Plasmodium vivax causes approximately 100 million clinical malaria cases yearly
. The basis of protective immunity is poorly understood and thought to be mediated by antibodies
. Cytotoxic CD8
T ...cells protect against other intracellular parasites by detecting parasite peptides presented by human leukocyte antigen class I on host cells. Cytotoxic CD8
T cells kill parasite-infected mammalian cells and intracellular parasites by releasing their cytotoxic granules
. Perforin delivers the antimicrobial peptide granulysin and death-inducing granzymes into the host cell, and granulysin then delivers granzymes into the parasite. Cytotoxic CD8
T cells were thought to have no role against Plasmodium spp. blood stages because red blood cells generally do not express human leukocyte antigen class I
. However, P. vivax infects reticulocytes that retain the protein translation machinery. Here we show that P. vivax-infected reticulocytes express human leukocyte antigen class I. Infected patient circulating CD8
T cells highly express cytotoxic proteins and recognize and form immunological synapses with P. vivax-infected reticulocytes in a human leukocyte antigen-dependent manner, releasing their cytotoxic granules to kill both host cell and intracellular parasite, preventing reinvasion. P. vivax-infected reticulocytes and parasite killing is perforin independent, but depends on granulysin, which generally efficiently forms pores only in microbial membranes
. We find that P. vivax depletes cholesterol from the P. vivax-infected reticulocyte cell membrane, rendering it granulysin-susceptible. This unexpected T cell defense might be mobilized to improve P. vivax vaccine efficacy.
Piplartine (piperlongumine) is a plant-derived compound found in some Piper species that became a novel potential antineoplastic agent. In the present study, we synthesized a novel platinum complex ...containing a piplartine derivative cis-PtCl(PIP-OH)(PPh
)
PF
(where, PIP-OH = piplartine demethylated derivative; and PPh
= triphenylphosphine) with enhanced cytotoxicity in different cancer cells, and investigated its apoptotic action in human promyelocytic leukemia HL-60 cells. The structure of PIP-OH ligand was characterized by X-ray crystallographic analysis and the resulting platinum complex was characterized by infrared, molar conductance measurements, elemental analysis and NMR experiments. We found that the complex is more potent than piplartine in a panel of cancer cell lines. Apoptotic cell morphology, increased internucleosomal DNA fragmentation, without cell membrane permeability, loss of the mitochondrial transmembrane potential, increased phosphatidylserine externalization and caspase-3 activation were observed in complex-treated HL-60 cells. Treatment with the complex also caused a marked increase in the production of reactive oxygen species (ROS), and the pretreatment with N-acetyl-L-cysteine, an antioxidant, reduced the complex-induced apoptosis, indicating activation of ROS-mediated apoptosis pathway. Important, pretreatment with a p38 MAPK inhibitor (PD 169316) and MEK inhibitor (U-0126), known to inhibit ERK1/2 activation, also prevented the complex-induced apoptosis. The complex did not induce DNA intercalation in cell-free DNA assays. In conclusion, the complex exhibits more potent cytotoxicity than piplartine in a panel of different cancer cells and triggers ROS/ERK/p38-mediated apoptosis in HL-60 cells.
In this work, nine new rare‐earth metal–organic frameworks (RE‐MOFs, where RE = Lu(III), Yb(III), Tm(III), Er(III), Ho(III), Dy(III), Tb(III), Gd(III), and Eu(III)) isostructural to Zr‐MOF‐808 are ...synthesized, characterized, and studied regarding their photophysical properties. Materials with high crystallinity and surface area are obtained from a reproducible synthetic procedure that involves the use of two fluorinated modulators. At the same time, these new RE‐MOFs display tunable photoluminescent properties due to efficient linker‐to‐metal energy transfer promoted by the antenna effect, resulting in a series of RE‐MOFs displaying lanthanoid‐based emissions spanning the visible and near‐infrared regions of the electromagnetic spectrum.
Latent fingermarks contain precise information about the identities of individuals present at the crime scene. Cyanoacrylate (CA) fuming is a popular and effective technique for fingermark ...development on non-porous surfaces, but few approaches have been proposed for processing vehicles. We report the use of a large CA fuming chamber for latent fingermark development in vehicles related to serious crimes in Brasilia, Brazil. The chamber consists of a fuming compartment with a stainless-steel structure and is supplied with movable heating trays, air circulation fans, humidifying system, gas evacuation system, and an integrated control unit for process monitoring. Processing an entire regular vehicle requires 16 g of liquid CA and ~2 h. Identifiable fingermarks were recognized on the exterior and interior of the examined vehicles, including the door handles and the seat belt metallic tongue. Detected fingermarks were positively matched to individuals whose involvement in criminal activities was confirmed. The results support the efficiency of the CA fuming technique for fingermark development in the interior and exterior of vehicles and indicate certain parts of vehicles as being of potential interest. Considering the efficiency of the CA polymerization reaction for fingermark development in vehicles involved in crimes, large-scale chambers may offer important advantages.
