Genetic contribution of SCARB1 variants to lipid traits in African Blacks: A candidate gene association study

Background: High-density lipoprotein cholesterol (HDL-C) exerts many anti-atherogenic properties including its role in reverse cholesterol transport (RCT). Scavenger receptor class B member 1 (SCARB1) plays a key role in RCT by selective uptake of HDL cholesteryl esters. We aimed to explore the genetic contribution of SCARB1 to affecting lipid levels in African Blacks from Nigeria. Methods: We resequenced 13 exons and exon-intron boundaries of SCARB1 in 95 individuals with extreme HDL-C levels using Sanger method. Then, we genotyped 147 selected variants (78 sequence variants, 69 HapMap tagSNPs, and 2 previously reported relevant variants) in the entire sample of 788 African Blacks using either the iPLEX Gold or TaqMan methods. A total of 137 successfully genotyped variants were further evaluated for association with major lipid traits. Results: The initial gene-based analysis demonstrated evidence of association with HDL-C and apolipoprotein A-I (ApoA-I). The follow-up single-site analysis revealed nominal evidence of novel associations of nine common variants with HDL-C and/or ApoA-I (P < 0.05). The strongest association was between rs11057851 and HDL-C (P = 0.0043), which remained significant after controlling for multiple testing using false discovery rate. Rare variant association testing revealed a group of 23 rare variants (frequencies ≤1 %) associated with HDL-C (P = 0.0478). Haplotype analysis identified four SCARB1 regions associated with HDL-C (global P < 0.05). Conclusions: To our knowledge, this is the first report of a comprehensive association study of SCARB1 variations with lipid traits in an African Black population. Our results showed the consistent association of SCARB1 variants with HDL-C across various association analyses, supporting the role of SCARB1 in lipoprotein-lipid regulatory mechanism

Comprehensive evaluation of the association of APOE genetic variation with plasma lipoprotein traits in U.S. Whites and African Blacks

Although common APOE genetic variation has a major influence on plasma LDL-cholesterol, its role in affecting HDL-cholesterol and triglycerides is not well established. Recent genome-wide association studies suggest that APOE also affects plasma variation in HDL-cholesterol and triglycerides. It is thus important to resequence the APOE gene to identify both common and uncommon variants that affect plasma lipid profile. Here, we have sequenced the APOE gene in 190 subjects with extreme HDL-cholesterol levels selected from two well-defined epidemiological samples of U.S. non-Hispanic Whites (NHWs) and African Blacks followed by genotyping of identified variants in the entire datasets (623 NHWs, 788 African Blacks) and association analyses with major lipid traits. We identified a total of 40 sequence variants, of which 10 are novel. A total of 32 variants, including common tagSNPs (≥5% frequency) and all uncommon variants (<5% frequency) were successfully genotyped and considered for genotype-phenotype associations. Other than the established associations of APOE∗2 and APOE∗4 with LDL-cholesterol, we have identified additional independent associations with LDL-cholesterol. We have also identified multiple associations of uncommon and common APOE variants with HDL-cholesterol and triglycerides. Our comprehensive sequencing and genotype-phenotype analyses indicate that APOE genetic variation impacts HDL-cholesterol and triglycerides in addition to affecting LDL-cholesterol

Study of genetic diversity in Sudanese sesame (Sesamum indicum L.) germplasm using random amplified polymorphic DNA (RAPD) markers

The random amplified polymorphic DNA (RAPD) markers were used to assess genetic diversity in Sesame indicum (L.). RAPD technique was carried out in a set of 10 sesame germplasm collected from different regions of Sudan. A total of 64 polymorphisms (6.4 polymorphic markers per primer) out of 75 reproducible products (7.5 fragments per primer) were obtained from the 10 primers used. The number of bands per primer ranged from 4 to 13, whereas the number of polymorphic bands ranged from 3 to12, corresponding to 66.6% of the amplification products. Low level of genetic similarity was observed in the collected accessions. Unique bands were observed with the 10 primers. UPGMA clustering resulted in two major groups

A novel Ph-sensitive liposome to trigger delivery of afatinib to cancer cells: Impact on lung cancer therapy

A novel drug delivery system based on cationic (CL) and pH-sensitive liposomes (PSL) for tyrosine kinase inhibitor afatinib (AFT) were developed to enhance tumor-targetability against NSCLC cells and therapeutic effect. Optimal lipid to drug ratio was selected to prepare AFT-loaded PSL and CL with desirable physiochemical properties based on particle size, drug encapsulation efficiency (EE%), stability and release profiles. Moreover, antitumor activity was performed in vitro on human lung cancer cells (H-1975) using a WST-1 assay and Annexin-V apoptosis assay. The mean particle size of the liposomes was less than 100 nm, and EE% was more than 50% with lipid to drug ratio of 1:0.5. Stability data showed that PSL and CL were physically stable for 1 months at 4 and 25oC. In vitro drug release study demonstrated the sustained release of AFT at pH 7.5; while PSL exhibited fast drug release in pH 5.5. This effect revealed that PSL showed pH-sensitive release behaviors. In addition, the in vitro cytotoxicity study was employed for AFT-loaded PSL due to optimal characterizations. Thus, in vitro anticancer activity revealed that AFT loaded-PSL triggered apoptosis in H-1975 cells. In addition, the inhibitory effect towards H-1975 and HCC-827 was observed, indicating, which indicated high antitumor activity of AFT-loaded PSL. Then, PSL might potentially create practical clinical strategies for better targetability and delivery of AFT for treatment of lung cancer

A Novel Nano-Hydroxyapatite Agarose-Based Hydrogel for Biomimetic Remineralization of Demineralized Human Enamel: An in-vitro Study

