Morphological abnormalities in the brains of estrogen receptor β knockout mice

Estrogen receptor β (ERβ) is expressed at high levels in both neurons and glial cells of the central nervous system. The development of ERβ knockout (BERKO) mice has provided a model to study the function of this nuclear receptor in the brain. We have found that the brains of BERKO mice show several morphological abnormalities. There is a regional neuronal hypocellularity in the brain, with a severe neuronal deficit in the somatosensory cortex, especially layers II, III, IV, and V, and a remarkable proliferation of astroglial cells in the limbic system but not in the cortex. These abnormalities are evident as early as 2 mo of age in BERKO mice. As BERKO mice age, the neuronal deficit becomes more pronounced, and, by 2 yr of age, there is degeneration of neuronal cell bodies throughout the brain. This is particularly evident in the substantia nigra. We conclude that ERβ is necessary for neuronal survival and speculate that this gene could have an important influence on the development of degenerative diseases of the central nervous system, such as Alzheimer's disease and Parkinson's disease, as well as those resulting from trauma and stroke in the brain.

A role for estrogen receptor β in the regulation of growth of the ventral prostate

In normal rats and mice, immunostaining with specific antibodies revealed that nuclei of most prostatic epithelial cells harbor estrogen receptor β (ERβ). In rat ventral prostate, 530- and 549-aa isoforms of the receptor were identified. These sediment in the 4S region of low-salt sucrose gradients, indicating that prostatic ERβ does not contain the same protein chaperones that are associated with ERα. Estradiol (E2) binding and ERβ immunoreactivity coincide on the gradient, with no indication of ERα. In prostates from mice in which the ERβ gene has been inactivated (BERKO), androgen receptor (AR) levels are elevated, and the tissue contains multiple hyperplastic foci. Most epithelial cells express the proliferation antigen Ki-67. In contrast, prostatic epithelium from wild-type littermates is single layered with no hyperplasia, and very few cells express Ki-67. Rat ventral prostate contains an estrogenic component, which comigrates on HPLC with the testosterone metabolite 5α-androstane-3β,17β-diol (3βAdiol). This compound, which competes with E2 for binding to ERβ and elicits an estrogenic response in the aorta but not in the pituitary, decreases the AR content in prostates of wild-type mice but does not affect the elevated levels seen in ERβ knockout (BERKO) mice. Thus ERβ, probably as a complex with 3βAdiol, is involved in regulating the AR content of the rodent prostate and in restraining epithelial growth. These findings suggest that ligands specific for ERβ may be useful in the prevention and/or clinical management of prostatic hyperplasia and neoplasia.

Perpetuation of the agent of human granulocytic ehrlichiosis in a deer tick-rodent cycle.

A human-derived strain of the agent of human granulocytic ehrlichiosis, a recently described emerging rickettsial disease, has been established by serial blood passage in mouse hosts. Larval deer ticks acquired infection by feeding upon such mice and efficiently transmitted the ehrlichiae after molting to nymphs, thereby demonstrating vector competence. The agent was detected by demonstrating Feulgen-positive inclusions in the salivary glands of the experimentally infected ticks and from field-derived adult deer ticks. White-footed mice from a field site infected laboratory-reared ticks with the agent of human granulocytic ehrlichiosis, suggesting that these rodents serve as reservoirs for ehrlichiae as well as for Lyme disease spirochetes and the piroplasm that causes human babesiosis. About 10% of host-seeking deer ticks were infected with ehrlichiae, and of these, 20% also contained spirochetes. Cotransmission of diverse pathogens by the aggressively human-biting deer tick may have a unique impact on public health in certain endemic sites.

An RNA structure involved in feedback regulation of splicing and of translation is critical for biological fitness.

