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The Paleolithic-Threat hypothesis reviewed here posits that habitual efferent fainting can be traced back to fear-induced allelic polymorphisms that were selected into some genomes of anatomically, mitochondrially, and neurally modern humans (Homo sapiens sapiens) in the Mid-Paleolithic because of the survival advantage they conferred during periods of inescapable threat. We posit that during Mid-Paleolithic warfare an encounter with “a stranger holding a sharp object” was consistently associated with threat to life. A heritable hard- wired or firm-wired (prepotentiated) predisposition to abruptly increase vagal tone and collapse flaccidly rather than freeze or attempt to flee or fight in response to an approaching sharp object, a minor injury, or the sight of blood, polymorphism for the hemodynamically “paradoxical” flaccid- immobility in response to these stimuli may have increased some non-combatants’ chances of survival. This is consistent with the unusual age and sex pattern of fear-induced fainting. The Paleolithic-Threat hypothesis also predicts a link to various hypo-androgenic states (e.g. low dehydroxyepiandrosterone-sulfate. We offer five predictions testable via epidemiological, clinical, and ethological/primatological methods. The Paleolithic-Threat hypothesis has implications for research in the aftermath of man-made disasters, such as terrorism against civilians, a traumatic event in which this hypothesis predicts epidemics of fear-induced fainting

Developmental defects of enamel-stress histomarker rings (accentuated striae) may be a potential measure of diminished vagal tone in research on extreme stress such as exposure to combat. To develop an animal model of this measure, we examined the enamel of rat incisors which erupt continuously. We examined incisors from 15 stressed-colony rats and 7 control-rats for these histomarkers using the Visible Burrow System (VBS). VBS was developed to study combat stress in rats. No stress rings were found in any of the rat incisors examined. In contrast to humans, rats have likely evolved to prioritize incisor strength during combat stress. Studies of amelogenesis during combat stress in other rodents with continuously growing incisors are warranted. Laboratory animals such as rabbits or marmosets may be especially suitable, since they less frequently use their incisors for self defense.

Protocadherin X and Protocadherin Y (PCDHX and PCDHY) are cell-surface adhesion molecules expressed predominantly in the brain. The PCDHX/Y gene-pair was generated by an X-Y translocation approximately 3 million years ago (MYA) that gave rise to the Homo sapiens-specific region of Xq21.3 and Yp11.2 homology. Genes within this region are expected to code for sexually dimorphic human characteristics, including, for example, cerebral asymmetry a dimension of variation that has been suggested is relevant to psychosis. We examined differences in patients with schizophrenic or schizoaffective psychosis in the genomic sequence of PCDHX and PCDHY in coding and adjacent intronic sequences using denaturing high performance liquid chromatography (DHPLC). Three coding variants were detected in PCDHX and two in PCDHY. However, neither the coding variants nor the intronic polymorphisms could be related to psychosis within families. Low sequence variation suggests selective pressure against sequence change in modern humans in contrast to the structural chromosomal and sequence changes including fixed X-Y differences that occurred in this region earlier in hominid evolution. Our findings exclude sequence variation in PCDHX/Y as relevant to the aetiology of psychosis. However, we note the unusual status of this region with respect to X-inactivation. Further investigation of the epigenetic control of PCDHX/Y in relation to psychosis is warrant

The objective of this cross-sectional study was to determine how management practices on California dairies may be associated with bovine respiratory disease (BRD) in preweaned calves. A convenience sample of 100 dairies throughout California, providing a study population of 4,636 calves, were visited between May 2014 and April 2016. During each farm visit, in-person interviews with the herd manager or calf caretaker were conducted to collect information about herd demographics, maternity pen, colostrum and calf management, herd vaccinations, and dust abatement. A random sample of preweaned calves was identified and evaluated for the presence of BRD using a standardized tool. A survey-adjusted generalized linear mixed model with a logit link function was fitted with calf as the unit of analysis and dairy as the random effect. Mean study herd size (±SE) was 1,718 (±189.9) cows. Survey-adjusted estimates of breed types in the sample were 81.6% (±0.6) Holstein, 13.1% (±0.4) Jersey, and 5.3% (±0.5) crossbred or other purebred breeds, and calf sex proportions were 73.8% (±1.0) female and 26.2% (±1.0) male. Overall survey-adjusted BRD prevalence in the study herds was 6.91% (±0.69). Housing factors positively associated with BRD were metal hutches compared with wood hutches [odds ratio (OR) = 11.19; 95% confidence interval (CI) = 2.80-44.78], calf-to-calf contact in calves >75 d of age (OR = 9.95, 95% CI = 1.50-65.86), feeding Holstein calves 5.68 L of milk or replacer per day to Jersey calves (OR = 0.04; 95% CI = 0.01-0.28) were negatively associated with BRD. Our study identified management practices on California dairies with variability and that may contribute to differences in BRD prevalence, which will be incorporated into a risk-assessment tool to control and prevent BRD in preweaned dairy calves.

