The Way forward for the Origin of Life: Prions and Prion-Like Molecules First Hypothesis.

In this paper the hypothesis that prions and prion-like molecules could have initiated the chemical evolutionary process which led to the eventual emergence of life is reappraised. The prions first hypothesis is a specific application of the protein-first hypothesis which asserts that protein-based chemical evolution preceded the evolution of genetic encoding processes. This genetics-first hypothesis asserts that an "RNA-world era" came before protein-based chemical evolution and rests on a singular premise that molecules such as RNA, acetyl-CoA, and NAD are relics of a long line of chemical evolutionary processes preceding the Last Universal Common Ancestor (LUCA). Nevertheless, we assert that prions and prion-like molecules may also be relics of chemical evolutionary processes preceding LUCA. To support this assertion is the observation that prions and prion-like molecules are involved in a plethora of activities in contemporary biology in both complex (eukaryotes) and primitive life forms. Furthermore, a literature survey reveals that small RNA virus genomes harbor information about prions (and amyloids). If, as has been presumed by proponents of the genetics-first hypotheses, small viruses were present during an RNA world era and were involved in some of the earliest evolutionary processes, this places prions and prion-like molecules potentially at the heart of the chemical evolutionary process whose eventual outcome was life. We deliberate on the case for prions and prion-like molecules as the frontier molecules at the dawn of evolution of living systems.

High risk genotypes for schizophrenia may have been adaptive in the context of smallpox.

Schizophrenia is known to impair reproductive and occupational functioning, and thus, the condition would appear to be a poorly adaptive trait. In contrast to expectations, the high frequency of schizophrenia, coupled with the existence of differing but analogous high schizophrenia risk polymorphisms across the globe, suggest that high risk schizophrenia genotypes could have experienced some positive rather than negative selection pressures. Indeed, the set of cellular and tissue processes influenced by schizophrenia - including manipulations of oligodendrocyte development, complement mediated immunity, VRK2, sulfation of heparin, IL-18, availability of glutamate, and interactions with sex hormones - overlaps with the set of cellular and tissue processes affected during Vaccinia encephalitis. Many schizophrenia-associated influences appear to oppose orthopoxvirus related influences; and many of the proteins suppressed in the schizophrenia phenotype are proteins either produced by or necessary for Vaccinia. Accounts from the early part of the 20th century affirm that Vaccinia encephalitis resembles Variola encephalitis; and genomic sequencing studies confirm significant homology between the species. On the basis of similarity of Variola to Vaccinia, and on the basis of evidence derived from studies on Vaccinia and other orthopoxviruses, it is proposed that high schizophrenia risk genotypes may have served a protective function against smallpox.

M2-like cells from the macrophage lineage might play a central role in closure of the embryonic neural tube.

Herein it is hypothesized that M2-like macrophages or pre-macrophages of fetal origin might play a central role in development and closure of the neural tube. Early in embryonic development, pre-macrophages arise from the fetal yolk sac and track through the bloodstream to reach diverse embryonic tissues, where they mature. Most of these macrophages exhibit an M2-like phenotype. The critical period for neural tube closure is contained within the period of yolk sac-derived pre-macrophage tracking and distribution, which poses a question: might these pre-macrophages or macrophages exert an influence on the closing neural tube? Evidence suggests that perturbations in macrophage polarization or M2 macrophage function might contribute to the failure of neural tube closure associated with diabetes mellitus, one carbon metabolism (including folic acid deficit), inositol, arachidonic acid, and sphingosine-1-phosphate, as well as in the teratogenicity of nitric acid, valproic acid, and fumonisin. The influence of each of these factors is interpreted in light of potential interactions with M2-like macrophages or macrophage progenitors on the developing neural tube. By placing these anti inflammatory macrophages at the center of various epigenetic, neurochemical, and signaling processes suspected to be involved in neural tube closure, potential associations are revealed between macrophages and embryonic structural developmental processes such as collagen and actin dynamics. The choice of this model is also an attempt to explain why some etiologies for failure of neural tube closure are rescued by folic acid, whereas other etiologies are rescued only by formate, inositol, or not at all.

