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Seroprevalence of Toxoplasma gondii among Sylvatic Rodents in Poland
Get PDFToxoplasma gondii is an intracellular Apicomplexan parasite with a broad range of intermediate hosts, including humans and rodents. Rodents are considered to be reservoirs of infection for
their predators, including cats, felids, pigs, and wild boars. We conducted a multi-site, long-term
study on T. gondii in northeastern Poland. The study aimed to monitor the seroprevalence of T. gondii
in the four abundant vole species found in the region (Myodes glareolus, Microtus arvalis, Microtus
agrestis, and Alexandromys oeconomus) and to assess the influence of both extrinsic (year of study and
study site) and intrinsic (host sex and host age) factors on seroprevalence. A bespoke enzyme-linked
immunosorbent assay was used to detect antibodies against T. gondii. We examined 577 rodent
individuals and detected T. gondii antibodies in the sera of all four rodent species with an overall
seroprevalence of 5.5% [4.2–7.3] (3.6% [2.6–4.9] for M. glareolus and 20% [12–30.9] for M. arvalis, M.
agrestis, and A. oeconomus). Seroprevalence in bank voles varied significantly between host age and
sex. Seroprevalence increased with host age and was higher in females than males. These results
contribute to our understanding of the distribution and abundance of T. gondii in voles in Poland
and confirm that T. gondii also circulates in M. glareolus and M. arvalis, M. agrestis and A. oeconomus.
Therefore, they may potentially play a role as reservoirs of this parasite in the sylvatic environment
Rab-dependent vesicular traffic affects female gametophyte development in Arabidopsis
Get PDFEukaryotic cells rely on the accuracy and efficiency of vesicular traffic. In plants, disturbances in vesicular trafficking are well studied in quickly dividing root meristem cells or polar growing root hairs and pollen tubes. The
development of the female gametophyte, a unique haploid reproductive structure located in the ovule, has received
far less attention in studies of vesicular transport. Key molecules providing the specificity of vesicle formation and
its subsequent recognition and fusion with the acceptor membrane are Rab proteins. Rabs are anchored to membranes by covalently linked geranylgeranyl group(s) that are added by the Rab geranylgeranyl transferase (RGT)
enzyme. Here we show that Arabidopsis plants carrying mutations in the gene encoding the β-subunit of RGT
(rgtb1) exhibit severely disrupted female gametogenesis and this effect is of sporophytic origin. Mutations in rgtb1
lead to internalization of the PIN1 and PIN3 proteins from the basal membranes to vesicles in provascular cells of
the funiculus. Decreased transport of auxin out of the ovule is accompanied by auxin accumulation in tissue surrounding the growing gametophyte. In addition, female gametophyte development arrests at the uni- or binuclear
stage in a significant portion of the rgtb1 ovules. These observations suggest that communication between the
sporophyte and the developing female gametophyte relies on Rab-dependent vesicular traffic of the PIN1 and PIN3
transporters and auxin efflux out of the ovule
Molecular and Functional Characterization of MobK Protein—A Novel-Type Relaxase Involved in Mobilization for Conjugational Transfer of Klebsiella pneumoniae Plasmid pIGRK
Get PDFConjugation, besides transformation and transduction, is one of the main mechanisms of horizontal transmission of genetic information among bacteria. Conjugational transfer, due to its essential role in shaping bacterial genomes and spreading of antibiotics resistance genes, has been widely studied for more than 70 years. However, new and intriguing facts concerning the molecular basis of this process are still being revealed. Most recently, a novel family of conjugative relaxases (Mob proteins) was distinguished. The characteristic feature of these proteins is that they are not related to any of Mobs described so far. Instead of this, they share significant similarity to tyrosine recombinases. In this study MobK—a tyrosine recombinase-like Mob protein, encoded by pIGRK cryptic plasmid from the Klebsiella pneumoniae clinical strain, was characterized. This study revealed that MobK is a site-specific nuclease and its relaxase activity is dependent on both a conserved catalytic tyrosine residue (Y179) that is characteristic of tyrosine recombinases and the presence of Mg2+ divalent cations. The pIGRK minimal origin of transfer sequence (oriT) was also characterized. This is one of the first reports presenting tyrosine recombinase-like conjugative relaxase protein. It also demonstrates that MobK is a convenient model for studying this new protein family
