Geopsychology and geopsychopathology: mental processes and disorders associated with geochemical and geophysical factors

Temporal and regional variations in psychological processes have been associated with three geological factors. They are geochemical profiles, geomagnetic variations, and tectonic stresses. In the geochemical domain, copper, aluminum, zinc, and lithium may influence the incidence of thought disorders such as schizophrenia and senile dementia. These common elements are found in many soils and ground water. Geomagnetic variations have been correlated with enhanced anxiety, sleep disturbances, altered moods, and greater incidences of psychiatric admissions. The effects are usually brief but pervasive. Transient and very local epidemics of bizarre and unusual behaviors are sociological phenomena that sometimes precede increases in earthquake activity within a region; they have been hypothesized to be associated with tectonic strain. Many of the contemporary correlations between geological factors and human behavior are also apparent within historical data. The effects of geophysical and geochemical factors upon human behavior are not artifactual, but they are complex and often not detected by the limited scope of most studies.     

The emerging roles for the chromatin structure regulators CTCF and cohesin in neurodevelopment and behavior

Recent genetic and technological advances have determined a role for chromatin structure in neurodevelopment. In particular, compounding evidence has established roles for CTCF and cohesin, two elements that are central in the establishment of chromatin structure, in proper neurodevelopment and in regulation of behavior. Genetic aberrations in CTCF, and in subunits of the cohesin complex, have been associated with neurodevelopmental disorders in human genetic studies, and subsequent animal studies have established definitive, although sometime opposing roles, for these factors in neurodevelopment and behavior. Considering the centrality of these factors in cellular processes in general, the mechanisms through which dysregulation of CTCF and cohesin leads specifically to neurological phenotypes is intriguing, although poorly understood. The connection between CTCF, cohesin, chromatin structure, and behavior is likely to be one of the next frontiers in our understanding of the development of behavior in general, and neurodevelopmental disorders in particular.     

The epidemiology of dental caries in relation to environmental trace elements

This paper reviews the influence of the geochemical environment on the epidemiology of human dental caries. The best documented association is that between water borne fluoride and reduced caries prevalence. The influence of fluoride was first reported during the early decades of this century in Colorado, USA, and led to the fluoridation of some public water supplies in several countries. In all cases, fluoridation has been followed by significant improvements in dental health and no adverse effects in general health. Other trace elements in food and water have now been linked with dental caries. Molybdenum has been associated with reduced caries prevalence whereas selenium and lead appear to have adverse effects. Cavity formation in teeth probably involves a localised dissolution of the enamel surface by the products of bacterial activity. It is possible that the incorporation of trace metals into the apatite microcrystals of enamel may alter their physical properties, especially solubility, and hence their susceptibility to degradation.     

Cerebral lateralization as a source of interindividual differences in behavior

Cerebral laterality can no longer be considered an exclusively human trait, as over the last 15 years there has been an emergence of data to suggest that animal brains are also lateralized. Morphologic, chemical and behavioral indices of brain asymmetry in the rodent have been reported, and it is suggested that variations in the magnitude and direction of these indices are determined by a complex interaction of genetic, hormonal and experiential factors. Interindividual differences in cerebral laterality have been shown to covary with, or predict, individual differences in spatial behavior and stress reactivity, as well as susceptibility to stress pathology and drug sensitivity. Such findings suggest that it is possible to study individual differences in lateralized brain function through the use of animal models.     

Structural analysis of leucine-rich-repeat variants in proteins associated with human diseases

A number of human diseases have been shown to be associated with mutation in the genes encoding leucine-rich-repeat (LRR)-containing proteins. They include 16 different LRR proteins. Mutations of these proteins are associated with 19 human diseases. The mutations occur frequently within the LRR domains as well as their neighboring domains, including cysteine clusters. Here, based on the sequence analysis of the LRR domains and the known structure of LRR proteins, we describe some features of different sequence variants and discuss their adverse effects. The mutations in the cysteine clusters, which preclude the formation of sulfide bridges or lead to a wrong paring of cysteines in extracellular proteins or extracellular domains, occur with high frequency. In contrast, missense mutations at some specific positions in LRRs are very rare or are not observed at all. Received 4 May 2005; received after revision 18 August 2005; accepted 1 September 2005     

