The Therapeutic Potential of Natural Products from \u3ci\u3eVaccinium\u3c/i\u3e Berries for Viral and Lung Diseases Through an Improved LC-MS-Based Chemometric Approach

Smoking is a global epidemic that creates serious health and economic burden. It is the primary, preventative factor for the majority of causes of death worldwide. Analysis of publicly available data revealed that smoking prevalence rates among the youth in developing countries, especially in Bulgaria, are alarmingly high. The Bulgarian population has one of the highest percentages of smokers and the second highest rate among teenage girls. Consequently, chronic diseases affected by smoking, such as chronic obstructive pulmonary disorder (COPD), have been increasing there in the last five years. Poland, on the other hand, is an exemplary outlier for the region with much lower smoking prevalence rates and COPD incidence growth like those in the developed countries, such as the United States. A survey among college-aged people at Lehman College, City University of New York, determined that there were behavioral sensitivities predictive of cigarette use. Experimenters were highly sensitive to fun seeking and reward responsiveness. A larger portion of the experimenters knew people that have COPD but were not related to them. Most experimenters were not interested in learning more about smoke-related diseases. Hispanics were the majority within the experimenter group and they seemed to eat antioxidant-rich foods less often than others. Therefore, tailored anti-tobacco efforts focused on developing countries are needed to reduce country disparities of smoking prevalence and chronic diseases, such as COPD. COPD is a disease for which there is no cure and current therapies only temporarily control symptoms. Still, evidence suggests a diet rich in polyphenol-rich foods, such as apples and berries, may hold a promise in the treatment of the disease. Antioxidant-rich blueberries, cranberries, and lingonberries are temperate species in the Vaccinium genus, which produce several classes of secondary metabolites potent against aging and chronic diseases, such as COPD. A literature review of their chemistry, bioavailability, and bioactivity was conducted. Growing consumer awareness of the health-promoting effects of cranberry and blueberry compounds combined with trends towards organic farming may offer further areas of growth and development for these crops. Vaccinium berries have been studied for centuries, but their full potential to ameliorate lung and viral diseases remains to be established. These studies focused on a class of berry compounds that have not been studied extensively – the oligomeric procyanidins. Procyanidin dimer B2 and an A-type trimer were found to counteract smoke-induced responses in airway epithelial cells by decreasing an inflammatory marker interleukin 8 (IL-8) and downregulating proteolytic enzyme collagenase matrix metalloproteinase-1 (MMP-1). In contrast, procyanidin dimer A2 induced inflammation alone. Furthermore, jaboticabin, an anti-inflammatory depside, was found in several Vaccinium berries for the first time. Procyanidins have low bioavailability and upon ingestion most of these compounds pass unabsorbed through the small intestine as they enter the colon where they get metabolized by the gut microflora. Consumption of foods rich in procyanidins has been found to impact the concentration of certain microbial metabolites. The study investigated four of these metabolites for their anti-inflammatory potency in small airway epithelium, and hippuric acid was determined to significantly inhibit smoke-induced IL-8 levels. Other indirect, favorable health effects of procyanidin B2 were explored in relation to its ability to modify gene expression of antioxidant enzymes and epigenetics factors. The tested procyanidins were selected with an improved natural product discovery approach whose success was further measured by searching for the most antiviral compounds from three highbush blueberry cultivars. The approach builds on previous chemometric methods which prioritized markers with higher relative abundance in the bioactive samples. The improved approach utilized a vast chemical data set from state-of-the-art LC-MS techniques, but reduced the number of highest-ranked, potentially active markers. This first improvement was achieved by employing very similar samples, such as parallel fractions from the three cultivars. Additionally, the approach helped prioritize compounds with strong anti-HSV-1 activity while decreasing the priority of markers with weaker antiviral potency. This second improvement accounted for different levels of fractions’ antiviral activity by making two separate chemometric comparisons among the three fractions and considering only the overlapping markers. Out of the tested compounds, quercetin 3-β-D-glucoside was determined to have the strongest viricidal effect against acyclovir resistant HSV-1 strain. This study also led to the identification of antiviral cinchonain in the fruits of blueberry species for the first time. The novel chemometric approach integrates improvements in the analysis of big chemical data sets that could make the natural products drug discovery process more targeted and efficient. Procyanidin dimer B2 and the A-type trimers, prioritized through this approach, merit additional studies of their pharmacological potential for chronic lung diseases. Dark-colored berries should be further investigated for other potent antimicrobial compounds

