A phase 1b/pharmacokinetic trial of PTC299, a novel post-transcriptional VEGF inhibitor, for AIDS-related Kaposi’s sarcoma: AIDS Malignancy Consortium trial 059

Vascular endothelial growth factor (VEGF) plays an important role in Kaposi’s sarcoma (KS). We administered PTC299, a post-transcriptional inhibitor of pathogenic VEGF, to persons with HIV-related KS. Seventeen participants received three different doses of PTC299. Adverse events typically observed with VEGF-inhibition were absent. Three participants had partial tumor responses and 11 had stable disease. There were no differences in exposure to PTC299 by antiretroviral regimen. Serum VEGF, but not KSHV DNA, decreased on treatment. Given redundancies in the VEGF feedback loop, future trials should consider combining PTC299 with agents that inhibit different pathways implicated in KS and KSHV proliferation

Transcriptional Landscape of the Prenatal Human Brain

Summary The anatomical and functional architecture of the human brain is largely determined by prenatal transcriptional processes. We describe an anatomically comprehensive atlas of mid-gestational human brain, including de novo reference atlases, in situ hybridization, ultra-high resolution magnetic resonance imaging (MRI) and microarray analysis on highly discrete laser microdissected brain regions. In developing cerebral cortex, transcriptional differences are found between different proliferative and postmitotic layers, wherein laminar signatures reflect cellular composition and developmental processes. Cytoarchitectural differences between human and mouse have molecular correlates, including species differences in gene expression in subplate, although surprisingly we find minimal differences between the inner and human-expanded outer subventricular zones. Both germinal and postmitotic cortical layers exhibit fronto-temporal gradients, with particular enrichment in frontal lobe. Finally, many neurodevelopmental disorder and human evolution-related genes show patterned expression, potentially underlying unique features of human cortical formation. These data provide a rich, freely-accessible resource for understanding human brain development

A Holy Baptism of Fire & Blood: The Bible and the American Civil War

All told—and there is much in James Byrd’s insightful narrative—A Holy Baptism of Fire & Blood is a unique and powerful first-hand recounting of the Civil War’s ebb and flow through the elastic prism of the book most familiar to nineteenth-century Americans

Putative <i>C</i>. <i>jejuni</i> F38011 Restriction Modification systems.

<p>Putative <i>C</i>. <i>jejuni</i> F38011 Restriction Modification systems.</p

Genomic map of the <i>C</i>. <i>jejuni</i> F38011 strain.

<p>A 1.69 Mbp circular chromosome of the <i>C</i>. <i>jejuni</i> F38011 strain, beginning with DnaA and encoding a putative 1613 CDSs. Direction of the predicted protein coding sequences (CDS), transfer RNAs (tRNA), ribosomal RNAs (rRNA), mol.% (G+C) content, and GC skew are indicated.</p

The methylome of <i>C</i>. <i>jejuni</i> F38011 contains 5 dominant methylation motifs.

<p>The methylation consensus sequences identified by PacBio with adenine methylations found in motifs 1, 2, 3, and 4 (motifs 1, 2 and 4 have a partner motif; RAATTY partner motif not shown) and cytosine methylation found in motif 5. Consensus sequences for each motif is represented as logos, where the height of each stack indicates conservation of sequence (bits) and the height of the symbols represent the relative frequency of the base. An asterisk below a base indicates the modified nucleotide in each consensus sequence. The consensus sequence on the circular genome is indicated with a black line. The numbers within each genome represent methylated sequences compared to the total number of each identified consensus sequence.</p

Analysis of the <i>Campylobacter jejuni</i> Genome by SMRT DNA Sequencing Identifies Restriction-Modification Motifs

<div><p><i>Campylobacter jejuni</i> is a leading bacterial cause of human gastroenteritis. The goal of this study was to analyze the <i>C. jejuni</i> F38011 strain, recovered from an individual with severe enteritis, at a genomic and proteomic level to gain insight into microbial processes. The <i>C. jejuni</i> F38011 genome is comprised of 1,691,939 bp, with a mol.% (G+C) content of 30.5%. PacBio sequencing coupled with REBASE analysis was used to predict <i>C. jejuni</i> F38011 genomic sites and enzymes that may be involved in DNA restriction-modification. A total of five putative methylation motifs were identified as well as the <i>C. jejuni</i> enzymes that could be responsible for the modifications. Peptides corresponding to the deduced amino acid sequence of the <i>C. jejuni</i> enzymes were identified using proteomics. This work sets the stage for studies to dissect the precise functions of the <i>C. jejuni</i> putative restriction-modification enzymes. Taken together, the data generated in this study contributes to our knowledge of the genomic content, methylation profile, and encoding capacity of <i>C. jejuni</i>.</p></div