Intranuclear inclusions in pericytes of the hypothalamus of the rat

Summary This paper deals with the ultrastructure of two types of intranuclear inclusions, nuclear bodies and membranous lamellar bodies, present in hypothalamic pericytes of intact adult rats. The nuclear bodies exhibited simple and granular forms, whereas the membranous lamellar bodies were entirely made up of myelin-like membrane whorls.The occurrence of these bodies in nuclei of pericytes has never been previously reported. The origin and functional meaning of such structures is discussed in the light of recent ultrastructural and biochemical studies on nuclear inclusions.     

Neuronal cytoplasmic inclusions in the dorsal horn and supraoptic nucleus of the squirrel monkey,Saimiri sciureus

In the squirrel monkey (Saimiri sciureus) two types of cytoplasmic inclusion bodies have been observed sporadically in neurons of both the dorsal horn (Rexed's laminae I-III in the lumbosacral region) and the supraoptic nucleus. One of these, designated here the "vesicular body", is a round inclusion which measures up to 1.4 mu in diameter. It occurs only in perikarya and is composed of vesicular-like chambers 300-400 A in diameter. We have not found previous references to this structure in the literature, but its 50 A substructural particles are similar in size to those described in nematosomes. The other inclusion, a "filamentous whorl", is found in nerve cell bodies and dendrites and it is structurally similar to the Hirano body. The structure measures up to 2.2 mu in diameter and is composed of circularly arrayed filaments which vary in configuration and size depending on the plane of section. There are no indications that the vesicular body and the filamentous whorl are in any way related to each other; and usually both are not found in the same cell profiles.     

Preantral intra-ovarian oocyte release in the white-footed mouse,Peromyscus leucopus

Summary Optical diffraction analysis was carried out on crystalline inclusions in the rough endoplasmic reticulum of the insulin and somatostatin cells in the islet organ of the hagfish. A striking difference in crystalline arrangement was observed between the inclusions of the insulin and somatostatin cells. The crystallographic arrangement of the inclusions observed in situ in the insulin cells differed from that previously found by means of X-ray diffraction analyses of hagfish insulin crystals formed in vitro.     

Purification of neuronal inclusions of patients with Huntington's disease reveals a broad range of N-terminal fragments of expanded huntingtin and insoluble polymers

Huntington's disease resulting from huntingtin containing an expanded polyglutamine is associated with aggregates largely confined to neuronal inclusions, and with neuronal death. Inclusions are thought to originate from discrete N-terminal fragments of expanded huntingtin produced by specific endopeptidases. We have now purified the neuronal inclusions of Huntington's disease brain. When incubated in concentrated formic acid, purified inclusions release a polymer, an oligomer and a broad range of N-terminal fragments of expanded huntingtin. The fragments and the polymeric forms are linked to each other by non-covalent bonds as they are both released by formic acid, whereas the polymeric forms themselves are presumably stabilized by covalent bonds, as they are resistant to formic acid. We also demonstrate the presence in affected areas of the brain but not in unaffected areas of a broad range of soluble N-terminal fragments of expanded huntingtin not yet associated with the inclusions and which are likely to be the precursors of the inclusions. Fragmentation of expanded huntingtin in Huntington's disease must result from the operation of multiple proteolytic activities with little specificity and not from that of a specific endopeptidase; subsequent aggregation of the fragments by covalent and non-covalent bonds leads to the formation of the inclusions.     

Cofilin-mediated neurodegeneration in alzheimer’s disease and other amyloidopathies

Transport defects may arise in various neurodegenerative diseases from failures in molecular motors, microtubule abnormalities, and the chaperone/proteasomal degradation pathway leading to aggresomal-lysosomal accumulations. These defects represent important steps in the neurodegenerative cascade, although in many cases, a clear consensus has yet to be reached regarding their causal relationship to the disease. A growing body of evidence lends support to a link between neurite transport defects in the very early stages of many neurodegenerative diseases and alterations in the organization and dynamics of the actin cytoskeleton initiated by filament dynamizing proteins in the ADF/cofilin family. This article focuses on cofilin, which in neurons under stress, including stress induced by the amyloid-β (Aβ) 1–42 peptide, undergoes dephosphorylation (activation) and forms rod-shaped actin boundles (rods). Rods inhibit transport, are sites of amyloid precursor protein accumulation, and contribute to the pathology of Alzheimer’s disease. Because rods form rapidly in response to anoxia, they could also contribute to synaptic deficits associated with ischemic brain injury (e.g., stroke). Surprisingly, cofilin undergoes phosphorylation (inactivation) in hippocampal neurons treated with Aβ_1–40 at high concentrations, and these neurons undergo dystrophic morphological changes, including accumulation of pretangle phosphorylated-τ. Therefore, extremes in phosphoregulation of cofilin by different forms of Aβ may explain much of the Alzheimer’s disease pathology and provide mechanisms for synaptic loss and plaque expansion. An erratum to this article is available at .     

