Are Frontal Cognitive and Atrophy Patterns Different in PSP and bvFTD? A Comparative Neuropsychological and VBM Study

Progressive supranuclear palsy (PSP) and frontotemporal lobar degeneration (FTD) are two clinicohistological entities that share a severe prefrontal syndrome. To what extent do the cognitive syndrome and the location of the underlying brain atrophy unify or segregate these entities? Here, we examined the clinical and radiological patterns of frontal involvement and the neural bases of the cognitive dysfunctions observed in the Richardson form of PSP and the behavioral variant of FTD (bvFTD). The cognitive profile and grey and white matter volume of PSP (n = 19) and bvFTD (n = 16) patients and control participants (n = 18) were compared using a standard battery of neuropsychological tests and voxel-based morphometry (VBM), respectively. Analyses of correlations between neuropsychological and morphometric data were additionally performed. The severity and qualitative pattern of cognitive dysfunction was globally similar between the two patient groups. Grey matter volume was decreased in widespread frontal areas and in the temporal uncus in bvFTD, while it was decreased in the frontal and temporal lobes as well as in the thalamus in PSP. We also found an unexpected involvement of the frontal rectal gyrus in PSP patients compared to controls. Correlation analyses yielded different results in the two groups, with no area showing significant correlations in PSP patients, while several frontal and some temporal areas did so in bvFTD patients. In spite of minor neuropsychological and morphological differences, this study shows that the patterns of cognitive dysfunction and atrophy are very similar in PSP and bvFTD. However, executive dysfunction in these diseases may stem from partially divergent cortical and subcortical neural circuits.     

FRAX?: Prediction of Major Osteoporotic Fractures in Women from the General Population: The OPUS Study

Purposes

The aim of this study was to analyse how well FRAX® predicts the risk of major osteoporotic and vertebral fractures over 6 years in postmenopausal women from general population.

Patients and methods

The OPUS study was conducted in European women aged above 55 years, recruited in 5 centers from random population samples and followed over 6 years. The population for this study consisted of 1748 women (mean age 74.2 years) with information on incident fractures. 742 (43.1%) had a prevalent fracture; 769 (44%) and 155 (8.9%) of them received an antiosteoporotic treatment before and during the study respectively. We compared FRAX® performance with and without bone mineral density (BMD) using receiver operator characteristic (ROC) c-statistical analysis with ORs and areas under receiver operating characteristics curves (AUCs) and net reclassification improvement (NRI).

Results

85 (4.9%) patients had incident major fractures over 6 years. FRAX® with and without BMD predicted these fractures with an AUC of 0.66 and 0.62 respectively. The AUC were 0.60, 0.66, 0.69 for history of low trauma fracture alone, age and femoral neck (FN) BMD and combination of the 3 clinical risk factors, respectively. FRAX® with and without BMD predicted incident radiographic vertebral fracture (n = 65) with an AUC of 0.67 and 0.65 respectively. NRI analysis showed a significant improvement in risk assignment when BMD is added to FRAX®.

Conclusions

This study shows that FRAX® with BMD and to a lesser extent also without FN BMD predict major osteoporotic and vertebral fractures in the general population.     

Evolution of Exchangeable Copper and Relative Exchangeable Copper through the Course of Wilson's Disease in the Long Evans Cinnamon Rat

Background

Wilson''s disease (WD) is an inherited disorder of copper metabolism leading to liver failure and/or neurological impairment. Its diagnosis often remains difficult even with genetic testing. Relative exchangeable copper (REC) has recently been described as a reliable serum diagnostic marker for WD.

Methodology/Principal Findings

The aim of this study was to validate the use of REC in the Long Evans Cinnamon (LEC) rat, an animal model for WD, and to study its relevance under different conditions in comparison with conventional markers. Two groups of LEC rats and one group of Long-Evans (LE) rats were clinically and biologically monitored from 6 to 28 weeks of age. One group of LEC rats was given copper-free food. The other groups had normal food. Blood samples were collected each month and different serum markers for WD (namely ceruloplasmin oxidase activity, exchangeable copper (CuEXC), total serum copper and REC) and acute liver failure (serum transaminases and bilirubinemia) were tested. Every LEC rat under normal food developed acute liver failure (ALF), with 40% global mortality. Serum transaminases and bilirubinemia along with total serum copper and exchangeable copper levels increased with the onset of acute liver failure. A correlation was observed between CuEXC values and the severity of ALF. Cut-off values were different between young and adult rats and evolved because of age and/or liver failure. Only REC, with values >19%, was able to discriminate LEC groups from the LE control group at every time point in the study. REC sensitivity and specificity reached 100% in adults rats.

Conclusions/Significance

REC appears to be independent of demographic or clinical data in LEC rats. It is a very simple and reliable blood test for the diagnosis of copper toxicosis owing to a lack of ATP7B function. CuEXC can be used as an accurate biomarker of copper overload.     

