USF binding sequences from the HS4 insulator element impose early replication timing on a vertebrate replicator

The nuclear genomes of vertebrates show a highly organized program of DNA replication where GC-rich isochores are replicated early in S-phase, while AT-rich isochores are late replicating. GC-rich regions are gene dense and are enriched for active transcription, suggesting a connection between gene regulation and replication timing. Insulator elements can organize independent domains of gene transcription and are suitable candidates for being key regulators of replication timing. We have tested the impact of inserting a strong replication origin flanked by the β-globin HS4 insulator on the replication timing of naturally late replicating regions in two different avian cell types, DT40 (lymphoid) and 6C2 (erythroid). We find that the HS4 insulator has the capacity to impose a shift to earlier replication. This shift requires the presence of HS4 on both sides of the replication origin and results in an advance of replication timing of the target locus from the second half of S-phase to the first half when a transcribed gene is positioned nearby. Moreover, we find that the USF transcription factor binding site is the key cis-element inside the HS4 insulator that controls replication timing. Taken together, our data identify a combination of cis-elements that might constitute the basic unit of multi-replicon megabase-sized early domains of DNA replication

Age and gender specific cut-off points for body fat parameters among adults in Qatar

© 2020 The Author(s). Background: Excessive body fat is the leading cause of many metabolic disorders. Therefore, assessing levels of body fat associated with risk of disease in specific populations is crucial. The present study aimed to identify optimal cut-off values of body fat composition including total body fat, body fat percentage, visceral fat, and trunk fat, in order to predict metabolic risk in the Qatari population. Methods: This cross-sectional study was based on Qatar Biobank data of 2407 Qatari adults (1269 male and 1138 female) aged 21-70 years old. Individuals' height, weight and body fat percentage were obtained. Blood test data including lipid profile, blood glucose and HbA1c data were also obtained. The area under the curve was calculated using ROC analysis to obtain the body fat percentage associated with risk of disease. Results: The cut-off points for total fat for those aged < 40 were 34.0 kg, and for those aged ≥40 were 30.7 kg and 35.6 kg in men and women, respectively. The cut-off for body fat percent for those aged < 40 were 35.1 and 45.1%, and for those aged ≥40 were 34.8 and 46.3% in men and women, respectively. The cut-off points for trunk fat percent for those aged < 40 were 19.5 and 22.4%, and for those aged ≥40 were 21.6 and 23.4% in men and women, respectively. The cut-off points for visceral fat percent for those aged < 40 were 1.4 and 1.0%, and for those aged ≥40 were 1.9 and 1.4% in men and women, respectively. Conclusion: This study established Qatari adult-specific cut-off values of body fat for different age and gender groups.This research is funded by Qatar University. J.A. Tur is funded by CIBEROBN (CB12/03/30038), Instituto de salud Carlos III, Spain and European Regional Development Fun

Measurement of the lethal concentration of thyme essential oils in rainbow trout (Onchorhynchus mykiss)

The importance of the use of medicinal plants against infectious and non-infectious diseases is completely obvious. The replacement of synthetic drugs due to their multiple properties in the prevention and treatment of many diseases, particularly in the aquaculture industry seems to be very important. This study was performed with the aim of assessing the acute toxicity (LC_50-96) of thyme essential oil on rainbow trout. To study the effect of the essential oils, 80 premature rainbow trout with an average weight of 10±0.5 in 9-liter tanks were exposed to different concentrations of essential oils of thyme and daily losses based on OECD protocol were calculated during 96 hours. All the physical and chemical factors such as water temperature, dissolved oxygen, pH, nitrite, nitrate, ammonium levels, electrical conductivity and water hardness were measured in different treatments. The acute toxicity of the essential oil of thyme was calculated using probit analysis and a concentration of 4.4 ppm was determined

Evaluación de microcápsulas de ácido acetilsalicílico preparadas con eftalato de acetilcelulosa, etilcelulosa o sus mezclas, mediante una técnica de adición de emulsión no disolvente

