Activation of the Left Inferior Frontal Gyrus in the First 200 ms of Reading: Evidence from Magnetoencephalography (MEG)

Background

It is well established that the left inferior frontal gyrus plays a key role in the cerebral cortical network that supports reading and visual word recognition. Less clear is when in time this contribution begins. We used magnetoencephalography (MEG), which has both good spatial and excellent temporal resolution, to address this question.

Methodology/Principal Findings

MEG data were recorded during a passive viewing paradigm, chosen to emphasize the stimulus-driven component of the cortical response, in which right-handed participants were presented words, consonant strings, and unfamiliar faces to central vision. Time-frequency analyses showed a left-lateralized inferior frontal gyrus (pars opercularis) response to words between 100–250 ms in the beta frequency band that was significantly stronger than the response to consonant strings or faces. The left inferior frontal gyrus response to words peaked at ∼130 ms. This response was significantly later in time than the left middle occipital gyrus, which peaked at ∼115 ms, but not significantly different from the peak response in the left mid fusiform gyrus, which peaked at ∼140 ms, at a location coincident with the fMRI–defined visual word form area (VWFA). Significant responses were also detected to words in other parts of the reading network, including the anterior middle temporal gyrus, the left posterior middle temporal gyrus, the angular and supramarginal gyri, and the left superior temporal gyrus.

Conclusions/Significance

These findings suggest very early interactions between the vision and language domains during visual word recognition, with speech motor areas being activated at the same time as the orthographic word-form is being resolved within the fusiform gyrus. This challenges the conventional view of a temporally serial processing sequence for visual word recognition in which letter forms are initially decoded, interact with their phonological and semantic representations, and only then gain access to a speech code.     

Of Mice and Men: Evolution and the Socialist Utopia. William Morris,H.G. Wells,and George Bernard Shaw

During the British socialist revival of the 1880s competing theories of evolution were central to disagreements about strategy for social change. In News from Nowhere (1891), William Morris had portrayed socialism as the result of Lamarckian processes, and imagined a non-Malthusian future. H.G. Wells, an enthusiastic admirer of Morris in the early days of the movement, became disillusioned as a result of the Malthusianism he learnt from Huxley and his subsequent rejection of Lamarckism in light of Weismann’s experiments on mice. This brought him into conflict with his fellow Fabian, George Bernard Shaw, who rejected neo-Darwinism in favour of a Lamarckian conception of change he called “creative evolution.”     

The Deubiquitinating Enzyme USP8 Promotes Trafficking and Degradation of the Chemokine Receptor 4 at the Sorting Endosome

Reversible ubiquitination orchestrated by the opposition of ubiquitin ligases and deubiquitinating enzymes mediates endocytic trafficking of cell surface receptors for lysosomal degradation. Ubiquitin-specific protease 8 (USP8) has previously been implicated in endocytosis of several receptors by virtue of their deubiquitination. The present study explores an indirect role for USP8 in cargo trafficking through its regulation of the chemokine receptor 4 (CXCR4). Contrary to the effects of USP8 loss on enhanced green fluorescent protein, we find that USP8 depletion stabilizes CXCR4 on the cell surface and attenuates receptor degradation without affecting its ubiquitination status. In the presence of ligand, diminished CXCR4 turnover is accompanied by receptor accumulation on enlarged early endosomes and leads to enhancement of phospho-ERK signaling. Perturbation in CXCR4 trafficking, resulting from USP8 inactivation, occurs at the ESCRT-0 checkpoint, and catalytic mutation of USP8 specifically targeted to the ESCRT-0 complex impairs the spatial and temporal organization of the sorting endosome. USP8 functionally opposes the ubiquitin ligase AIP4 with respect to ESCRT-0 ubiquitination, thereby promoting trafficking of CXCR4. Collectively, our findings demonstrate a functional cooperation between USP8, AIP4, and the ESCRT-0 machinery at the early sorting phase of CXCR4 and underscore the versatility of USP8 in shaping trafficking events at the early-to-late endosome transition.     

Impacts of dietary antioxidants and flight training on post-exercise oxidative damage in adult parrots

After intense physical activity animals generally experience a rise in metabolic rate, which is associated with a proliferation of pro-oxidants. If unchecked, these pro-oxidants can cause damage to DNA and peroxidation of lipids in cell walls. Two factors are thought to ameliorate post-exercise oxidative damage, at least in mammals: dietary antioxidants and exercise training. So far it is unknown whether birds benefit similarly from exercise training, although a positive effect of dietary antioxidants on take-off flight has been indicated. In this experiment, we maintained captive wildtype budgerigars Melopsittacus undulatus on enhanced (EQ) or reduced quality (RQ) diets differing in levels of the dietary antioxidants retinol, vitamin C and α-tocopherol for 12 months. Birds were then regularly trained to perform take-off escape flights, a strenuous and biologically relevant form of exercise. For these adult budgerigars, regular exercise training improved escape flight performance, particularly in males on the EQ diet. In terms of oxidative damage, post-exercise levels of malondialdehyde (MDA), a by-product of lipid peroxidation, were significantly decreased after 9 weeks of flight training than after a single exercise session. Thus, individuals achieved faster escape flights with lower oxidative damage, after training. Also, birds that were fatter for their skeletal size initially had higher post-exercise MDA levels than thinner birds, but this relationship was broken by 9 weeks of flight training. Interestingly, there was no impact of diet quality on levels of MDA, suggesting that improved protection against oxidative damage for all birds was due to an up-regulation of endogenous antioxidant systems. Given their diversity, bird species provide rich research opportunities for investigating the interactions between exercise training, pro-oxidants production and antioxidant defences.     

