kg of exogenous enzymes (IZ+, OZ+). Results showed that zinc proteinate increased the bioavailability of phosphorus, yet the zinc biomarkers remained unaffected by the zinc source, with the exception of lymphocyte subsets that benefit from zinc proteinate. The use of exogenous enzymes did not affect zinc availability nor nutrient and energy digestibility.

Nanoparticles affect the immune system as they may interact directly with immune cells and activate them. However, it is possible that nanoparticles also interact with released cytokines and immunologically active enzymes. To test this hypothesis, the activity of myeloperoxidase released from activated neutrophils was measured in the presence of nanoparticles with different chemistry and size. In high concentrations of nanoparticles, myeloperoxidase activity is decreased whereas in low concentrations of nanoparticles the activity is increased. The effect of the nanoparticles on myeloperoxidase is dependent on the total protein concentration as low concentrations of bovine serum albumin together with nanoparticles further increase the myeloperoxidase activity. The results herein show that nanoparticles affect the immune response not only at the cellular level but also on released immune effectors. In particular, they show that the nanoparticle effect on myeloperoxidase activity in the neutrophil degranulation environment is the result of an intricate interplay between the enzyme and protein concentrations in the environment and the available surface area on the nanoparticle.

Cancer is a disease that affects and kills millions of people worldwide. Breast cancer, especially, has a high incidence and mortality, and is challenging to treat. Due to its high impact on the health sector, oncological therapy is the subject of an intense and very expensive research. To improve this therapy and reduce its costs, strategies such as drug repurposing and drug combinations have been extensively studied. Drug repurposing means giving new usefulness to drugs which are approved for the therapy of various diseases, but, in this case, are not approved for cancer therapy. On the other hand, the purpose of combining drugs is that the response that is obtained is more advantageous than the response obtained by the single drugs. Using drugs with potential to be repurposed, combined with 5-fluorouracil, the aim of this project was to investigate whether this combination led to therapeutic benefits, comparing with the isolated drugs. We started with a screening of the most promising drugs, with verapamil and itraconazole being chosen. Several cellular viability studies, cell death and proliferation studies, mainly in MCF-7 cells (Michigan Cancer Foundation-7, human breast adenocarcinoma cells) were performed. Studies were also carried out to understand the effect of the drugs at the level of possible therapeutic resistance, evaluating the epithelial-mesenchymal transition. Combining all the results, the conclusion is that the combination of verapamil and itraconazole with 5-fluorouracil had benefits, mainly by decreasing cell viability and proliferation. Furthermore, the combination of itraconazole and 5-fluorouracil seemed to be the most effective, being an interesting focus in future studies.

Staphylococcus epidermidis biofilm formation on indwelling medical devices is frequently associated with the development of chronic infections. Nevertheless, it has been suggested that cells released from these biofilms may induce severe acute infections with bacteraemia as one of its major associated clinical manifestations. However, how biofilm-released cells interact with the host remains unclear. Here, using a murine model of hematogenously disseminated infection, we characterized the interaction of cells released from S. epidermidis biofilms with the immune system. Gene expression analysis of mouse splenocytes suggested that biofilm-released cells might be particularly effective at activating inflammatory and antigen presenting cells and inducing cellular apoptosis. Furthermore, biofilm-released cells induced a higher production of pro-inflammatory cytokines, in contrast to mice infected with planktonic cells, even though these had a similar bacterial load in livers and spleens. Overall, these results not only provide insights into the understanding of the role of biofilm-released cells in S. epidermidis biofilm-related infections and pathogenesis, but may also help explain the relapsing character of these infections.

AMP dephosphorylation via ecto-5′-nucleotidase/CD73 is the rate limiting step to generate extracellular adenosine (ADO) from released adenine nucleotides. ADO, via A2A receptors (A2ARs), is a potent modulator of neuromuscular and immunological responses. The pivotal role of ecto-5′-nucleotidase/CD73, in controlling extracellular ADO formation, prompted us to investigate its role in a rat model of experimental autoimmune myasthenia gravis (EAMG). Results show that CD4+CD25+FoxP3+ regulatory T cells express lower amounts of ecto-5′-nucleotidase/CD73 as compared to controls. Reduction of endogenous ADO formation might explain why proliferation of CD4+ T cells failed upon blocking A2A receptors activation with ZM241385 or adenosine deaminase in EAMG animals. Deficits in ADO also contribute to neuromuscular transmission failure in EAMG rats. Rehabilitation of A2AR-mediated immune suppression and facilitation of transmitter release were observed by incubating the cells with the nucleoside precursor, AMP. These findings, together with the characteristic increase in serum adenosine deaminase activity of MG patients, strengthen our hypothesis that the adenosinergic pathway may be dysfunctional in EAMG. Given that endogenous ADO formation is balanced by ecto-5′-nucleotidase/CD73 activity and that A2ARs exert a dual role to restore use-dependent neurocompetence and immune suppression in myasthenics, we hypothesize that stimulation of the two mechanisms may have therapeutic potential in MG.

