Deconstructing the evolutionary complexity between rust fungi (Pucciniales) and their plant hosts.

The rust fungi (Pucciniales) are the most speciose natural group of plant pathogens, members of which possess the most complex lifecycles in Fungi. How natural selection works on the Pucciniales has been the subject of several hypotheses in mycology. This study uses molecular age estimation using sequence data from multiple loci, and cophylogeny reconciliation analyses to test hypotheses regarding how the aecial and telial stages in the lifecycle of rust fungi may have differentially impacted their diversification. Molecular age estimates show that the timing of diversification in the Pucciniales correlates with the diversification of their gymnosperm and angiosperm hosts. Host reconciliation analyses suggest that systematic relationships of hosts from the aecial stage of the Pucciniales lifecycle better reflect the systematic relationships among the Pucciniales. The results demonstrate the relative importance of this stage on the overall evolution of the Pucciniales and supports hypotheses made by Leppik over half a century ago. This study represents the first evaluation of how different life stages in the Pucciniales shape the evolution of these fungi.

Rapid diversification of Tragopogon and ecological associates in Eurasia.

Tragopogon comprises approximately 150 described species distributed throughout Eurasia from Ireland and the UK to India and China with a few species in North Africa. Most of the species diversity is found in Eastern Europe to Western Asia. Previous phylogenetic analyses identified several major clades, generally corresponding to recognized taxonomic sections, although relationships both among these clades and among species within clades remain largely unresolved. These patterns are consistent with rapid diversification following the origin of Tragopogon, and this study addresses the timing and rate of diversification in Tragopogon. Using BEAST to simultaneously estimate a phylogeny and divergence times, we estimate the age of a major split and subsequent rapid divergence within Tragopogon to be ~2.6 Ma (and 1.7-5.4 Ma using various clock estimates). Based on the age estimates obtained with BEAST (HPD 1.7-5.4 Ma) for the origin of crown group Tragopogon and 200 estimated species (to accommodate a large number of cryptic species), the diversification rate of Tragopogon is approximately 0.84-2.71 species/Myr for the crown group, assuming low levels of extinction. This estimate is comparable in rate to a rapid Eurasian radiation in Dianthus (0.66-3.89 species/Myr), which occurs in the same or similar habitats. Using available data, we show that subclades of various plant taxa that occur in the same semi-arid habitats of Eurasia also represent rapid radiations occurring during roughly the same window of time (1.7-5.4 Ma), suggesting similar causal events. However, not all species-rich plant genera from the same habitats diverged at the same time, or at the same tempo. Radiations of several other clades in this same habitat (e.g. Campanula, Knautia, Scabiosa) occurred at earlier dates (45-4.28 Ma). Existing phylogenetic data and diversification estimates therefore indicate that, although some elements of these semi-arid communities radiated during the Plio-Pleistocene period, other clades sharing the same habitat appear to have diversified earlier.

Investigating potential for depensation in marine turtles: how low can you go?

Where mechanisms inherent within the biology of a species affect individual fitness at low density, demographic-scale depensation may occur, hastening further decline and leading ultimately to population extirpation and species extinction. Reduction in fertility at low population densities has been identified in marine and terrestrial species. Using data on hatch success and hatchling-emergence success as proxies for fertilization success, we conducted a global meta-analysis of data from breeding aggregations of green turtles (Chelonia mydas) and loggerhead turtles (Caretta caretta). We found that there has been no reduction in fertility in small nesting aggregations in either of these species worldwide. We considered mechanisms within the mating strategies and reproductive biology of marine turtles that may allow for novel genetic input and facilitate enhanced gene flow among rookeries. Behavioral reproductive mechanisms, such as natal philopatry and polyandry, may mitigate potential impacts of depensation and contribute to the resilience of these species.

Is mitotic chromatid segregation random?

