Variant genes and the spleen in Plasmodium vivax malaria

It is generally accepted that Plasmodium vivax, the most widely distributed human malaria, does not cytoadhere in the deep capillaries of inner organs and thus this malaria parasite must have evolved splenic evasion mechanism in addition to sequestration. The spleen is a uniquely adapted lymphoid organ whose central function is the selective clearance of cell and other particles from the blood, and microbes including malaria. Splenomegaly is a hallmark of malaria and no other disease seems to exacerbate this organ as this disease does. Besides this major selective clearance function however, the spleen is also an erythropoietic organ which, under stress conditions, can be responsible for close to 40% of the RBC populations. Data obtained in experimental infections of human patients with P. vivax showed that anaemia is associated with acute and chronic infections and it has been postulated that the continued parasitemia might have been sufficient to infect and destroy most circulating reticulocytes. We review here the basis of our current knowledge of variant genes in P. vivax and the structure and function of the spleen during malaria. Based on this data, we propose that P. vivax specifically adhere to barrier cells in the human spleen allowing the parasite to escape spleen-clearance while favouring the release of merozoites in an environment where reticulocytes, the predominant, if not exclusive, host cell of P. vivax, are stored before their release into circulation to compensate for the anaemia associated with vivax malaria.     

PD-L1 Blockade Differentially Impacts Regulatory T Cells from HIV-Infected Individuals Depending on Plasma Viremia

Blocking the PD-1/PD-L1 pathway has emerged as a potential therapy to restore impaired immune responses in human immunodeficiency virus (HIV)-infected individuals. Most reports have studied the impact of the PD-L1 blockade on effector cells and neglected possible effects on regulatory T cells (Treg cells), which play an essential role in balancing immunopathology and antiviral effector responses. The aim of this study was to define the consequences of ex vivo PD-L1 blockade on Treg cells from HIV-infected individuals. We observed that HIV infection led to an increase in PD-1+ and PD-L1+ Treg cells. This upregulation correlated with disease progression and decreased under antiretroviral treatment. Treg cells from viremic individuals had a particularly high PD-1 expression and impaired proliferative capacity in comparison with Treg cells from individuals under antiretroviral treatment. PD-L1 blockade restored the proliferative capacity of Treg cells from viremic individuals but had no effect on its suppressive capacity. Moreover, it increased the viral production in cell cultures from viremic individuals. This increase in viral production correlated with an increase in Treg cell percentage and a reduction in the CD4/Treg and CD8/Treg cell ratios. In contrast to the effect of the PD-L1 blockade on Treg cells from viremic individuals, we did not observe a significant effect on the proliferative capacity of Treg cells from individuals in whom viremia was controlled (either spontaneously or by antiretroviral treatment). However, PD-L1 blockade resulted in an increased proliferative capacity of HIV-specific-CD8 T cells in all subjects. Taken together, our findings suggest that manipulating PD-L1 in vivo can be expected to influence the net gain of effector function depending on the subject’s plasma viremia.     

Candida albicans Increases Tumor Cell Adhesion to Endothelial Cells In Vitro: Intraspecific Differences and Importance of the Mannose Receptor

The dimorphic fungus Candida albicans is able to trigger a cytokine-mediated pro-inflammatory response that increases tumor cell adhesion to hepatic endothelium and metastasis. To check the intraspecific differences in this effect, we used an in vitro murine model of hepatic response against C. albicans, which made clear that tumor cells adhered more to endothelium incubated with blastoconidia, both live and killed, than germ tubes. This finding was related to the higher carbohydrate/protein ratio found in blastoconidia. In fact, destruction of mannose ligand residues on the cell surface by metaperiodate treatment significantly reduced tumor cell adhesion induced. Moreover, we also noticed that the effect of clinical strains was greater than that of the reference one. This finding could not be explained by the carbohydrate/protein data, but to explain these differences between strains, we analyzed the expression level of ten genes (ADH1, APE3, IDH2, ENO1, FBA1, ILV5, PDI1, PGK1, QCR2 and TUF1) that code for the proteins identified previously in a mannoprotein-enriched pro-metastatic fraction of C. albicans. The results corroborated that their expression was higher in clinical strains than the reference one. To confirm the importance of the mannoprotein fraction, we also demonstrate that blocking the mannose receptor decreases the effect of C. albicans and its mannoproteins, inhibiting IL-18 synthesis and tumor cell adhesion increase by around 60%. These findings could be the first step towards a new treatment for solid organ cancers based on the role of the mannose receptor in C. albicans-induced tumor progression and metastasis.     