The epidemiology of dental caries in relation to environmental trace elements

Summary This paper reviews the influence of the geochemical environment on the epidemiology of human dental caries. The best documented association is that between water borne fluoride and reduced caries prevalence. The influence of fluoride was first reported during the early decades of this century in Colorado, USA, and led to the fluoridation of some public water supplies in several countries. In all cases, fluoridation has been followed by significant improvements in dental health and no adverse effects in general health. Other trace elements in food and water have now been linked with dental caries. Molybdenum has been associated with reduced caries prevalence whereas selenium and lead appear to have adverse effects. Cavity formation in teeth probably involves a localised dissolution of the enamel surface by the products of bacterial activity. It is possible that the incorporation of trace metals into the apatite microcrystals of enamel may alter their physical properties, especially solubility, and hence their susceptibility to degradation.     

Mechanisms and consequences of intestinal dysbiosis

The composition of the gut microbiota is in constant flow under the influence of factors such as the diet, ingested drugs, the intestinal mucosa, the immune system, and the microbiota itself. Natural variations in the gut microbiota can deteriorate to a state of dysbiosis when stress conditions rapidly decrease microbial diversity and promote the expansion of specific bacterial taxa. The mechanisms underlying intestinal dysbiosis often remain unclear given that combinations of natural variations and stress factors mediate cascades of destabilizing events. Oxidative stress, bacteriophages induction and the secretion of bacterial toxins can trigger rapid shifts among intestinal microbial groups thereby yielding dysbiosis. A multitude of diseases including inflammatory bowel diseases but also metabolic disorders such as obesity and diabetes type II are associated with intestinal dysbiosis. The characterization of the changes leading to intestinal dysbiosis and the identification of the microbial taxa contributing to pathological effects are essential prerequisites to better understand the impact of the microbiota on health and disease.     

基于多级模糊综合评判的隧道抗震安全性评价

通过对影响隧道抗震的因素的分析，从管理养护、抗震设计、抗震设备和地质条件4个方面选取了24项对隧道抗震安全性影响较大的因素作为评价指标，建立了隧道抗震安全性评价指标体系；运用模糊数学理论确定评价指标的权重以及建立隧道抗震安全性评价模型；提出一套科学的用于隧道抗震安全性多级模糊综合评价的方法；并采用此方法对丽水市某一隧道抗震安全性的实例计算分析。结果表明，多级模糊综合评判方法在隧道抗震安全性评价的结果与实际情况相符合。根据多级模糊综合评判结果，确定了隧道抗震安全性评价因素中的薄弱环节，为隧道抗震防灾的安全设计及维修加固提供了依据，其理论、方法、思路和结论可供同类工程借鉴。     

Tracking migration during human T cell development

Specialized microenvironments within the thymus are comprised of unique cell types with distinct roles in directing the development of a diverse, functional, and self-tolerant T cell repertoire. As they differentiate, thymocytes transit through a number of developmental intermediates that are associated with unique localization and migration patterns. For example, during one particular developmental transition, immature thymocytes more than double in speed as they become mature T cells that are among the fastest cells in the body. This transition is associated with dramatic changes in the expression of chemokine receptors and their antagonists, cell adhesion molecules, and cytoskeletal components to direct the maturing thymocyte population from the cortex to medulla. Here we discuss the dynamic changes in behavior that occur throughout thymocyte development, and provide an overview of the cell-intrinsic and extrinsic mechanisms that regulate human thymocyte migration.     