Within the Southern Ocean, the greatest warming is occurring on the Antarctic Peninsula (AP) where clear cryospheric and biological consequences are being observed. Antarctic coastal systems harbour ...a high diversity of marine and terrestrial ecosystems heavily influenced by Antarctic seaweeds (benthonic macroalgae) and bird colonies (mainly penguins). Primary sea spray aerosols (SSA) formed by the outburst of bubbles via the sea-surface microlayer depend on the organic composition of the sea water surface. In order to gain insight into the influence of ocean biology and biogeochemistry on atmospheric aerosol, we performed in situ laboratory aerosol bubble chamber experiments to study the effect of different leachates of biogenic material - obtained from common Antarctic seaweeds as well as penguin guano - on primary SSA. The addition of different leachate materials on a seawater sample showed a dichotomous effect depending on the leachate material added - either suppressing (up to 52%) or enhancing (22–88%) aerosol particle production. We found high ice nucleating particle number concentrations resulting from addition of guano leachate material. Given the evolution of upper marine polar coastal ecosystems in the AP, further studies on ocean-atmosphere coupling are needed in order to represent the currently poorly understood climate feedback processes.
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•We conducted sea spray aerosol (SSA) chamber experiments in Antarctic coastal systems.•We studied the effect of leachate material from macroalgae and penguin guano on SSA production.•The addition of different leachate materials affects SSA production.•Marine organic matter in the surface ocean biogeochemistry should be considered in global climate models.
The global prevalence of Alzheimer's disease (AD) points to endemic levels, especially considering the increase of average life expectancy worldwide. AD diagnosis based on early biomarkers and better ...knowledge of related pathophysiology are both crucial in the search for medical interventions that are able to modify AD progression. In this study we used unsupervised spectral unmixing statistical techniques to identify the vibrational spectral signature of amyloid β aggregation in neural tissues, as early biomarkers of AD in an animal model. We analyzed spectral images composed of a total of 55 051 Raman spectra obtained from the frontal cortex and hippocampus of five bitransgenic APPswePS1ΔE9 mice, and colocalized amyloid β plaques by other fluorescence techniques. The Raman signatures provided a multifrequency fingerprint consistent with the results of synthesized amyloid β fibrils. The fingerprint obtained from unmixed analysis in neural tissues is shown to provide a detailed image of amyloid plaques in the brain, with the potential to be used as biomarkers for non-invasive early diagnosis and pathophysiology studies in AD on the retina.
SGTs (small glutamine-rich TPR-containing proteins) are dimeric proteins that belong to the class of co-chaperones characterized by the presence of TPR domains (containing tetratricopeptide repeats). ...Human (SGTA) and yeast (Sgt2) SGTs are characterized by three distinct domains: an N-terminal dimerization domain, a central TPR-domain important for binding to other proteins (chaperones included) and a C-terminal domain involved in hydrophobic interactions. Both these SGTs are involved in the cellular PQC (protein quality control) system, as they interact with chaperones and have functions that aid stress recovery. However, there are differences between them, such as structural features and binding specificities, that could be better understood if other orthologous proteins were studied. Therefore, we produced and characterized a putative SGT protein, designated AaSGT, from the mosquito Aedes aegypti, which is a vector of several diseases, such as dengue and Zika. The protein was produced as a folded dimer which was stable up to 40 °C and was capable of binding to AaHsp90 and fully protecting a model protein, α-synuclein, from aggregation. The conformation of AaSGT was investigated by biophysical tools and small angle X-ray scattering, which showed that the protein had an elongated conformation and that its C-terminal domain was mainly disordered. The results with a C-terminal deletion mutant supported these observations. Altogether, these results are consistent with those from other functional SGT proteins and add to the understanding of the PQC system in Aedes aegypti, an important aim that may help to develop inhibitory strategies against this vector of neglected diseases.
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•AaSGT provides phenotype complementation in yeast using a heat sensitivity assay.•AaSGT is capable of fully protecting α-Synuclein from aggregation.•AaSGT has an elongated conformation with a disordered C-terminus.
