Enzymatic and genetic polymorphisms of paraoxonase- 1 in the Gabonese population: The relation to lipid parameters in patients with diabetes

Background: The objective was to study the relationship between the paraoxonase-1 activity, genetic polymorphisms and lipid parameters in a black patient population.Method: This study investigates patients with type 2 diabetes and hypertension for which concentrations of total high-density lipoprotein (HDL) and low-density lipoprotein (LDL) cholesterol, triglycerides, apolipoprotein AI, apolipoprotein B100, the latency time of oxidation of small and dense LDL, arylesterase activity and genetic polymorphism of paraoxonase-1 at positions T(-107)C, L55M and Q192R were determined and compared to healthy subjects.Results: Concerning the T(-107C) polymorphism, the -107T allele is higher in healthy subjects (0.325) than in those with diabetes (0.660). This was the same for the 55M allele, whereas the -107C allele was lower in healthy patients (0.675) than in patients with diabetes (0.340). Paraoxonase-1 activity was lower in patients with diabetes than in healthy subjects, irrespective of genotype. The -107CC genotypes had higher HDL cholesterol AI apolipoprotein I concentrations than -107TT in the control group (p-value = 0.0001), patients with diabetes (p-value = 0.002), and patients with hyptertension (p-value = 0.001). This result was also obtained with the 55LL genotype.Conclusion: The prevalence of paraoxonase-1 alleles associated with lesser enzyme activities was found to be more common in patients with diabetes than in the control group. Possibly, this genetic distribution contributes to the high cardiovascular risk that is observed in certain black patients, compared to that in white patients

The relationship between CSF tau markers, hippocampal volume and delayed primacy performance in cognitively intact elderly individuals.

BACKGROUND: Primacy performance in recall has been shown to predict cognitive decline in cognitively intact elderly, and conversion from mild cognitive impairment (MCI) to Alzheimer's disease (AD). Delayed primacy performance, but not delayed non-primacy performance, has been shown to be associated with hippocampal volume in cognitively intact older individuals. Since presence of neurofibrillary tangles is an early sign of AD-related pathology, we set out to test whether cerebrospinal fluid (CSF) levels of tau had an effect on delayed primacy performance, while controlling for hippocampal volume and CSF Aβ 1-42 levels. METHODS: Forty-seven individuals, 60 or older and cognitively intact, underwent a multi-session study including lumbar puncture, an MRI scan of the head and memory testing. RESULTS: Our regression analyses show that CSF levels of hyperphosphorylated (P) tau are only associated with reduced delayed primacy performance when hippocampal volumes are smaller. CONCLUSION: Our findings suggest that hippocampal size may play a protective role against the negative effects of P tau on memory

Loss of SRY-box2 (SOX2) expression and its impact on survival of patients with oesophageal adenocarcinoma.

BACKGROUND: Oesophageal adenocarcinoma (OAC) is a highly aggressive malignancy with poor survival, which is highly variable amongst patients with comparable conventional prognosticators. Therefore molecular biomarkers are urgently needed to improve the prediction of survival in these patients. SRY (sex determining region Y)-box 2, also known as SOX2, is a transcription factor involved in embryonal development of the gastrointestinal tract as well as in carcinogenesis. The purpose of this study was to see whether SOX2 expression is associated with survival in patients with OAC. METHODS: SOX2 was studied by immunohistochemistry in patients who had undergone potentially curative oesophagectomy for adenocarcinoma. Protein expression of SOX2 was evaluated using tissue microarrays from resection specimens, and results were analysed in relation to the clinical data by Cox regression analysis. SOX2 was evaluated in two independent OAC cohorts (Rotterdam cohort and a multicentre UK cohort). RESULTS: Loss of SOX2 expression was independently predictive of adverse overall survival in the multivariable analysis, adjusted for known factors influencing survival, in both cohorts (Rotterdam cohort: hazard ratio (HR) 1·42, 95 per cent c.i. 1·07 to 1·89, P = 0·016; UK cohort: HR 1·54, 1·08 to 2·19, P = 0·017). When combined with clinicopathological staging, loss of SOX2 showed an increased effect in patients with pT1-2 tumours (P = 0·010) and node-negative OAC (P = 0·038), with an incrementally adverse effect on overall survival for stage I OAC with SOX2 loss (HR 3·18, 1·18 to 8·56; P = 0·022). CONCLUSION: SOX2 is an independent prognostic factor for long-term survival in OAC, especially in patients with stage I OAC