Nineteenth-Century Homeopathic Repertories Predict Increased Urinary Excretion of Bile in Cholestasis but Not in Non-Cholestatic Infant Jaundice.

INTRODUCTION: There are two types of bilirubin: conjugated bilirubin, prevalent in cholestatic jaundice, and unconjugated bilirubin, prevalent in hematologic jaundice. Conjugated bilirubin is water soluble and is excreted in urine, whereas unconjugated bilirubin is neither water soluble nor excreted in urine. Homeopathic repertories published prior to the discovery of the two types of bilirubin in 1913 present an opportunity to test the reliability of homeopathic repertories and associated materia medica. If procedures involved in the collecting of homeopathic observations are reliable, then in repertories published prior to 1913, medicines listed for cholestatic jaundice should exhibit a stronger association with urine bile than medicines listed for hematologic jaundice. MATERIALS AND METHODS: In three repertories published prior to 1913, medicines associated with jaundice were further classified into groups labeled "Cholestatic" or "Infant, mostly hematologic". Medicines were identified as "Cholestatic" if associated with both white/clay-colored stool and liver/gallbladder symptoms. Medicines were identified as "Infant, mostly hematologic" if associated with infant jaundice without meeting criteria for the "Cholestatic" group. Controls were medicines appearing in Hahnemann's Materia Medica Pura. Each category was assessed for green urine-usually reflective of bile in urine. RESULTS: In Knerr's repertory, the "Cholestatic" group demonstrated a significantly greater association with green urine than controls (p < 0.05, Fisher's exact test), whereas the "Infant, mostly hematologic" group did not differ significantly from controls. For Lippe's and Boenninghausen's repertories, statistical significance was not demonstrated. Across repertories, the overall weighted pooled odds ratio (OR) demonstrated significance in the association between the "Cholestatic" group and green urine (OR, 2.384; 95% confidence interval, 1.234 to 4.607), whereas the "Infant, mostly hematologic" group was similar to that of controls (OR, 0.754; 95% confidence interval, 0.226 to 2.514). CONCLUSIONS: Based on the presence or absence of bile in the urine, homeopathic repertories from the 19th century can distinguish between disease processes involving conjugated bilirubin and disease processes involving unconjugated bilirubin.

Nineteenth-Century Homeopathic Materia Medica Texts Predict Source Materials Whose Physiological Actions Influence Thyroid Activity.

INTRODUCTION: The homeopathic materia medica contains hundreds of thousands of observations collected over the course of two centuries. It includes both clinical observations of potentized medicines and observations of the actions of potentized medicines on healthy subjects (provings). This current study was undertaken to determine the degree to which observations within the materia medica were associated with the physiological mechanisms for thyroid activity-inhibiting substances in their undiluted state. MATERIALS AND METHODS: Four specific symptoms for iodine deficiency were selected to describe the hypothyroid state: (1) generalized aggravation by or sensitivity to cold; (2) chronic painless hoarseness; (3) goiter; (4) painless diffuse non-scarring alopecia. Symptom representation for the four selected symptoms within the homeopathic materia medica was compared for 2 halogen inhibitors, for 3 substances that influence thyroid hormone target tissues, for 6 substances known or suspected to increase thyroid-stimulating hormone or decrease thyroid hormone levels, and for 11 substances not known to inhibit thyroid activity. To avoid knowledge bias, only those compilations of materia medica whose publication dates preceded the discoveries of crucial aspects of thyroid physiology were used as source materials for investigation. RESULTS: Homeopathic medicines derived from 11 substances with mechanisms for inhibition of thyroid activity were more likely to exhibit selected symptoms than the medicines derived from the 11 substances without known physiological mechanisms for thyroid activity inhibition. The difference between groups was analyzed via the Mann-Whitney non-parametric U test and was statistically significant to p < 0.01. After observations obtained from provings alone were removed from analysis, the difference remained significant to p < 0.01. Only the two halogen inhibitors of iodine (bromine and fluoric acid) and one of the influencers of thyroid hormone target tissue (calcium carbonate) were significantly goitrogenic. CONCLUSIONS: With respect to thyroid activity inhibition, there is a statistically significant association between observations recorded within the homeopathic materia medica and the expected physiological mechanisms for the corresponding undiluted substances.