Vaccinia virus (VACV) is a notorious virus for a number of scientific reasons; however, most of its notoriety comes from the fact that it was used as a vaccine against smallpox, being ultimately ...responsible for the eradication of that disease. Nonetheless, many different vaccinia virus strains have been obtained over the years; some are suitable to be used as vaccines, whereas others are virulent and unsuitable for this purpose. Interestingly, different vaccinia virus strains elicit different immune responses
, and this is a direct result of the genomic differences among strains. In order to evaluate the net result of virus-encoded immune evasion strategies of vaccinia viruses, we compared antiviral immune responses in mice intranasally infected by the highly attenuated and nonreplicative MVA strain, the attenuated and replicative Lister strain, or the virulent WR strain. Overall, cell responses elicited upon WR infections are downmodulated compared to those elicited by MVA and Lister infections, especially in determined cell compartments such as macrophages/monocytes and CD4
T cells. CD4
T cells are not only diminished in WR-infected mice but also less activated, as evaluated by the expression of costimulatory molecules such as CD25, CD212, and CD28 and by the production of cytokines, including tumor necrosis factor alpha (TNF-α), gamma interferon (IFN-γ), interleukin-4 (IL-4), and IL-10. On the other hand, MVA infections are able to induce strong T-cell responses in mice, whereas Lister infections consistently induced responses that were intermediary between those induced by WR and MVA. Together, our results support a model in which the virulence of a VACV strain is proportional to its potential to downmodulate the host's immune responses.
Vaccinia virus was used as vaccine against smallpox and was instrumental in the successful eradication of that disease. Although smallpox vaccination is no longer in place in the overall population, the use of vaccinia virus in the development of viral vector-based vaccines has become popular. Nonetheless, different vaccinia virus strains are known and induce different immune responses. To look into this, we compared immune responses triggered by mouse infections with the nonreplicative MVA strain, the attenuated Lister strain, or the virulent WR strain. We observed that the WR strain was capable of downmodulating mouse cell responses, whereas the highly attenuated MVA strain induced high levels of cell-mediated immunity. Infections by the intermediately attenuated Lister strain induced cell responses that were intermediary between those induced by WR and MVA. We propose that the virulence of a vaccinia virus strain is directly proportional to its ability to downmodulate specific compartments of antiviral cell responses.
The potential emergence of zoonotic diseases has raised significant concerns, particularly in light of the recent pandemic, emphasizing the urgent need for scientific preparedness. The bioprospection ...and characterization of new molecules are strategically relevant to the research and development of innovative drugs for viral and bacterial treatment and disease management. Amphibian species possess a diverse array of compounds, including antimicrobial peptides. This study identified the first bioactive peptide from
in a transcriptome analysis. The synthetic peptide sequence, which belongs to the defensin family, was characterized through MALDI TOF/TOF mass spectrometry. Molecular docking assays hypothesized the interaction between the identified peptide and the active binding site of the spike WT RBD/hACE2 complex. Although additional studies are required, the preliminary evaluation of the antiviral potential of synthetic SS-I was conducted through an in vitro cell-based SARS-CoV-2 infection assay. Additionally, the cytotoxic and hemolytic effects of the synthesized peptide were assessed. These preliminary findings highlighted the potential of SS-I as a chemical scaffold for drug development against COVID-19, hindering viral infection. The peptide demonstrated hemolytic activity while not exhibiting cytotoxicity at the antiviral concentration.
The objective of the present work was to use MAS in self-pollinated cassava populations for obtaining individuals with high inbreeding (f) aimed at rapid development of partial inbred lines. Three ...progenies (F0222, F1378 and F1662) were self-pollinated, generating a total of 233 S1 individuals. The progenies and the S1 individuals were evaluated in the seedlings and clonal evaluation trials (CETs). In the CET, plants were evaluated for the following traits: plant height (PH), root dry matter content (DMC), above ground yield (AGY), root (RY) and starch yield (SY). Twenty-seven microsatellites and five minisatellites were used to determine the level of inbreeding of the S1 individuals. Inbreeding (f) values varied from 0.15 to 0.89 within progenies, whereas most of the S1 individuals presented f values above 0.50. In average, 25% of the S1 individuals were selected, which resulted in a 38% inbreeding increase in the cassava progenies. In contrast, phenotypic selection showed no differences in inbreeding increase. Furthermore, there was no correlation between the level of inbreeding and agronomic traits. MAS was efficient for the identification and selection of cassava S1 individuals, with higher inbreeding values contributing to the decrease in the breeding cycles necessary to obtain new cassava inbred lines.
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