Evidence for Thalamic Involvement in the Thermal Grill Illusion: An fMRI Study

Perceptual illusions play an important role in untangling neural mechanisms underlying conscious phenomena. The thermal grill illusion (TGI) has been suggested as a promising model for exploring percepts involved in neuropathic pain, such as cold-allodynia (pain arising from contact with innocuous cold). The TGI is an unpleasant/painful sensation from touching juxtapositioned bars of cold and warm innocuous temperatures.To develop an MRI-compatible TGI-unit and explore the supraspinal correlates of the illusion, using fMRI, in a group of healthy volunteers.We constructed a TGI-thermode allowing the rapid presentation of warm(41°C), cold(18°C) and interleaved(41°C+18°C = TGI) temperatures in an fMRI-environment. Twenty volunteers were tested. The affective-motivational (“unpleasantness”) and sensory-disciminatory (“pain-intensity”) dimensions of each respective stimulus were rated. Functional images were analyzed at a corrected α-level <0.05.The TGI was rated as significantly more unpleasant and painful than stimulation with each of its constituent temperatures. Also, the TGI was rated as significantly more unpleasant than painful. Thermal stimulation versus neutral baseline revealed bilateral activations of the anterior insulae and fronto-parietal regions. Unlike its constituent temperatures the TGI displayed a strong activation of the right (contralateral) thalamus. Exploratory contrasts at a slightly more liberal threshold-level also revealed a TGI-activation of the right mid/anterior insula, correlating with ratings of unpleasantness(rho = 0.31).To the best of our knowledge, this is the first fMRI-study of the TGI. The activation of the anterior insula is consistent with this region's putative role in processing of homeostatically relevant feeling-states. Our results constitute the first neurophysiologic evidence of thalamic involvement in the TGI. Similar thalamic activity has previously been observed during evoked cold-allodynia in patients with central neuropathic pain. Our results further the understanding of the supraspinal correlates of the TGI-phenomenon and pave the way for future inquiries into if and how it may relate to neuropathic pain

Asymmetrical Gene Flow in a Hybrid Zone of Hawaiian Schiedea (Caryophyllaceae) Species with Contrasting Mating Systems

Asymmetrical gene flow, which has frequently been documented in naturally occurring hybrid zones, can result from various genetic and demographic factors. Understanding these factors is important for determining the ecological conditions that permitted hybridization and the evolutionary potential inherent in hybrids. Here, we characterized morphological, nuclear, and chloroplast variation in a putative hybrid zone between Schiedea menziesii and S. salicaria, endemic Hawaiian species with contrasting breeding systems. Schiedea menziesii is hermaphroditic with moderate selfing; S. salicaria is gynodioecious and wind-pollinated, with partially selfing hermaphrodites and largely outcrossed females. We tested three hypotheses: 1) putative hybrids were derived from natural crosses between S. menziesii and S. salicaria, 2) gene flow via pollen is unidirectional from S. salicaria to S. menziesii and 3) in the hybrid zone, traits associated with wind pollination would be favored as a result of pollen-swamping by S. salicaria. Schiedea menziesii and S. salicaria have distinct morphologies and chloroplast genomes but are less differentiated at the nuclear loci. Hybrids are most similar to S. menziesii at chloroplast loci, exhibit nuclear allele frequencies in common with both parental species, and resemble S. salicaria in pollen production and pollen size, traits important to wind pollination. Additionally, unlike S. menziesii, the hybrid zone contains many females, suggesting that the nuclear gene responsible for male sterility in S. salicaria has been transferred to hybrid plants. Continued selection of nuclear genes in the hybrid zone may result in a population that resembles S. salicaria, but retains chloroplast lineage(s) of S. menziesii

Stroke genetics informs drug discovery and risk prediction across ancestries

Previous genome-wide association studies (GWASs) of stroke - the second leading cause of death worldwide - were conducted predominantly in populations of European ancestry(1,2). Here, in cross-ancestry GWAS meta-analyses of 110,182 patients who have had a stroke (five ancestries, 33% non-European) and 1,503,898 control individuals, we identify association signals for stroke and its subtypes at 89 (61 new) independent loci: 60 in primary inverse-variance-weighted analyses and 29 in secondary meta-regression and multitrait analyses. On the basis of internal cross-ancestry validation and an independent follow-up in 89,084 additional cases of stroke (30% non-European) and 1,013,843 control individuals, 87% of the primary stroke risk loci and 60% of the secondary stroke risk loci were replicated (P < 0.05). Effect sizes were highly correlated across ancestries. Cross-ancestry fine-mapping, in silico mutagenesis analysis(3), and transcriptome-wide and proteome-wide association analyses revealed putative causal genes (such as SH3PXD2A and FURIN) and variants (such as at GRK5 and NOS3). Using a three-pronged approach(4), we provide genetic evidence for putative drug effects, highlighting F11, KLKB1, PROC, GP1BA, LAMC2 and VCAM1 as possible targets, with drugs already under investigation for stroke for F11 and PROC. A polygenic score integrating cross-ancestry and ancestry-specific stroke GWASs with vascular-risk factor GWASs (integrative polygenic scores) strongly predicted ischaemic stroke in populations of European, East Asian and African ancestry(5). Stroke genetic risk scores were predictive of ischaemic stroke independent of clinical risk factors in 52,600 clinical-trial participants with cardiometabolic disease. Our results provide insights to inform biology, reveal potential drug targets and derive genetic risk prediction tools across ancestries.</p

Plant hybrid zones affect biodiversity: tools for a genetic-based understanding of community structure

