Direct evidence for a critical role of myosin II in budding yeast cytokinesis and the evolvability of new cytokinetic mechanisms in the absence of myosin II

In the budding yeast Saccharomyces cerevisiae, an actomyosin-based contractile ring is present during cytokinesis, as occurs in animal cells. However, the precise requirement for this structure during budding yeast cytokinesis has been controversial. Here we show that deletion of MYO1, the single myosin II gene, is lethal in a commonly used strain background. The terminal phenotype of myo1Delta is interconnected chains of cells, suggestive of a cytokinesis defect. To further investigate the role of Myo1p in cytokinesis, we conditionally disrupted Myo1 function by using either a dominant negative Myo1p construct or a strain where expression of Myo1p can be shut-off. Both ways of disruption of Myo1 function result in a failure in cytokinesis. Additionally, we show that a myo1Delta strain previously reported to grow nearly as well as the wild type contains a single genetic suppressor that alleviates the severe cytokinesis defects of myo1Delta. Using fluorescence time-lapse imaging and electron microscopy techniques, we show that cytokinesis in this strain is achieved through formation of multiple aberrant septa. Taken together, these results strongly suggest that the actomyosin ring is crucial for successful cytokinesis in budding yeast, but new cytokinetic mechanisms can evolve through genetic changes when myosin II function is impaired.     

Anti-cyclic citrullinated peptide antibody titer predicts time to rheumatoid arthritis onset in patients with undifferentiated arthritis: results from a 2-year prospective study

Introduction

The diagnostic, predictive and prognostic role of anti-cyclic citrullinated peptide (CCP) antibodies in rheumatoid arthritis (RA) patients is widely accepted. Moreover, detection of these antibodies in subjects presenting with undifferentiated arthritis (UA) is associated with a significant risk to develop the disease. On the other hand, clinical and prognostic significance of evaluating anti-CCP levels in subjects with inflammatory arthritis at disease onset has not been fully clarified. The goal of this prospective study is to analyze the value and prognostic significance of anti-CCP titer quantification in UA subjects.

Methods

Serial anti-CCP assays were measured in 192 consecutive patients presenting with UA lasting less than 12 weeks. Clinical and serological data and arthritis outcome were evaluated every 6 months until two years of follow-up.

Results

Anti-CCP positivity, at both low and high titer, and arthritis of hand joints significantly predicted RA at two years, risk increasing in subjects with high anti-CCP titers at baseline. Moreover, time to RA diagnosis was shorter in patients with high anti-CCP2 titers at enrollment with respect to those with low antibody concentration.

Conclusions

Presence of anti-CCP antibodies, at both low and high concentration, is significantly associated with RA development in subjects with recent onset UA. However, time interval from the onset of the first symptoms to the fulfilment of the classification criteria appears to be directly related to the initial anti-CCP level.     

Stevens-Johnson Syndrome Associated with Drugs and Vaccines in Children: A Case-Control Study

Objective

Stevens-Johnson Syndrome (SJS) is one of the most severe muco-cutaneous diseases and its occurrence is often attributed to drug use. The aim of the present study is to quantify the risk of SJS in association with drug and vaccine use in children.

Methods

A multicenter surveillance of children hospitalized through the emergency departments for acute conditions of interest is currently ongoing in Italy. Cases with a diagnosis of SJS were retrieved from all admissions. Parents were interviewed on child’s use of drugs and vaccines preceding the onset of symptoms that led to the hospitalization. We compared the use of drugs and vaccines in cases with the corresponding use in a control group of children hospitalized for acute neurological conditions.

Results

Twenty-nine children with a diagnosis of SJS and 1,362 with neurological disorders were hospitalized between 1^st November 1999 and 31^st October 2012. Cases were more frequently exposed to drugs (79% vs 58% in the control group; adjusted OR 2.4; 95% CI 1.0–6.1). Anticonvulsants presented the highest adjusted OR: 26.8 (95% CI 8.4–86.0). Significantly elevated risks were also estimated for antibiotics use (adjusted OR 3.3; 95% CI 1.5–7.2), corticosteroids (adjusted OR 4.2; 95% CI 1.8–9.9) and paracetamol (adjusted OR 3.2; 95% CI 1.5–6.9). No increased risk was estimated for vaccines (adjusted OR: 0.9; 95% CI 0.3–2.8).

Discussion

Our study provides additional evidence on the etiologic role of drugs and vaccines in the occurrence of SJS in children.     

Elastic properties of the hind foot of the Donkey, Equus asinus

The elastic properties of the hind feet of Donkeys, and of tendons removed from the feet, have been investigated by methods similar to those used in a previous study of the forefoot. The elastic strain energy stored in the foot, during a trotting step, is calculated to be approximately the optimum which would minimize the work required of the muscles in this gait.     

