Scanning Electron Microscopy of Microcorrosion Casts: Applications in Ophthalmologic Research

In light of the complicated nature of the ocular vasculature, it has been difficult to define the normal ocular anatomy by reference to two-dimensional tissue sections. Since it provides three-dimensional replicas, scanning electron microscopy (SEM) of vascular corrosion casts has therefore been an invaluable addition to the study of ocular vasculature. This technique also often permits identification of a normal vessel\u27s arterial, venous, or capillary nature by its surface features. In addition, this technique is finding increased use in defining anatomical features of human vascular disease and is especially well suited for the study of experimental neovascularization as it relates to the eye. This paper reviews the application of SEM of microscopic casts to the study of normal and diseased ocular vessels, as well as the contribution of this method to studies of experimental ocular neovascularization

The Influence of Decoys on the Noise and Dynamics of Gene Expression

Many transcription factors bind to DNA with a remarkable lack of specificity, so that regulatory binding sites compete with an enormous number of non-regulatory 'decoy' sites. For an auto-regulated gene, we show decoy sites decrease noise in the number of unbound proteins to a Poisson limit that results from binding and unbinding. This noise buffering is optimized for a given protein concentration when decoys have a 1/2 probability of being occupied. Decoys linearly increase the time to approach steady state and exponentially increase the time to switch epigenetically between bistable states.Comment: 8 pages, 4 figure

Time resolved spectrometry on the CLIC Test Facility 3

The high charge (>6ìC) electron beam produced in the CLIC Test Facility 3 (CTF3) is accelerated in fully beam loaded cavities. To be able to measure the resulting strong transient effects, the time evolution of the beam energy and its energy spread must be determined with at least 50MHz bandwidth. Three spectrometer lines are installed along the linac in order to control and tune the beam. The electrons are deflected by dipole magnets onto Optical Transition Radiation (OTR) screens which are observed by CCD cameras. The measured horizontal beam size is then directly related to the energy spread. In order to provide time-resolved energy spectra, a fraction of the OTR photons is sent onto a multi-channel photomultiplier. The overall setup is described, special focus is given to the design of the OTR screen with its synchrotron radiation shielding. The performance of the time-resolved measurements are discussed in detail. Finally, the limitations of the system, mainly due to radiation problems are discussed

The Neurospora mitochondrial genome:the region coding for the polycistronic cytochrome oxidase subunit I transcript is preceded by a transfer RNA gene

AbstractWe have sequenced a 682 bp fragment of Neurospora crassa mitochondrial DNA to complete the sequence between the gene for cytochrome b and the unassigned reading frame, URF U. The sequence contains a gene for a cysteine tRNA. The 5' end of the 6 kb polycistronic transcript of cytochrome c oxidase subunit 1 is immediately downstream from this tRNA. This shows that also in fungal mitochondria tRNAs can be used as processing signals, whereas palindromic sequences containing double Pst I sites, also present in this region, are not used for processing

The 2007 WHO Classification of Tumours of the Central Nervous System

The fourth edition of the World Health Organization (WHO) classification of tumours of the central nervous system, published in 2007, lists several new entities, including angiocentric glioma, papillary glioneuronal tumour, rosette-forming glioneuronal tumour of the fourth ventricle, papillary tumour of the pineal region, pituicytoma and spindle cell oncocytoma of the adenohypophysis. Histological variants were added if there was evidence of a different age distribution, location, genetic profile or clinical behaviour; these included pilomyxoid astrocytoma, anaplastic medulloblastoma and medulloblastoma with extensive nodularity. The WHO grading scheme and the sections on genetic profiles were updated and the rhabdoid tumour predisposition syndrome was added to the list of familial tumour syndromes typically involving the nervous system. As in the previous, 2000 edition of the WHO ‘Blue Book’, the classification is accompanied by a concise commentary on clinico-pathological characteristics of each tumour type. The 2007 WHO classification is based on the consensus of an international Working Group of 25 pathologists and geneticists, as well as contributions from more than 70 international experts overall, and is presented as the standard for the definition of brain tumours to the clinical oncology and cancer research communities world-wide

Genome-scale analysis identifies paralog lethality as a vulnerability of chromosome 1p loss in cancer.

