Evolution of the human fear-circuitry and acute sociogenic pseudoneurological symptoms: The Neolithic balanced-polymorphism hypothesis

In light of the increasing threat of large-scale massacres such as terrorism against non-combatants (civilians), more attention is warranted not only to posttraumatic stress disorder (PTSD) but also to acute sociogenic pseudoneurological ("conversion") symptoms, especially epidemic sociogenic symptoms. We posit that conversion disorders are etiologically related to specific evolutionary pressures (inescapable threats to life) in the late stage of the human environment of evolutionary adaptedness (EEA). Bracha et al. have recently argued that from the neuroevolutionary perspective, medically unexplained efferent vasovagal syncope and medically unexplained craniofacial musculoskeletal pain in young otherwise healthy individuals, may be taxonomized as stress and fear-circuitry disorders. In the present article, we extend neuroevolutionary perspectives to acute pseudoneurological sociogenic ("conversive") symptoms: psychogenic non-epileptic attacks ("pseudoseizures"), epidemic sociogenic disorders (DSM-IV-TR Epidemic "Hysteria"), conversive motor deficits (pseudo-paralysis and pseudo-cerebellar symptoms), and psychogenic blindness. We hypothesize that these perplexing pseudoneurological stress-triggered symptoms, which constitute psychopathology in extant humans, are traceable to allele-variant polymorphisms which spread during the Neolithic EEA. During Neolithic warfare, conversive symptoms may have increased the survival odds for some non-combatants by visually (i.e., "non-verbally") signaling to predatory conspecifics that one does not present a danger. This is consistent with the age and sex pattern of conversive disorders. Testable and falsifiable predictions are presented; e.g., at the genome-transcriptome interface, one of the major oligogenic loci involved in conversive spectrum disorders may carry a developmentally sensitive allele in a stable polymorphism (balanced polymorphism) in which the gene expression mechanism is gradually suppressed by pleiotropic androgens especially dehydroxyepiandrosterone sulfate (DHEA-S). Taxonomic implications for the much-needed rapprochement between the forthcoming Diagnostic and Statistical Manual for Mental Disorders, Fifth Edition (DSM-V) and the International Classification of Diseases (ICD) are discussed

Combat and Warfare in the Early Paleolithic and Medically Unexplained Musculo-Facial Pain in the 21st Century War Veterns and Active-Duty Military Personnel

In a series of recent articles, we suggest that family dentists, military dentists and psychiatrists with expertise in posttraumatic stress disorder (especially in the Veterans Health Administration) are likely to see an increased number of patients with symptomatic jaw-clenching and early stages of tooth- grinding (Bracha et al., 2005). Returning warfighters and other returnees from military deployment may be especially at risk for high rates of clenching- induced masticatory muscle disorders at early stages of incisor grinding. The literature we have recently reviewed strongly supports the conclusion that clenching and grinding may primarily be a manifestation of experiencing extreme fear or severe chronic distress (respectively). We have recently reviewed the clinical and paleoanthropological literature and have noted that ancestral warfare and ancestral combat, in the early Paleolithic Environment of Evolutionary Adaptedness (EEA) may be a neglected factor explaining the conservation of the archaic trait of bite-muscle strengthening. We have hypothesized that among ancestral warriors, jaw clenching may have rapidly strengthened the two primary muscles involved in biting, the masseter muscles and the much larger temporalis muscles. The strengthening of these muscles may have served the purpose of enabling a stronger, deeper, and therefore more lethal, defensive bite for early Paleolithic humans. The neuroevolutionary perspective presented here may be novel to many dentists. However, it may be useful in patient education and in preventing progression from jaw-clenching to chronic facial pain

Spatiotemporal Analysis of the Molecular Interaction between PICK1 and PKC

PICK1 is a protein which was initially identified as a protein kinase Cα (αPKC) binding protein using the yeast two-hybrid system. In addition to αPKC, the PICK1 complex binds to and regulates various transmembrane proteins including receptors and transporters. However, it has not been clarified when and where PICK1 binds to αPKC. We examined the spatio­temporal interaction of PICK1 and PKC using live imaging techniques and showed that the activated αPKC binds to PICK1 and transports it to the plasma membrane. Although the membrane translocation of PICK1 requires the activation of αPKC, PICK1 is retained on the membrane even after PKC moves back to the cytosol. These results suggest that the interaction between αPKC and PICK1 is transient and may not be necessary for the regulation of receptors/transporters by PICK1 or by αPKC on the membrane

Effect of acute copper sulfate exposure on olfactory responses to amino acids and pheromones in goldfish (Carassius auratus)