The question of whether mitotic segregation of chromatids is random or programmed assumes great significance for cellular differentiation if one recognizes that sister chromatids may have epigenetic differences and carry them from one generation into the next. The literature was examined for evidence of non-random chromosomal and chromatid segregation. Many organisms were described as undergoing non-random homologue segregation in meiosis I. The explanations for these phenomena were attributed in some instances, to peculiarities of the meiotic spindle, though in some convincing experiments, the epigenetic heterochromatin of the kinetochores was implicated. The few existing descriptions of non-random mitotic segregation were also described. Existing literature on ultrastructural, immunohistochemical, and physiological features of the chromatid kinetochores during the mitotic process was searched for evidence of asymmetry or structural differences between sister chromatids, which is presented. Also reported are descriptions of how epigenetic changes and cell differentiation can influence centromeric function and ultimately, kinetochore function. Fundamental to the hypothesis of gene regulation presented here, is the assumption that genetic foci on different chromosomes interact, and must be proximate to each other and stereologically compatible for interactions to occur. Also described are spatial changes in chromosomal territories associated with function and differentiation. These territories can be in varying nuclear locations depending on gene function, and may show asymmetry between daughter cells. Despite evidence presented for the possibility of non-random chromatid segregation at mitosis, this question will remain unanswered until the matter is specifically addressed by experiment.

The significance of secretory features and coincident hyperplastic changes in endometrial biopsy specimens.

The clinical and pathological characteristics of endometrial hyperplasia simulating or coexisting with secretory endometrium were studied in 35 cases of women with at least one biopsy diagnosed as secretory endometrium and another biopsy diagnosed as endometrial hyperplasia or neoplasia. The biopsy samples were examined histologically by semiquantitative methods to detect features that could aid in distinguishing secretory endometrium from hyperplastic endometrium existing focally in secretory endometrium or simulating secretory endometrium. Important histologic features were focal architectural abnormalities, epithelial pseudopalisading, a vesicular nuclear appearance, nuclear atypia, mitoses, the presence of metaplastic ciliated and "clear" cells, and a sharp luminal margin indicating absence of cytoplasmic secretion. The distribution of patients' ages fell between that of perimenopausal women with only secretory features on biopsy (curettage) and that of women with hyperplastic endometrium on biopsy. Twenty-nine per cent of the women in the study group had diabetes or hypertension, and 29 per cent had leiomyomata or adenomyosis at eventual hysterectomy. Patients followed up showed persistence of hyperplasia and progression to a more severe degree of cytologic atypia on later biopsy samples. Recommendations are made for improved detection of these hyperplastic changes and for careful follow-up of patients.

The relationship of nuclear staining density and mode of stromal invasion with axillary metastases and hormone receptor status in human breast cancer.

Biopsies from 52 cases of infiltrating duct carcinoma of breast were assessed for proportions of tumor infiltrating stroma as "thin" strands and as confluent cell sheets. The proportions of cell nuclei arbitrarily designated "dark" were determined for each whole tumor and for their above-mentioned invasive compartments and were compared with the tumor's nuclear grade, mitotic index, gross size, axillary metastatic status, and hormone receptivity. Well-differentiated tumors tended to have more cells with "dark" nuclei and more of the tumor mass invading the stroma as "thin" strands than poorly differentiated ones. Tumors that had axillary metastases also tended to have high mitotic indices, low proportions of cells with "dark" nuclei (and conversely high proportions of cells with vesicular nuclei) in confluent sheets. Tumors that had positive results for one or both hormone receptors had a greater component of trabecular stromal invasion than tumors with negative results for both hormone receptors that grew as confluent cell sheets. It is suggested that tumor cell nuclear staining "density" might be a clinically useful prognostic index despite the finding that semiquantitative assessments of nuclear density can be modified by the mode of stromal invasion.

Symmetry applied to nuclear microanatomy: a review of gene function and cell differentiation.

The purpose of this paper is to review current knowledge and understandings of gene control and cell differentiation, based upon an appreciation of a possible role that nuclear microanatomy and considerations of steric symmetry might play. Metaphase sister chromatids have identical base codes but show a mirror image symmetry of higher order coiling. Chromosomes in the interphase nucleus have spatially well defined domains and are anatomically distinct and ordered. Chromosomes are known to have interactions i.e. sex chromosome inactivation, PEV, etc. An hypothesis of gene activation is made based on steric interactions among chromosomes and between chromosomes and activating and repressor proteins. These interactions may be influenced by the handedness of higher order chromatid coiling, since homologues show mirror-image symmetrical coiling in metaphase, which might be retained to a certain degree in interphase. This may result in a binary switching of genes. All possible combinations of chromatids in the interphase nucleus, would be enabled by a differential segregation of homologous chromatids at mitosis. To conserve patterns of interchromatid interactions, there must be a programmed segregation of chromatids towards one of the two spindle pole attachments. This orientation might be effected by preferential attachment of microtubules to kinetochore attachment sites, by steric hindrance of the kinetochore by condensed chromatin which initially allows only unidirectional tubule attachment, or possibly by a tethering of interacting chromatids which would migrate en masse. An attempt to apply this hypothesis to some illustrative pathological conditions is made.

