Characterisation of CYP2C8, CYP2C9 and CYP2C19 polymorphisms in a Ghanaian population

<p>Abstract</p> <p>Background</p> <p>Genetic influences on drug efficacy and tolerability are now widely known. Pharmacogenetics has thus become an expanding field with great potential for improving drug efficacy and reducing toxicity. Many pharmacologically-relevant polymorphisms do show variability among different populations. Knowledge of allelic frequency distribution within specified populations can be useful in explaining therapeutic failures, identifying potential risk groups for adverse drug reactions (ADRs) and optimising doses for therapeutic efficacy. We sought to determine the prevalence of clinically relevant Cytochrome P450 (<it>CYP) 2C8</it>, <it>CYP2C9</it>, and <it>CYP2C19 </it>variants in Ghanaians. We compared the data with other ethnic groups and further investigated intra country differences within the Ghanaian population to determine its value to pharmacogenetics studies.</p> <p>Methods</p> <p>RFLP assays were used to genotype <it>CYP2C8 </it>(<it>*2</it>, <it>*3</it>, <it>*4</it>) variant alleles in 204 unrelated Ghanaians. <it>CYP2C9*2 </it>and <it>CYP2C19 </it>(<it>*2 </it>and <it>*3</it>) variants were determined by single-tube tetra-primer assays while <it>CYP2C9 </it>(<it>*3, *4, *5 </it>and <it>*11</it>) variants were assessed by direct sequencing.</p> <p>Results</p> <p>Allelic frequencies were obtained for <it>CYP2C8*2 </it>(17%), <it>CYP2C8*3 </it>(0%), <it>CYP2C8*4 </it>(0%), <it>CYP2C9*2 </it>(0%), <it>CYP2C9*3 </it>(0%), <it>CYP2C9*4 </it>(0%), <it>CYP2C9</it>*5 (0%), <it>CYP2C9*11 </it>(2%), <it>CYP2C19*2 </it>(6%) and <it>CYP2C19*3 </it>(0%).</p> <p>Conclusion</p> <p>Allele frequency distributions for <it>CYP2C8</it>, <it>CYP2C9 </it>and <it>CYP2C19 </it>among the Ghanaian population are comparable to other African ethnic groups but significantly differ from Caucasian and Asian populations. Variant allele frequencies for <it>CYP2C9 </it>and <it>CYP2C19 </it>are reported for the first time among indigenous Ghanaian population.</p

Response of rice cultivars to phosphorus supply on an oxisol.

Genotypic differences in absorption or utilization of P might be exploited to improve efficiency of fertilizer use or to obtain higher productivity on P-deficient soils. The objective of this study was to evaluate responses by 75 genotypes of upland rice (Oryza sativa L.) to two soil P levels in two field experiments. In the first experiment, soil P levels (Mehlich 1) were 1.5 mg kg-1 and 5 mg kg-1, and in the second experiment, 3 mg kg-1 and 4.7 mg kg-1 of soil, respectively. Rice cultivars differed significantly in shoot dry matter production at flowering, grain yield, and plant P status. Based on a grain yield efficiency index, cultivars were classified as P-efficient or P-inefficient. Shoot dry matter was more sensitive to P-deficiency but was not related to grain yield. Phosphorus use efficiency was higher under the low P treatment. Phosphorus uptake was significantly correlated with dry matter, P concentration and P-efficiency ratio. Results of this study indicate that genetic differences in P-use efficiency exist among upland rice cultivars and may be exploited in breeding programs

Cervical lymph node metastasis in adenoid cystic carcinoma of the larynx: a collective international review

Adenoid cystic carcinoma (AdCC) of the head and neck is a well-recognized pathologic entity that rarely occurs in the larynx. Although the 5-year locoregional control rates are high, distant metastasis has a tendency to appear more than 5 years post treatment. Because AdCC of the larynx is uncommon, it is difficult to standardize a treatment protocol. One of the controversial points is the decision whether or not to perform an elective neck dissection on these patients. Because there is contradictory information about this issue, we have critically reviewed the literature from 1912 to 2015 on all reported cases of AdCC of the larynx in order to clarify this issue. During the most recent period of our review (1991-2015) with a more exact diagnosis of the tumor histology, 142 cases were observed of AdCC of the larynx, of which 91 patients had data pertaining to lymph node status. Eleven of the 91 patients (12.1%) had nodal metastasis and, based on this low proportion of patients, routine elective neck dissection is therefore not recommended

Differential gene expression in male and female rainbow trout embryos prior to the onset of gross morphological differentiation of the gonads

