Rho-related ROP proteins are molecular switches that essentially regulate a wide variety of processes. Of central interest is their influence on the plant cytoskeleton by which they affect vital ...processes like cell division, growth, morphogenesis, and pathogen defense. ROPs switch between GTP- and GDP-bound conformations by strictly regulated nucleotide exchange and GTP-hydrolysis, and only the active GTP-form interacts with downstream effectors to ultimately provoke a biological response. However, the mode of action of the engaged regulators and effectors as well as their upstream and downstream interaction partners have long been largely unknown. As opposed to analogous systems in animals and fungi, plants use specific GTPase activating proteins (RopGAPs) with a unique domain composition and novel guanine nucleotide exchange factors (RopGEFs) with a probable link to cell surface receptors. Moreover, plants comprise novel effector molecules and adapters connecting ROPs to mostly unknown downstream targets on the route to the cytoskeleton. This review aims to summarize recent knowledge on the molecular mechanisms and reaction cascades involved in ROP dependent cytoskeletal rearrangements, addressing the structure and function of the unusual RopGAPs, RopGEFs and effectors, and the upstream and downstream pathways linking ROPs to cell receptor-like kinases, actin filaments, and microtubules.
RIP3 belongs to a group of recently identified proteins, classified as the ICR/RIP family whose members were described to interact with Rho proteins of plants (ROPs). Our
in vivo and
in vitro data ...demonstrate that RIP3 is a true ROP effector, interacting specifically with the active form of ROPs. We found that RIP3 has properties and cellular roles different from the previously described RIP family member ICR1/RIP1. We show that RIP3 is localized at microtubules and interacts with the kinesin-13 family member AtKinesin-13A, suggesting a role for RIP3 in microtubule reorganization and a possible function in ROP-regulated polar growth.
The pollen-specific receptor-like kinases (PRKs) from
Solanum lycopersicum,
LePRK1 and
LePRK2, are believed to be involved in the regulation of pollen germination and pollen tube growth. They appear ...to be part of a multimeric complex in which the transmembranic
LePRKs presumably have a key position in transducing exogenous signals through the plasma membrane. Here, we focused on extra- and intracellular interactions involving the
LePRKs. We show in yeast two-hybrid experiments a cross-interaction of putative PRK-ligands, the oligomerization of
LePRK2 and a direct contact of
LePRKs to activated Rho proteins of plants (ROPs). Moreover, we observed that pollen-specific RopGEFs, which catalyze ROP activation and may be regulated by PRK interaction, are active
in vitro while autoinhibition seems to occur
in vivo. We suggest that activation of RopGEFs as a checkpoint in PRK signal transduction is a more complex event including further components
in planta. Our findings point to some new aspects in PRK-mediated signal transduction implying a
LePRK2 complex with different signaling activity and a further direct control of
LePRKs by activated ROP.
Abstract
The beekeeping sector plays an important role in maintaining biodiversity and the ecosystem, in addition to its production function. The European beekeeping sector is facing a number of ...constraints that make it difficult to operate, and the Covid-19 pandemic has posed new challenges for beekeepers. The purpose of the study is to examine the resilience of beekeeping businesses to the most important problems affecting beekeepers and the Covid-19 pandemic. The research analyses the role of marketing and profitability and how they influence the resilience. Variables obtained from online questioning of a representative sample of Hungarian beekeepers (N = 297). Cluster analysis was used to validate the results. Using a Two-step clustering model, three clusters of beekeepers were identified: a non-resilient; a resilient, but not proactive and not very profitable and a resilient, proactive and profitable cluster. According to the research, the resilience of beekeepers is shaped by several factors. Well-trained, long-established beekeepers who seek to differentiate their products from their competitors' overcome the difficulties caused by the pandemic and other beekeeping problems much more easily. Very important factors resulting in remarkable business resilience are the number of used subsidies and the number of cooperations.
The respiratory tract of swine is colonized by several bacteria among which are three Mycoplasma species: Mycoplasma flocculare, Mycoplasma hyopneumoniae and Mycoplasma hyorhinis. While colonization ...by M. flocculare is virtually asymptomatic, M. hyopneumoniae is the causative agent of enzootic pneumonia and M. hyorhinis is present in cases of pneumonia, polyserositis and arthritis. The genomic resemblance among these three Mycoplasma species combined with their different levels of pathogenicity is an indication that they have unknown mechanisms of virulence and differential expression, as for most mycoplasmas.
In this work, we performed whole-genome metabolic network reconstructions for these three mycoplasmas. Cultivation tests and metabolomic experiments through nuclear magnetic resonance spectroscopy (NMR) were also performed to acquire experimental data and further refine the models reconstructed in silico.
Even though the refined models have similar metabolic capabilities, interesting differences include a wider range of carbohydrate uptake in M. hyorhinis, which in turn may also explain why this species is a widely contaminant in cell cultures. In addition, the myo-inositol catabolism is exclusive to M. hyopneumoniae and may be an important trait for virulence. However, the most important difference seems to be related to glycerol conversion to dihydroxyacetone-phosphate, which produces toxic hydrogen peroxide. This activity, missing only in M. flocculare, may be directly involved in cytotoxicity, as already described for two lung pathogenic mycoplasmas, namely Mycoplasma pneumoniae in human and Mycoplasma mycoides subsp. mycoides in ruminants. Metabolomic data suggest that even though these mycoplasmas are extremely similar in terms of genome and metabolism, distinct products and reaction rates may be the result of differential expression throughout the species.
We were able to infer from the reconstructed networks that the lack of pathogenicity of M. flocculare if compared to the highly pathogenic M. hyopneumoniae may be related to its incapacity to produce cytotoxic hydrogen peroxide. Moreover, the ability of M. hyorhinis to grow in diverse sites and even in different hosts may be a reflection of its enhanced and wider carbohydrate uptake. Altogether, the metabolic differences highlighted in silico and in vitro provide important insights to the different levels of pathogenicity observed in each of the studied species.
