Rapid Publication Navajo Microvillous Inclusion Disease Is Due to a Mutation in MYO5B

Microvillous Inclusion Disease (MID) is a rare, autosomal recessive gastrointestinal disease of increased frequency among the Navajos. Previous work has shown a deficiency of RAB8 in one Japanese patient, while homozygous mutations in MYO5B were found in 7 of 10 mostly Middle Eastern families. We have identified a shared homozygous mutation in MYO5B in seven affected Navajos with the expected heterozygosity in five parents. We have developed a simple restriction enzyme based assay that allows for rapid screening for this mutation.

Cognitive deficits caused by prefrontal cortical and hippocampal neural disinhibition

We review recent evidence concerning the significance of inhibitory GABA transmission and of neural disinhibition, i.e. deficient GABA transmission, within prefrontal cortex and hippocampus for clinically relevant cognitive functions. Both regions support important cognitive functions, including attention and memory, and their dysfunction has been implicated in cognitive deficits characterizing neuropsychiatric disorders. GABAergic inhibition shapes cortico-hippocampal neural activity and, recently, prefrontal and hippocampal neural disinhibition has emerged as a pathophysiological feature of major neuropsychiatric disorders, especially schizophrenia and age-related cognitive decline. Regional neural disinhibition, disrupting spatio-temporal control of neural activity and causing aberrant drive of projections, may disrupt processing within the disinhibited region and efferent regions. Recent studies in rats showed that prefrontal and hippocampal neural disinhibition (by local GABA antagonist microinfusion) dysregulates burst firing, which has been associated with important aspects of neural information processing. Using translational tests of clinically-relevant cognitive functions, these studies showed that prefrontal and hippocampal neural disinhibition disrupts regional cognitive functions (including prefrontal attention and hippocampal memory function); moreover, hippocampal neural disinhibition disrupted attentional performance, which does not require the hippocampus, but requires prefrontal-striatal circuits modulated by the hippocampus. However, some prefrontal and hippocampal functions (including inhibitory response control) are spared by regional disinhibition. We consider conceptual implications of these findings, regarding the distinct relationships of distinct cognitive functions to prefrontal and hippocampal GABA tone and neural activity. Moreover, the findings support that prefrontal and hippocampal neural disinhibition contributes to clinically relevant cognitive deficits, and we consider pharmacological strategies for ameliorating cognitive deficits by rebalancing disinhibition-induced aberrant neural activity

Peralkaline Felsic Magmatism of the Atlantic Islands

The oceanic-island magmatic systems of the Atlantic Ocean exhibit significant diversity in their respective sizes, ages, and the compositional ranges of their eruptive products. Nevertheless, almost all of the Atlantic islands and island groups have produced peralkaline felsic magmas, implying that similar petrogenetic regimes may be operating throughout the Atlantic Ocean, and arguably elsewhere. The origins of peralkaline magmas are frequently linked to low-degree partial melting of enriched mantle, followed by protracted differentiation in the shallow crust. However, additional petrogenetic processes such as magma mixing, crustal melting, and contamination have been identified at numerous peralkaline centers. The onset of peralkalinity leads to magma viscosities lower than those typical for metaluminous felsic magmas, which has profound implications for processes such as crystal settling. This study represents a compilation of published and original data which demonstrates trends that suggest that the peralkaline magmas of the Atlantic Ocean islands are generated primarily via extended (up to ∼ 95%), open system fractional crystallization of mantle-derived mafic magmas. Crustal assimilation is likely to become more significant as the system matures and fusible material accumulates in the crust. Magma mixing may occur between various compositional end-members and may be recognized via hybridized intermediate magmas. The peralkaline magmas are hydrous, and frequently zoned in composition, temperature, and/or water content. They are typically stored in shallow crustal magma reservoirs (∼ 2–5 km), maintained by mafic replenishment. Low melt viscosities (1 × 101.77 to 1 × 104.77 Pa s) facilitate two-phase flow, promoting the formation of alkali-feldspar crystal mush. This mush may then contribute melt to an overlying melt lens via filter pressing or partial melting. We utilize a three-stage model to account for the establishment, development, and termination of peralkaline magmatism in the ocean island magmatic systems of the Atlantic. We suggest that the overall control on peralkaline magmatism in the Atlantic is magma flux rate, which controls the stability of upper crustal magma reservoirs. The abundance of peralkaline magmas in the Atlantic suggests that their development must be a common, but not inevitable, stage in the evolution of ocean islands

Some geomorphological aspects of the Azores Archipelago

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