Genetically determined epithelial dysfunction and its consequences for microflora–host interactions

The intestinal epithelium forms a highly active functional interface between the relatively sterile internal body surfaces and the enormously complex and diverse microbiota that are contained within the lumen. Genetic models that allow for manipulation of genes specifically in the intestinal epithelium have provided an avenue to understand the diverse set of pathways whereby intestinal epithelial cells (IECs) direct the immune state of the mucosa associated with homeostasis versus either productive or non-productive inflammation as occurs during enteropathogen invasion or inflammatory bowel disease (IBD), respectively. These pathways include the unfolded protein response (UPR) induced by stress in the endoplasmic reticulum (ER), autophagy, a self-cannibalistic pathway important for intracellular bacterial killing and proper Paneth cell function as well as the interrelated functions of NOD2/NF-κB signaling which also regulate autophagy induction. Multiple genes controlling these IEC pathways have been shown to be genetic risk factors for human IBD. This highlights the importance of these pathways not only for proper IEC function but also suggesting that IECs may be one of the cellular originators of organ-specific and systemic inflammation as in IBD.     

Genetic models in brain and behavior research,part IV

Four reviews on the the role of developmental factors in hypertension are introduced and set in historical context. Recent research in the laboratory rat has shown that the preweaning environment makes an important contribution to the level of blod-pressure reached in adult life in genetic models of hypertension. Both of the most commonly used models of hypertension, the SHR and SS/Jr rat strains, exhibit lower BP in adult life, if they are fostered shortly after birth to mothers from their normotensive control strains. It has been suggested that it is the idiosyncratic maternal behavior of the hypertensive mothers which contributes to the elevated BP of their offspring, and it has been amply demonstrated that there is an association between a constellation of behaviors emitted by rat mothers and the adult BP of their offspring in a wide variety of genetic groups (inbred hypertensive animals, F1's and F2's). In addition to the above, maternal environment has been demonstrated to have a significant impact on the pathophysiological response of hypertensive animals to a high salt diet. Being raised by an SHR mother, versus an SS/Jr mother, increases the magnitude of BP increases to a high salt diet, susceptibility to hemorrhagic stroke, body weight loss and the risk of mortality. A variety of physiological systems are undergoing rapid change during the preweaning period and may mediate the effects of differences in the maternal environment. These include the renin-angiotensin system and the peripheral sympathetic nervous system. Nutritional factors may be involved in all of the phenomena referred to above. Thus, any physiological mechanisms that are proposed to link maternal behavior to its effects on the physiology of adult animals should recognize the involvement of nutritional factors. Research on the role of developmental factors such as maternal behavior in genetic models of hypertension is at the interface of two growing disciplines: behavior genetics and developmental psychobiology. The methodological and conceptual contributions of these fields to advancing our understanding of these phenomena is emphasized.     

Heritable trinucleotide repeats and neurological disorders

In the past 3 years, seven human neurological disorders have been found to be associated with an abnormal number of unstable trinucleotide repeats within exons or non-expressed regions of a gene. These forms of mutations are called dynamic mutations. The expansion in copy number of trinucleotide repeats may represent a large number of hereditary disorders. The correlation between the length of the repeated size and the disease severity and variable onset has provided some genetic explanation for a phenomenon called anticipation. However, there are numerous questions which cannot be explained by anticipation. Many other factors such as genomic imprinting and variable DNA methylation may also contribute to the puzzling features of these phenotypes.     

Nature/nurture and the nature of nurture in the etiology of hypertension.