Do Prostitution Laws Affect Rape Rates? Evidence from Europe

We identify a causal effect of the liberalization and prohibition of commercial sex on rape rates, using staggered legislative changes in European countries. Liberalizing prostitution leads to a significant decrease in rape rates, while prohibiting it leads to a significant increase. The results are stronger when rape is less severely underreported and when it is more difficult for men to obtain sex via marriage or partnership. We also provide the first evidence for the asymmetric effect of prostitution regulation on rape rates: the magnitude of prostitution prohibition is much larger than that of prostitution liberalization. Placebo tests show that prostitution laws have no impact on nonsexual crimes. Overall, our results indicate that prostitution is a substitute for sexual violence and that the recent global trend of prohibiting commercial sex (especially the Nordic model) could have the unforeseen consequence of proliferating sexual violence

BREEDING OF CEREAL CROPS AT DOBRUDZHA AGRICULTURAL INSTITUTE – GENERAL TOSHEVO, BULGARIA

The climate of Bulgaria is very diverse in spite of its small territory. The soil and climatic conditions in the region where Dobrudzha Agricultural Institute is situated are suitable for obtaining high and stable yields from all winter cereals. The breeding program of the institute is aimed at developing high-yielding cultivars of common and durum wheat, triticale, malting and feed barley adaptable to growing under variable soil and climatic conditions. The aim of this investigation is to present the major directions, problems and achievements of the breeding work on the winter cereals at Dobrudzha Agricultural Institute.The results were summarized on several levels:Evaluation of the risk factors for the development, the yield formation and the quality indices;Developing and study on a gene pool of the best world and Bulgarian accessions;Developing of own initial material by using the methods of intervarietal hybridization, experimental mutagenesis and other biotechnology approaches;Developing of a more efficient methodology for field and laboratory evaluation of the breeding materials;Testing of new varieties and production of certified planting material.The portfolio of the institute is quite variable. From the cultivars developed here, 36 genotypes of common wheat and 5 genotypes of durum wheat, 11 triticale cultivars and 6 winter barley varieties have been included in the National Vareital List of Bulgaria

The genetic history of the Southern Arc: a bridge between West Asia and Europe

By sequencing 727 ancient individuals from the Southern Arc (Anatolia and its neighbors in Southeastern Europe and West Asia) over 10,000 years, we contextualize its Chalcolithic period and Bronze Age (about 5000 to 1000 BCE), when extensive gene flow entangled it with the Eurasian steppe. Two streams of migration transmitted Caucasus and Anatolian/Levantine ancestry northward, and the Yamnaya pastoralists, formed on the steppe, then spread southward into the Balkans and across the Caucasus into Armenia, where they left numerous patrilineal descendants. Anatolia was transformed by intra–West Asian gene flow, with negligible impact of the later Yamnaya migrations. This contrasts with all other regions where Indo-European languages were spoken, suggesting that the homeland of the Indo-Anatolian language family was in West Asia, with only secondary dispersals of non-Anatolian Indo-Europeans from the steppe

Do Prostitution Laws Affect Rape Rates? Evidence from Europe

We identify a causal effect of the liberalization and prohibition of commercial sex on rape rates, using staggered legislative changes in European countries. Liberalizing prostitution leads to a significant decrease in rape rates, while prohibiting it leads to a significant increase. The results are stronger when rape is less severely underreported and when it is more difficult for men to obtain sex via marriage or partnership. We also provide the first evidence for the asymmetric effect of prostitution regulation on rape rates: the magnitude of prostitution prohibition is much larger than that of prostitution liberalization. Placebo tests show that prostitution laws have no impact on nonsexual crimes. Overall, our results indicate that prostitution is a substitute for sexual violence and that the recent global trend of prohibiting commercial sex (especially the Nordic model) could have the unforeseen consequence of proliferating sexual violence

