Dengue is recognized as a health problem that causes significant socioeconomic impacts throughout the world, affecting millions of people each year. A commonly used method for monitoring the dengue ...vector is to count the eggs that Aedes aegypti mosquitoes have laid in spatially distributed ovitraps. Given this approach, the present study uses a database collected from 397 ovitraps allocated across the city of Natal, RN-Brazil. The Egg Density Index for each neighborhood was computed weekly, over four complete years (from 2016 to 2019), and simultaneously analyzed with the dengue case incidence. Our results illustrate that the incidence of dengue is related to the socioeconomic level of the neighborhoods in the city of Natal. A deep learning algorithm was used to predict future dengue case incidence, either based on the previous weeks of dengue incidence or the number of eggs present in the ovitraps. The analysis reveals that ovitrap data allows earlier prediction (four to six weeks) compared to dengue incidence itself (one week). Therefore, the results validate that the quantification of Aedes aegypti eggs can be valuable for the early planning of public health interventions.
We determined the filtered tree species pool of Amazonian wetland forests, based on confirmed occurrence records, to better understand how tree diversity in wetland environments compares to tree ...diversity in the entire Amazon region. The tree species pool was determined using data from two main sources: 1) a compilation of published tree species lists plus one unpublished list of our own, derived from tree plot inventories and floristic surveys; 2) queries on botanical collections that include Amazonian flora, curated by herbaria and available through the SpeciesLink digital biodiversity database. We applied taxonomic name resolution and determined sample-based species accumulation curves for both datasets, to estimate sampling effort and predict the expected species richness using Chao's analytical estimators. We report a total of 3 615 valid tree species occurring in Amazonian wetland forests. After surveying almost 70 years of research efforts to inventory the diversity of Amazonian wetland trees, we found that 74% these records were registered in published species lists (2 688 tree species). Tree species richness estimates predicted from either single dataset underestimated the total pooled species richness recorded as occurring in Amazonian wetlands, with only 41% of the species shared by both datasets. The filtered tree species pool of Amazonian wetland forests comprises 53% of the 6 727 tree species taxonomically confirmed for the Amazonian tree flora to date. This large proportion is likely to be the result of significant species interchange among forest habitats within the Amazon region, as well as in situ speciation processes due to strong ecological filtering. The provided tree species pool raises the number of tree species previously reported as occurring in Amazonian wetlands by a factor of 3.2.
The severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) disclose the variants of concern (VOC) including Alpha (B.1.1.7), Beta (B.1.351), Gamma (P1), Delta (B.1.617.2), and Omicron ...(B.1.1.529). Its spike protein (S) present on the surface of the virus is recognized by the host cell receptor, the angiotensin-2 converting enzyme (ACE2) which promotes their entry into the cell. The mutations presented by VOCs are found in RBD and the N-terminal region of S protein. Therefore, mutations occurring in RBD can modify the biological and immunogenic characteristics of the virus, such as modifying the spike affinity for ACE2, increasing the virus transmissibility, or conferring the ability to escape the immune responses. The raise of a potential new SARS-CoV-2 variant capable of evading the host defenses at the same time maintaining its fitness justifies the importance of continued genetic monitoring of the pandemic coronavirus.
The lipase from Rhizomucor miehei (RML) has been immobilized on chitosan-based hybrid (sodium alginate or carrageenan) matrices activated with glycidol (GLY), epichlorohydrin (EPI) or glutaraldehyde ...(GLU) groups. Then, the properties of the different biocatalysts have been evaluated and compared with the soluble RML. Thermal stability (at pH 7.0 and 60 °C) was significantly increased when compared to the soluble enzyme: 154-fold for chitosan 5.0% - GLU, 80-fold for chitosan 2.5% - carrageenan 2.5% - GLY and 93-fold for chitosan 2.5% - alginate 2.5% - EPI. The best biocatalyst preparation, which was 154-fold more stable than the soluble enzyme, was obtained when RML was immobilized on chitosan activated with glutaraldehyde 5.0% v/v. According to the results, it was concluded that RML immobilization on chitosan-based hybrid matrices using different chemistries greatly produced biocatalysts with different properties.