Pre-Columbian treponemal disease from 14th century AD Safed,Israel, and implications for the medieval eastern Mediterranean

In 1912, 68 medieval crania were excavated from a cave at Safed in the eastern Mediterranean and brought to the United Kingdom. It is only recently that these skulls have been studied for evidence of disease. One adult individual demonstrates multiple lesions of the cranial vault, compatible with treponematosis. Radiocarbon dating suggests the year of death to be between 1290-1420 AD. This range equates to the mamluk period, just after the crusades. This is the oldest dated case of treponematosis in the Middle East, and the first to confirm its presence there before the epidemiologically important transatlantic voyage of Christopher Columbus. The finding has significant implications for our understanding of the introduction of the disease to the Middle East and of the medieval diagnosis of ulcerating skin conditions by medical practitioners in the Mediterranean world.     

Manipulation of EphB2 regulatory motifs and SH2 binding sites switches MAPK signaling and biological activity

Signaling by the Eph family of receptor tyrosine kinases (RTKs) is complex, because they can interact with a variety of intracellular targets, and can potentially induce distinct responses in different cell types. In NG108 neuronal cells, activated EphB2 recruits p120RasGAP, in a fashion that is associated with down-regulation of the Ras-Erk mitogen-activated kinase (MAPK) pathway and neurite retraction. To pursue the role of the Ras-MAPK pathway in EphB2-mediated growth cone collapse, and to explore the biochemical and biological functions of Eph receptors, we sought to re-engineer the signaling properties of EphB2 by manipulating its regulatory motifs and SH2 binding sites. An EphB2 mutant that retained juxtamembrane (JM) RasGAP binding sites but incorporated a Grb2 binding motif at an alternate RasGAP binding site within the kinase domain had little effect on basal Erk MAPK activation. In contrast, elimination of all RasGAP binding sites, accompanied by the addition of a Grb2 binding site within the kinase domain, led to an increase in phospho-Erk levels in NG108 cells following ephrin-B1 stimulation. Functional assays indicated a correlation between neurite retraction and the ability of the EphB2 mutants to down-regulate Ras-Erk MAPK signaling. These data suggest that EphB2 can be designed to repress, stabilize, or activate the Ras-Erk MAPK pathway by the manipulation of RasGAP and Grb2 SH2 domain binding sites and support the notion that Erk MAPK regulation plays a significant role in axon guidance. The behavior of EphB2 variants with mutations in the JM region and kinase domains suggests an intricate pattern of regulation and target recognition by Eph receptors.     

Is there evidence for an age-related reduction in metabolic rate?

To determinewhether the age-related reduction in basal metabolic rate (BMR) isexplained by a quantitative and/or qualitative change in thecomponents of lean tissue, we conducted a cross-sectional study ingroups of young (n = 38, 18-35yr) and older (n = 24, 50-77 yr)healthy individuals. BMR was measured by indirect calorimetry. Bodycomposition was obtained by using dual-energy X-ray absorptiometry (DEXA), which permitted four compartments to be quantified [bone mineral mass, fat mass (FM), appendicular lean tissue mass(A_LTM), and nonappendicular leantissue mass (NA_LTM)].Absolute BMR and A_LTM were lower,whereas FM was significantly higher in the older, compared with young,subjects. BMR, adjusted for differences in FM,A_LTM, andNA_LTM, was significantly lower inthe older subjects by 644 kJ/day. In separate regression analyses ofBMR on body compartments, older subjects had significantly lowerregression coefficients for A_LTMand NA_LTM, compared with youngsubjects. Hence, the age-related decline in BMR is partly explained bya reduction in the quantity, as well as the metabolic activity, ofDEXA-derived lean tissue components.

     

A New Eurypterid (Chelicerata: Eurypterida) from the Upper Devonian Gogo Formation of Western Australia, With A Review of the Rhenopteridae

A new eurypterid, Rhenopterus waterstoni sp. nov., is described from the Gogo Formation (Frasnian, Upper Devonian) of Western Australia. This species is distinguished from related forms by the tuberculation of the anteriormost tergite and crenulated posterior margins of the carapace and opisthosomal segments. It is the only eurypterid specimen known from the Gogo Formation, the most complete eurypterid from Australia, and also the youngest representative of Rhenopterus in the fossil record. Structures retrieved from between the prosomal-opisthosomal juncture comprise polygonal tubes 30–40 μm in diameter, which are interpreted as sarcomeral sheaths of muscular tissue. Rhenopterus is reviewed: R. latus Størmer, 1936 is synonymized with R. diensti Størmer, 1936 as it is here recognized as a female sexual dimorph; R. maccarthyi (Kjellesvig-Waering, 1934) is an orthocone nautiloid.