The evaluation of hazardous element content in the needles of the Norway spruce (Picea abies L.) that originated from anthropogenic activities in the vicinity of the native habitats.

The aim of this research was to quantify the content of hazardous elements in the needles of Norway spruce (Picea abies L.) in the natural habitats that were accumulated from thermal power plants, mines, and metal processing industry. Fifteen natural populations of the Norway spruce were sampled from the mountain ranges in Southeastern Europe (Dinaric Alps and Balkan Mountains). Two-year-old spruce needles were evaluated the content of the following hazardous elements: heavy metals cadmium, mercury, nickel, lead and zinc, and metalloid arsenic. The effect of the distance between air pollution emitters and the Norway spruce natural habitats on the hazardous elements content in needles was also evaluated. The results of the analysis of variance confirmed interpopulation differences in the content of all analyzed hazardous elements. The effect of the air pollution source (thermal power plants, mines, and industry) on the content of hazardous elements in the spruce needles was also assessed. Significant correlation was found between the distance of air pollution emitters and the amount of zinc. This study could serve as the startup point of future monitoring programs and provide new prospect of using Norway spruce needles as the bioindicator of air pollution with hazardous elements on Balkan Peninsula since the fact that the Norway spruce natural populations inhabit wide geographic range of the continental Europe, from the Balkan Peninsula, over European Alps to Scandinavia and a large-scale of altitude from 980 to 1860 m above sea level.

Variability of Silver Fir Needle (Abies alba Mill.) Anatomical Features in the Southeast Europe Natural Populations.

The survival of marginal/peripheral silver fir (Abies alba Mill.) populations in the broader region of Southeast Europe is endangered due to climate change and population decline. This study aimed to determine the level and pattern of variability for the anatomical traits of needles and the possibility of linking the pattern of phenotypic variability with environmental factors. In most of the analyzed needle traits, the statistically significant variability between populations was determined. According to the results of the multivariate principal component analysis, it is evident that the populations are distinct from each other, in three groups. The climatic factors Hargreaves reference evaporation, mean annual temperature, and growing degree-days, were statistically significantly correlated. The altitude and heating degree-days are statistically significantly correlated with the following three environmental factors: Hargreaves reference evaporation, mean annual temperature and growing degree-days, but negatively with others. The paper's findings indicate significant moderate and high correlations between the anatomical traits of the needles' central bundle diameter with the resin duct diameter, the distance between the vascular bundle and the resin duct and the epidermis thickness with cuticle, the resin duct diameter with the distance between the vascular bundle and the resin duct and the epidermis thickness with cuticle, as well as the distance between the vascular bundle and the resin duct with the hypodermis height and the epidermis thickness with cuticle. The results of agglomerative hierarchical clustering analysis, performed for anatomical and climatic traits, confirmed the existence of three groups of tested populations according to the altitude gradient. Research results provide knowledge on the diversity and structure of Abies alba populations of Southeast Europe, important for further research and guidelines for the species' conservation and genetic variability preservation in the southern marginal distribution area and keeping in line with climate change projections.

Shifting the selectivity of pyrido[2,3-d]pyrimidin-7(8H)-one inhibitors towards the salt-inducible kinase (SIK) subfamily.

Salt-inducible kinases 1-3 (SIK1-3) are key regulators of the LKB1-AMPK pathway and play an important role in cellular homeostasis. Dysregulation of any of the three isoforms has been associated with tumorigenesis in liver, breast, and ovarian cancers. We have recently developed the dual pan-SIK/group I p21-activated kinase (PAK) chemical probe MRIA9. However, inhibition of p21-activated kinases has been associated with cardiotoxicity in vivo, which complicates the use of MRIA9 as a tool compound. Here, we present a structure-based approach involving the back-pocket and gatekeeper residues, for narrowing the selectivity of pyrido[2,3-d]pyrimidin-7(8H)-one-based inhibitors towards SIK kinases, eliminating PAK activity. Optimization was guided by high-resolution crystal structure analysis and computational methods, resulting in a pan-SIK inhibitor, MR22, which no longer exhibited activity on STE group kinases and displayed excellent selectivity in a representative kinase panel. MR22-dependent SIK inhibition led to centrosome dissociation and subsequent cell-cycle arrest in ovarian cancer cells, as observed with MRIA9, conclusively linking these phenotypic effects to SIK inhibition. Taken together, MR22 represents a valuable tool compound for studying SIK kinase function in cells.