Glycosylation changes are a feature of disease states. One clear example is cancer cells, which commonly express glycans at atypical levels or with different structural attributes than those found in ...normal cells. Epithelial-mesenchymal transition (EMT) was initially recognized as an important step for morphogenesis during embryonic development, and is now shown to be one of the key steps promoting tumor metastasis. Cancer cells undergoing EMT are characterized by significant changes in glycosylation of the extracellular matrix (ECM) components and cell-surface glycoconjugates. Current scientific methodology enables all hallmarks of EMT to be monitored in vitro and this experimental model has been extensively used in oncology research during the last 10 years. Several studies have shown that cell-surface carbohydrates attached to proteins through the amino acids, serine, or threonine (O-glycans), are involved in tumor progression and metastasis, however, the impact of O-glycans on EMT is poorly understood. Recent studies have demonstrated that transforming growth factor-beta (TGF-β), a known EMT inducer, has the ability to promote the up-regulation of a site-specific O-glycosylation in the IIICS domain of human oncofetal fibronectin, a major ECM component expressed by cancer cells and embryonic tissues. Armed with the knowledge that cell-surface glycoconjugates play a major role in the maintenance of cell homeostasis and that EMT is closely associated with glycosylation changes, we may benefit from understanding how unusual glycans can govern the molecular pathways associated with cancer progression. This review initially focuses on some well-known changes found in O-glycans expressed by cancer cells, and then discusses how these alterations may modulate the EMT process.
The tumor microenvironment (TME) is composed by cellular and non-cellular components. Examples include the following: (i) bone marrow-derived inflammatory cells, (ii) fibroblasts, (iii) blood ...vessels, (iv) immune cells, and (v) extracellular matrix components. In most cases, this combination of components may result in an inhospitable environment, in which a significant retrenchment in nutrients and oxygen considerably disturbs cell metabolism. Cancer cells are characterized by an enhanced uptake and utilization of glucose, a phenomenon described by Otto Warburg over 90 years ago. One of the main products of this reprogrammed cell metabolism is lactate. "Lactagenic" or lactate-producing cancer cells are characterized by their immunomodulatory properties, since lactate, the end product of the aerobic glycolysis, besides acting as an inducer of cellular signaling phenomena to influence cellular fate, might also play a role as an immunosuppressive metabolite. Over the last 10 years, it has been well accepted that in the TME, the lactate secreted by transformed cells is able to compromise the function and/or assembly of an effective immune response against tumors. Herein, we will discuss recent advances regarding the deleterious effect of high concentrations of lactate on the tumor-infiltrating immune cells, which might characterize an innovative way of understanding the tumor-immune privilege.
Chagas disease is a neglected disease caused by the protozoan
and affects 8 million people worldwide. The main chemotherapy is based on benznidazole. The efficacy in the treatment depends on factors ...such as the parasite strain, which may present different sensitivity to treatment. In this context, the expression of ABC transporters has been related to chemotherapy failure. ABC transporters share a well-conserved ABC domain, responsible for ATP binding and hydrolysis, whose the energy released is coupled to transport of molecules through membranes. The most known ABC transporters are ABCB1 and ABCC1, involved in the multidrug resistance phenotype in cancer, given their participation in cellular detoxification. In
, 27 ABC genes were identified in the genome. Nonetheless, only four ABC genes were characterized: ABCA3, involved in vesicular trafficking; ABCG1, overexpressed in strains naturally resistant to benznidazole, and P-glycoprotein 1 and 2, whose participation in drug resistance is controversial. Considering P-glycoprotein genes are related to ABCC subfamily in
according to the demonstration using BLASTP alignment, we evaluated both ABCB1-like and ABCC-like activities in epimastigote and trypomastigote forms of the Y strain. The transport activities were evaluated by the efflux of the fluorescent dyes Rhodamine 123 and Carboxyfluorescein in a flow cytometer. Results indicated that there was no ABCB1-like activity in both
forms. Conversely, results demonstrated ABCC-like activity in both epimastigote and trypomastigote forms of
. This activity was inhibited by ABCC transport modulators (probenecid, indomethacin, and MK-571), by ATP-depleting agents (sodium azide and iodoacetic acid) and by the thiol-depleting agent N-ethylmaleimide. Additionally, the presence of ABCC-like activity was supported by direct inhibition of the thiol-conjugated compound efflux with indomethacin, characteristic of ABCC subfamily members. Taken together, the results provide the first description of native ABCC-like activity in
epimastigote and trypomastigote forms, indicating that the study of the biological role for that thiol transporter is crucial to reveal new molecular mechanisms for therapeutic approaches in the Chagas disease.