Functional redundancy shared by paralog genes may afford protection against genetic perturbations, but it can also result in genetic vulnerabilities due to mutual interdependency1-5. Here, we surveyed genome-scale short hairpin RNA and CRISPR screening data on hundreds of cancer cell lines and identified MAGOH and MAGOHB, core members of the splicing-dependent exon junction complex, as top-ranked paralog dependencies6-8. MAGOHB is the top gene dependency in cells with hemizygous MAGOH deletion, a pervasive genetic event that frequently occurs due to chromosome 1p loss. Inhibition of MAGOHB in a MAGOH-deleted context compromises viability by globally perturbing alternative splicing and RNA surveillance. Dependency on IPO13, an importin-β receptor that mediates nuclear import of the MAGOH/B-Y14 heterodimer9, is highly correlated with dependency on both MAGOH and MAGOHB. Both MAGOHB and IPO13 represent dependencies in murine xenografts with hemizygous MAGOH deletion. Our results identify MAGOH and MAGOHB as reciprocal paralog dependencies across cancer types and suggest a rationale for targeting the MAGOHB-IPO13 axis in cancers with chromosome 1p deletion

Embryonal tumors with abundant neuropil and true Rosettes: A distinctive CNS primitive neuroectodermal tumor

Embryonal neoplasms of the central nervous system (CNS) generally arise in the early years of life and behave in a clinically aggressive manner, but vary somewhat in their microscopic appearance. Several groups have reported examples of an embryonal tumor with combined histologic features of ependymoblastoma and neuroblastoma, a lesion referred to as "embryonal tumor with abundant neuropil and true rosettes" (ETANTR). Herein, we present 22 new cases, and additional clinical follow-up on our 7 initially reported cases, to better define the histologic features and clinical behavior of this distinctive neoplasm. It affects infants and arises most often in cerebral cortex, the cerebellum and brainstem being less frequent sites. Unlike other embryonal tumors of the CNS, girls are more commonly affected than boys. On neuroimaging, the tumors appear as large, demarcated, solid masses featuring patchy or no contrast enhancement. Five of our cases (18%) were at least partly cystic. Distinctive microscopic features include a prominent background of mature neuropil punctuated by true rosettes formed of pseudo-stratified embryonal cells circumferentially disposed about a central lumen (true rosettes). Of the 25 cases with available follow-up, 19 patients have died, their median survival being 9 months. Performed on 2 cases, cytogenetic analysis revealed extra copies of chromosome 2 in both. We believe that the ETANTR represents a histologically distinctive form of CNS embryonal tumor. ©2009 by Lippincott Williams & Wilkins

Invasive adenoma and pituitary carcinoma: a SEER database analysis

Invasive pituitary adenomas and pituitary carcinomas are clinically indistinguishable until identification of metastases. Optimal management and survival outcomes for both are not clearly defined. The purpose of this study is to use the Surveillance, Epidemiology, and End Results (SEER) database to report patterns of care and compare survival outcomes in a large series of patients with invasive adenomas or pituitary carcinomas. One hundred seventeen patients diagnosed between 1973 and 2008 with pituitary adenomas/adenocarcinomas were included. Eighty-three invasive adenomas and seven pituitary carcinomas were analyzed for survival outcomes. Analyzed prognostic factors included age, sex, race, histology, tumor extent, and treatment. A significant decrease in survival was observed among carcinomas compared to invasive adenomas at 1, 2, and 5 years (p=0.047, 0.001, and 0.009). Only non-white race, male gender, and age ≥65 were significant negative prognostic factors for invasive adenomas (p=0.013, 0.033, and <0.001, respectively). There was no survival advantage to radiation therapy in treating adenomas at 5, 10, 20, or 30 years (p=0.778, 0.960, 0.236, and 0.971). In conclusion, pituitary carcinoma patients exhibit worse overall survival than invasive adenoma patients. This highlights the need for improved diagnostic methods for the sellar phase to allow for potentially more aggressive treatment approaches