Bostonia

Founded in 1900, Bostonia magazine is Boston University's main alumni publication, which covers alumni and student life, as well as university activities, events, and programs

The Role of Protein Crystallography in Defining the Mechanisms of Biogenesis and Catalysis in Copper Amine Oxidase

Copper amine oxidases (CAOs) are a ubiquitous group of enzymes that catalyze the conversion of primary amines to aldehydes coupled to the reduction of O2 to H2O2. These enzymes utilize a wide range of substrates from methylamine to polypeptides. Changes in CAO activity are correlated with a variety of human diseases, including diabetes mellitus, Alzheimer’s disease, and inflammatory disorders. CAOs contain a cofactor, 2,4,5-trihydroxyphenylalanine quinone (TPQ), that is required for catalytic activity and synthesized through the post-translational modification of a tyrosine residue within the CAO polypeptide. TPQ generation is a self-processing event only requiring the addition of oxygen and Cu(II) to the apoCAO. Thus, the CAO active site supports two very different reactions: TPQ synthesis, and the two electron oxidation of primary amines. Crystal structures are available from bacterial through to human sources, and have given insight into substrate preference, stereospecificity, and structural changes during biogenesis and catalysis. In particular both these processes have been studied in crystallo through the addition of native substrates. These latter studies enable intermediates during physiological turnover to be directly visualized, and demonstrate the power of this relatively recent development in protein crystallography

Bostonia

Founded in 1900, Bostonia magazine is Boston University's main alumni publication, which covers alumni and student life, as well as university activities, events, and programs

Comparative analysis of the transcriptome across distant species

The transcriptome is the readout of the genome. Identifying common features in it across distant species can reveal fundamental principles. To this end, the ENCODE and modENCODE consortia have generated large amounts of matched RNA-sequencing data for human, worm and fly. Uniform processing and comprehensive annotation of these data allow comparison across metazoan phyla, extending beyond earlier within-phylum transcriptome comparisons and revealing ancient, conserved features. Specifically, we discover co-expression modules shared across animals, many of which are enriched in developmental genes. Moreover, we use expression patterns to align the stages in worm and fly development and find a novel pairing between worm embryo and fly pupae, in addition to the embryo-to-embryo and larvae-to-larvae pairings. Furthermore, we find that the extent of non-canonical, non-coding transcription is similar in each organism, per base pair. Finally, we find in all three organisms that the gene-expression levels, both coding and non-coding, can be quantitatively predicted from chromatin features at the promoter using a 'universal model' based on a single set of organism-independent parameters

Progressive spread of tauopathy in NT mice identified by antibody CP27.

<p><a href="http://www.plosone.org/article/info:doi/10.1371/journal.pone.0031302#pone-0031302-g003" target="_blank">Fig. 3</a> shows mice immunolabeled with CP27 (total human tau) at low power in a young NT mouse (<a href="http://www.plosone.org/article/info:doi/10.1371/journal.pone.0031302#pone-0031302-g003" target="_blank">Fig. 3A</a>), an old NT mouse (<a href="http://www.plosone.org/article/info:doi/10.1371/journal.pone.0031302#pone-0031302-g003" target="_blank">Fig. 3B</a>) or a control mouse (<a href="http://www.plosone.org/article/info:doi/10.1371/journal.pone.0031302#pone-0031302-g003" target="_blank">Fig. 3C</a>). Higher power images from the young NT mouse (<a href="http://www.plosone.org/article/info:doi/10.1371/journal.pone.0031302#pone-0031302-g003" target="_blank">Figs. 3D, F</a>), old NT mouse (<a href="http://www.plosone.org/article/info:doi/10.1371/journal.pone.0031302#pone-0031302-g003" target="_blank">Figs. 3E, G</a>) with antibody CP27. CP27 is one of several antibodies that show non-specific staining of mossy fibers in the control mouse. <a href="http://www.plosone.org/article/info:doi/10.1371/journal.pone.0031302#pone-0031302-g003" target="_blank">Figs. 3D</a> and E show the EC and subiculum whereas <a href="http://www.plosone.org/article/info:doi/10.1371/journal.pone.0031302#pone-0031302-g003" target="_blank">Figs. 3F</a> and G show the CA and DG regions of the hippocampus. <a href="http://www.plosone.org/article/info:doi/10.1371/journal.pone.0031302#pone-0031302-g003" target="_blank">Figs. 3A–C</a> magnification = 2×, <a href="http://www.plosone.org/article/info:doi/10.1371/journal.pone.0031302#pone-0031302-g003" target="_blank">Figs. 3D–G</a> magnification = 10×.</p

Mature, filamentous neurofibrillary tangle formation in the EC of old NT mice.