Queratitis fúngica por Curvularia hominis: primer caso descrito en España

Background

Dematiaceous fungal genus Curvularia is a causal agent of keratitis, onychomycosis, and skin infections. In 2014, using DNA sequencing techniques, five new species, including Curvularia hominis, were described. In this article, a report is presented on the first clinical case of C. hominis infection in Spain. It concerns a corneal ulcer caused by this recently described species.

Circadian rhythms of omitted stimulus potentials in the crayfish brain

The omitted stimulus potential (OSP) is a type of event-related potentials elicited by cognitively-relevant stimuli associated with mental processes in humans. Crayfish also emit OSP when an expected stimulus does not arrive, although this is not considered to index a high-level cognitive event, but it is endogenous in nature because this depends on the recent history and arousal state of the animal. Although OSP is highly conserved in evolution, it had not been the subject of circadian study. Our hypothesis is that OSP, recorded in crayfish brain (Procambarus clarkii) has a circadian behaviour in its firing pattern. OSPs show circadian rhythms in both the latency and in the OSP/Sp ratio, under free-running (light:light, LL) and photoperiod (light:dark, LD) conditions, with main peaks during the daytime. This is the first report that shows a circadian pattern of OSP.     

Interplay between mobility,multi-seeding and lockdowns shapes COVID-19 local impact

Assessing the impact of mobility on epidemic spreading is of crucial importance for understanding the effect of policies like mass quarantines and selective re-openings. While many factors affect disease incidence at a local level, making it more or less homogeneous with respect to other areas, the importance of multi-seeding has often been overlooked. Multi-seeding occurs when several independent (non-clustered) infected individuals arrive at a susceptible population. This can lead to independent outbreaks that spark from distinct areas of the local contact (social) network. Such mechanism has the potential to boost incidence, making control efforts and contact tracing less effective. Here, through a modeling approach we show that the effect produced by the number of initial infections is non-linear on the incidence peak and peak time. When case importations are carried by mobility from an already infected area, this effect is further enhanced by the local demography and underlying mixing patterns: the impact of every seed is larger in smaller populations. Finally, both in the model simulations and the analysis, we show that a multi-seeding effect combined with mobility restrictions can explain the observed spatial heterogeneities in the first wave of COVID-19 incidence and mortality in five European countries. Our results allow us for identifying what we have called epidemic epicenter: an area that shapes incidence and mortality peaks in the entire country. The present work further clarifies the nonlinear effects that mobility can have on the evolution of an epidemic and highlight their relevance for epidemic control.     

A new species of Micragasma J. Sahlberg, 1900 (Coleoptera: Hydraenidae) from Crete

We describe a new species of Micragasma J. Sahlberg, 1900 (Coleoptera, Hydraenidae), which is here treated as a subgenus of Ochthebius Leach, 1815 Leach, W.E. (1815), ‘Entomology’, in The Edinburgh Encyclopaedia (Vol. 9), ed. D. Brewster, Balfour: Edinburgh, pp. 57–172. [Google Scholar]. The new species, O. (Micragasma) minoicus sp. n., was found at the margins of a coastal rockpool in the island of Crete. The species differs from the other two known species of Micragasma in both external and genital characters, but shares with them the presence of small setiferous tubercles on the surface of the head, pronotum and elytra, and a strong medial gibbosity on the head. In some characters, such as the structure and shape of the aedeagus, O. (M.) minoicus sp. n. is similar to other species of the genus Ochthebius, in particular of the subgenus Cobalius Rey, 1886 Rey, C. (1886), ‘Histoire naturelle des coléoptères de France (suite)’, Annales de la Société Linnéenne de Lyon, 32, 1–187, pl. 1–2.[Crossref] , [Google Scholar], typical of coastal rockpools.

