High-temperature fracturing and subsequent grain-size-sensitive creep in lower crustal gabbros:Evidence for coseismic loading followed by creep during decaying stress in the lower crust?

The mechanism of shear zone formation in lower crustal, relatively “dry” rocks is still poorly understood. We have studied the high-temperature deformation of the Hasvik gabbro (northern Norway) which commences by fracturing. The 10–20 μm wide fractures show little displacement. The fine-grained plagioclase and orthopyroxene in the fractures lack a crystallographic preferred orientation (CPO) or a systematic crystallographic orientation with respect to the host grains. Fractures grade into narrow shear zones, which are composed of fine (10–20 μm), equant grains of recrystallized plagioclase, amphibole, and pyroxene. Recrystallized plagioclase and pyroxene have compositions different from the magmatic grains, suggesting that they have formed by nucleation and growth. Based on conventional plagioclase-amphibole thermobarometry, the shear zones have formed at temperatures and pressures of 700–750°C and 0.5–0.6 GPa. The observed primary minerals cut by fractures suggest high-temperature fracturing in the absence of high pore pressures, which implies a high strength of the lower crustal gabbros and high stresses at fracturing. The shear zones are characterized by the lack of CPO and a small grain size, suggesting that the mechanism of deformation of the fine-grained plagioclase and orthopyroxene has been grain boundary sliding accommodated by diffusive mass transfer. The amphibole grains have strong CPOs, which most likely result from oriented growth and/or rigid body rotations during deformation. The process that initiated the fracturing and subsequent viscous creep in the Hasvik gabbro may have resulted from a process of coseismic loading followed by creep during decaying stress in the lower crust

Analysis of shared heritability in common disorders of the brain

ience, this issue p. eaap8757 Structured Abstract INTRODUCTION Brain disorders may exhibit shared symptoms and substantial epidemiological comorbidity, inciting debate about their etiologic overlap. However, detailed study of phenotypes with different ages of onset, severity, and presentation poses a considerable challenge. Recently developed heritability methods allow us to accurately measure correlation of genome-wide common variant risk between two phenotypes from pools of different individuals and assess how connected they, or at least their genetic risks, are on the genomic level. We used genome-wide association data for 265,218 patients and 784,643 control participants, as well as 17 phenotypes from a total of 1,191,588 individuals, to quantify the degree of overlap for genetic risk factors of 25 common brain disorders. RATIONALE Over the past century, the classification of brain disorders has evolved to reflect the medical and scientific communities' assessments of the presumed root causes of clinical phenomena such as behavioral change, loss of motor function, or alterations of consciousness. Directly observable phenomena (such as the presence of emboli, protein tangles, or unusual electrical activity patterns) generally define and separate neurological disorders from psychiatric disorders. Understanding the genetic underpinnings and categorical distinctions for brain disorders and related phenotypes may inform the search for their biological mechanisms. RESULTS Common variant risk for psychiatric disorders was shown to correlate significantly, especially among attention deficit hyperactivity disorder (ADHD), bipolar disorder, major depressive disorder (MDD), and schizophrenia. By contrast, neurological disorders appear more distinct from one another and from the psychiatric disorders, except for migraine, which was significantly correlated to ADHD, MDD, and Tourette syndrome. We demonstrate that, in the general population, the personality trait neuroticism is significantly correlated with almost every psychiatric disorder and migraine. We also identify significant genetic sharing between disorders and early life cognitive measures (e.g., years of education and college attainment) in the general population, demonstrating positive correlation with several psychiatric disorders (e.g., anorexia nervosa and bipolar disorder) and negative correlation with several neurological phenotypes (e.g., Alzheimer's disease and ischemic stroke), even though the latter are considered to result from specific processes that occur later in life. Extensive simulations were also performed to inform how statistical power, diagnostic misclassification, and phenotypic heterogeneity influence genetic correlations. CONCLUSION The high degree of genetic correlation among many of the psychiatric disorders adds further evidence that their current clinical boundaries do not reflect distinct underlying pathogenic processes, at least on the genetic level. This suggests a deeply interconnected nature for psychiatric disorders, in contrast to neurological disorders, and underscores the need to refine psychiatric diagnostics. Genetically informed analyses may provide important "scaffolding" to support such restructuring of psychiatric nosology, which likely requires incorporating many levels of information. By contrast, we find limited evidence for widespread common genetic risk sharing among neurological disorders or across neurological and psychiatric disorders. We show that both psychiatric and neurological disorders have robust correlations with cognitive and personality measures. Further study is needed to evaluate whether overlapping genetic contributions to psychiatric pathology may influence treatment choices. Ultimately, such developments may pave the way toward reduced heterogeneity and improved diagnosis and treatment of psychiatric disorders