PD-L1 Overexpression, SWI/SNF Complex Deregulation, and Profound Transcriptomic Changes Characterize Cancer-Dependent Exhaustion of Persistently Activated CD4+ T Cells
Get PDFGrowing tumors avoid recognition and destruction by the immune system. During
continuous stimulation of tumor-infiltrating lymphocytes (TILs) by tumors, TILs become functionally
exhausted; thus, they become unable to kill tumor cells and to produce certain cytokines and lose
their ability to proliferate. This collectively results in the immune escape of cancer cells. Here, we
show that breast cancer cells expressing PD-L1 can accelerate exhaustion of persistently activated
human effector CD4+ T cells, manifesting in high PD-1 and PD-L1 expression level son T cell surfaces,
decreased glucose metabolism genes, strong downregulation of SWI/SNF chromatin remodelingcomplex subunits, and p21 cell cycle inhibitor upregulation. This results in inhibition of T cell
proliferation and reduction of T cell numbers. The RNAseq analysis on exhausted CD4+ T cells
indicated strong overexpression of IDO1 and genes encoding pro-inflammatory cytokines and
chemokines. Some interleukins were also detected in media from CD4+ T cells co-cultured with
cancer cells. The PD-L1 overexpression was also observed in CD4+ T cells after co-cultivation with
other cell lines overexpressing PD-L1, which suggested the existence of a general mechanism of CD4+
T cell exhaustion induced by cancer cells. The ChIP analysis on the PD-L1 promoter region indicated
that the BRM recruitment in control CD4+ T cells was replaced by BRG1 and EZH2 in CD4+ T cells
strongly exhausted by cancer cells. These findings suggest that epi-drugs such as EZH2 inhibitors
may be used as immunomodulators in cancer treatment
The Lrp/AsnC-Type Regulator PA2577 Controls the EamA-Like Transporter Gene PA2576 in Pseudomonas aeruginosa
Get PDFThe regulatory network of gene expression in Pseudomonas aeruginosa, an opportunistic human pathogen, is very complex. In the PAO1 reference strain, about 10% of genes encode transcriptional regulators, many of which have undefined regulons and unknown functions. The aim
of this study is the characterization of PA2577 protein, a representative of the Lrp/AsnC family of transcriptional regulators. This family encompasses proteins involved in the amino acid metabolism, regulation of transport processes or cell morphogenesis. The transcriptome profiling of P. aeruginosa cells with mild PA2577 overproduction revealed a decreased expression of the PA2576 gene oriented
divergently to PA2577 and encoding an EamA-like transporter. A gene expression analysis showed a higher mRNA level of PA2576 in P. aeruginosa DPA2577, indicating that PA2577 acts as a repressor. Concomitantly, ChIP-seq and EMSA assays confirmed strong interactions of PA2577 with the PA2577/PA2576 intergenic region. Additionally, phenotype microarray analyses indicated an impaired metabolism of DPA2576 and DPA2577 mutants in the presence of polymyxin B, which suggests disturbances of membrane functions in these mutants. We show that PA2576 interacts with two proteins, PA5006 and PA3694, with a predicted role in lipopolysaccharide (LPS) and membrane biogenesis. Overall, our results indicate that PA2577 acts as a repressor of the PA2576 gene coding for the EamA-like transporter and may play a role in the modulation of the cellular response to stress conditions, including antimicrobial peptides, e.g., polymyxin B
SARS-CoV-2 variant Omicron (B.1.1.529) is in a rising trend of mutations increasing the positive electric charge in crucial regions of the spike protein S
No full textAn increase in the positive electric charge of SARS-CoV-2
variant Omicron (B.1.1.529) was reported and the elec�trostatic interaction between the spike protein S and
ACE2 receptor was estimated. The results presented here
suggest that electrogenic mutations in specific regions
of the S protein and the electrostatic force may facilitate
viral infection of the host cell
Use of cytokine mix-, imiquimod-, and serum-induced monoculture and lipopolysaccharide- and interferon gamma-treated co-culture to establish in vitro psoriasis-like inflammation models