Two consanguineous families with Uner Tan Syndrome (UTS) were analyzed in relation to self-organizing processes in complex systems, and the evolutionary emergence of human bipedalism. The cases had the key symptoms of previously reported cases of UTS, such as quadrupedalism, mental retardation, and dysarthric or no speech, but the new cases also exhibited infantile hypotonia and are designated UTS Type-II. There were 10 siblings in Branch I and 12 siblings in Branch II. Of these, there were seven cases exhibiting habitual quadrupedal locomotion (QL): four deceased and three living. The infantile hypotonia in the surviving cases gradually disappeared over a period of years, so that they could sit by about 10 years, crawl on hands and knees by about 12 years. They began walking on all fours at around 14 years, habitually using QL. Neurological examinations showed normal tonus in their arms and legs, no Babinski sign, brisk tendon reflexes especially in the legs, and mild tremor. The patients could not walk in a straight line, but (except in one case) could stand up and maintain upright posture with truncal ataxia. Cerebello-vermial hypoplasia and mild gyral simplification were noted in their MRIs. The results of the genetic analysis were inconclusive: no genetic code could be identified as the triggering factor for the syndrome in these families. Instead, the extremely low socio-economic status of the patients was thought to play a role in the emergence of UTS, possibly by epigenetically changing the brain structure and function, with a consequent selection of ancestral neural networks for QL during locomotor development. It was suggested that UTS may be regarded as one of the unpredictable outcomes of self-organization within a complex system. It was also noted that the prominent feature of this syndrome, the diagonal-sequence habitual QL, generated an interference between ipsilateral hands and feet, as innon-humanprimates. It was suggested that this may have been the triggering factor for the attractor state “bipedal locomotion” (BL), which had visual and manual benefits for our ape-like ancestors, and therefore enhancing their chances for survival, with consequent developments in the psychomotor domain of humans. This was put forward as a novel theory of the evolution of BL in human beings.

This research sought to discover how readers of crime fiction novels interact with these texts utilizing a co-creative lens. A qualitative online survey was conducted on three popular crime fiction websites and the responses were analyzed using thematic analysis. It was found that, in contrast to prior research, crime fiction novel readers do not simply view crime fiction as a puzzle to be solved. Instead, they place a high degree of importance on the substantive elements of the fiction such as the quality and details of the plot, setting, and the characters constructed by the author. These findings indicate that crime fiction novel authors should note that their readers desire a more general and pleasurable reading experience than was previously thought. [ABSTRACT FROM AUTHOR]

Michael Gold1, Stefan Lorenzl2, Alistair J Stewart1, Bruce H Morimoto1, David R Williams3, Illana Gozes1,41Allon Therapeutics Inc, Vancouver, BC, Canada; 2Interdisciplinary Center for Palliative Medicine, Munich University Hospital Klinikum Grosshadern, Munich, Germany; 3Van Cleef/Roet Centre for Nervous Diseases, Monash University, Melbourne, Australia; 4The Dr Diana and Zelman Elton (Elbaum) Laboratory for Molecular Neuroendocrinology, The Lily and Avraham Gildor Chair for the Investigation of Growth Factors, The Adams Super Center for Brain Studies, and the Department of Human Molecular Genetics and Biochemistry, School of Neuroscience, Sackler Faculty of Medicine, Tel Aviv University, Tel Aviv, IsraelAbstract: Progressive supranuclear palsy (PSP) is a rare neurodegenerative disease characterized by the accumulation of tau protein aggregates in the basal ganglia, brainstem and cerebral cortex leading to rapid disease progression and death. The neurofibrillary tangles that define the neuropathology of PSP are comprised of aggregated 4R tau and show a well-defined distribution. Classically, PSP is diagnosed by symptoms that include progressive gait disturbance, early falls, vertical ophthalmoparesis, akinetic-rigid features, prominent bulbar dysfunction and fronto-subcortical dementia. There are currently no effective therapies for the treatment of this rapidly degenerating and debilitating disease. Davunetide is a novel neuroprotective peptide that is thought to impact neuronal integrity and cell survival through the stabilization of microtubules. Preclinical activity in models of tauopathy has been translated to clinical studies, demonstrating pharmacologic activity that has supported further development. Davunetide's efficacy and tolerability are being tested in a placebo-controlled study in PSP patients, making it the most advanced drug candidate in this indication. This review examines the disease characteristics of PSP, the rationale for treating PSP with davunetide and assesses some of the challenges of clinical trials in this patient population.Keywords: tau protein aggregates, neurodegenerative, neurofibrillary tangles

ABSTRACT The wave of democratisation that has occurred in many African countries has also had direct and profound implications for the manner in which the security sector in general, and [...]