Targeted Genotyping of MIS-C Patients Reveals a Potential Alternative Pathway Mediated Complement Dysregulation during COVID-19 Infection

Complement dysregulation has been documented in adults with COVID-19 and implicated in relevant pediatric inflammatory responses against SARS-CoV-2. We propose that signatures of complement missense coding SNPs associated with dysregulation could also be identified in children with multisystem inflammatory syndrome (MIS-C). We investigated 71 pediatric patients with RT-PCR validated SARS-CoV-2 hospitalized in pediatric COVID-19 care units (November 2020–March 2021) in three major groups. Seven (7) patients suffered from MIS-C (MIS-C group), 32 suffered from COVID-19 and were hospitalized (admitted group), whereas 32 suffered from COVID-19, but were sent home. All patients survived and were genotyped for variations in the C3, C5, CFB, CFD, CFH, CFHR1, CFI, CD46, CD55, MASP1, MASP2, MBL2, COLEC11, FCN1, and FCN3 genes. Upon evaluation of the missense coding SNP distribution patterns along the three study groups, we noticed similarities, but also considerably increased frequencies of the alternative pathway (AP) associated with SNPs rs12614 CFB, rs1061170, and rs1065489 CFH in the MIS-C patients. Our analysis suggests that the corresponding substitutions potentially reduce the C3b-inactivation efficiency and promote slower and weaker AP C3bBb pre-convertase assembly on virions. Under these circumstances, the complement AP opsonization capacity may be impaired, leading to compromised immune clearance and systemic inflammation in the MIS-C syndrome.     

The paleoanthropology of Greece

European paleoanthropology and paleolithic archeology were already well‐established by the early twentieth century. The human fossil record from this continent is the longest known and perhaps most intensively studied. Nonetheless, important gaps remain to this day in the map of Pleistocene Europe; perhaps the most glaring of these is located in the southeastern corner of the continent. This region's record is critical for addressing questions about the course of human evolution in Europe because its geographic position lends it a dual role: on one hand, it encompasses a frequently hypothesized dispersal corridor from Africa into Europe for both archaic and early modern humans; on the other, as one of the three Mediterranean peninsulas, it acted as a refugium for plant, animal, and, most likely, human populations during glacial conditions. This article is a review of the paleoanthopological record of Greece, one of the least known in Europe.     

Tumour necrosis factors in immune regulation: Everything that''s interesting is … New!

Tumour necrosis factors have been classically studied as molecules central to the pathogenesis of infectious, inflammatory and autoimmune diseases. The recent generation of mice deficient in TNFα, LTα, or their receptors, has provided exciting new insights into the physiological role of these molecules in the development of secondary lymphoid tissues and in the organisation of the Immoral immune response.     

Fast Bayesian inference for large occupancy datasets

In recent years, the study of species' occurrence has benefited from the increased availability of large-scale citizen-science data. While abundance data from standardized monitoring schemes are biased toward well-studied taxa and locations, opportunistic data are available for many taxonomic groups, from a large number of locations and across long timescales. Hence, these data provide opportunities to measure species' changes in occurrence, particularly through the use of occupancy models, which account for imperfect detection. These opportunistic datasets can be substantially large, numbering hundreds of thousands of sites, and hence present a challenge from a computational perspective, especially within a Bayesian framework. In this paper, we develop a unifying framework for Bayesian inference in occupancy models that account for both spatial and temporal autocorrelation. We make use of the Pólya-Gamma scheme, which allows for fast inference, and incorporate spatio-temporal random effects using Gaussian processes (GPs), for which we consider two efficient approximations: subset of regressors and nearest neighbor GPs. We apply our model to data on two UK butterfly species, one common and widespread and one rare, using records from the Butterflies for the New Millennium database, producing occupancy indices spanning 45 years. Our framework can be applied to a wide range of taxa, providing measures of variation in species' occurrence, which are used to assess biodiversity change.     

Invagination of Ectodermal Placodes Is Driven by Cell Intercalation-Mediated Contraction of the Suprabasal Tissue Canopy

Ectodermal organs such as teeth, hair follicles, and mammary glands begin their development as placodes. These are local epithelial thickenings that invaginate into mesenchymal space. There is currently little mechanistic understanding of the cellular processes driving the early morphogenesis of these organs and of why they lead to invagination rather than simple tissue thickening. Here, we show that placode invagination depends on horizontal contraction of superficial layers of cells that form a shrinking and thickening canopy over underlying epithelial cells. This contraction occurs by cell intercalation and is mechanically coupled to the basal layer by peripheral basal cells that extend apically and centripetally while remaining attached to the basal lamina. This process is topologically analogous to well-studied apical constriction mechanisms, but very different from them both in scale and molecular mechanism. Mechanical cell–cell coupling is propagated through the tissue via E-cadherin junctions, which in turn depend on tissue-wide tension. We further present evidence that this mechanism is conserved among different ectodermal organs and is, therefore, a novel and fundamental morphogenetic motif widespread in embryonic development.     