Black chokeberry (Aronia melanocarpa) copigmentation reaction: Thermodynamic and kinetic investigations

Two type of parameters (thermodynamics and kinetics) were used to determine thermal stability of copigmentation process in black chokeberry: chlorogenic acid system. According to thermodynamic investigations copigmentation complex was destroyed at high temperature and restored again at low temperature. Different parameters kinetic rate constant, energy of activation and z-factor were presented and the reaction Based on them the order of the reaction was determined as first order

Thermodynamic investigations of the copigmentation process between strawberry anthocyanins and rose petal polyphenols (Rosa damascena Mill.) at different temperatures

In this study the model systems between strawberry anthocyanins as pigment and rose polyphenols as copigment was investigated. The solutions were prepared from 1:2 to 1:10 pigment:copigment. The addition of increasing concentrations of rose petal polyphenols resulted in a gradual increase of hyperchromic effect. The absorption was determined at heating system from 20 to 50 oC and following cooling the same system from 50 to 20 oC. All calculated thermodynamic parameters were negative. The copigmentation reaction was determined as spontaneous, exothermic and thermally reversible

Klasyfikacja semantyczna ojkonimów z terenu gminy Smolian

The paper presents a semantic classification of oykonyms from the municipality of Smolyan. The classification allows to divide the research material into geographical, culture-historical and possessive oykonyms. Different sociocultural factors over the choice, attitude, preference and preservance of the relevant oykonyms are revealed. These factors show that the world of the Rhodope people is firmly connected to land and ancestral memory.Celem artykułu jest przedstawienie klasyfikacji semantycznej ojkonimów z terenu gminy Smolian w południowej Bułgarii. Oparta jest ona na podziale materiału na trzy grupy ojkonimów: geograficzne, historyczno-kulturowe oraz posesywne. Na podstawie analizy czynników mających wpływ na proces kształtowania się nazw miejscowych w gminie Smolian można sformułować wniosek, że ludność Rodopów nadal jest nierozerwalnie związana z ziemią i pamięcią rodową

Dynamic viscosity, centrifugation test and kinetic investigation in emulsions with pumpkin oil

The emulsion stability of different pumpkin O/W emulsions was investigated. Preparation of emulsions were performed with oil phase between 10 and 40 percent, water and soybean protein isolate. To determine emulsion properties different methods were used. Density, viscosity, centrifugation tests and spectroscopic measurements were performed for their investigations. The emulsions were stored for two weeks to determine their kinetic. Influence of the oil phase was presented and connected with the stability of them

New Activity of a Protein from Canavalia ensiformis

Concanavalin A is a legume lectin which preferentially agglutinates transformed cells and shows antitumor effects on human breast carcinoma cells in vitro and in vivo. It is considered as a new potential antineoplastic agent targeting apoptosis, autophagy, and anti-angiogenesis in preclinical or clinical trials for cancer therapeutics, which has recently become the object of intensive study. In the present investigation, we show the capacity of the lectin to bind manganese, gold, iron, and zinc porphyrins: all potential anticancer agents. The interaction of the legume lectin with the studied compounds has been investigated by tryptophan fluorescence, showing conformational changes within the quaternary and tertiary structures of the protein. The binding of Con A with manganese, gold, and iron porphyrins, as well as adenine, was studied by fluorescence quenching. In contrast, the interaction of Con A with zinc porphyrin caused an increase in Trp fluorescence and a red shift of 10 nm of the emission maximum position. However, the binding of Con A to iron porphyrin was accompanied by a 5 nm blue shift of the emission maximum, and a kD of 0.95 ± 0.13 μM was calculated, respectively. The sigmoidal shape of the curve showed cooperative interactions, which indicated the presence of more than one class of binding site within the Con A molecule for iron porphyrin, confirmed by the Hill slope (h = 1.89±0.46). We have found that the legume lectin interacts with porphyrins and adenine with an affinity (0.14–1.89 μM) similar to that of the non-legume lectin, wheat germ agglutinin. In conclusion, the protein Con A shows new binding activity towards porphyrins with anticancer activities and could find prospective application as a drug delivery molecule that specifically targets cancer cells