El ácido acetilsalicílico (AAS) se encapsuló con eftalato de acetilcelulosa (EAC), etilcelulosa (EC) o sus mezclasmediante un método de adición de emulsión no disolvente. Se evaluaron los perfiles de liberación de AAS enmicrocápsulas preparadas en diversas proporciones de fármaco y polímero (10:1 y 4:1) y microcápsulas en comprimidosen un pH 1,2 ó 6. Los resultados mostraron que al reducir la proporción de fármaco respecto al polímero sereducía la velocidad de liberación. Las microcápsulas preparadas con EC presentaron el índice de liberación másbajo. Los estudios de liberación in vitro indicaron que la velocidad de liberación del fármaco disminuía tras lapreparación del comprimido, debido a la formación de una matriz no desintegrable. La liberación de AAS en un pH6 es significativamente mayor en todas las microcápsulas, incluso si se utiliza EC, que no es hidrosoluble. Esto sedebe probablemente a la mayor solubilidad del AAS en un pH 6, lo que indica la formación incompleta de la películaalrededor de las partículas de AAS. Los datos de liberación se examinaron cinéticamente y se calcularon los modelosideales para la liberación del fármaco. Los resultados mostraron que en las microcápsulas en comprimidos elcoeficiente de correlación más elevado se obtuvo con la liberación de orden cero. En las microcápsulas en comprimidosque contenían EAC o una mezcla de EAC y EC, la contribución de la erosión fue mayor que en las microcápsulasque no estaban en comprimidos

Evaluation of microcapsules of acetyl salicylic acid prepared with cellulose acetate phthalate, ethycellulose or their mixtures by an emulsion non-solvent addition technique

El ácido acetilsalicílico (AAS) se encapsuló con eftalato de acetilcelulosa (EAC), etilcelulosa (EC) o sus mezclas mediante un método de adición de emulsión no disolvente. Se evaluaron los perfiles de liberación de AAS en microcápsulas preparadas en diversas proporciones de fármaco y polímero (10:1 y 4:1) y microcápsulas en comprimidos en un pH 1,2 ó 6. Los resultados mostraron que al reducir la proporción de fármaco respecto al polímero se reducía la velocidad de liberación. Las microcápsulas preparadas con EC presentaron el índice de liberación más bajo. Los estudios de liberación in vitro indicaron que la velocidad de liberación del fármaco disminuía tras la preparación del comprimido, debido a la formación de una matriz no desintegrable. La liberación de AAS en un pH 6 es significativamente mayor en todas las microcápsulas, incluso si se utiliza EC, que no es hidrosoluble. Esto se debe probablemente a la mayor solubilidad del AAS en un pH 6, lo que indica la formación incompleta de la película alrededor de las partículas de AAS. Los datos de liberación se examinaron cinéticamente y se calcularon los modelos ideales para la liberación del fármaco. Los resultados mostraron que en las microcápsulas en comprimidos el coeficiente de correlación más elevado se obtuvo con la liberación de orden cero. En las microcápsulas en comprimidos que contenían EAC o una mezcla de EAC y EC, la contribución de la erosión fue mayor que en las microcápsulas que no estaban en comprimidos.Acetyl salicylic acid (ASA) was encapsulated with cellulose acetate phthalate (CAP), ethylcellulose (EC) or their mixtures by an emulsion non-solvent addition method. The release profiles of ASA from prepared microcapsules with different ratios of drug to polymer (10:1 and 4:1) and tableted microcapsules were evaluated at pH 1.2 or 6. The results showed that a reduction in the ratio of drug to polymer resulted in a reduction in release rate. The microcapsules prepared with EC showed the lowest release rate. The in vitro release studies showed that the drug release rate decreased after tableting, because of the formation of a non-disintegrating matrix. Release of ASA at pH 6 is significantly higher in all microcapsules, even when using EC which is not water soluble. This is probably due to higher solubility of ASA at pH 6 indicating incomplete film formation around the ASA particles. Release data were examined kinetically and the ideal kinetic models were estimated for drug release. The results showed that for tableted microcapsules the highest correlation coefficient was achieved with the zero-order release. For tableted microcapsules containing CAP or the mixture of CAP and EC contribution of erosion was higher than that of untableted microcapsules

Utjecaj različitih površinski aktivnih tvari i njihovih koncentracija na kontrolirano oslobađanje kaptoprila iz polimernih matriksa

