Characterization of Diclofenac Liposomes Formulated with Palm Oil Fractions

Purpose: To characterize diclofenac sodium (DS) liposomes prepared using palm oil fractions.Methods: Reverse-phase evaporation method was used to prepare liposomes containing 10, 20, 30 , 40 or 50% palm oil fractions. The effect of palm oil content on liposome formation, surface morphology, shape, size and zeta potential of the liposomes were studied using scanning electron microscopy (SEM) transmission electron microscopy (TEM) and particle analyzer. Drug loading, entrapment efficiency and in vitro drug release were measured in phosphate-buffered saline (PBS, pH 7.4) by UV spectrophotometry.Results: TEM and SEM images showed formation of liposomes for all formulations, However, increase in the proportion of palm oil in the formulations significantly reduced particle size and increased zeta potential. The effect on drug loading and drug release varied with palm oil fraction. The best release pattern with appropriate entrapment efficiency and stability was obtained with liposomes containing 33 % palm oil fraction. Introduction of 46 and 56 % of palm oil fractions yielded zeta potential of -42.8 and - 50.7 mV, respectively, compared with -31.2 mV for the formulation without palm oil.Conclusion: The results demonstrate the potentials of palm oil fractions in the preparation of suitable DS liposomes with good bioavailability.Keywords: Liposome, Drug delivery, Palm oil, Diclofenac

Population Genetic Study of the Brain-Derived Neurotrophic Factor (BDNF) Gene

Genetic variants in the brain-derived neurotrophic factor (BDNF) gene, predominantly the functional Val66Met polymorphism, have been associated with risk of bipolar disorder and other psychiatric disorders. However, not all studies support these findings, and overall the evidence for the association of BDNF with disease risk is weak. As differences in population genetic structure between patient samples could cause discrepant or spurious association results, we investigated this possibility by carrying out population genetic analyses of the BDNF genomic region. Substantial variation was detected in BDNF coding region single-nucleotide polymorphism (SNP) allele and haplotype frequencies between 58 global populations, with the derived Met allele of Val66Met ranging in frequency from 0 to 72% across populations. FST analyses to assess diversity in the HapMap populations determined that the Val66Met FST value was at the 99.8th percentile among all SNPs in the genome. As the BDNF population genetic differences may be due to local selection, we performed the long-range haplotype test for selection using 68 SNPs spanning the BDNF genomic region in 12 European-derived pedigrees. Evidence for positive selection was found for a high-frequency Val-carrying haplotype, with a relative extended haplotype homozygosity value above the 99th percentile compared with HapMap data $(P=4.6 \times 10^{−4})$. In conclusion, we observed considerable BDNF allele and haplotype diversity among global populations and evidence for positive selection at the BDNF locus. These phenomena can have a profound impact on the detection of disease susceptibility genes and must be considered in gene association studies of BDNF.Organismic and Evolutionary BiologyOther Research Uni

Genetic Signatures of Strong Recent Positive Selection at the Lactase Gene

In most human populations, the ability to digest lactose contained in milk usually disappears in childhood, but in European-derived populations, lactase activity frequently persists into adulthood (Scrimshaw and Murray 1988). It has been suggested (Cavalli-Sforza 1973; Hollox et al. 2001; Enattah et al. 2002; Poulter et al. 2003) that a selective advantage based on additional nutrition from dairy explains these genetically determined population differences (Simoons 1970; Kretchmer 1971; Scrimshaw and Murray 1988; Enattah et al. 2002), but formal population-genetics–based evidence of selection has not yet been provided. To assess the population-genetics evidence for selection, we typed 101 single-nucleotide polymorphisms covering 3.2 Mb around the lactase gene. In northern European–derived populations, two alleles that are tightly associated with lactase persistence (Enattah et al. 2002) uniquely mark a common (∼77%) haplotype that extends largely undisrupted for >1 Mb. We provide two new lines of genetic evidence that this long, common haplotype arose rapidly due to recent selection: (1) by use of the traditional FST measure and a novel test based on pexcess, we demonstrate large frequency differences among populations for the persistence-associated markers and for flanking markers throughout the haplotype, and (2) we show that the haplotype is unusually long, given its high frequency—a hallmark of recent selection. We estimate that strong selection occurred within the past 5,000–10,000 years, consistent with an advantage to lactase persistence in the setting of dairy farming; the signals of selection we observe are among the strongest yet seen for any gene in the genome

Combining genomics and epidemiology to track mumps virus transmission in the United States.

Unusually large outbreaks of mumps across the United States in 2016 and 2017 raised questions about the extent of mumps circulation and the relationship between these and prior outbreaks. We paired epidemiological data from public health investigations with analysis of mumps virus whole genome sequences from 201 infected individuals, focusing on Massachusetts university communities. Our analysis suggests continuous, undetected circulation of mumps locally and nationally, including multiple independent introductions into Massachusetts and into individual communities. Despite the presence of these multiple mumps virus lineages, the genomic data show that one lineage has dominated in the US since at least 2006. Widespread transmission was surprising given high vaccination rates, but we found no genetic evidence that variants arising during this outbreak contributed to vaccine escape. Viral genomic data allowed us to reconstruct mumps transmission links not evident from epidemiological data or standard single-gene surveillance efforts and also revealed connections between apparently unrelated mumps outbreaks

Different level of population differentiation among human genes

<p>Abstract</p> <p>Background</p> <p>During the colonization of the world, after dispersal out of African, modern humans encountered changeable environments and substantial phenotypic variations that involve diverse behaviors, lifestyles and cultures, were generated among the different modern human populations.</p> <p>Results</p> <p>Here, we study the level of population differentiation among different populations of human genes. Intriguingly, genes involved in osteoblast development were identified as being enriched with higher <it>F</it>_STSNPs, a result consistent with the proposed role of the skeletal system in accounting for variation among human populations. Genes involved in the development of hair follicles, where hair is produced, were also found to have higher levels of population differentiation, consistent with hair morphology being a distinctive trait among human populations. Other genes that showed higher levels of population differentiation include those involved in pigmentation, spermatid, nervous system and organ development, and some metabolic pathways, but few involved with the immune system. Disease-related genes demonstrate excessive SNPs with lower levels of population differentiation, probably due to purifying selection. Surprisingly, we find that Mendelian-disease genes appear to have a significant excessive of SNPs with high levels of population differentiation, possibly because the incidence and susceptibility of these diseases show differences among populations. As expected, microRNA regulated genes show lower levels of population differentiation due to purifying selection.</p> <p>Conclusion</p> <p>Our analysis demonstrates different level of population differentiation among human populations for different gene groups.</p