An immunohistochemical study of the substance P neuronal system in the primate brain : basal ganglia and neocortex

Using immunohistochemical methods I have studied the distribution of substance P fibers, terminals and perikarya throughout the basal ganglia and neocortex of baboons and at selected levels of the human brain. Immunoreactivity in the substantia nigra pars reticulata, internal segment of the globus pallidus and ventral pallidum was dense and of a characteristic, "woolly fiber" morphology. The caudate nucleus and putamen contained sharply circumscribed patches of dense immunoreactivity superimposed on a moderately stained background. The external division of the globus pallidus displayed very little immunoreactivity. Two morphological types of immunoreactive cell bodies were present in the caudate nucleus, putamen and nucleus accumbens, and were clustered within the dense patches. The distribution of immunoreactive perikarya within the striatum differed from that reported for rats, as stained neurons were distributed evenly throughout the rostro-caudal extent rather than being concentrated in the rostral portions. This work represents the first detailed examination of the distribution of substance P-containing neuronal structures in the primate basal ganglia. It confirms recent published reports which have shown that the striatum is not a homogeneous structure, as it has long been regarded, but is subdivided into zones with differing neuroanatomical connections and neurotransmitter content. The neocortex was not studied as intensively as the basal ganglia, but it was conclusively established that substance P-immunoreactive neurons exist throughout the neocortex.Medicine, Faculty ofGraduat

A neuroanatomical analysis of the distribution of histopathologic lesions in alzheimer's disease

The thesis was designed to address two major questions about the pathogenesis of Alzheimer's disease. These are: one, does Alzheimer's disease "spread" throughout the brain along neuroanatomical pathways? And two, can the histopathological lesions of Alzheimer's disease be the result of degeneration of a single neuronal system? The investigation began by comparing the pattern of cerebral gliosis in Alzheimer's disease (AD) with that seen in normal aging. This was done using an immunoperoxidase stain for glial fibrillary acidic protein (GFAP) to reveal astrocytic gliosis within whole-hemisphere sections. Gliosis was most severe, and most consistently seen, in the cerebral cortex and hippocampus. Subcortical nuclei were inconsistently affected. Within the cortex, the laminae which are most severely affected are II, III and V. Distinct bands of gliosis were present in these laminae in at least some cortical areas in every AD brain. The pattern of gliosis within area 17, the primary visual area, was anomalous in that there was the a thin band of gliosis at the border between layers IVc and V. This was matched by a line of senile plaques at the same site, revealed using an enhanced Bielschowsky stain. Such a precise disposition implies a neuronal origin for these plaques, but there is no known afferent system which is concentrated along this line. Specific afferent systems to layers IVc and V of area 17 were then examined histologically for evidence of morphological relationships to senile plaques. Only cholinergic elements were in obvious relation to senile plaques; in addition, only cholinergic elements showed evidence of depletion and morphological abnormality. In the last part of the thesis, the distribution of amyloid ß-protein (AßP) in area 17 was studied using an immunoperoxidase method. This was found to differ substantially from the distribution of senile plaques, with obvious bands of dense staining in layers I and IVc, layers that did not possess significantly larger numbers of plaques as seen with the enhanced Bielschowsky method. Acetylcholinesterase-positive fibres within area 17 were co-distributed with AßP to layers I and IVc, providing further evidence that amyloid may be formed at cholinergic fibres. The results of this thesis are most compatible with the hypothesis that Alzheimer's disease represents a primary degeneration of the cholinergic system of the nucleus basalis of Meynert. A review of the literature suggests that current opinion relegating the cholinergic degeneration to a secondary role is not adequately substantiated.Medicine, Faculty ofGraduat

Wetland geomorphology and paleoecology near Akab Muclil, Rio Bravo floodplain of the Belize coastal plain