Metal Phytoremediation by the Halophyte Limoniastrum monopetalum (L.) Boiss: Two Contrasting Ecotypes

The phytoremediation potential of the halophyte Limoniastrum monopetalum for the removal of Cd and Pb from polluted sites is assessed in this work. Two pot experiments were conducted; the first with wild L. monopetalum grown on soil polluted with Cd and Pb irrigated at different salinities, and the second with commonly cultivated ornamental L. monopetalum grown on soil polluted with Cd irrigated also at different salinities. The data revealed that wild L. monopetalum is a Cd and Pb tolerant plant able to accumulate at least 100 ppm of cadmium in its shoots without showing any significant decrease in terms of biomass production, chlorophyll content or water content suggesting that it could be an accumulator of Cd. Pb above-ground accumulation was kept at low levels with the majority of Pb localized in the roots. On the other hand, contrasting results were obtained for ornamental L. monopetalum which although it was found to be also Cd tolerant, Cd accumulation in its tissues was kept at significantly lower levels especially compared to that of the wild ecotype. In addition for ornamental L. monopetalum salinity did not have a positive effect on Cd accumulation and translocation as observed in the wild type and in other halophytes. Analysis of the salt excretion crystals on the leaf surface confirmed that wild and cultivated ornamental L. monopetalum excrete cadmium and lead through their salt glands as a possible metal detoxification mechanism, although the amount excreted by the ornamental L. monopetalum is significantly less.     

Modification of human β-globin locus PAC clones by homologous recombination in Escherichia coli

We report here modifications of human β-globin PAC clones by homologous recombination in Escherichia coli DH10B, utilising a plasmid temperature sensitive for replication, the recA gene and a wild-type copy of the rpsL gene which allows for an efficient selection for plasmid loss in this host. High frequencies of recombination are observed even with very small lengths of homology and the method has general utility for introducing insertions, deletions and point mutations. No rearrangements were detected with the exception of one highly repetitive genomic sequence when either the E.coli RecA- or the lambdoid phage encoded RecT and RecE-dependent recombination systems were used.     

Gut bacteria associated with different diets in reared Nephrops norvegicus

The impact of different diets on the gut microbiota of reared Nephrops norvegicus was investigated based on bacterial 16S rRNA gene diversity. Specimens were collected from Pagasitikos Gulf (Greece) and kept in experimental rearing tanks, under in situ conditions, for 6 months. Treatments included three diets: frozen natural (mussel) food (M), dry formulated pellet (P) and starvation (S). Gut samples were collected at the initiation of the experiment, and after 3 and 6 months. Tank water and diet samples were also analyzed for bacterial 16S rRNA gene diversity. Statistical analysis separated the two groups fed or starved (M and P vs. S samples). Most gut bacteria were not related to the water or diet bacteria, while bacterial diversity was higher in the starvation samples. M and P samples were dominated by Gammaproteobacteria, Epsilonproteobacteria and Tenericutes. Phylotypes clustering in Photobacterium leiognathi, Shewanella sp. and Entomoplasmatales had high frequencies in the M and P samples but low sequence frequencies in S samples. The study showed that feeding resulted in the selection of specific species, which also occurs in the natural population, and might be associated with the animal's nutrition.     

Total Phenolic Fraction (TPF) from Extra Virgin Olive Oil: Induction of apoptotic-like cell death in Leishmania spp. promastigotes and in vivo potential of therapeutic immunomodulation

BackgroundLeishmaniasis is a serious multifactorial parasitic disease with limited treatment options. Current chemotherapy is mainly consisted of drugs with serious drawbacks such as toxicity, variable efficacy and resistance. Alternative bioactive phytocompounds may provide a promising source for discovering new anti-leishmanial drugs. Extra Virgin Olive Oil (EVOO), a key-product in the Mediterranean diet, is rich in phenols which are associated with anti-inflammatory, anti-cancer and anti-microbial effects. In this study, we investigate the anti-leishmanial effect of Total Phenolic Fraction (TPF) derived from EVOO in both in vitro and in vivo systems by investigating the contributing mechanism of action.Methodology/Principal findingsWe tested the ability of TPF to cause apoptotic-like programmed cell death in L. infantum and L. major exponential-phase promastigotes by evaluating several apoptotic indices, such as reduction of proliferation rate, sub-G0/G1 phase cell cycle arrest, phosphatidylserine externalization, mitochondrial transmembrane potential disruption and increased ROS production, by using flow cytometry and microscopy techniques. Moreover, we assessed the therapeutic effect of TPF in L. major-infected BALB/c mice by determining skin lesions, parasite burden in popliteal lymph nodes, Leishmania-specific antibodies and biomarkers of tissue site cellular immune response, five weeks post-treatment termination. Our results show that TPF triggers cell-cycle arrest and apoptotic-like changes in Leishmania spp. promastigotes. Moreover, TPF treatment induces significant reduction of parasite burden in draining lymph nodes together with an antibody profile indicative of the polarization of Th1/Th2 immune balance towards the protective Th1-type response, characterized by the presence of IFN-γ-producing CD4+ T-cells and increased Tbx21/GATA-3 gene expression ratio in splenocytes.Conclusions/SignificanceTPF exhibits chemotherapeutic anti-leishmanial activity by inducing programmed cell death on cell-free promastigotes and immunomodulatory properties that induce in vivo T cell-mediated responses towards the protective Th1 response in experimental cutaneous leishmaniasis. These findings enable deeper understanding of TPF’s dual mode of action that encourages further studies.