Genetic correlation between amyotrophic lateral sclerosis and schizophrenia

A. Palotie on työryhmän Schizophrenia Working Grp Psychiat jäsen.We have previously shown higher-than-expected rates of schizophrenia in relatives of patients with amyotrophic lateral sclerosis (ALS), suggesting an aetiological relationship between the diseases. Here, we investigate the genetic relationship between ALS and schizophrenia using genome-wide association study data from over 100,000 unique individuals. Using linkage disequilibrium score regression, we estimate the genetic correlation between ALS and schizophrenia to be 14.3% (7.05-21.6; P = 1 x 10(-4)) with schizophrenia polygenic risk scores explaining up to 0.12% of the variance in ALS (P = 8.4 x 10(-7)). A modest increase in comorbidity of ALS and schizophrenia is expected given these findings (odds ratio 1.08-1.26) but this would require very large studies to observe epidemiologically. We identify five potential novel ALS-associated loci using conditional false discovery rate analysis. It is likely that shared neurobiological mechanisms between these two disorders will engender novel hypotheses in future preclinical and clinical studies.Peer reviewe

Perfumery Radar 2.0: A Step toward Fragrance Design and Classification

Product design and engineering is one of the novel paradigms of the 21st century, aiming for the development of novel added-value products for consumers. Its application to the fragrance business for the purpose of enhancing the design and performance of perfumed products is of prime interest because nowadays three-fourths of consumer goods contain fragrances in their composition. Furthermore, fragrance design and classification is still performed on a trial-and-error basis which consequently increases products' time to market and consumption of raw materials. The Perfumery Radar methodology was developed in the recent past as a tool for fragrance design and classification with predictive capabilities. In this study, we extend it to the Perfumery Radar 2.0, which uses typical olfactory families used by the industry but also introduces outer and inner layers for a detailed description of the odor space of fine fragrances. Furthermore, we fully validated this methodology with sensorial classifications of perfumers using several formulated fragrances with known compositions and physicochemical properties with very good predictive accuracy. Finally, and for the first time, we applied the Perfumery Radar 2.0 to 36 commercial fragrances differing in gender (feminine, masculine, and unisex) and covering the odor space. Correlations between olfactory families or odor descriptors with gender trends as well as with richer olfactory families such as chypre and fougere were also derived

Oryzisolibacter propanilivorax gen. nov., sp. nov., a propanil-degrading bacterium

Strain EPL6(T), a Gram-negative, motile, short rod was isolated from a propanil and 3,4-dichloroaniline enrichment culture produced from rice paddy soil. Based on the analyses of the 16S rRNA gene sequence, strain EPL6(T) was observed to be a member of the family Comamonadaceae, sharing the highest pairwise identity with type strains of the species Alicycliphilus denitrificans K601(T) (96.8 %) and Melaminivora alkalimesophila CY1(T) (96.8 %). Strain EPL6(T) was able to grow in a temperature range of 15-37 degrees C, pH 6-9 and in the presence of up to 4% (w/v) NaCl and tested positive for catalase and oxidase reactions. The major respiratory quinone was Q8. The genomic DNA had a G+C content of 69.4 +/- 0.9 mol%. The major polar lipids were phosphatidylethanolamine, phosphatidylglycerol and diphosphatidylglycerol, and the major fatty acid methyl esters comprised C-16 : 0, C-18 : 1 omega 7c and summed feature 3 (C-16 : 1 omega 7c/iso-C-15 : 0 2-OH). Comparison of the genome sequence of strain EPL6(T) and of its closest neighbours, Melaminivora alkalimesophila CY1(T) and Alicycliphilus denitrificans K601(T), yielded values of ANI <= 84.1% and of AAI <= 80.3 %. Therefore, the genetic, phylogenetic, phenotypic and chemotaxonomic characteristics support the classification of this organism into a new taxon. Considering the genetic divergence of strain EPL6(T) from the type strains of the closest species, which belong to distinct genera, we propose a new genus within the family Comamonadaceae, named Oryzisolibacter propanilivorax gen. nov., sp. nov., represented by the isolate EPL6(T) as the type strain of the species (=LMG 28427(T)=CECT 8927(T))

Genetic correlation between amyotrophic lateral sclerosis and schizophrenia

We have previously shown higher-than-expected rates of schizophrenia in relatives of patients with amyotrophic lateral sclerosis (ALS), suggesting an aetiological relationship between the diseases. Here, we investigate the genetic relationship between ALS and schizophrenia using genome-wide association study data from over 100,000 unique individuals. Using linkage disequilibrium score regression, we estimate the genetic correlation between ALS and schizophrenia to be 14.3% (7.05-21.6; P=1 × 10) with schizophrenia polygenic risk scores explaining up to 0.12% of the variance in ALS (P=8.4 × 10). A modest increase in comorbidity of ALS and schizophrenia is expected given these findings (odds ratio 1.08-1.26) but this would require very large studies to observe epidemiologically. We identify five potential novel ALS-associated loci using conditional false discovery rate analysis. It is likely that shared neurobiological mechanisms between these two disorders will engender novel hypotheses in future preclinical and clinical studies

Dissociated lower limb muscle involvement in amyotrophic lateral sclerosis

It has been suggested that corticomotoneuronal drive to ankle dorsiflexors is greater than to ankle plantar flexor muscles, despite the finding that plantar flexors are no less active than TA during walking and standing. The present study was undertaken to determine whether there was differential involvement of distal lower limb muscles in amyotrophic lateral sclerosis (ALS), to elucidate pathophysiological mechanisms of selective muscle involvement. Prospective studies were undertaken in 52 ALS patients, including clinical assessment, disease staging (revised ALS functional rating scale), Medical Research Council sum score, and a scale of upper motor neurone (UMN) dysfunction. Motor unit number estimates (MUNE) and compound muscle action potentials (CMAP) from ankle dorsiflexors and plantar flexors were used to provide objective measures. A novel ‘split leg index’ was calculated as follows: SLI = CMAPDF 7 CMAPPF. In ALS, there was significantly greater reduction of MUNE and CMAP amplitude recorded from plantar flexors when compared to dorsiflexors, suggesting preferential involvement of plantar flexor muscles, underpinning a ‘split leg’ appearance. The SLI correlated with clinical plantar flexor strength (R= -0.56, p\0.001). In no patient did the SLI suggest preferential dorsiflexor involvement. In subgroup analyses, mean SLI was greatest in lower limb-onset ALS. In conclusion, the present study has established dissociated involvement of muscles acting around the ankle in ALS. We suggest this reflects underlying differences in cortical, descending or local spinal modulation of these muscles