Conservation and divergence of meiotic DNA double strand break forming mechanisms in Arabidopsis thaliana

In the current meiotic recombination initiation model, the SPO11 catalytic subunits associate with MTOPVIB to form a Topoisomerase VI-like complex that generates DNA double strand breaks (DSBs). Four additional proteins, PRD1/AtMEI1, PRD2/AtMEI4, PRD3/AtMER2 and the plant specific DFO are required for meiotic DSB formation. Here we show that (i) MTOPVIB and PRD1 provide the link between the catalytic sub-complex and the other DSB proteins, (ii) PRD3/AtMER2, while localized to the axis, does not assemble a canonical pre-DSB complex but establishes a direct link between the DSB-forming and resection machineries, (iii) DFO controls MTOPVIB foci formation and is part of a divergent RMM-like complex including PHS1/AtREC114 and PRD2/AtMEI4 but not PRD3/AtMER2, (iv) PHS1/AtREC114 is absolutely unnecessary for DSB formation despite having a conserved position within the DSB protein network and (v) MTOPVIB and PRD2/AtMEI4 interact directly with chromosome axis proteins to anchor the meiotic DSB machinery to the axis.     

Variability measures of positive random variables

During the stationary part of neuronal spiking response, the stimulus can be encoded in the firing rate, but also in the statistical structure of the interspike intervals. We propose and discuss two information-based measures of statistical dispersion of the interspike interval distribution, the entropy-based dispersion and Fisher information-based dispersion. The measures are compared with the frequently used concept of standard deviation. It is shown, that standard deviation is not well suited to quantify some aspects of dispersion that are often expected intuitively, such as the degree of randomness. The proposed dispersion measures are not entirely independent, although each describes the interspike intervals from a different point of view. The new methods are applied to common models of neuronal firing and to both simulated and experimental data.     

Large old trees increase growth under shifting climatic constraints: Aligning tree longevity and individual growth dynamics in primary mountain spruce forests

In a world of accelerating changes in environmental conditions driving tree growth, tradeoffs between tree growth rate and longevity could curtail the abundance of large old trees (LOTs), with potentially dire consequences for biodiversity and carbon storage. However, the influence of tree-level tradeoffs on forest structure at landscape scales will also depend on disturbances, which shape tree size and age distribution, and on whether LOTs can benefit from improved growing conditions due to climate warming. We analyzed temporal and spatial variation in radial growth patterns from ~5000 Norway spruce (Picea abies [L.] H. Karst) live and dead trees from the Western Carpathian primary spruce forest stands. We applied mixed-linear modeling to quantify the importance of LOT growth histories and stand dynamics (i.e., competition and disturbance factors) on lifespan. Finally, we assessed regional synchronization in radial growth variability over the 20th century, and modeled the effects of stand dynamics and climate on LOTs recent growth trends. Tree age varied considerably among forest stands, implying an important role of disturbance as an age constraint. Slow juvenile growth and longer period of suppressed growth prolonged tree lifespan, while increasing disturbance severity and shorter time since last disturbance decreased it. The highest age was not achieved only by trees with continuous slow growth, but those with slow juvenile growth followed by subsequent growth releases. Growth trend analysis demonstrated an increase in absolute growth rates in response to climate warming, with late summer temperatures driving the recent growth trend. Contrary to our expectation that LOTs would eventually exhibit declining growth rates, the oldest LOTs (>400 years) continuously increase growth throughout their lives, indicating a high phenotypic plasticity of LOTs for increasing biomass, and a strong carbon sink role of primary spruce forests under rising temperatures, intensifying droughts, and increasing bark beetle outbreaks.     

Light scattering on PHA granules protects bacterial cells against the harmful effects of UV radiation

Numerous prokaryotes accumulate polyhydroxyalkanoates (PHA) in the form of intracellular granules. The primary function of PHA is the storage of carbon and energy. Nevertheless, there are numerous reports that the presence of PHA granules in microbial cells enhances their stress resistance and fitness when exposed to various stress factors. In this work, we studied the protective mechanism of PHA granules against UV irradiation employing Cupriavidus necator as a model bacterial strain. The PHA-accumulating wild type strain showed substantially higher UV radiation resistance than the PHA non-accumulating mutant. Furthermore, the differences in UV-Vis radiation interactions with both cell types were studied using various spectroscopic approaches (turbidimetry, absorption spectroscopy, and nephelometry). Our results clearly demonstrate that intracellular PHA granules efficiently scatter UV radiation, which provides a substantial UV-protective effect for bacterial cells and, moreover, decreases the intracellular level of reactive oxygen species in UV-challenged cells. The protective properties of the PHA granules are enhanced by the fact that granules specifically bind to DNA, which in turn provides shield-like protection of DNA as the most UV-sensitive molecule. To conclude, the UV-protective action of PHA granules adds considerable value to their primary storage function, which can be beneficial in numerous environments.

     

GRACE Score among Six Risk Scoring Systems (CADILLAC,PAMI, TIMI,Dynamic TIMI,Zwolle) Demonstrated the Best Predictive Value for Prediction of Long-Term Mortality in Patients with ST-Elevation Myocardial Infarction

Aim

To compare the prognostic accuracy of six scoring models for up to three-year mortality and rates of hospitalisation due to acute decompensated heart failure (ADHF) in STEMI patients.

Methods and Results

A total of 593 patients treated with primary PCI were evaluated. Prospective follow-up of patients was ≥3 years. Thirty-day, one-year, two-year, and three-year mortality rates were 4.0%, 7.3%, 8.9%, and 10.6%, respectively. Six risk scores—the TIMI score and derived dynamic TIMI, CADILLAC, PAMI, Zwolle, and GRACE—showed a high predictive accuracy for six- and 12-month mortality with area under the receiver operating characteristic curve (AUC) values of 0.73–0.85. The best predictive values for long-term mortality were obtained by GRACE. The next best-performing scores were CADILLAC, Zwolle, and Dynamic TIMI. All risk scores had a lower prediction accuracy for repeat hospitalisation due to ADHF, except Zwolle with the discriminatory capacity for hospitalisation up to two years (AUC, 0.80–0.83).