Four reviews on the the role of developmental factors in hypertension are introduced and set in historical context. Recent research in the laboratory rat has shown that the preweaning environment makes an important contribution to the level of blood-pressure reached in adult life in genetic models of hypertension. Both of the most commonly used models of hypertension, the SHR and SS/Jr rat strains, exhibit lower BP in adult life, if they are fostered shortly after birth to mothers from their normotensive control strains. It has been suggested that it is the idiosyncratic maternal behavior of the hypertensive mothers which contributes to the elevated BP of their offspring, and it has been amply demonstrated that there is an association between a constellation of behaviors emitted by rat mothers and the adult BP of their offspring in a wide variety of genetic groups (inbred hypertensive animals, F1's and F2's). In addition to the above, maternal environment has been demonstrated to have a significant impact on the pathophysiological response of hypertensive animals to a high salt diet. Being raised by an SHR mother, versus an SS/Jr mother, increases the magnitude of BP increases to a high salt diet, susceptibility to hemorrhagic stroke, body weight loss and the risk of mortality. A variety of physiological systems are undergoing rapid change during the preweaning period and may mediate the effects of differences in the maternal environment. These include the renin-angiotensin system and the peripheral sympathetic nervous system. Nutritional factors may be involved in all of the phenomena referred to above. Thus, any physiological mechanisms that are proposed to link maternal behavior to its effects on the physiology of adult animals should recognize the involvement of nutritional factors. Research on the role of developmental factors such as maternal behavior in genetic models of hypertension is at the interface of two growing disciplines: behavior genetics and developmental psychobiology. The methodological and conceptual contributions of these fields to advancing our understanding of these phenomena is emphasized.     

Pre-menstrual steroids

A number of steroid hormones and their metabolites fluctuate in the circulation across the human menstrual cycle. In addition to their classic actions on the hypothalamo-pituitary-gonadal axis, many of these hormones act as 'neuroactive steroids' to alter the function of neurotransmitters, such as GABA, within central nervous system circuits. Clinically, these steroids are important because they have not only acute but also long-term effects, and 'withdrawal' properties. This review discusses the effects of steroids such as 3alpha-OH-5alpha-pregnan-20-one (3alpha,5alpha-THP or allopregnanolone) which alter GABA function in distinct ways dependent upon the time course of exposure, to either enhance or decrease inhibition in the brain. These effects are discussed in light of recent clinical findings which seek to further characterize the steroid milieu which underlies pre-menstrual dysphoria.     

Long Memory of Financial Time Series and Hidden Markov Models with Time‐Varying Parameters

Hidden Markov models are often used to model daily returns and to infer the hidden state of financial markets. Previous studies have found that the estimated models change over time, but the implications of the time‐varying behavior have not been thoroughly examined. This paper presents an adaptive estimation approach that allows for the parameters of the estimated models to be time varying. It is shown that a two‐state Gaussian hidden Markov model with time‐varying parameters is able to reproduce the long memory of squared daily returns that was previously believed to be the most difficult fact to reproduce with a hidden Markov model. Capturing the time‐varying behavior of the parameters also leads to improved one‐step density forecasts. Finally, it is shown that the forecasting performance of the estimated models can be further improved using local smoothing to forecast the parameter variations. Copyright © 2016 John Wiley & Sons, Ltd.     

Using computational models to discover and understand mechanisms

Areas of biology such as cell and molecular biology have been dominated by research directed at constructing mechanistic explanations that identify parts and operations that when organized appropriately are responsible for the various phenomena they investigate. Increasingly the mechanisms hypothesized involve non-sequential organization of non-linear operations and so exceed the ability of researchers to mentally rehearse their behavior. Accordingly, scientists rely on tools of computational modeling and dynamical systems theory in advancing dynamic mechanistic explanations. Using circadian rhythm research as an exemplar, this paper explores the variety of roles computational modeling is playing. They serve not just to determine whether the mechanism will produce the desired behavior, but in the discovery process of hypothesizing mechanisms and in understanding why proposed mechanisms behave as they do.     

Sickle cell vasoocclusion: Many issues and some answers

The pathophysiology of sickle (SS) cell vasoocclusion is derived from the presence of hemoglobin S (HbS) which forms polymeric fibers in the deoxygenated state. Nevertheless, phenotypic expression of sickle cell disease (i.e., clinical severity) shows marked individual variations and is influenced by genetic modifiers such as epistatic effects of linked and unlinked genes. Furthermore, the polymerization of HbS is central but not the only event, and is more likely a consequence of disruptions of the steady state of flow. The available evidence indicates that the vasoocclusive crisis is a microcirculatory event in which multiple factors could be involved. We present a model of vasoocclusion as a two step process in which adhesion of deformable cells occurs first, followed by obstruction induced by less deformable SS cells. This review discusses, in addition, rheologic and microcirculatory behavior of SS erythrocytes and the interacting role of vascular factors, red cell heterogeneity, deoxygenation rates, and red cell-endothelial interactions in the pathophysiology of SS cell vasoocclusion.     