Various methods are available to formulate water soluble drugs into sustained release dosage forms by retarding the dissolution rate. One of the methods used to control drug release and thereby prolong therapeutic activity is to use hydrophilic and lipophilic polymers. In this study, the effects of various polymers such as hydroxypropyl methylcellulose (HPMC), ethylcellulose (EC) and sodium carboxymethylcellulose (CMC) and surfactants (sodium lauryl sulphate, cetyltrimethylammonium bromide and Arlacel 60) on the release rate of captopril were investigated. The results showed that an increase in the amount of HPMC K15M resulted in reduction of the release rate of captopril from these matrices. When HPMC was partly replaced by NaCMC (the ratio of HPMC/NaCMC was 5:1), the release rate of the drug significantly decreased. However, there was no significant difference in release rate of captopril from matrices produced with ratios of 5:1 and 2:1 of HPMC/NaCMC. The presence of lactose in matrices containing HPMC and NaCMC increased the release rate of captopril. It was interesting to note that although partial replacement of HPMC by EC reduced the release rate of the drug (ratio of HPMC/EC 2:1), the release rate was increased when the ratio of HPMC/EC was reduced to 1:1. The effects of various surfactants on the release rate of captopril from HPMC/EC 1:1 matrices were also investigated. The results showed that the surfactants did not significantly change the release rate of the drug. Release data were examined kinetically and the ideal kinetic models were estimated for the drug release. The kinetic analysis of drug release data from various formulations showed that incorporation of surfactants in HPMC/EC matrices did not produce a zero-order release pattern.Postoje različite metode formuliranja vodotopljivih lijekova u dozirane ljekovite oblike s polaganim oslobađanjem. Jedan od načina postizanja kontroliranog otpuštanja, a prema tome i produljenog učinka je upotreba hidrofilnih i lipofilnih polimera. U ovom radu proučavan je utjecaj različitih polimera poput hidroksipropil metilceluloze (HPMC), etilceluloze (EC) i natrijeve soli karboksimetilceluloze (NaCMC) i površinski aktivnih tvari (natrijevog lauril-sulfata, cetiltrimetilamonijevog bromida i Arlacela 60) na oslobađanje kaptoprila. Rezultati pokazuju da povećanje količine HPMC K15M ima za posljedicu smanjenje oslobađanja kaptoprila iz matriksa. Ako se HPMC djelomično zamijeni s NaCMC (omjer HPMC/NaCMC 5:1), oslobađanje ljekovite tvari značajno se smanjuje. Međutim, nema značajne razlike u oslobađanju kaptoprila iz matriksa s omjerom HPMC/NaCMC 5:1 i 2:1. Prisutnost laktoze u matriksu koji sadrži HPMC i NaCMC povećalo je oslobađanje kaptoprila. Iako djelomična zamjena HPMC s EC smanjuje oslobađanje ljekovite tvari (omjer HPMC/EC 2:1), oslobađanje se povećava uz omjer HPMC/EC 1:1. Nadalje, ispitivan je utjecaj površinski aktivnih tvari na oslobađanje kaptoprila iz matriksa u kojima je omjer HPMC/EC (1:1). Može se zaključiti da površinski aktivne tvari ne utječu značajno na oslobađanje ljekovite tvari. U sklopu istraživanja određen je i kinetički model oslobađanja kaptoprila. Analiza kinetičkih podataka ukazuje da dodatak površinski aktivnih tvari u HPMC/EC matrikse ne slijedi kinetiku nultog reda

Multimodal Imaging in a Patient with Hemidystonia Responsive to GPi Deep Brain Stimulation