Candida albicans cell wall is important for growth and interaction with the environment. RLM1 is one of the putative transcription factors involved in the cell wall integrity pathway, which plays an important role in the maintenance of the cell wall integrity. In this work we investigated the involvement of RLM1 in the cell wall biogenesis and in virulence. Newly constructed C. albicans Δ/Δrlm1 mutants showed typical cell wall weakening phenotypes, such as hypersensitivity to Congo Red, Calcofluor White, and caspofungin (phenotype reverted in the presence of sorbitol), confirming the involvement of RLM1 in the cell wall integrity. Additionally, the cell wall of C. albicans Δ/Δrlm1 showed a significant increase in chitin (213%) and reduction in mannans (60%), in comparison with the wild-type, results that are consistent with cell wall remodelling. Microarray analysis in the absence of any stress showed that deletion of RLM1 in C. albicans significantly down-regulated genes involved in carbohydrate catabolism such as DAK2, GLK4, NHT1 and TPS1, up-regulated genes involved in the utilization of alternative carbon sources, like AGP2, SOU1, SAP6, CIT1 or GAL4, and genes involved in cell adhesion like ECE1, ALS1, ALS3, HWP1 or RBT1. In agreement with the microarray results adhesion assays showed an increased amount of adhering cells and total biomass in the mutant strain, in comparison with the wild-type. C. albicans mutant Δ/Δrlm1 strain was also found to be less virulent than the wild-type and complemented strains in the murine model of disseminated candidiasis. Overall, we showed that in the absence of RLM1 the modifications in the cell wall composition alter yeast interaction with the environment, with consequences in adhesion ability and virulence. The gene expression findings suggest that this gene participates in the cell wall biogenesis, with the mutant rearranging its metabolic pathways to allow the use of alternative carbon sources.

The incidence of Candida albicans infections and the relapse episodes after antifungal treatment have increased in recent decades. Recurrences are mainly due to the persistence of the original infecting strain that may present genetic and genomic rearrangements during interaction with the host, reflecting strain adaptation. In this study, four isolates recovered from a patient during recurrent candidemia episodes were genotyped by microsatellite length polymorphism (MLP) and by multilocus sequence typing (MLST) and found to be genetic variants of the same strain. Using experimental mouse infections, a progressive reduction in the virulence of the four isolates was observed, with the first two isolates more virulent than the third and fourth. Additionally, in the mouse model, the first isolate resisted host control more efficiently, resulting in higher kidney fungal burdens and necrosis as compared to the third isolate. The resolution of inflammation was delayed in mice challenged with the first isolate and the message for IFN-gamma and TNF-alpha in the spleen was lower within the first few hours post-infection. Original and recurrent isolates also displayed different phenotypes regarding activity of secreted enzymes and response to stress agents. Overall, the comparative analysis indicated that the virulence decrease of these isolates was related to a lower ability to resist to the host anticandida effector mechanisms. We showed for the first time that C. albicans genetic variants of the same strain, sequentially isolated from an immunocompromised patient, underwent adaptations in the human host that resulted in virulence attenuation when tested in mice.

Background: Students of color disproportionately experience racial discrimination and food insecurity, which both lead to poor academic and health outcomes. This study explores the extent to which the location of racial discrimination experienced is associated with food insecurity, stress, physical health and grade point average among college students Methods: A cross sectional study design was implemented to survey 143 students from a racially diverse public university. Logistic regression models assessed if discrimination at various locations was associated with food insecurity and linear models assessed how racial discrimination was associated with physical health, stress and grade point average Results: Student's experiencing food security had an average discrimination score of 2.3 (1.23, 3.37), while those experiencing food insecurity had a statistically significant (P < 0.001) higher average discrimination score 7.3 (5.4, 9.21). Experiencing any racial discrimination was associated with increased odds of experiencing food insecurity when experienced from the police (OR 11.76, 95% CI: 1.41, 97.86), in the housing process (OR 7.9, 95% CI: 1.93, 32.34) and in the hiring process (OR 6.81, 95% CI: 1.98, 23.48) compared to those experiencing no racial discrimination after adjusting for race, gender, age and income. Conclusion: The location in which a student experienced racial discrimination impacted the extent to which the racial discrimination was associated with food security status. Further research is needed to explore potential mechanisms for how racial discrimination may lead to food insecurity. [ABSTRACT FROM AUTHOR]

This document is a summary of a special issue of the journal Nanomaterials titled "Catalysis by Metal-Oxide Nanostructures." The issue features several research papers that highlight the diverse applications of metal-oxide nanostructures in catalytic processes. The papers cover topics such as selective hydrogenation, electrocatalysis, magnetic core-shell catalysts, functionalized magnetic nanoparticles, photocatalysis, biomass conversion, heterojunction synthesis, nucleic acid interactions, wastewater treatment, partial hydrogenation, CO2 conversion, metal-organic-framework-supported nanocatalysts, Fenton catalysts, hydrogen evolution reactions, gold catalysts, metal-support interactions, and catalytic methane decomposition. The papers provide insights into the potential of metal-oxide nanostructures for sustainable and efficient catalysis. [Extracted from the article]

This document is a summary of a special issue of the journal Catalysts, which focuses on the research and discoveries in gold, silver, and copper catalysis. The issue features a diverse collection of research papers that highlight the versatility and effectiveness of these metallic catalysts in various catalytic processes. The papers cover topics such as the design of new catalysts, the development of advanced photocatalysts, the use of bimetallic catalysts, the influence of shape effects on catalytic performance, and the catalytic degradation of pollutants. The papers collectively contribute to the advancement of catalysis science and provide valuable insights for researchers and practitioners in the field. [Extracted from the article]

This document is an editorial from the journal Processes, titled "Advances in Supported Nanoparticle Catalysts." It highlights a collection of research papers that showcase the forefront of innovation in developing and utilizing supported nanoparticle catalysts. The research papers cover various topics such as the efficient removal of anionic dyes from water, the synthesis of metal nanoparticles for environmentally benign processes, the fabrication of superhydrophobic carbon nanomaterials, and the enhancement of polymer nanoparticles for immunoanalysis applications. The document emphasizes the importance of understanding supported nanoparticle systems for optimizing photocatalytic processes and tailoring catalysts for diverse catalytic reactions. [Extracted from the article]