Prediction of historical and contemporary luminosity (UFO) reports by seismic variables within Western Europe

Summary Changes in tectonic strain within the earth's crust have been hypothesized to be the primary energetic source for most documented UFO (unidentified flying object) reports. Discriminant and multiple regression analyses indicated that seismic variables that correctly classified and predicted years that contained reports of spectacular spherical luminous phenomena during the 19th century, also correctly predicted major UFO episodes during the present century. The results indicate that phenomena once labelled as odd luminosities, mysterious airships and phantom airplanes in previous decades are associated with UFOs now.Acknowledgments. Thanks to Dr B. D. Eastman, Professor of Economics and Dr Abraham Barnett, Professor of Sociology for our many enlightening discussions concerning sampling and multivariate analyses. Special appreciation to Claudette Larcher and to Mr Steve Beynon, Mr Douglas Flemming and the DEC2020 System Support Staff for their technical assistance.     

Production of pharmaceutical proteins in milk

There is every reason to expect that it will be possible within the next few years to begin to use farm animals to produce large quantities of some of the human proteins that are needed for the treatment of disease. Revolutionary new opportunities for the production of novel proteins in milk have been created by the development of methods for gene transfer. Exploitation of these opportunities depends upon selection and cloning of milk protein genes and identification of the sequences that govern tissue specific hormonally induced expression in the mammary gland. Studies with three genes, ovine beta-lactoglobulin, rat beta-casein and whey acidic protein of rat and mouse, suggest that they may all meet this requirement. Fragments of the ovine beta-lactoglobulin, murine whey acidic protein and rabbit beta-casein genes have directed production of novel proteins in the milk of transgenic mice, sheep, rabbits and pigs. The proteins were biologically active and usually co-migrated with authentic proteins. In early experiments, protein concentration was low, but our recent observations suggest that fusion genes containing genomic clones direct production of concentrations of protein that are suitable for commercial exploitation. In the longer term, two approaches may offer the potential of more reliable expression. Control elements capable of directing expression that is independent of site of insertion of the gene, but dependent on the number of copies of the gene, have been identified for a small number of genes. The availability of such elements for the milk protein genes would increase the reliability of gene expression considerably. Alternatively, targeted mutation of genes may allow the insertion of coding sequences within an existing gene so avoiding position effects.     

Adult neurogenesis in Parkinson’s disease

Parkinson’s disease (PD), the second most common neurodegenerative disorder, affects 1–2 % of humans aged 60 years and older. The diagnosis of PD is based on motor symptoms such as bradykinesia, rigidity, tremor, and postural instability associated with the striatal dopaminergic deficit that is linked to neurodegenerative processes in the substantia nigra (SN). In the past, cellular replacement strategies have been evaluated for their potential to alleviate these symptoms. Adult neurogenesis, the generation of new neurons within two proliferative niches in the adult brain, is being intensively studied as one potential mode for cell-based therapies. The subventricular zone provides new neurons for the olfactory bulb functionally contributing to olfaction. The subgranular zone of the hippocampus produces new granule neurons for the dentate gyrus, required for memory formation and proper processing of anxiety provoking stimuli. Recent years have revealed that PD is associated with non-motor symptoms such as hyposmia, anhedonia, lack of novelty seeking behavior, depression, and anxiety that are not directly associated with neurodegenerative processes in the SN. This broad spectrum of non-motor symptoms may partly rely on proper olfactorial processing and hippocampal function. Therefore, it is conceivable that some non-motor deficits in PD are related to defective adult neurogenesis. Accordingly, in animal models and postmortem studies of PD, adult neurogenesis is severely affected, although the exact mechanisms and effects of these changes are not yet fully understood or are under debate due to conflicting results. Here, we review the current concepts related to the dynamic interplay between endogenous cellular plasticity and PD-associated pathology.