Alzheimer's disease might depend on enabling pathogens which do not necessarily cross the blood-brain barrier.

The development of Alzheimer's Disease (AD) might reflect, in its acquired aspects, a cooperative pathogenesis whereby infectious enablers which do not necessarily cross the blood-brain barrier augment the invasive properties of a less virulent organism, thus enabling it to infect the brain. An example interaction is described which involves Chlamydia species, Human papillomavirus (HPV), microbiota, and yeast, where yeast is a pathogen of low virulence which crosses the blood-brain barrier. The cooperative pathogenesis begins at the mucosal epithelium. Infection by Chlamydia, HPV, or dysbiosis of commensal bacteria disrupts the integrity of the mucosal epithelium, thereby allowing colonizing yeast to penetrate the epithelial barrier and enter into the bloodstream. Chlamydia and enabling commensals promote insulin resistance, which provides yeast with glucose and also sets the stage for accumulation of amyloid beta protein (ABP). Meanwhile, HPV-induced and hyperglycemia-induced immunological changes enable the spread of newly invasive yeast to the brain, where the release of inflammatory cytokines in response to yeast promotes production of ABP. Chlamydia also cross reacts with Candida species, which may stimulate further brain inflammation in response to Candida and may augment production of ABP thereby The yeast's less virulent origins, coupled with immune modulation by enablers, might explain why AD as a model of infectious encephalitis is always slow and insidious rather than occasionally febrile, accompanied by seizures, or marked by signs of meningeal inflammation.

Ethnodrama: An Innovative Knowledge Translation Tool in the Management of Lymphedema.

BACKGROUND: Lymphedema can cause significant physical impairment and quality-of-life issues. Yet there is a gap in knowledge about lymphedema among breast cancer survivors (BCS), and health care professionals (HCP). Ethnodrama is an innovative knowledge translation strategy that uses theatrical performances for dissemination of research results. We evaluated the impact of live ethnodrama on HCP' and BCS' awareness and attitudes in relation to impact of lymphedema on BCS' lives. METHODS: Ethnodrama performances were developed by script writers and a theatre director in collaboration with the investigators and BCS using data from published research and pre-performances workshops. Six interactive live performances were given to audiences of BCS, HCP, and community members in four cities across Canada. After watching these live performances, members of the audiences were asked to complete a paper-based questionnaire regarding their knowledge of lymphedema, and their attitudes and practices toward lymphedema. RESULTS: Of 238 audience members who participated in the survey, 55 (23%) were BCS and 85 (37.5%) were HCP. Most members rated the performances as very effective in changing their (84%) or other people's (93%) understanding of lymphedema; 96% reported being motivated to seek additional information on lymphedema, and 72% of HCP anticipated changes in their practices related to lymphedema screening. Overall no significant differences were noted in responses to ethnodrama between BCS and HCP. Open-ended responses were supportive of the findings from the closed-ended questions. CONCLUSIONS: Our results indicate that ethnodrama performances effectively convey information and positively affecting changes in HCP' and BCS' attitudes toward lymphedema.

The aesthetic rationality of the popular expressive arts: Lifeworld communication among breast cancer survivors living with lymphedema.

The use of popular expressive arts as antidotes to the pathologies of the parallel processes of lifeworld colonization and cultural impoverishment has been under-theorized. This article enters the void with a project in which breast cancer survivors used collages and installations of everyday objects to solicit their authentic expression of the psycho-social impacts of lymphedema. The article enlists Jurgen Habermas' communicative action theory to explore the potential of these expressive arts to expand participants' meaningful engagement with their lifeworlds. The findings point to the unique non-linguistic discursivity of these non-institutional artistic forms as their liberating power to disclose silenced human needs: the images 'spoke' for themselves for group members to recognize shared subjectivities. The authenticity claims inherent in the art forms fostered collective reflexivity and spontaneous, affective responses and compelled the group to create new collective understandings of the experience of living with lymphedema. The article contributes theoretical insights regarding the emancipatory potential of aesthetic-expressive rationality, an under-developed area of Habermasian theory of communicative action, and to the burgeoning literature on arts-based methods in social scientific research.