Arc-parallel flow in the mantle wedge beneath Costa Rica and Nicaragua

Resolving flow geometry in the mantle wedge is central to understanding the thermal and chemical structure of subduction zones, subducting plate dehydration, and melting that leads to arc volcanism, which can threaten large populations and alter climate through gas and particle emission. Here we show that isotope geochemistry and seismic velocity anisotropy provide strong evidence for trench-parallel flow in the mantle wedge beneath Costa Rica and Nicaragua. This finding contradicts classical models, which predict trench-normal flow owing to the overlying wedge mantle being dragged downwards by the subducting plate. The isotopic signature of central Costa Rican volcanic rocks is not consistent with its derivation from the mantle wedge or eroded fore-arc complexes but instead from seamounts of the Galapagos hotspot track on the subducting Cocos plate. This isotopic signature decreases continuously from central Costa Rica to northwestern Nicaragua. As the age of the isotopic signature beneath Costa Rica can be constrained and its transport distance is known, minimum northwestward flow rates can be estimated (63-190 mm yr(-1)) and are comparable to the magnitude of subducting Cocos plate motion (approximately 85 mm yr(-1)). Trench-parallel flow needs to be taken into account in models evaluating thermal and chemical structure and melt generation in subduction zones.     

Epigenetic dysregulation of brainstem nuclei in the pathogenesis of Alzheimer’s disease: looking in the correct place at the right time?

Even though the etiology of Alzheimer’s disease (AD) remains unknown, it is suggested that an interplay among genetic, epigenetic and environmental factors is involved. An increasing body of evidence pinpoints that dysregulation in the epigenetic machinery plays a role in AD. Recent developments in genomic technologies have allowed for high throughput interrogation of the epigenome, and epigenome-wide association studies have already identified unique epigenetic signatures for AD in the cortex. Considerable evidence suggests that early dysregulation in the brainstem, more specifically in the raphe nuclei and the locus coeruleus, accounts for the most incipient, non-cognitive symptomatology, indicating a potential causal relationship with the pathogenesis of AD. Here we review the advancements in epigenomic technologies and their application to the AD research field, particularly with relevance to the brainstem. In this respect, we propose the assessment of epigenetic signatures in the brainstem as the cornerstone of interrogating causality in AD. Understanding how epigenetic dysregulation in the brainstem contributes to AD susceptibility could be of pivotal importance for understanding the etiology of the disease and for the development of novel diagnostic and therapeutic strategies.     

Releasement and Nihilism in the Art of Living with Technology

In this contribution the author tries to formulate an approach to the art of living with technology based on Heidegger’s The Principle of Reason, a work often overlooked by contemporary commentators in the philosophy of technology. This approach couples the concept of releasement to insights hailing from Wolfgang Schirmacher concerning Heidegger’s nihilism.     

De novo mutations in ATP1A3 cause alternating hemiplegia of childhood

Alternating hemiplegia of childhood (AHC) is a rare, severe neurodevelopmental syndrome characterized by recurrent hemiplegic episodes and distinct neurological manifestations. AHC is usually a sporadic disorder and has unknown etiology. We used exome sequencing of seven patients with AHC and their unaffected parents to identify de novo nonsynonymous mutations in ATP1A3 in all seven individuals. In a subsequent sequence analysis of ATP1A3 in 98 other patients with AHC, we found that ATP1A3 mutations were likely to be responsible for at least 74% of the cases; we also identified one inherited mutation in a case of familial AHC. Notably, most AHC cases are caused by one of seven recurrent ATP1A3 mutations, one of which was observed in 36 patients. Unlike ATP1A3 mutations that cause rapid-onset dystonia-parkinsonism, AHC-causing mutations in this gene caused consistent reductions in ATPase activity without affecting the level of protein expression. This work identifies de novo ATP1A3 mutations as the primary cause of AHC and offers insight into disease pathophysiology by expanding the spectrum of phenotypes associated with mutations in ATP1A3.     

Comparative genome sequencing of Escherichia coli allows observation of bacterial evolution on a laboratory timescale

We applied whole-genome resequencing of Escherichia coli to monitor the acquisition and fixation of mutations that conveyed a selective growth advantage during adaptation to a glycerol-based growth medium. We identified 13 different de novo mutations in five different E. coli strains and monitored their fixation over a 44-d period of adaptation. We obtained proof that the observed spontaneous mutations were responsible for improved fitness by creating single, double and triple site-directed mutants that had growth rates matching those of the evolved strains. The success of this new genome-scale approach indicates that real-time evolution studies will now be practical in a wide variety of contexts.     

Mutations in X-linked PORCN, a putative regulator of Wnt signaling, cause focal dermal hypoplasia

Focal dermal hypoplasia is an X-linked dominant disorder characterized by patchy hypoplastic skin and digital, ocular and dental malformations. We used array comparative genomic hybridization to identify a 219-kb deletion in Xp11.23 in two affected females. We sequenced genes in this region and found heterozygous and mosaic mutations in PORCN in other affected females and males, respectively. PORCN encodes the human homolog of Drosophila melanogaster porcupine, an endoplasmic reticulum protein involved in secretion of Wnt proteins.