1′-Methyl-4′-(4-methyl­phen­yl)dispiro­[1-benzopyran-3(4H),3′-pyrrolidine-2′,3′′-indoline]-2,2′′-dione

In the title compound, C27H24N2O3, the pyrroldine ring adopts a twist conformation, while the six-membered pyran­one ring of the coumarin ring system is in a sofa conformation. In the crystal, pairs of N—H⋯O hydrogen bonds link the mol­ecules into inversion R 2 2(8) dimers. These dimers are further connected via C—H⋯O hydrogen bonds

Identification and characterization of 3-substituted pyrazolyl esters as alternate substrates for cathepsin B: The confounding effects of DTT and cysteine in biological assays

Substituted pyrazole esters were identified as hits in a high throughput screen (HTS) of the NIH Molecular Libraries Small Molecule Repository (MLSMR) to identify inhibitors of the enzyme cathepsin B. Members of this class, along with functional group analogs, were synthesized in an effort to define the structural requirements for activity. Analog characterization was hampered by the need to include a reducing agent such as dithiothreitol (DTT) or cysteine in the assay, highlighting the caution required in interpreting biological data gathered in the presence of such nucleophiles. Despite the confounding effects of DTT and cysteine, our studies demonstrate that the pyrazole 1 acts as alternate substrate for cathepsin B, rather than as an inhibitor

Використання поліфенолкарбонового комплексу з антарктичних чорних дріжджів Nadsoniella nigra в раціон птиці та їх вплив на інкубаційні якос-ті яєць перепілок несучок

The results of research on the influence of the polyphenol carbon complex from the Antarctic black yeast Nadsoniella nigra, which is additionally introduced into compound feed, are presented on the hatching qualities of quail eggs. Experimental studies were conducted in the conditions of the problematic research laboratory of feed additives of the National University of Bioresources and Nature Management of Ukraine. The material for the scientific and economic experiment was adult quail of the Pharaoh breed. Experiments were conducted using the group method. Accordingly, 192 heads of quails were selected for the experiment at 42 days, from which four groups were formed according to the principle of analogs - a control group and three experimental ones, 48 heads in each with four replications). When selecting analogs, the sex, age, and body weight of the bird were taken into account. The main period lasting 210 days, was divided into seven sub-periods, each of which lasted 30 days. The composition of the compound feed for the quails of the control and experimental groups and the set and number of ingredients in it were identical. The chemical composition of the combined feed used for feeding quails was the same and differed only in the content of PFC. During the experiment, the preservation of livestock and productivity were recorded, and feed conversion was also calculated. It was experimentally established that adding 0.1, 0.5, and 1.0 mg/kg polyphenol-carbon complex from the Antarctic black yeast Nadsoniella nigra to compound feed positively affects the hatching properties of eggs and, at the same time, reduces the percentage of hatching waste. At the same time, in the birds of the 3rd experimental group, which were fed 0.5 mg/kg of PFC as part of the compound feed, respectively, the percentage of fertilization was 2.2%; hatchability of eggs by 3.8%; and the yield of young by 5%, compared to birds that were not given PFC compound feed.Наведено результати досліджень з установлення впливу поліфенолкарбонового комплексу з антарктичних чорних дріжджів Nadsoniella nigra, який додатково вводять у комбікорми, на інкубаційні якості яєць перепелів. Експериментальні дослідження проводилися в умовах проблемної науково-дослідної лабораторії кормових добавок Національного університету біоресурсів і природокористування України. Матеріалом для науково-господарського досліду були дорослі перепели породи фараон. Досліди проводили за методом груп. Відповідно до цього для досліду у 42-добовому віці було відібрано 192 голови перепелів, з яких за принципом аналогів сформовано 4 групи – контрольну і три дослідні, по 48 голів у кожній з чотирма реплікаціями). При підборі аналогів враховували стать, вік і масу тіла птиці. Основний період тривалістю 210 діб було поділено на 7 підперіодів, кожен із яких тривав 30 діб. Склад комбікорму для перепелів контрольної та дослідних груп, набір і кількість інгредієнтів у ньому були ідентичними. Хімічний склад комбікорму, який використовували для годівлі перепелів, був однаковим і різнився лише за вмістом ПФК. Упродовж досліду проводився облік збереженості поголів’я, продуктивності, а також розраховували конверсію корму. Експериментально встановлено, що додавання до комбікорму 0,1, 0,5 та 1,0 мг/кг поліфенолкарбонового комплексу з антарктичних чорних дріжджів Nadsoniella nigra позитивно впливає на інкубаційні властивості яєць і при цьому знижує відсоток відходів інкубації. Водночас у птиці 3-ї дослідної групи, якій у складі комбікорму згодовували 0,5 мг/кг ПФК, відповідно за відсотком запліднення на 2,2 %; виводимістю яєць на 3,8 %; та виходом молодняку на 5 %, порівняно з птицею, якій не вводили до складу комбікорму ПФК