An SIS epidemiology game with two subpopulations

There is significant current interest in the application of game theory to problems in epidemiology. Most mathematical analyses of epidemiology games have studied populations where all individuals have the same risks and interests. This paper analyses the rational-expectation equilibria in an epidemiology game with two interacting subpopulations of equal size where decisions change the prevalence and transmission patterns of an infectious disease. The transmission dynamics are described by an SIS model and individuals are only allowed to invest in daily prevention measures like hygiene. The analysis shows that disassortative mixing may lead to multiple Nash equilibria when there are two interacting subpopulations affecting disease prevalence. The dynamic stability of these equilibria is analysed under the assumption that strategies change slowly in the direction of self-interest. When mixing is disassortative, interior Nash equilibria are always unstable. When mixing is positively assortative, there is a unique Nash equilibrium that is globally stable.     

Ultrastructure of ferritin in the leaves of <Emphasis Type="Italic">Mesembryanthemum crystallinum</Emphasis> under stress conditions

The location and structure of ferritin in the parenchyma of leaf minor veins of the common ice plant (Mesembryanthemum crystallinum L.) treated with exogenous putrescine under salinity conditions were investigated by electron microscopy. Considerable aggregates of ferritin were detected in the chloroplasts of bundle sheath cells, in companion phloem cells, and other parenchyma cells of leaf minor veins. The structure of ferritin in the vascular parenchyma chloroplasts suggests that it was partially degraded and converted to phytosiderin. This point of view is based on indistinct structure of Fe-containing cores of ferritin molecules, break of distance between the cores, and their pronounced ability to aggregate and produce larger structures. Aggregation of Fe-containing cores apparently pointed to the destruction of ferritin protein envelope or its partial degradation. In a certain stage of ferritin destruction, electron-dense material and the structures resembling small vesicles appeared between the Fe-containing cores. Electron-dense inclusions, whose structure was similar to that of phytosiderin, were also detected in the vacuoles. Examination of the cross sections done without additional staining showed that the same as ferritin, phytosiderin in the chloroplasts and vacuoles was dark-colored against weakly colored cellular structures. In the vascular parenchyma of control plant leaves, the level of ferritin and phytosiderin was greater than in the mesophyll and much lower than in the plants simultaneously treated with NaCl and putrescine. In control material, iron cores of ferritin and phytosiderin were more light-colored and 2–3 times smaller in size than in the experimental treatment. Destruction of ferritin essentially did not occur in the mesophyll but was observed in the chloroplasts of bundle sheath cells on the border between the mesophyll and vascular bundle. The presence of much ferritin and phytosiderin on the border between the mesophyll and the vessels is accounted for by the fact that the vascular parenchyma is a buffer area that maintains a specific concentration of iron in the mesophyll of leaves and other parts of the plant. Within the cell, the role of such a buffer is performed by ferritin and vacuoles. Transformation of ferritin to insoluble hydrophobic phytosiderin is supposed to be an efficient way of withdrawing the excess of active iron from the cellular metabolism and therefore of relaxing oxidative stress. Ferritin and phytosiderin were detected not only in parenchyma cells of leaf minor veins but in sieve tubes as well. This suggests that iron may be transported within the plant as a component of protein complex.     

Molecular Characterization of Novel Serovars of Bacillus thuringiensis Isolates from India

Novel Bacillus thuringiensis isolates GS4, GN24 and UP1 were isolated and characterized by determination of serotyping, insecticidal protein by SDS-PAGE, plasmid composition, cry gene content and insect toxicity. Serologically two isolates GS4 and UP1 were allocated to the H3abce which is a new serovar while isolate GN24 was of H3ab type. Isolate GS4 produced flat crystal inclusions while UP1 produced cuboidal crystals. PCR analysis found that both isolates contained cry1 and cry1Ac genes. The major protein bands found of isolate GS4 were of molecular weights 175, 135, 97, 88, 66, 54 and 27 kDa, isolate UP1 were of 85, 60 and 40 kDa and isolate GN24 were of 130, 90, 66 and 45 kDa. Though isolates GS4 and UP1 belonged to a new serovar H3abce, they showed different crystal inclusions and cry gene content. Isolate GS4 was toxic to lepidopteran insect larvae of Helicoverpa armigera but UP1 did not showed any toxicity.