To understand wetland geomorphology and paleoecology, we collected a 2.6 m sediment core from a flooded swamp adjacent to the Maya archaeological site of Akab Muclil in the Maya Lowlands of northwestern Belize. The site of Akab Muclil has a known occupation that persisted from Early Maya Classic (1700–1350 BP) through the Terminal Maya Classic (1180–1050 BP) and into the Postclassic (1050–450 BP) and lies near a vast network of ancient Maya canal and field systems. We analyzed this core using a combination of paleoecological and geochemical techniques to determine the history of land use and natural change over time within this wetland. Accelerator Mass Spectrometry dating, pollen, charcoal analysis, micropaleontology, geochemical analysis, and magnetic susceptibility provide a suite of methods from which we interpret the geomorphic and ecological history of this wetland system. Four AMS dates from the length of the core provide us with an age model that runs from 1675 cal BP through the Maya Classic onward to the present. At the base of this system, soil composition and chemistry provide evidence that the system changed from a seasonally wet terrestrial soil to a perennially wet swamp, as the basal Mollisol soil lies buried by peats and calcareous sediments. This shift to a perennial wetland could be related to ancient Maya water management or a natural geomorphic change, though we suspect the former because of nearby ancient Maya large-scale geomorphic and hydrological manipulation in the form of intensive canalization and agriculture. Evidence of ancient Maya uses and impacts, including sedimentation, Zea mays pollen, and high charcoal counts occur from the lowest levels of the sequence through the Classic and into the Postclassic period. Above this level, the strata change to stable peats, laminated deposits of light gray/dark gray gypsum, authigenic carbonate, and layers of fibrist peat, with little evidence of human impact until recent increases in charcoal and phosphorous. This study, compared with other regional studies, indicates a later transition from terrestrial to wetland, later human impacts in the Postclassic, and a geomorphic impact record closely tied to the history of the adjacent site rather than broader land use trends

Altered expression patterns of inflammation-associated and trophic molecules in substantia nigra and striatum brain samples from Parkinson’s disease, incidental Lewy body disease and normal control cases

Evidence of inflammation has been consistently associated with pathology in Parkinson’s disease (PD)-affected brains, and has been suggested as a causative factor. Dopaminergic neurons in the substantia nigra (SN) pars compacta, whose loss results in the clinical symptoms associated with PD, are particularly susceptible to inflammatory damage and oxidative stress. Inflammation in the striatum, where SN dopaminergic neurons project, is also a feature of PD brains. It is not known whether inflammatory changes occur first in striatum or SN. Many animal models of PD have implicated certain inflammatory molecules with dopaminergic cell neuronal loss; however, there have been few studies to validate these findings by measuring the levels of these and other inflammatory factors in human PD brain samples. This study also included samples from incidental Lewy body disease (ILBD) cases, since ILBD is considered a non-symptomatic precursor to PD, with subjects having significant loss of tyrosine hydroxylase-producing neurons. We hypothesized that there may be a progressive change in key inflammatory factors in ILBD samples intermediate between neurologically normal and PD. To address this, we used a quantitative antibody-array platform (Raybiotech-Quantibody arrays) to measure the levels of 160 different inflammation-associated cytokines, chemokines, growth factors, and related molecules in extracts of SN and striatum from clinically and neuropathologically characterized PD, ILBD and normal control cases. Patterns of changes in inflammation and related molecules were distinctly different between SN and striatum. Our results showed significantly different levels of interleukin (IL)-5, IL-15, monokine induced by gamma interferon, and IL-6 soluble receptor in SN between disease groups. A different panel of 13 proteins with significant changes in striatum, with IL-15 as the common feature, was identified. Although the ability to detect some proteins was limited by sensitivity, patterns of expression indicated involvement of certain T-cell cytokines, vascular changes and loss of certain growth factors, with disease progression. The results demonstrate the feasibility of profiling inflammatory molecules using diseased human brain samples, and have provided additional targets to validate in relation to PD pathology

Neuropathological findings of PSP in the elderly without clinical PSP: Possible incidental PSP?

Aims: We aimed to describe cases with incidental neuropathological findings of progressive supranuclear palsy (PSP) from the Banner Sun Health Research Institute Brain and Body Donation Program. Methods: We performed a retrospective review of 277 subjects with longitudinal motor and neuropsychological assessments who came to autopsy. The mean Gallyas-positive PSP features grading for subjects with possible incidental neuropathological PSP was compared to those of subjects with clinically manifest disease. Results: There were 5 cases with histopathological findings suggestive of PSP, but no parkinsonism, dementia or movement disorder during life. Cognitive evaluation revealed 4 of the 5 cases to be cognitively normal; one case had amnestic mild cognitive impairment (MCI) in her last year of life. The mean age at death of the 5 cases was 88.9 years (range 80-94). All 5 individuals had histopathologic microscopic findings suggestive of PSP. Mean Gallyas-positive PSP features grading was significantly lower in subjects with possible incidental neuropathological PSP than subjects with clinical PSP, particularly in the subthalamic nucleus. Conclusions: We present 5 patients with histopathological findings suggestive of PSP, without clinical PSP, dementia or parkinsonism during life. These incidental neuropathological PSP findings may represent the early or pre-symptomatic stage of PSP. The mean Gallyas-positive PSP features grading was significantly lower in possible incidental PSP than in clinical PSP, thus suggesting that a threshold of pathological burden needs to be reached within the typically affected areas in PSP before clinical signs and symptoms appear. © 2011 Elsevier Ltd