Phospholipase A2-activating protein is associated with a novel form of leukoencephalopathy

Leukoencephalopathies are a group of white matter disorders related to abnormal formation, maintenance, and turnover of myelin in the central nervous system. These disorders of the brain are categorized according to neuroradiological and pathophysiological criteria. Herein, we have identified a unique form of leukoencephalopathy in seven patients presenting at ages 2 to 4 months with progressive microcephaly, spastic quadriparesis, and global developmental delay. Clinical, metabolic, and imaging characterization of seven patients followed by homozygosity mapping and linkage analysis were performed. Next generation sequencing, bioinformatics, and segregation analyses followed, to determine a loss of function sequence variation in the phospholipase A2-activating protein encoding gene (PLAA). Expression and functional studies of the encoded protein were performed and included measurement of prostaglandin E2 and cytosolic phospholipase A2 activity in membrane fractions of fibroblasts derived from patients and healthy controls. Plaa-null mice were generated and prostaglandin E2 levels were measured in different tissues. The novel phenotype of our patients segregated with a homozygous loss-of-function sequence variant, causing the substitution of leucine at position 752 to phenylalanine, in PLAA, which causes disruption of the protein's ability to induce prostaglandin E2 and cytosolic phospholipase A2 synthesis in patients' fibroblasts. Plaa-null mice were perinatal lethal with reduced brain levels of prostaglandin E2 The non-functional phospholipase A2-activating protein and the associated neurological phenotype, reported herein for the first time, join other complex phospholipid defects that cause leukoencephalopathies in humans, emphasizing the importance of this axis in white matter development and maintenance

Root-emitted volatile organic compounds: can they mediate belowground plant-plant interactions?

peer reviewedBackground Aboveground, plants release volatile organic compounds (VOCs) that act as chemical signals between neighbouring plants. It is now well documented that VOCs emitted by the roots in the plant rhizosphere also play important ecological roles in the soil ecosystem, notably in plant defence because they are involved in interactions between plants, phytophagous pests and organisms of the third trophic level. The roles played by root-emitted VOCs in between- and within-plant signalling, however, are still poorly documented in the scientific literature. Scope Given that (1) plants release volatile cues mediating plant-plant interactions aboveground, (2) roots can detect the chemical signals originating from their neighbours, and (3) roots release VOCs involved in biotic interactions belowground, the aim of this paper is to discuss the roles of VOCs in between- and within-plant signalling belowground. We also highlight the technical challenges associated with the analysis of root-emitted VOCs and the design of experiments targeting volatile-mediated root-root interactions. Conclusions We conclude that root-root interactions mediated by volatile cues deserve more research attention and that both the analytical tools and methods developed to study the ecological roles played by VOCs in interplant signalling aboveground can be adapted to focus on the roles played by root-emitted VOCs in between- and within-plant signalling

The Cockayne Syndrome Natural History (CoSyNH) study:clinical findings in 102 individuals and recommendations for care

Purpose: Cockayne syndrome (CS) is a rare, autosomal-recessive disorder characterized by microcephaly, impaired postnatal growth, and premature pathological aging. It has historically been considered a DNA repair disorder; fibroblasts from classic patients often exhibit impaired transcription-coupled nucleotide excision repair. Previous studies have largely been restricted to case reports and small series, and no guidelines for care have been established. Methods: One hundred two study participants were identified through a network of collaborating clinicians and the Amy and Friends CS support groups. Families with a diagnosis of CS could also self-recruit. Comprehensive clinical information for analysis was obtained directly from families and their clinicians. Results and Conclusion: We present the most complete evaluation of Cockayne syndrome to date, including detailed information on the prevalence and onset of clinical features, achievement of neurodevelopmental milestones, and patient management. We confirm that the most valuable prognostic factor in CS is the presence of early cataracts. Using this evidence, we have created simple guidelines for the care of individuals with CS. We aim to assist clinicians in the recognition, diagnosis, and management of this condition and to enable families to understand what problems they may encounter as CS progresses

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