Get PDFElectrospray-Induced Mass Spectrometry Is Not Suitable for Determination of Peptidic Cu(II) Complexes
Get PDFThe toolset of mass spectrometry (MS) is still expanding, and the number of metal ion complexes researched this way is growing. The Cu(II) ion forms particularly strong peptide complexes of biological interest which are frequent objects of MS studies, but quantitative aspects of some reported results are at odds with those of experiments performed in solution. Cu(II) complexes are usually characterized by fast ligand exchange rates, despite their high affinity, and we speculated that such kinetic lability could be responsible for the observed discrepancies. In order to resolve this issue, we selected peptides belonging to the ATCUN family characterized with high and thoroughly determined Cu(II) binding constants and re-estimated them using two ESI-MS techniques: standard conditions in combination with serial dilution experiments and very mild conditions for competition experiments. The sample acidification, which accompanies the electrospray formation, was simulated with the pH–jump stopped-flow technique. Our results indicate that ESI-MS should not be used for quantitative studies of Cu(II)–peptide complexes because the electrospray formation process compromises the entropic contribution to the complex stability, yielding underestimations of complex stability constants
Palm Oil-Rich Diet Affects Murine Liver Proteome and S-Palmitoylome
Get PDFPalmitic acid (C16:0) is the most abundant saturated fatty acid in animals serving as a substrate in synthesis and β-oxidation of other lipids, and in the modification of proteins called palmitoylation. The influence of dietary palmitic acid on protein S-palmitoylation remains largely unknown. In this study we performed high-throughput proteomic analyses of a membrane-enriched fraction of murine liver to examine the influence of a palm oil-rich diet (HPD) on S-palmitoylation of proteins. HPD feeding for 4 weeks led to an accumulation of C16:0 and C18:1 fatty acids in livers which disappeared after 12-week feeding, in contrast to an accumulation of C16:0 in peritoneal macrophages. Parallel proteomic studies revealed that HPD feeding induced a sequence of changes of the level and/or S-palmitoylation of diverse liver proteins involved in fatty acid, cholesterol and amino acid metabolism, hemostasis, and neutrophil degranulation. The HPD diet did not lead to liver damage, however, it caused progressing obesity, hypercholesterolemia and hyperglycemia. We conclude that the relatively mild negative impact of such diet on liver functioning can be attributed to a lower bioavailability of palm oil-derived C16:0 vs. that of C18:1 and the efficiency of mechanisms preventing liver injury, possibly including dynamic protein S-palmitoylation
Metabolic fingerprinting of the Antarctic cyanolichen Leptogium puberulum – associated bacterial community (Western Shore of Admiralty Bay, King George Island, Maritime Antarctica)
Get PDFLichens are presently regarded as stable biotopes, small ecosystems providing a safe haven for the development of a diverse and numerous microbiome. In this study we conducted a functional diversity assessment of the microbial community residing on the surface and within the thalli of Leptogium puberulum, a eurytopic cyanolichen endemic to Antarctica, employing the widely used Biolog EcoPlates which test the catabolism of 31 carbon compounds in a colorimetric respiration assay. Lichen thalli occupying moraine ridges of differing age within a proglacial chronosequence, as well as those growing in sites of contrasting nutrient concentrations, were procured from the diverse landscape of the western shore of Admiralty Bay in Maritime Antarctica. The L. puberulum bacterial community catabolized photobiont- (glucose containing carbohydrates) and mycobiont-specific carbon compounds (D-Mannitol). The bacteria also had the ability to process degradation products of lichen thalli components (D-Cellobiose and N-Acetyl-D-Glucosamine). Lichen thalli growth site characteristics had an impact on metabolic diversity and respiration intensity of the bacterial communities. While high nutrient contents in lichen specimens from ‘young’ proglacial locations and in those from nitrogen enriched sites stimulated bacterial catabolic activity, in old proglacial locations and in nutrient-lacking sites a metabolic activity restriction was apparent, presumably due to lichen-specific microbial control mechanisms