Characterization of a MOB1 Homolog in the Apicomplexan Parasite Toxoplasma gondii

Monopolar spindle One Binder1 (MOB1) proteins are conserved components of the tumor-suppressing Hippo pathway, regulating cellular processes such as cytokinesis. Apicomplexan parasites present a life cycle that relies on the parasites’ ability to differentiate between stages and regulate their proliferation; thus, Hippo signaling pathways could play an important role in the regulation of the apicomplexan life cycle. Here, we report the identification of one MOB1 protein in the apicomplexan Toxoplasma gondii. To characterize the function of MOB1, we generated gain-of-function transgenic lines with a ligand-controlled destabilization domain, and loss-of-function clonal lines obtained through CRISPR/Cas9 technology. Contrary to what has been characterized in other eukaryotes, MOB1 is not essential for cytokinesis in T. gondii. However, this picture is complex since we found MOB1 localized between the newly individualized daughter nuclei at the end of mitosis. Moreover, we detected a significant delay in the replication of overexpressing tachyzoites, contrasting with increased replication rates in knockout tachyzoites. Finally, using the proximity-biotinylation method, BioID, we identified novel members of the MOB1 interactome, a probable consequence of the observed lack of conservation of some key amino acid residues. Altogether, the results point to a complex evolutionary history of MOB1 roles in apicomplexans, sharing properties with other eukaryotes but also with divergent features, possibly associated with their complex life cycle.

Ekdik (defensor civitatis) u Rimskom carstvu i Vizantiji

During the 5th and 6th centuries a significant change occurred in the nature of defensor civitatis, in line with the social and political context. After the reign of Emperor Justinian I, the competences of the defensor decreased. In cities, bishops took over tasks previously carried out by the defensores, a probable consequence being the disappearance of ekdikoi from administration and civil law, believed to have occurred in the 6th and 7th centuries. The conclusions of this study support the thesis that the ekdikoi functioned in the Eastern Roman Empire as late as in the 8th century, and in some forms until the 9th century. In some parts of the Empire the ekdikoi acted until the early 10th century, which was proven by the discovery of the Cherson seals. The methods used are linguistic interpretation of middle-Byzantine legal codes and comparative-historical method based on identification of Byzantine adoptions of Roman provisions.

Impact of Environmental Stressors on Gene Expression in the Embryo of the Italian Wall Lizard

The cleidoic eggs of oviparous reptiles are protected from the external environment by membranes and a parchment shell permeable to water and dissolved molecules. As a consequence, not only physical but also chemical insults can reach the developing embryos, interfering with gene expression. This review provides information on the impact of the exposure to cadmium contamination or thermal stress on gene expression during the development of Italian wall lizards of the genus Podarcis. The results obtained by transcriptomic analysis, although not exhaustive, allowed to identify some stress-reactive genes and, consequently, the molecular pathways in which these genes are involved. Cadmium-responsive genes encode proteins involved in cellular protection, metabolism and proliferation, membrane trafficking, protein interactions, neuronal transmission and plasticity, immune response, and transcription regulatory factors. Cold stress changes the expression of genes involved in transcriptional/translational regulation and chromatin remodeling and inhibits the transcription of a histone methyltransferase with the probable consequence of modifying the epigenetic control of DNA. These findings provide transcriptome-level evidence of how terrestrial vertebrate embryos cope with stress, giving a key to use in population survival and environmental change studies. A better understanding of the genes contributing to stress tolerance in vertebrates would facilitate methodologies and applications aimed at improving resistance to unfavourable environments.

Identification of nitric oxide (NO)-responsive genes under hypoxia in tomato (Solanum lycopersicum L.) root

Flooding periods, as one probable consequence of climate change, will lead more frequently to plant hypoxic stress. Hypoxia sensing and signaling in the root, as the first organ encountering low oxygen, is therefore crucial for plant survival under flooding. Nitric oxide has been shown to be one of the main players involved in hypoxia signaling through the regulation of ERFVII transcription factors stability. Using SNP as NO donor, we investigated the NO-responsive genes, which showed a significant response to hypoxia. We identified 395 genes being differentially regulated under both hypoxia and SNP-treatment. Among them, 251 genes showed up- or down-regulation under both conditions which were used for further biological analysis. Functional classification of these genes showed that they belong to different biological categories such as primary carbon and nitrogen metabolism (e.g. glycolysis, fermentation, protein and amino acid metabolism), nutrient and metabolites transport, redox homeostasis, hormone metabolism, regulation of transcription as well as response to biotic and abiotic stresses. Our data shed light on the NO-mediated gene expression modulation under hypoxia and provides potential targets playing a role in hypoxia tolerance. These genes are interesting candidates for further investigating their role in hypoxia signaling and survival.

Behavioural variability among captive African elephants in the use of the trunk while feeding

The Proboscideans, an order of mammals including elephants, are the largest of the Earth lands animals. One probable consequence of the rapid increase of their body size is the development of the trunk, a multitask highly sensitive organ used in a large repertoire of behaviours. The absence of bones in the trunk allows a substantial degree of freedom for movement in all directions, and this ability could underlie individual-level strategies. We hypothesised a stronger behavioural variability in simple tasks, and a correlation between the employed behaviours and the shape and size of the food. The observations of a captive group of African elephants allowed us to create a complete catalogue of trunk movements in feeding activities. We noted manipulative strategies and impact of food item properties on the performed behaviours. The results show that a given item is manipulated with a small panel of behaviours, and some behaviours are specific to a single shape of items. The study of the five main feeding behaviours emphasises a significant variability between the elephants. Each individual differed from every other individual in the proportion of at least one behaviour, and every behaviour was performed in different proportions by the elephants. Our findings suggest that during their lives elephants develop individual strategies adapted to the manipulated items, which increases their feeding efficiency.