Oral tongue cancer gene expression profiling: Identification of novel potential prognosticators by oligonucleotide microarray analysis

<p>Abstract</p> <p>Background</p> <p>The present study is aimed at identifying potential candidate genes as prognostic markers in human oral tongue squamous cell carcinoma (SCC) by large scale gene expression profiling.</p> <p>Methods</p> <p>The gene expression profile of patients (n=37) with oral tongue SCC were analyzed using Affymetrix HG_U95Av2 high-density oligonucleotide arrays. Patients (n=20) from which there were available tumor and matched normal mucosa were grouped into stage (early vs. late) and nodal disease (node positive vs. node negative) subgroups and genes differentially expressed in tumor vs. normal and between the subgroups were identified. Three genes, <it>GLUT3</it>, <it>HSAL2</it>, and <it>PACE4</it>, were selected for their potential biological significance in a larger cohort of 49 patients via quantitative real-time RT-PCR.</p> <p>Results</p> <p>Hierarchical clustering analyses failed to show significant segregation of patients. In patients (n=20) with available tumor and matched normal mucosa, 77 genes were found to be differentially expressed (P< 0.05) in the tongue tumor samples compared to their matched normal controls. Among the 45 over-expressed genes, <it>MMP-1</it> encoding interstitial collagenase showed the highest level of increase (average: 34.18 folds). Using the criterion of two-fold or greater as overexpression, 30.6%, 24.5% and 26.5% of patients showed high levels of <it>GLUT3</it>, <it>HSAL2</it> and <it>PACE4</it>, respectively. Univariate analyses demonstrated that <it>GLUT3</it> over-expression correlated with depth of invasion (P<0.0001), tumor size (P=0.024), pathological stage (P=0.009) and recurrence (P=0.038). <it>HSAL2</it> was positively associated with depth of invasion (P=0.015) and advanced T stage (P=0.047). In survival studies, only <it>GLUT3</it> showed a prognostic value with disease-free (P=0.049), relapse-free (P=0.002) and overall survival (P=0.003). <it>PACE4</it> mRNA expression failed to show correlation with any of the relevant parameters. </p> <p>Conclusion</p> <p>The characterization of genes identified to be significant predictors of prognosis by oligonucleotide microarray and further validation by real-time RT-PCR offers a powerful strategy for identification of novel targets for prognostication and treatment of oral tongue carcinoma.</p

Identification of Novel Inhibitors of Dietary Lipid Absorption Using Zebrafish

Pharmacological inhibition of dietary lipid absorption induces favorable changes in serum lipoprotein levels in patients that are at risk for cardiovascular disease and is considered an adjuvant or alternative treatment with HMG-CoA reductase inhibitors (statins). Here we demonstrate the feasibility of identifying novel inhibitors of intestinal lipid absorption using the zebrafish system. A pilot screen of an unbiased chemical library identified novel compounds that inhibited processing of fluorescent lipid analogues in live zebrafish larvae. Secondary assays identified those compounds suitable for testing in mammals and provided insight into mechanism of action, which for several compounds could be distinguished from ezetimibe, a drug used to inhibit cholesterol absorption in humans that broadly inhibited lipid absorption in zebrafish larvae. These findings support the utility of zebrafish screening assays to identify novel compounds that target complex physiological processes

Spatial distribution of bivalves in relation to environmental conditions (middle Danube catchment, Hungary)

The spatial distribution of bivalves in relation to environmental conditions was studied along a second- and third order stream – medium-sized river (River Ipoly) – large river (River Danube) continuum in the Hungarian Danube River system. Quantitative samples were collected four times in 2007 and a total of 1662 specimens, belonging to 22 bivalve species were identified. Among these species, two are endangered (Pseudanodonta complanata, Unio crassus) and five are invasive (Dreissena polymorpha, D. rostriformis bugensis, Corbicula fluminea, C. fluminalis, Anodonta woodiana) in Hungary. The higher density presented by Pisidium subtruncatum, P. supinum, P. henslowanum and C. fluminea suggests that these species may have a key role in this ecosystem. Three different faunal groups were distinguished but no significant temporal change was detected. The lowest density and diversity with two species (P. casertanum and P. personatum) occurred in streams. The highest density and diversity was found in the River Ipoly, in the side arms of the Danube and in the main arm of the Danube with sand and silt substrate, being dominated by P. subtruncatum and P. henslowanum. Moderate density and species richness were observed in the main arm of the Danube with pebble and stone substrate, being dominated by C. fluminea and S. rivicola. Ten environmental variables were found to have significant influence on the distribution of bivalves, the strongest explanatory factors being substrate types, current velocity and sedimentological characteristics.The project was financially supported by the Hungarian Scientific Research Fund under the contract No. OTKA T/046180. Special thanks to the DanubeIpoly National Park for the help in field work.info:eu-repo/semantics/publishedVersio