One versus two eyes makes a difference! Early face perception is modulated by featural fixation and feature context

The final publication is available at Elsevier via https://doi.org/10.1016/j.cortex.2018.08.025 © 2018. This manuscript version is made available under the CC-BY-NC-ND 4.0 license http://creativecommons.org/licenses/by-nc-nd/4.0/The N170 event-related potential component is an early marker of face perception that is particularly sensitive to isolated eye regions and to eye fixations within a face. Here, this eye sensitivity was tested further by measuring the N170 to isolated facial features and to the same features fixated within a face, using a gaze-contingent procedure. The neural response to single isolated eyes and eye regions (two eyes) was also compared. Pixel intensity and contrast were controlled at the global (image) and local (featural) levels. Consistent with previous findings, larger N170 amplitudes were elicited when the left or right eye was fixated within a face, compared to the mouth or nose, demonstrating that the N170 eye sensitivity reflects higher-order perceptual processes and not merely low-level perceptual effects. The N170 was also largest and most delayed for isolated features, compared to equivalent fixations within a face. Specifically, mouth fixation yielded the largest amplitude difference, and nose fixation yielded the largest latency difference between these two contexts, suggesting the N170 may reflect a complex interplay between holistic and featural processes. Critically, eye regions elicited consistently larger and shorter N170 responses compared to single eyes, with enhanced responses for contralateral eye content, irrespective of eye or nasion fixation. These results confirm the importance of the eyes in early face perception, and provide novel evidence of an increased sensitivity to the presence of two symmetric eyes compared to only one eye, consistent with a neural eye region detector rather than an eye detector per se.Natural Sciences and Engineering Research Council of Canada || NSERC #418431 Canada Foundation for Innovation || CFI # 213322 Canada Research Chair program || CRC #213322 and 23040

From eye to face: The impact of face outline, feature number, and feature saliency on the early neural response to faces

The final publication is available at Elsevier via https://doi.org/10.1016/j.brainres.2019.146343. © 2019. This manuscript version is made available under the CC-BY-NC-ND 4.0 license http://creativecommons.org/licenses/by-nc-nd/4.0/The LIFTED model of early face perception postulates that the face-sensitive N170 event-related potential may reflect underlying neural inhibition mechanisms which serve to regulate holistic and featural processing. It remains unclear, however, what specific factors impact these neural inhibition processes. Here, N170 peak responses were recorded whilst adults maintained fixation on a single eye using a gaze-contingent paradigm, and the presence/absence of a face outline, as well as the number and type of parafoveal features within the outline, were manipulated. N170 amplitudes and latencies were reduced when a single eye was fixated within a face outline compared to fixation on the same eye in isolation, demonstrating that the simple presence of a face outline is sufficient to elicit a shift towards a more face-like neural response. A monotonic decrease in the N170 amplitude and latency was observed with increasing numbers of parafoveal features, and the type of feature(s) present in parafovea further modulated this early face response. These results support the idea of neural inhibition exerted by parafoveal features onto the foveated feature as a function of the number, and possibly the nature, of parafoveal features. Specifically, the results suggest the use of a feature saliency framework (eyes > mouth > nose) at the neural level, such that the parafoveal eye may play a role in down-regulating the response to the other eye (in fovea) more so than the nose or the mouth. These results confirm the importance of parafoveal features and the face outline in the neural inhibition mechanism, and provide further support for a feature saliency mechanism guiding early face perception.This work was supported by the Natural Sciences and Engineering Research Council of Canada (NSERC #418431), the Canada Research Chair program (CRC #213322 and 230407) and the Canada Foundation for Innovation (CFI # 213322), awarded to RJI. KBP was supported by an NSERC Alexander Graham Bell Canada Graduate Scholarship Master’s Award and a Canadian Institutes of Health Research (CIHR) Charles Best and Frederick Banking Doctoral Research Award for the course of this work

Alcohol exposure during late gestation: Multiple developmental outcomes in sheep

Alcohol consumption during pregnancy remains common in many countries. Exposure to even low amounts of alcohol (i.e. ethanol) in pregnancy can lead to the heterogeneous fetal alcohol spectrum disorders (FASD), while heavy alcohol consumption can result in the fetal alcohol syndrome (FAS). FAS is characterized by cerebral dysfunction, growth restriction and craniofacial malformations. However, the effects of lower doses of alcohol during pregnancy, such as those that lead to FASD, are less well understood. In this article, we discuss the findings of recent studies performed in our laboratories on the effects of fetal alcohol exposure using sheep, in which we investigated the effects of late gestational alcohol exposure on the developing brain, arteries, kidneys, heart and lungs. Our studies indicate that alcohol exposure in late gestation can (1) affect cerebral white matter development and increase the risk of hemorrhage in the fetal brain, (2) cause left ventricular hypertrophy with evidence of altered cardiomyocyte maturation, (3) lead to a decrease in nephron number in the kidney, (4) cause altered arterial wall stiffness and endothelial and smooth muscle function and (5) result in altered surfactant protein mRNA expression, surfactant phospholipid composition and pro-inflammatory cytokine mRNA expression in the lung. These findings suggest that fetal alcohol exposure in late gestation can affect multiple organs, potentially increasing the risk of disease and organ dysfunction in later life