Cryptococcosis is an opportunistic disease caused by the fungus Cryptococcus neoformans and Cryptococcus gattii. It starts as a pulmonary infection that can spread to other organs, such as the brain, ...leading to the most serious occurrence of the disease, meningoencephalitis. The humoral response has already been described in limiting the progression of cryptococcosis where the B-1 cell seems to be responsible for producing natural IgM antibodies, crucial for combating fungal infections. The role of the B-1 cell in C. neoformans infection has been initially described, however the role of the humoral response of B-1 cells has not yet been evaluated during C. gattii infections. In the present study we tried to unravel this issue using XID mice, a murine model deficient in the Btk protein which compromises the development of B-1 lymphocytes. We use the XID mice compared to BALB/c mice that are sufficient for the B-1 population during C. gattii infection. Our model of chronic lung infection revealed that XID mice, unlike the sufficient group of B-1, had early mortality with significant weight loss, in addition to reduced levels of IgM and IgG specific to GXM isolated from the capsule of C. neoformans. In addition to this, we observed an increased fungal load in the blood and in the brain. We described an increase in the capsular size of C. gattii and the predominant presence of cytokines with a Th2 profile was also observed in these animals. Thus, the present study strongly points to a higher susceptibility of the XID mouse to C. gattii, which suggests that the presence of B-1 cells and anti-GXM antibodies is fundamental during the control of infection by C. gattii.
The last decades have produced a plethora of evidence on the role of glycans, from cell adhesion to signaling pathways. Much of that information pertains to their role on the immune system and their ...importance on the surface of many human pathogens. A clear example of this is the flagellated protozoan
, which displays on its surface a great variety of glycoconjugates, including
-glycosylated mucin-like glycoproteins, as well as multiple glycan-binding proteins belonging to the
-sialidase (TS) family. Among the latter, different and concurrently expressed molecules may present or not TS activity, and are accordingly known as active (aTS) and inactive (iTS) members. Over the last thirty years, it has been well described that
is unable to synthesize sialic acid (SIA) on its own, making use of aTS to steal the host's SIA. Although iTS did not show enzymatic activity, it retains a substrate specificity similar to aTS (α-2,3 SIA-containing glycotopes), displaying lectinic properties. It is accepted that aTS members act as virulence factors in mammals coursing the acute phase of the
infection. However, recent findings have demonstrated that iTS may also play a pathogenic role during
infection, since it modulates events related to adhesion and invasion of the parasite into the host cells. Since both aTS and iTS proteins share structural substrate specificity, it might be plausible to speculate that iTS proteins are able to assuage and/or attenuate biological phenomena depending on the catalytic activity displayed by aTS members. Since SIA-containing glycotopes modulate the host immune system, it should not come as any surprise that changes in the sialylation of parasite's mucin-like molecules, as well as host cell glycoconjugates might disrupt critical physiological events, such as the building of effective immune responses. This review aims to discuss the importance of mucin-like glycoproteins and both aTS and iTS for
biology, as well as to present a snapshot of how disturbances in both parasite and host cell sialoglycophenotypes may facilitate the persistence of
in the infected mammalian host.
THE POTENTIAL OF NATURAL XANTHONE α-MANGOSTIN IN THE DEVELOPMENT OF NOVEL ANTIINFECTIVE AGENTS: A REVIEW. The mangosteen (Garcinia mangostana, Linn.) is a tropical fruit cultivated in the tropical ...forests of Southeast Asian countries. It is recognized as the queen of fruits due to its unique color, aroma, and flavor. It has been used for centuries in Southeastern Asian traditional medicine for the treatment of various diseases. Many functional molecules with high medicinal value are obtained from the pericarp of mangosteen fruit, whose major constituent is xanthone α-mangostin. Several studies have been carried out over the last decades to further investigate and understand the pharmacological properties associated with the plant and its main chemical constituents, belonging to the class of xanthones. In addition, numerous in vitro and in vivo studies related to mangosteen have been published, indicating its importance and its potential application in medicinal chemistry. Prenylated xanthones, which include α-mangostin, are secondary metabolites particularly common in plants belonging to the Clusiaceae family. These substances have been intensively investigated for their potential as biologically active agents. This article describes a critical analysis of published data related to the properties of α-mangostin, aiming to provide a more detailed view of its potential as a chemotherapeutic agent for the prevention and treatment of infectious diseases.
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