While studies of the regulation of gene expression have generally concerned qualitative changes in the selection or the level of expression of a gene, much of the regulation that occurs within a cell involves the continuous subtle optimization of the levels of proteins used in macromolecular complexes. An example is the biosynthesis of the ribosome, in which equimolar amounts of nearly 80 ribosomal proteins must be supplied by the cytoplasm to the nucleolus. We have found that the transcript of one of the ribosomal protein genes of Saccharomyces cerevisiae, RPL32, participates in such fine tuning. Sequences from exon I of the RPL32 transcript interact with nucleotides from the intron to form a structure that binds L32 to regulate splicing. In the spliced transcript, the same sequences interact with nucleotides from exon II to form a structure that binds L32 to regulate translation, thus providing two levels of autoregulation. We now show, by using a sensitive cocultivation assay, that these RNA structures and their interaction with L32 play a role in the fitness of the cell. The change of a single nucleotide within the 5' leader of the RPL32 transcript, which abolishes the site for L32 binding, leads to detectably slower growth and to eventual loss of the mutant strain from the culture. Experiments designed to assess independently the regulation of splicing and the regulation of translation are presented. These observations demonstrate that, in evolutionary terms, subtle regulatory compensations can be critical. The change in structure of an RNA, due to alteration of just one noncoding nucleotide, can spell the difference between biological success and failure.

Impacto do pH final na maciez do músculo Longissimus lumborum de animais zebuínos: mudanças estruturais de proteínas da carne crua e cozida durante a maturação

O objetivo do presente trabalho foi determinar a força de cisalhamento Warner-Bratzler do músculo Longissimus lumborum de animais zebuínos machos inteiros (Bos indicus) durante o período de maturação, nas faixas de pH final (pHf 48 horas post mortem) normal (pH entre 5,5 e 5,8) e anormal (pH entre 5,81 e 6,19) e temperaturas internas de cozimento. Concomitante com a avaliação de força de cisalhamento, foram avaliadas também a degradação da desmina e troponina T, o comprimento do sarcômero, o teor de colágeno total e solúvel, as temperaturas máximas de desnaturação das proteínas e a morfologia geral de agregação das fibras do músculo no cozimento. A degradação da desmina e troponina T foi maior no pHf normal, aparecendo produtos de degradação a partir do dia 7 nessa faixa de pHf. Não houve diferenças nos valores de comprimento do sarcômero, descartando-se assim, a contribuição desse parâmetro sobre a temperatura máxima de desnaturação (Tmáx) das proteínas, determinada utilizando calorímetro exploratório diferencial (DSC). Similarmente, não foram encontradas diferenças para os teores de colágeno total e solúvel, e os valores de colágeno total foram baixos, sugerindo que sua contribuição na segunda transição térmica e nos valores de força de cisalhamento foi mínima. As Tmáx1 e Tmáx2, correspondentes à desnaturação da meromiosina leve e pesada, respectivamente, foram menores no pHf normal, mas o efeito foi maior para a Tmáx2. A Tmáx3 da actina e titina aumentou até 14 dias post mortem na faixa de pHf normal, e posteriormente diminuiu significativamente após 21 dias, sugerindo possível degradação dessas proteínas nesse período de dias. Não foram encontradas diferenças nos valores de Tmáx no pHf anormal, em todos os dias post mortem, o que sugere a contribuição de um possível mecanismo de proteção que estabiliza as miofibrilas no aquecimento. Houve maior agregação das fibras do músculo no pHf normal nas temperaturas internas de cozimento de 65 e 80°C, provavelmente devido à maior desnaturação térmica das miofibrilas. Os valores de força de cisalhamento foram maiores com o aumento da temperatura interna de cozimento, devido ao aumento da desnaturação térmica das miofibrilas do músculo. Independente da temperatura interna de cozimento, os valores de força de cisalhamento foram altos em quase todos os dias post mortem para ambas as faixas de pHf, o que sugere a necessidade de utilizar métodos físicos ou químicos para aumentar a maciez do músculo Longissimus lumborum de animais zebuínos.