Sara El Moshy,1 Israa Ahmed Radwan,1 Manal Matoug-Elwerfelli,2 Ahmed Abdou,3 Marwa MS Abbass1 1Oral Biology Department, Faculty of Dentistry, Cairo University, Cairo, Egypt; 2Pre-clinical Oral Sciences Department, College of Dental Medicine, QU Health, Qatar University, Doha, Qatar; 3Department of Restorative Dentistry, Faculty of Dentistry, Universiti Malaya, Kuala Lumpur, MalaysiaCorrespondence: Manal Matoug-Elwerfelli, College of Dental Medicine, QU Health, Qatar University, Doha, Qatar, Tel +974 44037316, Email [email protected]: This study aims to investigate the biomimetic effect of agarose hydrogel loaded with enamel matrix derivative (EMD-agarose) alone or in combination with nano-hydroxyapatite (n-HA-EMD-agarose) on the remineralization of human demineralized enamel.Methods: Extracted human mandibular third molars were sectioned into 54 buccal and lingual halves. Acid-resistant nail varnish was applied to each half, except for two enamel windows. Enamel surface microhardness, energy-dispersive X-ray spectroscopy (EDX), and scanning electron microscopy (SEM) analyses were conducted to evaluate enamel surfaces at baseline, following demineralization with 37% phosphoric acid, and after each hydrogel application and remineralization for two, four, and six days. Remineralization was performed using a phosphate solution at 37°C.Results: At day 6 following remineralization, a statistically significant higher mean microhardness was recorded in n-HA-EMD-agarose hydrogel (260.87 ± 3.52) as compared to EMD-agarose hydrogel (244.63 ± 2.76) (p = 0.027). Similarly, n-HA-EMD-agarose hydrogel showed a higher mean calcium (46.31 ± 2.78), phosphorous (24.92 ± 0.826), and fluoride (0.909 ± 0.053) weight percentage compared to EMD-agarose hydrogel calcium (19.64 ± 1.092), phosphorous (19.64 ± 1.092), and fluoride (0.7033 ± 0.0624) weight percentage (p < 0.05). Further, SEM analysis revealed a substantial deposition of n-HA following the application of the n-HA-EMD-agarose hydrogel, whereas the EMD-agarose exhibited a relatively smooth enamel surface with less visible enamel rods due to mineral deposition.Conclusion: The combined n-HA-EMD-agarose hydrogel demonstrated improved surface microhardness of the remineralized enamel and enhanced mineral content deposition, indicating its potential as a biomimetic approach for dental enamel repair.Keywords: agarose hydrogel, biomimetic, enamel matrix derivatives, nano-hydroxy apatite, remineralizatio

Population‐based cohort study of outcomes following cholecystectomy for benign gallbladder diseases

Background The aim was to describe the management of benign gallbladder disease and identify characteristics associated with all‐cause 30‐day readmissions and complications in a prospective population‐based cohort. Methods Data were collected on consecutive patients undergoing cholecystectomy in acute UK and Irish hospitals between 1 March and 1 May 2014. Potential explanatory variables influencing all‐cause 30‐day readmissions and complications were analysed by means of multilevel, multivariable logistic regression modelling using a two‐level hierarchical structure with patients (level 1) nested within hospitals (level 2). Results Data were collected on 8909 patients undergoing cholecystectomy from 167 hospitals. Some 1451 cholecystectomies (16·3 per cent) were performed as an emergency, 4165 (46·8 per cent) as elective operations, and 3293 patients (37·0 per cent) had had at least one previous emergency admission, but had surgery on a delayed basis. The readmission and complication rates at 30 days were 7·1 per cent (633 of 8909) and 10·8 per cent (962 of 8909) respectively. Both readmissions and complications were independently associated with increasing ASA fitness grade, duration of surgery, and increasing numbers of emergency admissions with gallbladder disease before cholecystectomy. No identifiable hospital characteristics were linked to readmissions and complications. Conclusion Readmissions and complications following cholecystectomy are common and associated with patient and disease characteristics

Alternative phenotypes of male mating behaviour in the two-spotted spider mite

Severe intraspecific competition for mates selects for aggressive individuals but may also lead to the evolution of alternative phenotypes that do not act aggressively, yet manage to acquire matings. The two-spotted spider mite, Tetranychus urticae, shows male mate-guarding behaviour and male–male combat for available females. This may provide opportunity for weaker males to avoid fighting by adopting alternative mating behaviour such as sneaker or satellite tactics as observed in other animals. We investigated male precopulatory behaviour in the two-spotted spider mite by means of video-techniques and found three types of male mating behaviour: territorial, sneaker and opportunistic. Territorial and sneaker males associate with female teleiochrysales and spend much time guarding them. Territorial males are easily disturbed by rival males and engage themselves in fights with them. However, sneaker males are not at all disturbed by rival males, never engage in fights and, strikingly, never face attack by territorial males. Opportunistic males wander around in search of females that are in the teleiochrysalis stage but very close to or at emergence. To quickly classify any given mate-guarding male as territorial or sneaker we developed a method based on the instantaneous response of males to disturbance by a live male mounted on top of a brush. We tested this method against the response of the same males to natural disturbance by two or three other males. Because this method proved to be successful, we used it to collect territorial and sneaker males, and subjected them to morphological analysis to assess whether the various behavioural phenotypes are associated with different morphological characters. However, we found no statistical differences between territorial and sneaker males, concerning the length of the first legs, the stylets, the pedipalps or the body. ELECTRONIC SUPPLEMENTARY MATERIAL: The online version of this article (doi:10.1007/s10493-013-9673-y) contains supplementary material, which is available to authorized users