Fire and human management of late Holocene ecosystems in southern Africa

Globally, fire is a primary agent for modifying environments through the long-term coupling of human and natural systems. In southern Africa, control of fire by humans has been documented since the late Middle Pleistocene, though it is unclear when or if anthropogenic burning led to fundamental shifts in the region\u27s fire regimes. To identify potential periods of broad-scale anthropogenic burning, we analyze aggregated Holocene charcoal sequences across southern Africa, which we compare to paleoclimate records and archaeological data. We show climate-concordant variability in mid-Holocene fire across much of the subcontinent. However, increased regional fire activity during the late Holocene (~2000 BP) coincides with archaeological change, especially the introduction and intensification of food production across the region. This increase in fire is not readily explained by climate changes, but rather reflects a novel way of using fire as a tool to manage past landscapes, with outcomes conditioned by regional ecosystem characteristics

TRPM8 and Nav1.8 sodium channels are required for transthyretin-induced calcium influx in growth cones of small-diameter TrkA-positive sensory neurons

<p>Abstract</p> <p>Background</p> <p>Familial amyloidotic polyneuropathy (FAP) is a peripheral neuropathy caused by the extracellular accumulation and deposition of insoluble transthyretin (TTR) aggregates. However the molecular mechanism that underlies TTR toxicity in peripheral nerves is unclear. Previous studies have suggested that amyloidogenic proteins can aggregate into oligomers which disrupt intracellular calcium homeostasis by increasing the permeability of the plasma membrane to extracellular calcium. The aim of the present study was to examine the effect of TTR on calcium influx in dorsal root ganglion neurons.</p> <p>Results</p> <p>Levels of intracellular cytosolic calcium were monitored in dorsal root ganglion (DRG) neurons isolated from embryonic rats using the calcium-sensitive fluorescent indicator Fluo4. An amyloidogenic mutant form of TTR, L55P, induced calcium influx into the growth cones of DRG neurons, whereas wild-type TTR had no significant effect. Atomic force microscopy and dynamic light scattering studies confirmed that the L55P TTR contained oligomeric species of TTR. The effect of L55P TTR was decreased by blockers of voltage-gated calcium channels (VGCC), as well as by blockers of Na_v1.8 voltage-gated sodium channels and transient receptor potential M8 (TRPM8) channels. siRNA knockdown of TRPM8 channels using three different TRPM8 siRNAs strongly inhibited calcium influx in DRG growth cones.</p> <p>Conclusions</p> <p>These data suggest that activation of TRPM8 channels triggers the activation of Na_v1.8 channels which leads to calcium influx through VGCC. We suggest that TTR-induced calcium influx into DRG neurons may contribute to the pathophysiology of FAP. Furthermore, we speculate that similar mechanisms may mediate the toxic effects of other amyloidogenic proteins such as the β-amyloid protein of Alzheimer's disease.</p

Erythrocyte transketolase activity coefficient (ETKAC) assay protocol for the assessment of thiamine status

Abstract: Vitamin B1 (thiamine) is an essential nutrient that acts as a cofactor for a number of metabolic processes, particularly in energy metabolism. Symptoms of classic thiamine deficiency are recognized as beriberi, although clinical symptoms are nonspecific and recognition of subclinical deficiency is difficult. Therefore, reliable biomarkers of thiamine status are required. Thiamine diphosphate is a cofactor for transketolase, including erythrocyte transketolase (ETK). The ETK activity assay as an indirect, functional marker of thiamine status has been used for over 50 years. The ETK activity assay provides a sensitive and specific biomarker of thiamine status; however, there is a lack of consensus over the cutoffs for deficiency, partly due to a lack of assay harmonization. Here, we provide a step‐by‐step protocol for the measurement of ETK activity and the calculation of the ETK activity coefficient, including detailed explanations of equipment and chemicals required and guidance for quality control procedures. Harmonization of the protocol will provide the basis for the development of internationally recognized cutoffs for thiamine insufficiency. The establishment of quality control materials and a quality assurance scheme are recommended to provide reliability. This will ensure that the ETK activity assay remains an important method for the assessment of thiamine status