The Use of the Rey 15-Item Test and Recognition Trial to Evaluate Suboptimal Effort in Neuropsychological Assessment with a Pediatric Mild TBI Sample

The utilization of symptom validity tests (SVTs) in pediatric assessment is receiving increasing empirical support. The Rey 15-Item Test (FIT) is an SVT commonly used in adult assessment, with limited research in pediatric populations. Given that FIT classification statistics across studies to date have been quite variable, Boone, Salazar, Lu, Warner-Chacon, and Razani (2002) developed a recognition trial to use with the original measure to enhance accuracy. The current study aims to assess the utility of the FIT and recognition trial in a pediatric mild traumatic brain injury (TBI) sample (N = 112; M = 14.6 years), in which a suboptimal effort base rate of 17% has been previously established (Kirkwood & Kirk, 2010). All participants were administered the FIT as part of an abbreviated neuropsychological evaluation; failure on the Medical Symptom Validity Test (MSVT) was used as the criterion for suspect effort. The traditional adult cut-off score of(99%), but poor sensitivity (6%). When the recognition trial was also utilized, a combination score of(sensitivity = 64%, specificity = 93%). Results indicate that the FIT with recognition trial may be useful in the assessment of pediatric suboptimal effort, at least among relatively high functioning children following mild TBI.

New Hampshire, 1816 (Image 4 of 6) (Raster Image)

This layer is a georeferenced raster image of the historic paper map entitled: New Hampshire by recent survey : made under the supreme authority and published according to law by Philip Carrigain ; J.J. Barralet, del. ; W. Harrison, sct., Philada. It was published by Philip Carrigain in 1816. Scale [ca. 1:200,000]. This layer is image 4 of 6 total images, representing the southwest portion of the six sheet source map. The image inside the map neatline is georeferenced to the surface of the earth and fit to the New Hampshire State Plane coordinate system (NAD 1983 in Feet) (Fipszone 2800). All map collar and inset information is also available as part of the raster image, including any inset maps, profiles, statistical tables, directories, text, illustrations, index maps, legends, or other information associated with the principal map. This map shows features such as roads, drainage, public buildings, schools, churches, industry locations (e.g. mills, factories, mines, etc.), selected private buildings with names of property owners, town boundaries, land grants, and more. Relief shown pictorially and by hachures. Includes area notes, text, and table of population. Also includes illustrations: View of the Great Boars Head and Hampton Beach -- The Cap of the White Mountains -- View of the White Mountains from Shelburne; inset maps: States of the Union east of the Hudson with the adjacent British colonies. Scale [ca. 1:1,920,000] -- The middle, southern and western sections of the United States with the territories. Scale [ca. 1:4,900,000]. Includes: ms. additions with updated county boundary & township names.This layer is part of a selection of digitally scanned and georeferenced historic maps of New England from the Harvard Map Collection. These maps typically portray both natural and manmade features. The selection represents a range of regions, originators, ground condition dates, scales, and map purposes.

New Hampshire, 1816 (Image 5 of 6) (Raster Image)

This layer is a georeferenced raster image of the historic paper map entitled: New Hampshire by recent survey : made under the supreme authority and published according to law by Philip Carrigain ; J.J. Barralet, del. ; W. Harrison, sct., Philada. It was published by Philip Carrigain in 1816. Scale [ca. 1:200,000]. This layer is image 5 of 6 total images, representing the center west portion of the six sheet source map. The image inside the map neatline is georeferenced to the surface of the earth and fit to the New Hampshire State Plane coordinate system (NAD 1983 in Feet) (Fipszone 2800). All map collar and inset information is also available as part of the raster image, including any inset maps, profiles, statistical tables, directories, text, illustrations, index maps, legends, or other information associated with the principal map. This map shows features such as roads, drainage, public buildings, schools, churches, industry locations (e.g. mills, factories, mines, etc.), selected private buildings with names of property owners, town boundaries, land grants, and more. Relief shown pictorially and by hachures. Includes area notes, text, and table of population. Also includes illustrations: View of the Great Boars Head and Hampton Beach -- The Cap of the White Mountains -- View of the White Mountains from Shelburne; inset maps: States of the Union east of the Hudson with the adjacent British colonies. Scale [ca. 1:1,920,000] -- The middle, southern and western sections of the United States with the territories. Scale [ca. 1:4,900,000]. Includes: ms. additions with updated county boundary & township names.This layer is part of a selection of digitally scanned and georeferenced historic maps of New England from the Harvard Map Collection. These maps typically portray both natural and manmade features. The selection represents a range of regions, originators, ground condition dates, scales, and map purposes.

