PLA2G6, encoding a phospholipase A2, is mutated in neurodegenerative disorders with high brain iron.

Neurodegenerative disorders with high brain iron include Parkinson disease, Alzheimer disease and several childhood genetic disorders categorized as neuroaxonal dystrophies. We mapped a locus for infantile neuroaxonal dystrophy (INAD) and neurodegeneration with brain iron accumulation (NBIA) to chromosome 22q12-q13 and identified mutations in PLA2G6, encoding a calcium-independent group VI phospholipase A2, in NBIA, INAD and the related Karak syndrome. This discovery implicates phospholipases in the pathogenesis of neurodegenerative disorders with iron dyshomeostasis.

Genetic, clinical, and radiographic delineation of Hallervorden-Spatz syndrome.

BACKGROUND: Hallervorden-Spatz syndrome is an autosomal recessive disorder characterized by dystonia, parkinsonism, and iron accumulation in the brain. Many patients with this disease have mutations in the gene encoding pantothenate kinase 2 (PANK2); these patients are said to have pantothenate kinase-associated neurodegeneration. In this study, we compared the clinical and radiographic features of patients with Hallervorden-Spatz syndrome with and without mutations in PANK2. METHODS: One hundred twenty-three patients from 98 families with a diagnosis of Hallervorden-Spatz syndrome were classified on the basis of clinical assessment as having classic disease (characterized by early onset with rapid progression) or atypical disease (later onset with slow progression). Their genomic DNA was sequenced for PANK2 mutations. RESULTS: All patients with classic Hallervorden-Spatz syndrome and one third of those with atypical disease had PANK2 mutations. Whereas almost all mutations in patients with atypical disease led to amino acid changes, those in patients with classic disease more often resulted in predicted protein truncation. Patients with atypical disease who had PANK2 mutations were more likely to have prominent speech-related and psychiatric symptoms than patients with classic disease or mutation-negative patients with atypical disease. In all patients with pantothenate kinase-associated neurodegeneration, whether classic or atypical, T2-weighted magnetic resonance imaging (MRI) of the brain showed a specific pattern of hyperintensity within the hypointense medial globus pallidus. This pattern was not seen in any patients without mutations. CONCLUSIONS: PANK2 mutations are associated with all cases of classic Hallervorden-Spatz syndrome and one third of cases of atypical disease. A specific MRI pattern distinguishes patients with PANK2 mutations. Predicted levels of pantothenate kinase 2 protein correlate with the severity of disease.

Rationale for a new generation of indicators for coastal waters.

More than half the world's human population lives within 100 km of the coast, and that number is expected to increase by 25% over the next two decades. Consequently, coastal ecosystems are at serious risk. Larger coastal populations and increasing development have led to increased loading of toxic substances, nutrients and pathogens with subsequent algal blooms, hypoxia, beach closures, and damage to coastal fisheries. Recent climate change has led to the rise in sea level with loss of coastal wetlands and saltwater intrusion into coastal aquifers. Coastal resources have traditionally been monitored on a stressor-by-stressor basis such as for nutrient loading or dissolved oxygen. To fully measure the complexities of coastal systems, we must develop a new set of ecologic indicators that span the realm of biological organization from genetic markers to entire ecosystems and are broadly applicable across geographic regions while integrating stressor types. We briefly review recent developments in ecologic indicators and emphasize the need for improvements in understanding of stress-response relationships, contributions of multiple stressors, assessments over different spatial and temporal scales, and reference conditions. We provide two examples of ecologic indicators that can improve our understanding of these inherent problems: a) the use of photopigments as indicators of the interactive effects of nutrients and hydrology, and b) biological community approaches that use multiple taxa to detect effects on ecosystem structure and function. These indicators are essential to measure the condition of coastal resources, to diagnose stressors, to communicate change to the public, and ultimately to protect human health and the quality of the coastal environment.

Dichotomy and perceptual distortions in absolute pitch ability.

Absolute pitch (AP) is the rare ability to identify the pitch of a tone without the aid of a reference tone. Understanding both the nature and genesis of AP can provide insights into neuroplasticity in the auditory system. We explored factors that may influence the accuracy of pitch perception in AP subjects both during the development of the trait and in later age. We used a Web-based survey and a pitch-labeling test to collect perceptual data from 2,213 individuals, 981 (44%) of whom proved to have extraordinary pitch-naming ability. The bimodal distribution in pitch-naming ability signifies AP as a distinct perceptual trait, with possible implications for its genetic basis. The wealth of these data has allowed us to uncover unsuspected note-naming irregularities suggestive of a "perceptual magnet" centered at the note "A." In addition, we document a gradual decline in pitch-naming accuracy with age, characterized by a perceptual shift in the "sharp" direction. These findings speak both to the process of acquisition of AP and to its stability.