X-linked muscular dystrophy in a Labrador Retriever strain: phenotypic and molecular characterization.

Background Canine models of Duchenne muscular dystrophy (DMD) are valuable to evaluate therapies because they faithfully reproduce the human disease. Several cases of dystrophinopathies have been described in canines, but the GRMD (Golden Retriever Muscular Dystrophy) model remains the one used in most preclinical studies. Methods We report a new spontaneous dystrophinopathy in a Labrador retriever strain, named LRMD (Labrador Retriever Muscular Dystrophy), for which a colony was established. Fourteen LRMD dogs were followed-up and compared to the GRMD standard. Results The clinical features of the GRMD disease were found in LRMD dogs, and the functional tests provided data roughly overlapping those measured in GRMD dogs, with similar inter-individual heterogeneity. Molecular techniques including RNA-sequencing allowed to map and identify the LRMD causal mutation, consisting in a 2.2-Mb inversion disrupting the DMD gene within its intron 20, and involving TMEM47 gene. In skeletal muscles, the Dp71 isoform was ectopically expressed as a probable consequence of the mutation. We found no evidence of polymorphism in the two LTBP4 and Jagged1 modifier genes that would explain the observed inter-individual variability. Conclusions This study provides a full comparative description of a new spontaneous canine dystrophinopathy, that we demonstrate is phenotypically equivalent to the GRMD model. We report a novel large DNA mutation within the DMD gene and provide evidence that LRMD is a relevant model to pinpoint additional DMD modifier genes.

Paraneoplastic syndrome as a possible cause of pulmonary thromboembolism in a female patient with nephrotic syndrome: Case report

A 59-year-old female patient was admitted to the hospital due to suffocation, lower leg swelling, and general weakness. She had been treated previously with immunosuppressive therapy for several years because of focal segmental glomerulosclerosis with nephrotic syndrome. The expected therapeutic response was not accomplished. Upon admission, the following were determined in the laboratory: hypoalbuminemia, hyperlipidemia and nephrotic range proteinuria. X-ray of the lungs showed bilateral pleural effusion, because of which a pleural puncture was performed and which drained 800 mL of fluid. Tumor markers test, breast echosonography and mammography were performed, along with bone scintigraphy, which was done upon the recommendation of an oncologist. Mammography described microcalcifications bilaterally while bone scintigraphy showed pathological accumulation of radiopharmaceuticals in the V thoracic vertebra and sternum corpus, and III and IV ribs on the left. On the fifth day of hospitalization, there was a deterioration of patient's general condition with hypotension, tachycardia and angina, as well as an increase in D-dimer. On the ECG sinus rhythm, f 80 / min, low voltage in standard and unipolar leads. Upon the recommendation of a cardiologist, CT was performed according to the program for pulmonary thromboembolism (PTE), which showed submassive PTE. Low molecular weight heparin therapy was used, along with oxygen therapy with dopaminergics, bronchodilators, human albumin and plasma infusions, statins and transient treatment of hypervolemia by means of hemodialysis. The patient was hospitalized for 61 days due to multiorgan dysfunction. Breast magnetic resonance imaging was not performed due to the poor general condition of the patient. Most likely it was breast cancer with secondary deposits, which was recognized late. PTE, as a probable consequence of paraneoplastic nephrotic syndrome, was diagnosed and treated in a timely manner.

Risk of cardiac rhythm disturbances and aortic regurgitation in different spondyloarthritis subtypes in comparison with general population: a register-based study from Sweden

ObjectivesTo describe the incidence of atrioventricular (AV) block II–III, atrial fibrillation (AF), pacemaker implantation (PM) and aortic regurgitation in patients with ankylosing spondylitis (AS), undifferentiated spondyloarthritis (uSpA) and psoriatic arthritis (PsA) compared with the general population (GP) and with each other.MethodsA prospective nationwide study with cohorts of patients with AS (n=6448), PsA (n=16 063) and uSpA (n=5190) and a GP (n=2 66 435) cohort, identified in 2001–2009 in the Swedish National Patient and Population registers. Follow-up began on 1 January 2006 and ended at event, death, emigration or 31 December 2012. Age-standardised and sex-standardised incidence rates and hazard ratios (HRs) were calculated.ResultsThe highest incidence rates were noted for AF (5.5–7.4 events per 1000 person-years), followed by PM (1.0–2.0 events per 1000 person-years). HRs for AV block, AF, PM and aortic regurgitation were significantly increased in AS (HRs 2.3, 1.3, 2.1 and 1.9), uSpA (HRs 2.9, 1.3, 1.9 and 2.0) and PsA (HRs 1.5, 1.5, 1.6 and 1.8) compared with the GP cohort. The highest HRs were seen for AV block in male uSpA (HR 4.2) and AS (HR 2.5) compared with GP. Compared with PsA, significantly increased HRs were noted for PM (HR 1.5) in AS and for AV block (HR 1.8) in uSpA.ConclusionsPatients with SpA are at increased risk of aortic regurgitation, cardiac rhythm disturbances and, as a probable consequence, also PM. Particularly for AF, the most common arrhythmia, increased caution is warranted, whereas AV block should be looked for especially in men with AS or uSpA.