BACKGROUND: Dystonia is a syndrome with varied phenomenology but our understanding of its mechanisms is deficient. With neuroimaging techniques, such as fiber tractography (FT) and magnetoencephalography (MEG), pathway connectivity can be studied to that end. We present a hemidystonia patient treated with deep brain stimulation (DBS). METHODS: After 10 years of left axial hemidystonia, a 45-year-old male underwent unilateral right globus pallidus internus (GPi) DBS. Whole brain MEG before and after anticholinergic medication was performed prior to surgery. 26-direction diffusion tensor imaging (DTI) was obtained in a 3 T MRI machine along with FT. The patient was assessed before and one year after surgery by using the Burke-Fahn-Marsden Dystonia Rating Scale (BFMDRS). RESULTS: In the eyes-closed MEG study there was an increase in brain coherence in the gamma band after medication in the middle and inferior frontal region. FT demonstrated over 50% more intense ipsilateral connectivity in the right hemisphere compared to the left. After DBS, BFMDRS motor and disability scores both dropped by 71%. CONCLUSION: Multimodal neuroimaging techniques can offer insights into the pathophysiology of dystonia and can direct choices for developing therapeutics. Unilateral pallidal DBS can provide significant symptom control in axial hemidystonia poorly responsive to medication

Rapid Assessment of Fish Freshness for Multiple Supply-Chain Nodes Using Multi-Mode Spectroscopy and Fusion-Based Artificial Intelligence

This study is directed towards developing a fast, non-destructive, and easy-to-use handheld multimode spectroscopic system for fish quality assessment. We apply data fusion of visible near infra-red (VIS-NIR) and short wave infra-red (SWIR) reflectance and fluorescence (FL) spectroscopy data features to classify fish from fresh to spoiled condition. Farmed Atlantic and wild coho and chinook salmon and sablefish fillets were measured. Three hundred measurement points on each of four fillets were taken every two days over 14 days for a total of 8400 measurements for each spectral mode. Multiple machine learning techniques including principal component analysis, self-organized maps, linear and quadratic discriminant analyses, k-nearest neighbors, random forest, support vector machine, and linear regression, as well as ensemble and majority voting methods, were used to explore spectroscopy data measured on fillets and to train classification models to predict freshness. Our results show that multi-mode spectroscopy achieves 95% accuracy, improving the accuracies of the FL, VIS-NIR and SWIR single-mode spectroscopies by 26, 10 and 9%, respectively. We conclude that multi-mode spectroscopy and data fusion analysis has the potential to accurately assess freshness and predict shelf life for fish fillets and recommend this study be expanded to a larger number of species in the future

Multimodal Imaging in a Patient with Hemidystonia Responsive to GPi Deep Brain Stimulation

Background. Dystonia is a syndrome with varied phenomenology but our understanding of its mechanisms is deficient. With neuroimaging techniques, such as fiber tractography (FT) and magnetoencephalography (MEG), pathway connectivity can be studied to that end. We present a hemidystonia patient treated with deep brain stimulation (DBS). Methods. After 10 years of left axial hemidystonia, a 45-year-old male underwent unilateral right globus pallidus internus (GPi) DBS. Whole brain MEG before and after anticholinergic medication was performed prior to surgery. 26-direction diffusion tensor imaging (DTI) was obtained in a 3 T MRI machine along with FT. The patient was assessed before and one year after surgery by using the Burke-Fahn-Marsden Dystonia Rating Scale (BFMDRS). Results. In the eyes-closed MEG study there was an increase in brain coherence in the gamma band after medication in the middle and inferior frontal region. FT demonstrated over 50% more intense ipsilateral connectivity in the right hemisphere compared to the left. After DBS, BFMDRS motor and disability scores both dropped by 71%. Conclusion. Multimodal neuroimaging techniques can offer insights into the pathophysiology of dystonia and can direct choices for developing therapeutics. Unilateral pallidal DBS can provide significant symptom control in axial hemidystonia poorly responsive to medication

Decision making under incompleteness based on soft set theory

[EN]Decision making with complete and accurate information is ideal but infrequent. Unfortunately, in most cases the available infor- mation is vague, imprecise, uncertain or unknown. The theory of soft sets provides an appropriate framework for decision making that may be used to deal with uncertain decisions. The aim of this paper is to propose and analyze an effective algorithm for multiple attribute decision-making based on soft set theory in an incomplete information environment, when the distribution of incomplete data is unknown. This procedure provides an accurate solution through a combinatorial study of possible cases in the unknown data. Our theoretical development is complemented by practical examples that show the feasibility and implementability of this algorithm. Moreover, we review recent research on decision making from the standpoint of the theory of soft sets under incomplete information