Exposure of olfactory epithelium to environmentally relevant concentrations of copper disrupts olfaction in fish. To examine the dynamics of recovery at both functional and morphological levels after acute copper exposure, unilateral exposure of goldfish olfactory epithelia to 100 μM CuSO4 (10 min) was followed by electro-olfactogram (EOG) recording and scanning electron microscopy. Sensitivity to amino acids (L-arginine and L-serine), generally considered food-related odorants, recovered most rapidly (three days), followed by that to catecholamines(3-O-methoxytyramine),bileacids(taurolithocholic acid) and the steroid pheromone, 17,20 -dihydroxy-4-pregnen- 3-one 20-sulfate, which took 28 days to reach full recovery. Sensitivity to the postovulatory pheromone prostaglandin F2R had not fully recovered even at 28 days. These changes in sensitivity were correlated with changes in the recovery of ciliated and microvillous receptor cell types. Microvillous cells appeared largely unaffected by CuSO4 treatment. Cilia in ciliated receptor neurones, however, appeared damaged one day post-treatment and were virtually absent after three days but had begun to recover after 14 days. Together, these results support the hypothesis that microvillous receptor neurones detect amino acids whereas ciliated receptor neurones were not functional and are responsible for detection of social stimuli (bile acidsandpheromones).Furthermore, differences in sensitivity to copper may be due to different transduction pathways in the different cell types

Hard X-ray Detector (HXD) on Board Suzaku

The Hard X-ray Detector (HXD) on board Suzaku covers a wide energy range from 10 keV to 600 keV by combination of silicon PIN diodes and GSO scintillators. The HXD is designed to achieve an extremely low in-orbit back ground based on a combination of new techniques, including the concept of well-type active shield counter. With an effective area of 142 cm^2 at 20 keV and 273 cm2 at 150 keV, the background level at the sea level reached ~1x10^{-5} cts s^{-1} cm^{-2} keV^{-1} at 30 keV for the PI N diodes, and ~2x10^{-5} cts s^{-1} cm^{-2} keV^{-1} at 100 keV, and ~7x10^{-6} cts s^{-1} cm^{-2} keV^{-1} at 200 keV for the phoswich counter. Tight active shielding of the HXD results in a large array of guard counters surrounding the main detector parts. These anti-coincidence counters, made of ~4 cm thick BGO crystals, have a large effective area for sub-MeV to MeV gamma-rays. They work as an excellent gamma-ray burst monitor with limited angular resolution (~5 degree). The on-board signal-processing system and the data transmitted to the ground are also described.Comment: 35 pages, 25 figures and 4 tables; acceted for Publication of the Astronomical Society of Japa

Characterizing Loop Dynamics and Ligand Recognition in Human- and Avian-Type Influenza Neuraminidases via Generalized Born Molecular Dynamics and End-Point Free Energy Calculations

The comparative dynamics and inhibitor binding free energies of group-1 and group-2 pathogenic influenza A subtype neuraminidase (NA) enzymes are of fundamental biological interest and relevant to structure-based drug design studies for antiviral compounds. In this work, we present seven generalized Born molecular dynamics simulations of avian (N1)- and human (N9)-type NAs in order to probe the comparative flexibility of the two subtypes, both with and without the inhibitor oseltamivir bound. The enhanced sampling obtained through the implicit solvent treatment suggests several provocative insights into the dynamics of the two subtypes, including that the group-2 enzymes may exhibit similar motion in the 430-binding site regions but different 150-loop motion. End-point free energy calculations elucidate the contributions to inhibitor binding free energies and suggest that entropic considerations cannot be neglected when comparing across the subtypes. We anticipate the findings presented here will have broad implications for the development of novel antiviral compounds against both seasonal and pandemic influenza strains

Exposure assessment of process-related contaminants in food by biomarker monitoring

Exposure assessment is a fundamental part of the risk assessment paradigm, but can often present a number of challenges and uncertainties. This is especially the case for process contaminants formed during the processing, e.g. heating of food, since they are in part highly reactive and/or volatile, thus making exposure assessment by analysing contents in food unreliable. New approaches are therefore required to accurately assess consumer exposure and thus better inform the risk assessment. Such novel approaches may include the use of biomarkers, physiologically based kinetic (PBK) modelling-facilitated reverse dosimetry, and/or duplicate diet studies. This review focuses on the state of the art with respect to the use of biomarkers of exposure for the process contaminants acrylamide, 3-MCPD esters, glycidyl esters, furan and acrolein. From the overview presented, it becomes clear that the field of assessing human exposure to process-related contaminants in food by biomarker monitoring is promising and strongly developing. The current state of the art as well as the existing data gaps and challenges for the future were defined. They include (1) using PBK modelling and duplicate diet studies to establish, preferably in humans, correlations between external exposure and biomarkers; (2) elucidation of the possible endogenous formation of the process-related contaminants and the resulting biomarker levels; (3) the influence of inter-individual variations and how to include that in the biomarker-based exposure predictions; (4) the correction for confounding factors; (5) the value of the different biomarkers in relation to exposure scenario’s and risk assessment, and (6) the possibilities of novel methodologies. In spite of these challenges it can be concluded that biomarker-based exposure assessment provides a unique opportunity to more accurately assess consumer exposure to process-related contaminants in food and thus to better inform risk assessment