Philadelphia, Pennsylvania, Reed's map, 1774 (Raster Image) (Image 1 of 2)

This layer is a georeferenced raster image of the historic paper map entitled: Fac simile of Reed's map : to the honourable House of Representatives of the freemen of Pennsylvania this map of the city and liberties of Philadelphia with the catalogue of purchasers is humbly dedicated by their most obedient humble servant, Iohn Reed, James Smither sculp. Facsimile of a map originally published in 1774. Republished by Charles L. Warner in 1870. Scale [1:23,760]. Covers portions of Philadelphia, Pa. This layer is image 1 of 2 total images of the two sheet source map, representing the eastern portion of the map. The image inside the map neatline is georeferenced to the surface of the earth and fit to the Pennsylvania South State Plane Coordinate System NAD83 (in Feet) (Fipszone 3702). All map collar and inset information is also available as part of the raster image, including any inset maps, profiles, statistical tables, directories, text, illustrations, index maps, legends, or other information associated with the principal map. Cadastral map showing property boundaries, areas, lot numbers, and names of landowers. Includes features such as roads, drainage, and more. Includes inset: A ground plan of the city of Philadelphia. Also includes extensive text and index of landowners. This layer is part of a selection of digitally scanned and georeferenced historic maps from The Harvard Map Collection as part of the Imaging the Urban Environment project. Maps selected for this project represent major urban areas and cities of the world, at various time periods. These maps typically portray both natural and manmade features at a large scale. The selection represents a range of regions, originators, ground condition dates, scales, and purposes.

Philadelphia, Pennsylvania, Reed's map, 1774 (Raster Image) (Image 2 of 2)

This layer is a georeferenced raster image of the historic paper map entitled: Fac simile of Reed's map : to the honourable House of Representatives of the freemen of Pennsylvania this map of the city and liberties of Philadelphia with the catalogue of purchasers is humbly dedicated by their most obedient humble servant, Iohn Reed, James Smither sculp. Facsimile of a map originally published in 1774. Republished by Charles L. Warner in 1870. Scale [1:23,760]. Covers portions of Philadelphia, Pa. This layer is image 2 of 2 total images of the two sheet source map, representing the western portion of the map. The image inside the map neatline is georeferenced to the surface of the earth and fit to the Pennsylvania South State Plane Coordinate System NAD83 (in Feet) (Fipszone 3702). All map collar and inset information is also available as part of the raster image, including any inset maps, profiles, statistical tables, directories, text, illustrations, index maps, legends, or other information associated with the principal map. Cadastral map showing property boundaries, areas, lot numbers, and names of landowers. Includes features such as roads, drainage, and more. Includes inset: A ground plan of the city of Philadelphia. Also includes extensive text and index of landowners. This layer is part of a selection of digitally scanned and georeferenced historic maps from The Harvard Map Collection as part of the Imaging the Urban Environment project. Maps selected for this project represent major urban areas and cities of the world, at various time periods. These maps typically portray both natural and manmade features at a large scale. The selection represents a range of regions, originators, ground condition dates, scales, and purposes.

Insight into the evolution of the Solanaceae from the parental genomes of Petunia hybrida

Petunia hybrida is a popular bedding plant that has a long history as a genetic model system. We report the whole-genome sequencing and assembly of inbred derivatives of its two wild parents, P. axillaris N and P. inflata S6. The assemblies include 91.3% and 90.2% coverage of their diploid genomes (1.4 Gb; 2n = 14) containing 32,928 and 36,697 protein-coding genes, respectively. The genomes reveal that the Petunia lineage has experienced at least two rounds of hexaploidization: the older gamma event, which is shared with most Eudicots, and a more recent Solanaceae event that is shared with tomato and other solanaceous species. Transcription factors involved in the shift from bee to moth pollination reside in particularly dynamic regions of the genome, which may have been key to the remarkable diversity of floral colour patterns and pollination systems. The high-quality genome sequences will enhance the value of Petunia as a model system for research on unique biological phenomena such as small RNAs, symbiosis, self-incompatibility and circadian rhythms.

Ten little niggers.

In verse (p. [1] - [12]) with music (p. [2] and [3] of cover)