Impact of an Extremely Dry Period on Tree Defoliation and Tree Mortality in Serbia.

This paper presents research results on forest decline in Serbia. The results were obtained through monitoring defoliation of 34 tree species at 130 sample plots during the period from 2004 to 2018. This research aimed to determine whether the occurrence of defoliation and tree mortality were caused by drought. Defoliation was assessed in 5% steps according to the International Co-operative Programme on Assessment and Monitoring of Air Pollution Effects on Forests (ICP Forests) methodology. All the trees recorded as dead were singled out, and annual mortality rates were calculated. To determine changes in air temperature and precipitation regimes during the study period, we processed and analysed climatic data related to air temperature and precipitation throughout the year and in the growing season at 28 main weather stations in Serbia. Tree mortality patterns were established by classifying trees into three groups. The first group of trees exhibited a gradual increase in defoliation during the last few years of monitoring, with dying as the final outcome. The second group was characterised by sudden death of trees. The third group of trees reached a higher degree of defoliation immediately after the first monitoring year, and the trees died after several years. Tree mortality rates were compared between years using the Standardised Precipitation Evaporation Index (SPI) and the Standardised Precipitation Evapotranspiration Index (SPEI), the most common methods used to monitor drought. The most intensive forest decline was recorded during the period from 2013 to 2016, when the largest percentage of the total number of all trees died. According to the annual mortality rates calculated for the three observation periods (2004-2008, 2009-2013, and 2014-2018) the highest forest decline rate was recorded in the period from 2014 to 2018, with no statistically significant difference between broadleaved and coniferous tree species. As the sample of coniferous species was small, the number of sample plots should be increased in order to achieve better systematic forest condition monitoring in Serbia. The analysis of the relationship between defoliation and climatic parameters proved the correlation between them. It was noted that the forest decline in Serbia was preceded by an extremely dry period with high temperatures from 2011 to 2013, supporting the hypothesis that it was caused by drought. We therefore conclude that these unfavourable climatic conditions had serious and long-term consequences on forest ecosystems in Serbia.

[Treatment of pregnancy related venous thromboembolism]. / Terapija venskog tromboembolizma tokom trudnoce.

INTRODUCTION: Prevention and treatment of venous thromboembolism during pregnancy are complicated since the use of antithrombotic drugs carries a certain risk to the mother, the fetus or both. Coumarins cross the placental barrier and may be responsible for bleeding, teratogenicity and central nervous system abnormalities. The risk of embriopathy is particularly high between 6 and 12 weeks of gestation. TREATMENT: Heparin is the treatment of choice for thrombosis during pregnancy because it is entirely safe for the fetus, unlike oral anticoagulants. The frequency of heparin-induced thrombocytopenia and osteoporosis is significantly lower if LMWH is applied, so this heparin type is preferable to UFH during pregnancy. Treatment of women with VTE during pregnancy, especially those with thrombophilia, requires individualized dosing and duration of antithrombotic therapy. PERIPARTAL MANAGEMENT: In order to avoid the peripartum anticoagulant heparin effect and possible bleeding, heparin should be discontinued prior to the delivery and reintroduced after the parturition. PROPHYLACTIC REGIMEN: Prophylactic antithrombotic regimen during subsequent pregnancies should also be individualized. The use of low molecular weight heparins is becoming more widespread. They have reliable pharmacokinetics, require less frequent injections than unfractionated heparin and carry a lower risk of treatment complications. LMW heparins are safe and effective and they are replacing UFH as the anticoagulant of choice during pregnancy. Both UFH and LMWH are not secreted into breast milk and can be safely given to nursing mothers. Warfarin does not induce an anticoagulant effect in the breast-fed infant, so it can be safely used in women who require postpartum anticoagulant therapy.