Plant hybrid zones are dynamic centers of ecological and evolutionary processes for plants and their associated communities. Studies in the wild and in gardens with synthetic crosses showed that hybrid eucalypts supported the greatest species richness and abundances of insect and fungal taxa. In an updated review of 152 case studies of taxa associated with diverse hybridizing systems, there were 43 (28%) cases of hybrids being more susceptible than their parent species, 7 (5%) resistant, 35 (23%) additive, 35 (23%) dominant, and 32 (21%) showed no response to hybridization. Thus, most taxa respond to hybrids in ways that result in equal or greater abundance, and hybrids tend to accumulate the taxa of their parent species. These studies suggest that genetic-based plant traits affect the distribution of many species and that the variation in hybrids can be used as tools to examine the genetic components of community structure and biodiversity. Several patterns have emerged thus far. (1) Genetic variation between classes of hybrids (e.g., F1's vs. backcrosses) may equal or even exceed that found between species. (2) As a reflection of this genetic variation, herbivores are more likely to differentiate between hybrid classes than they are to differentiate between pure plant species. (3) The communities associated with different hybrid classes can differ from one another as well as from their parental species. (4) Generalist and specialist herbivores predictably vary in their responses to hybrids. (5) Plant hybrid zones may represent essential habitat for some arthropod species. (6) Even nesting birds respond to hybridizing plants. (7) Including multiple trophic levels and taxa from microbes to vertebrates, susceptible hybrid genotypes support greater biodiversity than resistant genotypes. (8) The effects of hybridization on common or keystone species can either positively or negatively affect biodiversity. The indirect impacts of hybridization on biodiversity may exceed the direct impacts and may result in 'apparent' herbivore resistance or susceptibility at the community level. (9) Although hybrids are often maligned, exotic or problem hybrids generally result from human disturbances, whereas native hybrids are part of natural ecosystems and should be conserved. Three predictions are made: (1) Intermediate genetic differences between the parental species will result in the greatest genetic variation in the hybrid zone, which in turn will have a positive effect on biodiversity. (2) Bidirectional introgression enhances species richness on hybrids, whereas F1 sterility and unidirectional introgression limit the accumulation of species on hybrids. (3) Although susceptible hybrids are likely to support the greatest biodiversity, the impacts of hybridization on keystone species will be crucial in determining the overall effect

Plant hybrid zones affect biodiversity: tools for a genetic-based understanding of community structure

Plant hybrid zones are dynamic centers of ecological and evolutionary processes for plants and their associated communities. Studies in the wild and in gardens with synthetic crosses showed that hybrid eucalypts supported the greatest species richness and abundances of insect and fungal taxa. In an updated review of 152 case studies of taxa associated with diverse hybridizing systems, there were 43 (28%) cases of hybrids being more susceptible than their parent species, 7 (5%) resistant, 35 (23%) additive, 35 (23%) dominant, and 32 (21%) showed no response to hybridization. Thus, most taxa respond to hybrids in ways that result in equal or greater abundance, and hybrids tend to accumulate the taxa of their parent species. These studies suggest that genetic-based plant traits affect the distribution of many species and that the variation in hybrids can be used as tools to examine the genetic components of community structure and biodiversity. Several patterns have emerged thus far. (1) Genetic variation between classes of hybrids (e.g., F1's vs. backcrosses) may equal or even exceed that found between species. (2) As a reflection of this genetic variation, herbivores are more likely to differentiate between hybrid classes than they are to differentiate between pure plant species. (3) The communities associated with different hybrid classes can differ from one another as well as from their parental species. (4) Generalist and specialist herbivores predictably vary in their responses to hybrids. (5) Plant hybrid zones may represent essential habitat for some arthropod species. (6) Even nesting birds respond to hybridizing plants. (7) Including multiple trophic levels and taxa from microbes to vertebrates, susceptible hybrid genotypes support greater biodiversity than resistant genotypes. (8) The effects of hybridization on common or keystone species can either positively or negatively affect biodiversity. The indirect impacts of hybridization on biodiversity may exceed the direct impacts and may result in apparent‚ÄövÑvp herbivore resistance or susceptibility at the community level. (9) Although hybrids are often maligned, exotic or problem hybrids generally result from human disturbances, whereas native hybrids are part of natural ecosystems and should be conserved. Three predictions are made: (1) Intermediate genetic differences between the parental species will result in the greatest genetic variation in the hybrid zone, which in turn will have a positive effect on biodiversity. (2) Bidirectional introgression enhances species richness on hybrids, whereas F1 sterility and unidirectional introgression limit the accumulation of species on hybrids. (3) Although susceptible hybrids are likely to support the greatest biodiversity, the impacts of hybridization on keystone species will be crucial in determining the overall effect

Regulation of calcium channels in smooth muscle: new insights into the role of myosin light chain kinase

Smooth muscle myosin light chain kinase (MLCK) plays a crucial role in artery contraction, which regulates blood pressure and blood flow distribution. In addition to this role, MLCK contributes to Ca(2+) flux regulation in vascular smooth muscle (VSM) and in non-muscle cells, where cytoskeleton has been suggested to help Ca(2+) channels trafficking. This conclusion is based on the use of pharmacological inhibitors of MLCK and molecular and cellular techniques developed to down-regulate the enzyme. Dissimilarities have been observed between cells and whole tissues, as well as between large conductance and small resistance arteries. A differential expression in MLCK and ion channels (either voltage-dependent Ca(2+) channels or non-selective cationic channels) could account for these observations, and is in line with the functional properties of the arteries. A potential involvement of MLCK in the pathways modulating Ca(2+) entry in VSM is described in the present review