Non contiguous-finished genome sequence and description of Enorma massiliensis gen. nov., sp. nov., a new member of the Family Coriobacteriaceae

Enorma massiliensis strain phI^T is the type strain of E. massiliensis gen. nov., sp. nov., the type species of a new genus within the family Coriobacteriaceae, Enorma gen. nov. This strain, whose genome is described here, was isolated from the fecal flora of a 26-year-old woman suffering from morbid obesity. E. massiliensis strain phI^T is a Gram-positive, obligately anaerobic bacillus. Here we describe the features of this organism, together with the complete genome sequence and annotation. The 2,280,571 bp long genome (1 chromosome but no plasmid) exhibits a G+C content of 62.0% and contains 1,901 protein-coding and 51 RNA genes, including 3 rRNA genes.     

Masculinization of the X Chromosome in the Pea Aphid

Evolutionary theory predicts that sexually antagonistic mutations accumulate differentially on the X chromosome and autosomes in species with an XY sex-determination system, with effects (masculinization or feminization of the X) depending on the dominance of mutations. Organisms with alternative modes of inheritance of sex chromosomes offer interesting opportunities for studying sexual conflicts and their resolution, because expectations for the preferred genomic location of sexually antagonistic alleles may differ from standard systems. Aphids display an XX/X0 system and combine an unusual inheritance of the X chromosome with the alternation of sexual and asexual reproduction. In this study, we first investigated theoretically the accumulation of sexually antagonistic mutations on the aphid X chromosome. Our results show that i) the X is always more favourable to the spread of male-beneficial alleles than autosomes, and should thus be enriched in sexually antagonistic alleles beneficial for males, ii) sexually antagonistic mutations beneficial for asexual females accumulate preferentially on autosomes, iii) in contrast to predictions for standard systems, these qualitative results are not affected by the dominance of mutations. Under the assumption that sex-biased gene expression evolves to solve conflicts raised by the spread of sexually antagonistic alleles, one expects that male-biased genes should be enriched on the X while asexual female-biased genes should be enriched on autosomes. Using gene expression data (RNA-Seq) in males, sexual females and asexual females of the pea aphid, we confirm these theoretical predictions. Although other mechanisms than the resolution of sexual antagonism may lead to sex-biased gene expression, we argue that they could hardly explain the observed difference between X and autosomes. On top of reporting a strong masculinization of the aphid X chromosome, our study highlights the relevance of organisms displaying an alternative mode of sex chromosome inheritance to understanding the forces shaping chromosome evolution.     

A Comprehensive Analysis of In Vitro and In Vivo Genetic Fitness of Pseudomonas aeruginosa Using High-Throughput Sequencing of Transposon Libraries

High-throughput sequencing of transposon (Tn) libraries created within entire genomes identifies and quantifies the contribution of individual genes and operons to the fitness of organisms in different environments. We used insertion-sequencing (INSeq) to analyze the contribution to fitness of all non-essential genes in the chromosome of Pseudomonas aeruginosa strain PA14 based on a library of ∼300,000 individual Tn insertions. In vitro growth in LB provided a baseline for comparison with the survival of the Tn insertion strains following 6 days of colonization of the murine gastrointestinal tract as well as a comparison with Tn-inserts subsequently able to systemically disseminate to the spleen following induction of neutropenia. Sequencing was performed following DNA extraction from the recovered bacteria, digestion with the MmeI restriction enzyme that hydrolyzes DNA 16 bp away from the end of the Tn insert, and fractionation into oligonucleotides of 1,200–1,500 bp that were prepared for high-throughput sequencing. Changes in frequency of Tn inserts into the P. aeruginosa genome were used to quantify in vivo fitness resulting from loss of a gene. 636 genes had <10 sequencing reads in LB, thus defined as unable to grow in this medium. During in vivo infection there were major losses of strains with Tn inserts in almost all known virulence factors, as well as respiration, energy utilization, ion pumps, nutritional genes and prophages. Many new candidates for virulence factors were also identified. There were consistent changes in the recovery of Tn inserts in genes within most operons and Tn insertions into some genes enhanced in vivo fitness. Strikingly, 90% of the non-essential genes were required for in vivo survival following systemic dissemination during neutropenia. These experiments resulted in the identification of the P. aeruginosa strain PA14 genes necessary for optimal survival in the mucosal and systemic environments of a mammalian host.     

Spatiotemporal variations in density and biomass of rocky reef fish in a biogeographic climatic transition zone: trends over 9 years,inside and outside the only nearshore no-take marine-protected area on the southern Brazilian coast

Biogeographical transition zones are important areas to investigate evolutionary ecological questions, but long-term population monitoring is needed to better understand ecological processes that govern population variations in such edge environments. The southernmost Brazilian rocky reefs are the southern limit of distribution for 96% of the tropical ichthyofauna of the western Atlantic. The Arvoredo Marine Biological Reserve is the only nearshore no-take marine-protected area (MPA) located in this transition zone. The main aim was to investigate how the populations of rocky reef fish species vary in density and biomass in space and over time, inside and outside the Arvoredo MPA. This study presents results based on a 9 year (2008–2017) underwater visual census monitoring study to evaluate the density and biomass of key fish species. Variations in density and biomass were detected for most species. Factors and mechanisms that may have influenced spatial variation are habitat structural complexity and protection from fisheries. Temporal variations, otherwise, may have been influenced by species proximity to their distributional limit, in synergy with density-dependent mechanisms and stochastic winter temperature oscillations. The MPAs harbour higher density and biomass for most species. Nonetheless, a prominent temporal decline in the recruitment of Epinephelus marginatus calls into question the continuous effectiveness of the MPA.