Copper Toxicity in Maize: The Severity of the Stress is Reduced Depending on the Applied Fe-Chelating Agent

Journal of Plant Growth Regulation - The wide use of copper (Cu)-based fungicide has caused a stepwise accumulation of Cu in the environment increasing the occurrence of phytotoxicity in crops. To...     

Consequences of prenatal androgen exposure for the reproductive performance of female pheasants (Phasianus colchicus)

Maternal hormones in vertebrate eggs can mediate important forms of maternal effects. However, the function of hormone transfer to the eggs is still debated, especially because long-term fitness consequences have been little studied. We investigated the effect of prenatal exposure to physiologically elevated yolk testosterone (T) levels on reproduction of female pheasants (Phasianus colchicus) in captivity. We found that females hatching from T-injected eggs (T-females) had a lower egg-laying rate than controls, and their eggs were more frequently infertile than those laid by control females. There were no effects of prenatal maternal treatment on egg size and yolk T concentration, but eggs carrying a female embryo laid by T-females had smaller yolks than eggs with a male embryo, while there was no sex difference in yolk size among the eggs laid by control females. Progeny sex ratio was unaffected by maternal treatment. These findings suggest that the transfer of high androgen levels to the eggs by the mother is constrained by complex trade-offs between direct effects on her daughters' reproduction and by trans-generational differential consequences on male and female descendants.     

Species boundaries and phylogeography of the "Euscorpius carpathicus complex" (Scorpiones: Euscorpiidae) in Italy

Euscorpius tergestinus (C.L. Koch, 1837), Euscorpius concinnus (C.L. Koch, 1837) and Euscorpius sicanus (C.L. Koch, 1837), three presumed closely related species belonging to the "carpathicus group", occur in the Italian peninsula with a largely parapatric distribution and some zones of range overlap. These areas of sympatry represent interesting opportunities to investigate species boundaries in natural populations. Here we report on a study exploring genetic variation in sympatric populations of the three species from central Tuscany. Additional collecting sites, from different localities across Italy, were also included in the analysis in order to explore the phylogeographic structure of the group. Species boundaries and evolutionary relationships were examined by sequence comparison of mitochondrial 16S rRNA and nuclear ITS-1 rRNA gene fragments. DNA sequence data show no evidence of genetic introgression between different evolutionary lineages from the area of range overlap, suggesting the absence of either past or ongoing inter-specific gene flow. It is therefore probable that reproductive barriers exist, preventing gene pools from amalgamating. Furthermore, our results support the recent morphological distinction of E. tergestinus, as traditionally classified, into two different species: E. tergestinus and E. concinnus. Both mitochondrial and nuclear sequence data clearly indicate that the two taxa represent well-supported and deeply divergent lineages. Euscorpius sicanus seems to represent a monophyletic taxon, but the high genetic variability observed within this taxon calls for future investigation. The present distribution patterns across the Italian peninsula were mainly interpreted as the consequence of climatic oscillations.     

Molecular Typing of Lung Adenocarcinoma on Cytological Samples Using a Multigene Next Generation Sequencing Panel

Identification of driver mutations in lung adenocarcinoma has led to development of targeted agents that are already approved for clinical use or are in clinical trials. Therefore, the number of biomarkers that will be needed to assess is expected to rapidly increase. This calls for the implementation of methods probing the mutational status of multiple genes for inoperable cases, for which limited cytological or bioptic material is available. Cytology specimens from 38 lung adenocarcinomas were subjected to the simultaneous assessment of 504 mutational hotspots of 22 lung cancer-associated genes using 10 nanograms of DNA and Ion Torrent PGM next-generation sequencing. Thirty-six cases were successfully sequenced (95%). In 24/36 cases (67%) at least one mutated gene was observed, including EGFR, KRAS, PIK3CA, BRAF, TP53, PTEN, MET, SMAD4, FGFR3, STK11, MAP2K1. EGFR and KRAS mutations, respectively found in 6/36 (16%) and 10/36 (28%) cases, were mutually exclusive. Nine samples (25%) showed concurrent alterations in different genes. The next-generation sequencing test used is superior to current standard methodologies, as it interrogates multiple genes and requires limited amounts of DNA. Its applicability to routine cytology samples might allow a significant increase in the fraction of lung cancer patients eligible for personalized therapy.     

The lectotype of Sphenobaiera Ikorfatensis (Seward) Florin, a ginkgophyte from the Lower Cretaceous of western Greenland

Use of the genus Sphenobaiera Florin for deeply divided ginkgoalean leaves lacking a petiole is discussed. The type material of the species Sphenobaiera ikorfatensis (Seward) Florin from the Lower Cretaceous at Ikorfat in West Greenland is diagnosed, redescribed and the lectotype designated. The cuticle, which is described and figured in detail for the first time, shows the leaf to be amphistomatic and allows previous identifications of Sphenobaiera ikorfatensis in Lower Cretaceous floras from Siberia and China to be confirmed.