Celotno besedilo
Dostopno za:
DOBA, IZUM, KILJ, NUK, PILJ, PNG, SAZU, SIK, UILJ, UKNU, UL, UM, UPUK
Urinary 1-hydroxypyrene (1-OHP) is a biomarker of polycyclic aromatic hydrocarbon (PAH) exposure. We measured urinary 1-OHP in 48 children 3 years of age in Mariupol, Ukraine, who lived near a steel ...mill and coking facility and compared these with 1-OHP concentrations measured in 42 children of the same age living in the capital city of Kiev, Ukraine. Children living in Mariupol had significantly higher urinary 1-OHP and creatinine-adjusted urinary 1-OHP than did children living in Kiev (adjusted: 0.69 vs. 0.34 µmol/mol creatinine, p < 0.001; unadjusted: 0.42 vs. 0.30 ng/mL, p = 0.002). Combined, children in both cities exposed to environmental tobacco smoke in their homes had higher 1-OHP than did children not exposed (0.61 vs. 0.42 µmol/mol creatinine; p = 0.04; p = 0.07 after adjusting for city). In addition, no significant differences were seen with sex of the children. Our sample of children in Mariupol has the highest reported mean urinary 1-OHP concentrations in children studied to date, most likely due to their proximity to a large industrial point source of PAHs.
Abstract Introduction This study proposed to investigate aspects of cell proliferation and death in the epithelium of radicular (RCs) and dentigerous (DCs) cysts. Methods Serial sections of 17 RCs ...and 9 DCs were prepared for immunohistochemical detection of caspase-3, Bcl-2, and Ki-67 antigens. Results Caspase-3 was detected mainly in the suprabasal and superficial epithelial cells of RCs and DCs, whereas Ki-67 was detected predominantly in the basal layer. Both markers had significant expression in hyperplastic epithelium related to an intense inflammation in the capsule. Immunoreactivity for Bcl-2 was restricted to the basal layer and was significantly higher in atrophic epithelium of DCs than that of RCs. Conclusions These results suggest that epithelial proliferation is balanced by apoptosis and that the presence of inflammation inhibits the Bcl-2 expression. DCs and RCs have different formation mechanisms but have similar biological behavior in the presence of intense inflammatory infiltrate.
Tumour mutational burden (TMB) predicts immunotherapy outcome in non-small cell lung cancer (NSCLC), consistent with immune recognition of tumour neoantigens. However, persistent antigen exposure is ...detrimental for T cell function. How TMB affects CD4 and CD8 T cell differentiation in untreated tumours, and whether this affects patient outcomes is unknown. Here we paired high-dimensional flow cytometry, exome, single-cell and bulk RNA sequencing from patients with resected, untreated NSCLC to examine these relationships. TMB was associated with compartment-wide T cell differentiation skewing, characterized by loss of TCF7-expressing progenitor-like CD4 T cells, and an increased abundance of dysfunctional CD8 and CD4 T cell subsets, with significant phenotypic and transcriptional similarity to neoantigen-reactive CD8 T cells. A gene signature of redistribution from progenitor-like to dysfunctional states associated with poor survival in lung and other cancer cohorts. Single-cell characterization of these populations informs potential strategies for therapeutic manipulation in NSCLC.
The new LHCb Vertex Locator (VELO) for LHCb, comprising a new pixel detector and readout electronics, will be installed in 2021 for data taking in Run 3 at the LHC. The electronics centers around the ..."VeloPix" ASIC at the front-end operating in a trigger-less readout at 40MHz. A custom serializer, called gigabit wireline transmitter (GWT), and associated custom protocol have been designed for the VeloPix. The GWT data are sent from the serializers of the VeloPix at a line rate of 5.12 Gb/s, reaching a total data rate of 2-3 Tb/s for the full VELO detector. Data are sent over 300-m optic-fiber links to the control and readout electronics cards for deserialization and processing in Intel Arria 10 FPGAs. Because of the VeloPix trigger-less design, latency variances up to 12 <inline-formula> <tex-math notation="LaTeX">\mu \text{s} </tex-math></inline-formula> can occur between adjacent datagrams. It is therefore essential to buffer and synchronize the data in firmware prior to onward propagation or suffer a huge CPU-processing penalty. This article will describe the architecture of the readout firmware in detail with focus given to the resynchronization mechanism and techniques for cauterization. Issues found during readout commissioning, and scaling resource utilization, along with the their solutions, will be illustrated. The latest results of the firmware data-processing chain can be presented as well as the verification procedures employed in simulation. Challenges for the next generation of the detector will also be presented with ideas for a readout processing solution.
Lyme borreliosis is the most widespread vector-borne disease in temperate zones of Europe and North America. Although the infection is treatable, the symptoms are often overlooked resulting in ...infection of the neuronal system. In this work we uncover the underlying molecular mechanism of borrelial translocation across the blood-brain barrier (BBB). We demonstrate that neuroinvasive strain of Borrelia readily crosses monolayer of brain-microvascular endothelial cells (BMECs) in vitro and BBB in vivo. Using protein-protein interaction assays we found that CD40 of BMECs and OspA of Borrelia are the primary molecules in transient tethering of Borrelia to endothelium. OspA of neuroinvasive Borrelia, but not of non-neuroinvasive strain, binds CD40. Furthermore, only the neuroinvasive Borrelia and its recombinant OspA activated CD40-dependent pathway in BMECs and induced expression of integrins essential for stationary adhesion. Demonstration of the CD40-ligand interactions may provide a new possible perspective on molecular mechanisms of borrelial BBB translocation process.
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