Levels of ioglycamate (Biligram) in the bile of the rhesus monkey following intravenous infusion at different dose-rates.

The maximun rate of excretion of ioglycamate in the bile of the rhesus monkey was achieved when the rate of adminstration was at least twice the rate of excretion. A maximum concentration of ioglycamate in the bile was also established, and this is more important to the visualization of the bileducts than the quanity of ioglycamate excreted. The maximum concentration was obtained at the same rate of infusion as that which produced the maximum rate of excretion. The peak concentration was sustained longer with an infusion lasting two hours than with one lasting 36 minutes, althought the same quanity of ioglycamate had been administered. It is concluded that an infusion at a rate equal to twice the maximum excretory rate and continued for two hours or longer is a rational approach to intravenuous cholangiography particularly in those patients where there has been some diffculty in bile-duct visulization.

The concentration maximum concept in intravenous cholangiography.

The excretion of ioglycamate in the bile of the rhesus monkey was measured at 5% and at 100% bile diversion following an intravenous bolus injection of ioglycamate. At 100% diversion the bile volume was reduced and the concentration of ioglycamate was increased, but the quantity excreted was unchanged. A similar study using iodipamide reported previously gave the same result. When the ioglycamate was given by intravenous infusion, the effect of 100% bile diversion was quite different. The concentration of ioglycamate in the bile was unchanged by the bile diversion but the excretion was reduced. These results indicate that the transport maximum for the excretion of ioglycamate in bile is not a constant and is reduced by interruption of the enterohepatic circulation of bile salts. The maximum concentration of ioglycamate in bile was constant and was independent of the reduction in bile salt output produced by 100% bile diversion. Following a single bolus injection however, the reduction in bile flow produced by 100% bile diversion increased the biliary concentration of ioglycamate. These results suggest that the excretion of ioglycamate is limited by a maximum concentration rather than a transport maximum. The maximum rate of transport (Tm) is dependent on two factors--the maximum concentration of ioglycamate in the bile and the rate of bile flow. The maximum concentration is achieved by an infusion technique and not by a single bolus injection and this supports the view that an infusion technique should be used for intravenous cholangiography.

Histologic, immunohistochemical, and ultrastructural findings in a case of minocycline-associated "black thyroid".

We report on a 37-yr-old woman with known antemortem ingestion of minocyclin who died suddenly from a ruptured cerebral aneurysm. At autopsy, her thyroid gland, although not enlarged, was diffusely black, caused by the deposition of a melanin-like pigment that stained positive with Schmorl's reagent. The pigment could be bleached with permanganate, and on examination by electron microscopy, it appeared to be deposited within the thyrocyte lysosomes. Additional immunostaining with many antibodies revealed an increase in vimentin staining in the follicular epithelium compared with normal control thyroid glands. Staining for cytoplasmic thyroglobulin was markedly reduced, despite normal thyroid indices performed on stored antemortem blood. Stainable ubiquitin in the follicular epithelium appeared reduced compared with control thyroid tissues. These immunohistochemical findings may reflect disruptions of lysosomal transport and function associated with the abnormal accumulation of pigment. This appears to be the only case of minocyclin-associated "black thyroid" in which extensive immunohistochemical investigations have been performed.

The 'vapour-phase' migration of styrene from general purpose polystyrene and high impact polystyrene into cooking oil.

