Susceptibility to glaucoma: differential comparison of the astrocyte transcriptome from glaucomatous African American and Caucasian American donors

Comparison of gene expression in normal and glaucomatous eyes from Caucasian American and African American donors reveals differences that might reflect different susceptibility to glaucoma

The Elamite Cylinder Seal Corpus, c.3500 - 1000 BC

The ancient region of Elam (southwestern Iran) has produced a significant assemblage of cylinder seals across a considerable chronological span. Unlike the glyptic material from the related and neighbouring region Mesopotamia, the Elamite cylinder seals have not previously been studied in detailed reference to one another, nor has there been an established paradigm of stylistic development articulated. This study addresses this lacuna by compiling all the published cylinder seals from Elam (as defined here, thus incorporating the historical provinces of Khuzistan, Luristan and Fars), from their earliest appearance (c.3500 BC), throughout the era of their typological dominance (over stamp seals, thus this study departs c.1000 BC). This compilation is presented in the Elamite Cylinder Seal Catalogue (Volume II), and is annotated and described through the annunciation of eighteen chronologically defined developmental styles (with another two non-chronological type classifications and four miscellaneous groups). Through the further analysis of this data, including the newly formulated and articulated styles, several facets and problems of Elamite glyptic material have been addressed (and thus the reliance upon assumed similarity in type and function with the Mesopotamian glyptic material is abandoned). These problems particularly pertain to the function of cylinder seals in Elam and the type and form of the Elamite-Mesopotamian glyptic interaction. In regards to function, a standard administrative function can be discerned, though of varying types and forms across the region and the period of study. Other, non-standard, symbolic glyptic functions can also be demonstrated in the Corpus, including the apparent proliferation of a form known as the ‘votive’ seal, perhaps a specifically Elamite form. The analysis of the style type (whether ‘Elamite’, ‘Mesopotamian Related’ or ‘Shared Elamite-Mesopotamian’), in association with their relative geographical and chronological distribution, has also enabled the discussion of the nature of Elamite-Mesopotamian glyptic interaction, and thereby the constitution of Elamite civilisation (especially in regards to Mesopotamian cultural impact and influence, and thus the testing of several previously presented paradigms [Amiet 1979a; 1979b; Miroschedji 2003])

Protein Recognition by Short Peptide Reversible Inhibitors of the Chromatin-Modifying LSD1/CoREST Lysine Demethylase.

The combinatorial assembly of protein complexes is at the heart of chromatin biology. Lysine demethylase LSD1(KDM1A)/CoREST beautifully exemplifies this concept. The active site of the enzyme tightly associates to the N-terminal domain of transcription factors of the SNAIL1 family, which therefore can competitively inhibit the binding of the N-terminal tail of the histone substrate. Our enzymatic, crystallographic, spectroscopic, and computational studies reveal that LSD1/CoREST can bind to a hexapeptide derived from the SNAIL sequence through recognition of a positively charged α-helical turn that forms upon binding to the enzyme. Variations in sequence and length of this six amino acid ligand modulate affinities enabling the same binding site to differentially interact with proteins that exert distinct biological functions. The discovered short peptide inhibitors exhibit antiproliferative activities and lay the foundation for the development of peptidomimetic small molecule inhibitors of LSD1

Gene Expression and Functional Studies of the Optic Nerve Head Astrocyte Transcriptome from Normal African Americans and Caucasian Americans Donors

To determine whether optic nerve head (ONH) astrocytes, a key cellular component of glaucomatous neuropathy, exhibit differential gene expression in primary cultures of astrocytes from normal African American (AA) donors compared to astrocytes from normal Caucasian American (CA) donors.We used oligonucleotide Affymetrix microarray (HG U133A & HG U133A 2.0 chips) to compare gene expression levels in cultured ONH astrocytes from twelve CA and twelve AA normal age matched donor eyes. Chips were normalized with Robust Microarray Analysis (RMA) in R using Bioconductor. Significant differential gene expression levels were detected using mixed effects modeling and Statistical Analysis of Microarray (SAM). Functional analysis and Gene Ontology were used to classify differentially expressed genes. Differential gene expression was validated by quantitative real time RT-PCR. Protein levels were detected by Western blots and ELISA. Cell adhesion and migration assays tested physiological responses. Glutathione (GSH) assay detected levels of intracellular GSH.Multiple analyses selected 87 genes differentially expressed between normal AA and CA (P<0.01). The most relevant genes expressed in AA were categorized by function, including: signal transduction, response to stress, ECM genes, migration and cell adhesion.These data show that normal astrocytes from AA and CA normal donors display distinct expression profiles that impact astrocyte functions in the ONH. Our data suggests that differences in gene expression in ONH astrocytes may be specific to the development and/or progression of glaucoma in AA

Ramucirumab plus docetaxel versus placebo plus docetaxel in patients with locally advanced or metastatic urothelial carcinoma after platinum-based therapy (RANGE): a randomised, double-blind, phase 3 trial

Few treatments with a distinct mechanism of action are available for patients with platinum-refractory advanced or metastatic urothelial carcinoma. We assessed the efficacy and safety of treatment with docetaxel plus either ramucirumab-a human IgG1 VEGFR-2 antagonist-or placebo in this patient population

In Situ XAS Studies of Core-Shell PEM Fuel Cell Catalysts: The Opportunities and Challenges

Core-shell electrocatalysts are of increased interest in PEM fuel cells as a means of improving activity and reducing costs. In situ x-ray absorption spectroscopy (XAS) provides a unique opportunity to provide characterization of the structure of such materials under operating conditions, enabling the effects of the electrochemical environment on the structures to be explored. However, such measurements present numerous challenges in terms of both data collection and analysis. Here we present two case studies that illustrate both the opportunities and challenges; (i) the modification of a Pt catalyst by Ru and the potential dependent formation of a surface alloy and (ii) a Pt shell - Pd core catalyst with varying shell thickness

To alloy or not to alloy? Cr modified Pt/C cathode catalysts for PEM fuel cells

The cathode electrocatalysts for proton exchange membrane (PEM) fuel cells are commonly platinum and platinum based alloy nanoparticles dispersed on a carbon support. Control over the particle size and composition has, historically, been attained empirically, making systematic studies of the effects of various structural parameters difficult. The controlled surface modification methodology used in this work has enabled the controlled modification of carbon supported Pt nanoparticles by Cr so as to yield nanoalloy particles with defined compositions. Subsequent heat treatment in 5% H2 in N2 resulted in the formation of a distinct Pt3Cr alloy phase which was either restricted to the surface of the particles or present throughout the bulk of the particle structure. Measurement of the oxygen reduction activity of the catalysts was accomplished using the rotating thin film electrode method and the activities obtained were related to the structure of the nanoalloy catalyst particles, largely determined using Cr K edge and Pt L3 edge XAS