Wood mitigates the effect of hydropeaking scour on periphyton biomass and nutritional quality in semi-natural flume simulations

The daily fluctuating discharge from hydroelectric power plants, known as hydropeaking, has been shown to cause catastrophic drift in aquatic insect communities and limit secondary production, but relatively little attention has been given to its effects on periphyton, an important food resource for consumers. We simulated daily 5-h hydropeaking events over the course of 5 days in spring and summer in an open air, experimental flume system fed by a pristine 2nd order stream in the Italian Alps. We hypothesized that hydropeaking would suppress periphyton biomass and especially nutritional quality (i.e., fatty acid content). Hydropeaking resulted in decreased periphyton Chl-a and AFDM on tiles, but there was no corresponding loss on wood. Hydropeaking did not alter periphyton elemental nutrient stoichiometry but led to a disproportionate loss of periphyton fatty acid content on both substrates. Ordination of overall fatty acid profiles indicated different periphyton fatty acid profiles by substrate and a shift from physiologically important highly-unsaturated fatty acids to non-essential saturated fatty acids after hydropeaking. These results suggest that hydropeaking may have the potential to depress primary biomass and nutritional quality in downstream ecosystems, and that availability of wood substrate may mitigate part, but not all, of this effect. Since food nutritional quality, especially fatty acid content, has been suggested to be a limiting resource on production in aquatic systems, this may generate an indirect and potentially overlooked limiting effect on aquatic consumers in hydropeaking-impacted alpine rivers

"Particle Informatics": Advancing Our Understanding of Particle Properties through Digital Design

We introduce a combination of existing and novel approaches to the assessment and prediction of particle properties intrinsic to the formulation and manufacture of pharmaceuticals. Naturally following on from established solid form informatics methods, we return to the drug lamotrigine, re-evaluating its context in the Cambridge Structural Database (CSD). We then apply predictive digital design tools built around the CSD-System suite of software, including Synthonic Engineering methods that focus on intermolecular interaction energies, to analyze and understand important particle properties and their effects on several key stages of pharmaceutical manufacturing. We present a new, robust workflow that brings these approaches together to build on the knowledge gained from each step and explain how this knowledge can be combined to provide resolutions at decision points encountered during formulation design and manufacturing processes

Genetic diversity of Brazilian isolates of feline immunodeficiency virus

We isolated Feline immunodeficiency virus (FIV) from three adult domestic cats, originating from two open shelters in Brazil. Viruses were isolated from PBMC following co-cultivation with the feline T-lymphoblastoid cell line MYA-1. All amplified env gene products were cloned directly into pGL8MYA. The nucleic acid sequences of seven clones were determined and then compared with those of previously described isolates. The sequences of all of the Brazilian virus clones were distinct and phylogenetic analysis revealed that all belong to subtype B. Three variants isolated from one cat and two variants were isolated from each of the two other cats, indicating that intrahost diversity has the potential to pose problems for the treatment and diagnosis of FIV infection

Expression quantitative trait loci are highly sensitive to cellular differentiation state

Blood cell development from multipotent hematopoietic stem cells to specialized blood cells is accompanied by drastic changes in gene expression for which the triggers remain mostly unknown. Genetical genomics is an approach linking natural genetic variation to gene expression variation, thereby allowing the identification of genomic loci containing gene expression modulators (eQTLs). In this paper, we used a genetical genomics approach to analyze gene expression across four developmentally close blood cell types collected from a large number of genetically different but related mouse strains. We found that, while a significant number of eQTLs (365) had a consistent “static” regulatory effect on gene expression, an even larger number were found to be very sensitive to cell stage. As many as 1,283 eQTLs exhibited a “dynamic” behavior across cell types. By looking more closely at these dynamic eQTLs, we show that the sensitivity of eQTLs to cell stage is largely associated with gene expression changes in target genes. These results stress the importance of studying gene expression variation in well-defined cell populations. Only such studies will be able to reveal the important differences in gene regulation between different ce