Conclusions

All tested models showed a high predictive value for the estimation of one-year mortality, but GRACE appears to be the most suitable for the prediction for a longer follow-up period. The tested models exhibited an ability to predict the risk of ADHF, especially the Zwolle model.     

Circulating Serum MicroRNA-130a as a Novel Putative Marker of Extramedullary Myeloma

Poor outcome of extramedullary disease in multiple myeloma patients and lack of outcome predictors prompt continued search for new markers of the disease. In this report, we show circulating microRNA distinguishing multiple myeloma patients with extramedullary disease from myeloma patients without such manifestation and from healthy donors. MicroRNA-130a was identified by TaqMan Low Density Arrays and verified by quantitative PCR on 144 serum samples (59 multiple myeloma, 55 myeloma with extramedullary disease, 30 healthy donors) in test and validation cohorts as being down-regulated in myeloma patients with extramedullary disease. Circulating microRNA-130a distinguished myeloma patients with extramedullary disease from healthy donors with specificity of 90.0% and sensitivity of 77.1%, patients with extramedullary disease from newly diagnosed multiple myeloma patients with specificity of 77.1% and sensitivity of 34.3% in the test cohort and with specificity of 91.7% and sensitivity of 30.0% in the validation cohort of patients. Circulating microRNA-130a in patients with extramedullary myeloma was associated with bone marrow plasma cells infiltration. Further, microRNA-130a was decreased in bone marrow plasma cells obtained from patients with extramedullary myeloma in comparison to bone marrow plasma cells of myeloma patients without such manifestation, but it was increased in tumor site plasma cells of patients with extramedullary disease compared to bone marrow plasma cells of such patients (p<0.0001). Together, our data suggest connection between lower level of microRNA-130a and extramedullary disease and prompt further work to evaluate this miRNA as a marker of extramedullary disease in multiple myeloma.     

Changes in the lung bacteriome in relation to antipseudomonal therapy in children with cystic fibrosis

The lung in cystic fibrosis (CF) is home to numerous pathogens that shorten the lives of patients. The aim of the present study was to assess changes in the lung bacteriome following antibiotic therapy targeting Pseudomonas aeruginosa in children with CF. The study included nine children (9–18 years) with CF who were treated for their chronic or intermittent positivity for Pseudomonas aeruginosa. The bacteriomes were determined in 16 pairs of sputa collected at the beginning and at the end of a course of intravenous antibiotic therapy via deep sequencing of the variable region 4 of the 16S rRNA gene, and the total bacterial load and selected specific pathogens were assessed using quantitative real-time PCR. The effect of antipseudomonal antibiotics was observable as a profound decrease in the total 16S rDNA load (p = 0.001) as well as in a broad range of individual taxa including Staphylococcus aureus (p = 0.03) and several members of the Streptococcus mitis group (S. oralis, S. mitis, and S. infantis) (p = 0.003). Improvements in forced expiratory volume (FEV₁) were associated with an increase in Granulicatella sp. (p = 0.004), whereas a negative association was noted between the total bacterial load and white blood cell count (p = 0.007). In conclusion, the data show how microbial communities differ in reaction to antipseudomonal treatment, suggesting that certain rare species may be associated with clinical parameters. Our work also demonstrates the utility of absolute quantification of bacterial load in addition to the 16S rDNA profiling.     

Copy-number variation introduced by long transgenes compromises mouse male fertility independently of pachytene checkpoints

Chromosoma - Long transgenes are often used in mammalian genetics, e.g., to rescue mutations in large genes. In the course of experiments addressing the genetic basis of hybrid sterility caused by...     

Increased expression and altered subcellular distribution of PKC-delta in chronically hypoxic rat myocardium: involvement in cardioprotection

We examined the role of protein kinase C (PKC) in the cardioprotective mechanism induced by long-term adaptation to chronic intermittent hypoxia. Adult male Wistar rats were exposed to hypobaric hypoxia of 7,000 m for 8 h/day, 5 days/wk; the total number of exposures was 24-32. A control group was kept under normoxic conditions. Western blot analysis of PKC isoforms-delta and -epsilon was performed in the cytosol and three particulate fractions of left ventricular myocardium. Infarct size was determined in open-chest animals subjected to 20-min coronary artery occlusion and 3-h reperfusion. The PKC inhibitors chelerythrine (1 or 5 mg/kg) or rottlerin (selective for PKC-delta isoform; 0.3 mg/kg) were administered intravenously as a single bolus 15 min before ischemia. Chronic hypoxia had no effect on the expression and distribution of PKC-epsilon. The relative amount of PKC-delta increased in the cytosol and nuclear-cytoskeletal, mitochondrial, and microsomal fractions of chronically hypoxic myocardium by 100%, 212%, 237%, and 146%, respectively, compared with corresponding normoxic values. Chronic hypoxia decreased the size of myocardial infarction (normalized to the area at risk) by about one-third on the average (P < 0.05). Both doses of chelerythrine tended to reduce infarction in controls, and only the high dose completely abolished the improvement of ischemic tolerance in hypoxic hearts (P < 0.05). Rottlerin attenuated the infarct size-limiting effect of chronic hypoxia (P < 0.05), and it had no effect in controls. These results suggest that chronic intermittent hypoxia-induced cardioprotection in rats is partially mediated by PKC-delta; the contribution of other isoforms remains to be determined.