<p>Abstract</p> <p>Background</p> <p>There are large differences between the sexes at the genetic level; these differences include heterogametic sex chromosomes and/or differences in expression of genes between the sexes. In rainbow trout (<it>Oncorhynchus mykiss</it>) qRT-PCR studies have found significant differences in expression of several candidate sex determining genes. However, these genes represent a very small fraction of the genome and research in other species suggests there are large portions of the transcriptome that are differentially expressed between the sexes. These differences are especially noticeable once gonad differentiation and maturation has occurred, but less is known at earlier stages of development. Here we use data from a microarray and qRT-PCR to identify genes differentially expressed between the sexes at three time points in pre-hatch embryos, prior to the known timing of sexual differentiation in this species.</p> <p>Results</p> <p>The microarray study revealed 883 differentially expressed features between the sexes with roughly equal numbers of male and female upregulated features across time points. Most of the differentially expressed genes on the microarray were not related to sex function, suggesting large scale differences in gene expression between the sexes are present early in development. Candidate gene analysis revealed <it>sox9</it>, <it>DMRT1</it>, <it>Nr5a1 </it>and <it>wt1 </it>were upregulated in males at some time points and <it>foxl2</it>, <it>ovol1</it>, <it>fst </it>and <it>cyp19a1a </it>were upregulated in females at some time points.</p> <p>Conclusion</p> <p>This is the first study to identify sexual dimorphism in expression of the genome during embryogenesis in any fish and demonstrates that transcriptional differences are present before the completion of gonadogenesis.</p

Genus Paracoccidioides: Species Recognition and Biogeographic Aspects

Background: Paracoccidioidomycosis is a systemic mycosis caused by Paracoccidioides brasiliensis (species S1, PS2, PS3), and Paracoccidioides lutzii. This work aimed to differentiate species within the genus Paracoccidioides, without applying multilocus sequencing, as well as to obtain knowledge of the possible speciation processes. Methodology/Principal Findings: Single nucleotide polymorphism analysis on GP43, ARF and PRP8 intein genes successfully distinguished isolates into four different species. Morphological evaluation indicated that elongated conidia were observed exclusively in P. lutzii isolates, while all other species (S1, PS2 and PS3) were indistinguishable. To evaluate the biogeographic events that led to the current geographic distribution of Paracoccidioides species and their sister species, Nested Clade and Likelihood Analysis of Geographic Range Evolution (LAGRANGE) analyses were applied. The radiation of Paracoccidioides started in northwest South America, around 11–32 million years ago, as calculated on the basis of ARF substitution rate, in the BEAST program. Vicariance was responsible for the divergence among S1, PS2 and P. lutzii and a recent dispersal generated the PS3 species, restricted to Colombia. Taking into account the ancestral areas revealed by the LAGRANGE analysis and the major geographic distribution of L. loboi in the Amazon basin, a region strongly affected by the Andes uplift and marine incursions in the Cenozoic era, we also speculate about the effect of these geological events on the vicariance between Paracoccidioides and L. loboi. Conclusions/Significance: The use of at least 3 SNPs, but not morphological criteria, as markers allows us to distinguish among the four cryptic species of the genus Paracoccidioides. The work also presents a biogeographic study speculating on how these species might have diverged in South America, thus contributing to elucidating evolutionary aspects of the genus Paracoccidioides

Comparing the transcriptomes of embryos from domesticated and wild Atlantic salmon (Salmo salar L.) stocks and examining factors that influence heritability of gene expression

Background&nbsp; Due to selective breeding, domesticated and wild Atlantic salmon are genetically diverged, which raises concerns about farmed escapees having the potential to alter the genetic composition of wild populations and thereby disrupting local adaptation. Documenting transcriptional differences between wild and domesticated stocks under controlled conditions is one way to explore the consequences of domestication and selection. We compared the transcriptomes of wild and domesticated Atlantic salmon embryos, by using a custom 44k oligonucleotide microarray to identify perturbed gene pathways between the two stocks, and to document the inheritance patterns of differentially-expressed genes by examining gene expression in their reciprocal hybrids.&nbsp; Results&nbsp; Data from 24 array interrogations were analysed: four reciprocal cross types (W♀&times;W♂, D♀&times;W♂; W♀&times;D♂, D♀&times;D♂)&times;six biological replicates. A common set of 31,491 features on the microarrays passed quality control, of which about 62% were assigned a KEGG Orthology number. A total of 6037 distinct genes were identified for gene-set enrichment/pathway analysis. The most highly enriched functional groups that were perturbed between the two stocks were cellular signalling and immune system, ribosome and RNA transport, and focal adhesion and gap junction pathways, relating to cell communication and cell adhesion molecules. Most transcripts that were differentially expressed between the stocks were governed by additive gene interaction (33 to 42%). Maternal dominance and over-dominance were also prevalent modes of inheritance, with no convincing evidence for a stock effect.&nbsp; Conclusions&nbsp; Our data indicate that even at this relatively early developmental stage, transcriptional differences exist between the two stocks and affect pathways that are relevant to wild versus domesticated environments. Many of the identified differentially perturbed pathways are involved in organogenesis, which is expected to be an active process at the eyed egg stage. The dominant effects are more largely due to the maternal line than to the origin of the stock. This finding is particularly relevant in the context of potential introgression between farmed and wild fish, since female escapees tend to have a higher spawning success rate compared to males

Overview of biologically digested leachate treatment using adsorption

Biological process is effective in treating most biodegradable organic matter present in leachate; however, a significant amount of ammonia, metals and refractory organic compounds may still remain in this biologically digested leachate. This effluent cannot be released to receiving bodies until the discharge limit is met. Several physical/chemical processes have been practiced as post-treatment to remove the remaining pollutants including coagulation–flocculation, oxidation and adsorption. Adsorption is often applied in leachate treatment as it enhances removal of refractory organic compounds. This chapter will focus on works related to adsorption as one of the commonly used methods to treat biologically digested leachate further down to acceptable discharge limit