General purpose and high impact polystyrene (GPPS and HIPS, respectively) are used in many food packaging applications. In some packaging configurations, where there is no direct contact of a liquid surface with the polymer, 'vapour-phase' migration of styrene monomer from the polymer with subsequent absorption into food is thought to be a significant mode of transfer. Correlation of residual styrene concentrations in polystyrene with vapour-phase styrene migration is of interest in order to predict potential consumer exposure to styrene from food-packaging applications of this configuration. Studies of the migration of styrene from GPPS and HIPS into air with subsequent absorption of the monomer into cooking oil, 'vapour-phase' migration, was determined in a sealed system. The results showed that for both polymers the amount of styrene migrating from the polystyrene and being absorbed by the oil was proportional to the square root of the time of exposure. The diffusion coefficients calculated for the vapour-phase migration of styrene from both polymers were found to be in good agreement with the diffusion coefficients previously determined for the 'liquid-phase' migration of styrene from similar polymers where the polymers were completely submerged in the cooking oil. These results indicate that the styrene concentrations measured in both experiments were attributable to the intrinsic diffusion of styrene from polystyrene, and that contact with cooking oil did not accelerate migration in previous experiments.

Papillary carcinoma of thyroid metastatic to the pituitary gland.

We describe a 35-year-old woman who presented with diabetes insipidus caused by metastatic papillary carcinoma of the thyroid involving the pituitary gland, 25 years after treatment for a papillary carcinoma of thyroid and 17 years after treatment for multiple pulmonary metastases. The literature contains 10 previously described cases of metastatic thyroid carcinoma involving the sella, but only 2 of these cases had unequivocal metastases to the pituitary gland, making the present case, to our knowledge, the third reported case of unequivocal hematogenous metastasis of thyroid carcinoma to the pituitary gland. The pituitary tumor was removed by transsphenoidal surgery, and the tissue was examined by conventional histology, extensive immunohistochemistry, and electron microscopy. The findings confirmed the tumor to be papillary thyroid carcinoma. To our knowledge, this is the first report citing use of thyroid transcription factor-1 to establish a thyroid source of a pituitary metastasis.

Malignant oncocytic tumour of the parotid salivary gland.

A 49-year-old man developed a tumour mass in his right parotid salivary gland nine years after a histologically proven benign mixed tumour of the same salivary gland had been surgically removed. Radical resection of the right parotid salivary gland and associated lymph nodes and soft tissues of the neck was performed. The parotid tumour was composed of oncocytic cells which infiltrated the surviving salivary gland tissue. Most of the excised lymph nodes contained metastatic deposits of oncocytic cells identical to the tumour seen in the parotid. There are no previous reports of the occurrence of both pleomorphic adenoma and malignant oncocytoma in the same salivary gland.

Variability of cell size in primary and metastatic human breast carcinoma.

Macroscopic measurements and histometrical estimates of cell cytoplasmic (Cx) and nuclear areas (Nx) were made on 24 primary and 37 metastatic tumors from patients with human breast carcinoma. Within the small metastases, the cancer cells were smaller and showed greater variation in size (CVC, CVN) than those in their respective primary tumors. In the larger metastases, the cells were larger and more uniform in size. Studies of primary tumors showed that both Cx and Nx of tumor cells bore a direct relationship to the gross size of the primary tumor. Comparisons of measurements from the 14 primary tumors with metastases and the 10 primary tumors with no metastases revealed no significant differences between the groups. In all tumors, Cx bore a predictable and direct relationship to Nx.

Molecular phylogeny and biogeography of Linanthus (Polemoniaceae).

To better understand the evolutionary history of Linanthus (Polemoniaceae) and its relatives, molecular phylogenies based on DNA sequence data from the internal transcribed spacer (ITS) region of nrDNA and the chloroplast gene matK were estimated using several methods. Our data suggest two separate and well-supported lineages of Linanthus in close association with two other genera-Leptodactylon and Phlox. These results agree with previous molecular systematic work on the Polemoniaceae, but do not support the traditional classification of the genus as a natural group, nor do they support the sectional classification within the genus. With a distribution centered primarily in western North America and a high degree of endemism in the California Floristic Province, it has been suggested by Raven and Axelrod that the origin and diversification of Linanthus and its relatives were tied to the development of a summer-dry climate in western North America, which began around 13-15 million years ago (mya). Increased drying during the Pliocene (1.2-5 mya) has also been hypothesized by Axelrod to have led to an increase in plant speciation in California and adjacent areas. Divergence times within the Linanthus lineages were estimated from the ITS and matK gene trees. A log-likelihood ratio test could not reject clock-like evolution for the matK data; however, the clock was strongly rejected for the ITS data set. Although ITS molecular evolution was not clock-like, the estimated times of divergence were similar to those of the matK data set. Within both lineages of Linanthus there seems to have been considerable diversification that has occurred since the Pliocene.