Vascular responses of the extremities to transdermal application of vasoactive agents in Caucasian and African descent individuals

This is an accepted manuscript of an article published by Springer in European Journal of Applied Physiology on 04/04/2015, available online: https://doi.org/10.1007/s00421-015-3164-2 The accepted version of the publication may differ from the final published version.© 2015, Springer-Verlag Berlin Heidelberg. Purpose: Individuals of African descent (AFD) are more susceptible to non-freezing cold injury than Caucasians (CAU) which may be due, in part, to differences in the control of skin blood flow. We investigated the skin blood flow responses to transdermal application of vasoactive agents. Methods: Twenty-four young males (12 CAU and 12 AFD) undertook three tests in which iontophoresis was used to apply acetylcholine (ACh 1 w/v %), sodium nitroprusside (SNP 0.01 w/v %) and noradrenaline (NA 0.5 mM) to the skin. The skin sites tested were: volar forearm, non-glabrous finger and toe, and glabrous finger (pad) and toe (pad). Results: In response to SNP on the forearm, AFD had less vasodilatation for a given current application than CAU (P = 0.027–0.004). ACh evoked less vasodilatation in AFD for a given application current in the non-glabrous finger and toe compared with CAU (P = 0.043–0.014) with a lower maximum vasodilatation in the non-glabrous finger (median [interquartile], AFD n = 11, 41[234] %, CAU n = 12, 351[451] %, P = 0.011) and non-glabrous toe (median [interquartile], AFD n = 9, 116[318] %, CAU n = 12, 484[720] %, P = 0.018). ACh and SNP did not elicit vasodilatation in the glabrous skin sites of either group. There were no ethnic differences in response to NA. Conclusion: AFD have an attenuated endothelium-dependent vasodilatation in non-glabrous sites of the fingers and toes compared with CAU. This may contribute to lower skin temperature following cold exposure and the increased risk of cold injuries experienced by AFD.Published versio

Perilipin 5 Deletion Unmasks an Endoplasmic Reticulum Stress-Fibroblast Growth Factor 21 Axis in Skeletal Muscle.

Lipid droplets (LDs) are critical for the regulation of lipid metabolism, and dysregulated lipid metabolism contributes to the pathogenesis of several diseases, including type 2 diabetes. We generated mice with muscle-specific deletion of the LD-associated protein perilipin 5 (PLIN5, Plin5MKO ) and investigated PLIN5's role in regulating skeletal muscle lipid metabolism, intracellular signaling, and whole-body metabolic homeostasis. High-fat feeding induced changes in muscle lipid metabolism of Plin5MKO mice, which included increased fatty acid oxidation and oxidative stress but, surprisingly, a reduction in inflammation and endoplasmic reticulum (ER) stress. These muscle-specific effects were accompanied by whole-body glucose intolerance, adipose tissue insulin resistance, and reduced circulating insulin and C-peptide levels in Plin5MKO mice. This coincided with reduced secretion of fibroblast growth factor 21 (FGF21) from skeletal muscle and liver, resulting in reduced circulating FGF21. Intriguingly, muscle-secreted factors from Plin5MKO , but not wild-type mice, reduced hepatocyte FGF21 secretion. Exogenous correction of FGF21 levels restored glycemic control and insulin secretion in Plin5MKO mice. These results show that changes in lipid metabolism resulting from PLIN5 deletion reduce ER stress in muscle, decrease FGF21 production by muscle and liver, and impair glycemic control. Further, these studies highlight the importance for muscle-liver cross talk in metabolic regulation

A computational model of excitation and contraction in uterine myocytes from the pregnant rat

Aberrant uterine myometrial activities in humans are major health issues. However, the cellular and tissue mechanism(s) that maintain the uterine myometrium at rest during gestation, and that initiate and maintain long-lasting uterine contractions during delivery are incompletely understood. In this study we construct a computational model for describing the electrical activity (simple and complex action potentials), intracellular calcium dynamics and mechanical contractions of isolated uterine myocytes from the pregnant rat. The model reproduces variant types of action potentials – from spikes with a smooth plateau, to spikes with an oscillatory plateau, to bursts of spikes – that are seen during late gestation under different physiological conditions. The effects of the hormones oestradiol (via reductions in calcium and potassium selective channel conductance), oxytocin (via an increase in intracellular calcium release) and the tocolytic nifedipine (via a block of L-type calcium channels currents) on action potentials and contractions are also reproduced, which quantitatively match to experimental data. All of these results validated the cell model development. In conclusion, the developed model provides a computational platform for further investigations of the ionic mechanism underlying the genesis and control of electrical and mechanical activities in the rat uterine myocytes