http://zoobank.org/urn:lsid:zoobank.org:act:BCEAE1EE-7C5E-4017-A753-559738221502     

Analysis of the activity of a γ-gliadin promoter in transgenic wheat and characterization of gliadin synthesis in wheat by MALDI-TOF during grain development

The wheat grain is the most important organ for human food and therefore is the target for much research focused on modifying its composition to improve nutritional and functional components. Genetic transformation provides a precise tool to alter the composition of wheat grain by expressing new genes or by down-regulating groups of proteins encoded by multigene families such as gliadins, which contain clusters of epitopes that are active groups in triggering celiac disease. For such work, specific promoters are required to express such constructs in the wheat endosperm. In the present study we report the isolation and characterization of a γ-gliadin promoter from transgenic wheat, and the analysis of gliadin synthesis during grain development in bread wheat by Matrix-Assisted Laser Desorption/Ionization Time-Of-Flight Mass Spectrometry (MALDI/TOF MS). The γ-gliadin promoter fragment was isolated from bread wheat by genome walking and was re-introduced, driving the expression of the gusA gene, by particle bombardment, giving fifteen independent transgenic lines. Detailed analysis of the sequence of the 885 bp promoter fragment showed that it contains three prolamin boxes but only one is conserved according to the consensus sequence reported. The AACA/TA motif is present twice in published γ-gliadin promoter sequences. The RY element i.e., CATGCAT or CATGCAC, is also present twice in the published promoter. Transgenic lines were classified as high, medium, and low expressers. The expression of the gusA gene was found only in the seeds of the transgenic lines. GUS staining was first detected in the outer endosperm of the lobes, and then it extended to the whole outer endosperm. GUS staining was not found in the aleurone layer nor in the embryo. The qRT-PCR data confirmed the data obtained by GUS staining. The expression of the gusA gene determined by qRT-PCR for the high expresser line (B281) was 4 and 8 times higher than that of medium (B282) and low (B286) expresser lines, respectively. MALDI/TOF-MS showed that gliadins exhibited different patterns of synthesis during the course of seed maturation. Thus, gliadins with masses higher than 36,000 Da were synthesised within the first 12 days post anthesis while those with masses lower than 36,000 Da were synthesised later. Results of GUS staining, qRT-PCR and MALDI/TOF-MS showed that the γ-gliadin promoter reported in this work could be a good candidate to downregulate wheat gliadins.     

Analysis of genetic structure in a sample of coffee (Coffea arabica L.) using fluorescent SSR markers

The knowledge of population structure is important to determine the degree of linkage disequilibrium, which allows the selection of genotypes for association mapping. Using 47 SSR markers, the genetic variability and population structure of 68 accessions of C. arabica (wild and cultivated) and of three diploid species used as reference were evaluated. The analysis was done with the distance method and the structure model. The structure analysis inferred nine subpopulations (k = 9), for which the greatest values of probability were obtained. Three of the groups corresponded to the three diploid species as expected. There were six groups identified within C. arabica. The genetic subdivisions within C. arabica were based on geographical origin, degree of domestication, and dispersal history of coffee. One group consisted entirely of cultivated genotypes, where intense population bottleneck were associated with a founder effect. This was the most homogeneous group, as demonstrated by the reduced distance between cultivars in the dendrogram. Three of the cultivated genotypes, originating from Sudan, were separated into an independent group, presumably due to selective adaptation to a different set of environmental conditions. Another group consisted of genotypes of the type “ennarea” that were grown and cultivated in isolation on the shores of the Tana lake. The semi-wild genotypes clustered into three different groups. This type of analysis provides a strong evidence of population structure in C. arabica. Based on these findings, it is possible to better identify a balanced sample of diverse plants in germplasm.