<p><a href="http://www.plosone.org/article/info:doi/10.1371/journal.pone.0031302#pone-0031302-g006" target="_blank">Fig. 6A</a> shows lack of thioS staining of neurons in the EC of an old control mouse. The boxed area is shown in the high power image in <a href="http://www.plosone.org/article/info:doi/10.1371/journal.pone.0031302#pone-0031302-g006" target="_blank">Fig. 6C</a>. <a href="http://www.plosone.org/article/info:doi/10.1371/journal.pone.0031302#pone-0031302-g006" target="_blank">Fig. 6B</a> shows thioS positive neurons in the EC of an old NT mouse. The boxed area is shown in the high power image in <a href="http://www.plosone.org/article/info:doi/10.1371/journal.pone.0031302#pone-0031302-g006" target="_blank">Fig. 6E</a>. <a href="http://www.plosone.org/article/info:doi/10.1371/journal.pone.0031302#pone-0031302-g006" target="_blank">Fig. 6D</a> shows lack of thioS staining in the same region of the young NT mouse. <a href="http://www.plosone.org/article/info:doi/10.1371/journal.pone.0031302#pone-0031302-g006" target="_blank">Figs. 6A and B</a> magnification = 10×, <a href="http://www.plosone.org/article/info:doi/10.1371/journal.pone.0031302#pone-0031302-g006" target="_blank">Figs. 6C–E</a> magnification = 20×.</p

Monosynaptic and trans-synaptic cortico-hippocampal and cortico-cortico connections.

<p>Solid lines indicate projections radiating out from the EC, dotted lines indicate projections to the EC. Monosynaptically connected regions are connected across one synapse. Trans-synaptic regions are separated by more than one synapse.</p

Progressive spread of tauopathy in NT mice identified by antibody MC1.

<p><a href="http://www.plosone.org/article/info:doi/10.1371/journal.pone.0031302#pone-0031302-g002" target="_blank">Fig. 2A</a> shows tau immunolabeled with the human tau specific, conformational antibody MC1 in a young NT mouse at low power, and higher power (<a href="http://www.plosone.org/article/info:doi/10.1371/journal.pone.0031302#pone-0031302-g002" target="_blank">Figs. 2D, G</a>). <a href="http://www.plosone.org/article/info:doi/10.1371/journal.pone.0031302#pone-0031302-g002" target="_blank">Fig. 2B</a> shows MC1 immunolabeling in an old NT mouse at low power, and higher power (<a href="http://www.plosone.org/article/info:doi/10.1371/journal.pone.0031302#pone-0031302-g002" target="_blank">Figs. 2E, H</a>). <a href="http://www.plosone.org/article/info:doi/10.1371/journal.pone.0031302#pone-0031302-g002" target="_blank">Fig. 2F</a> shows high power image of cells immunolabeled with MC1 within the MEC. Old NT mice show extensive accumulation of human tau in cell bodies in the EC and subiculum (<a href="http://www.plosone.org/article/info:doi/10.1371/journal.pone.0031302#pone-0031302-g002" target="_blank">Fig. 2H</a>), and in synaptically connected areas in the hippocampus and neocortex (<a href="http://www.plosone.org/article/info:doi/10.1371/journal.pone.0031302#pone-0031302-g002" target="_blank">Fig. 2E</a>). <a href="http://www.plosone.org/article/info:doi/10.1371/journal.pone.0031302#pone-0031302-g002" target="_blank">Fig. 2I</a> shows accumulation of human tau in neurons of the perirhinal cortex and into the parietal region in the old NT mouse. Note the lack of neurite staining in the perirhinal cortex compared to the LEC. <a href="http://www.plosone.org/article/info:doi/10.1371/journal.pone.0031302#pone-0031302-g002" target="_blank">Fig. 2C</a> shows lack of immunolabeling with the human specific antibody in an old, littermate control mouse (single transgenic tau responder mouse, no tTA) except for the non-specific staining of the fornix that was seen with all antibodies. MEC = medial entorinal cortex, LEC = lateral entorhinal cortex, Pe = perirhinal cortex, Par = parietal cortex, DG = dentate gyrus, CA1, CA3 = CA fields of hippocampus, Su = subiculum, Prp-PaS = pre-parasubiculum, pp = perforant pathway endzone. <a href="http://www.plosone.org/article/info:doi/10.1371/journal.pone.0031302#pone-0031302-g002" target="_blank">Figs. 2A–C</a> magnification = 2×, <a href="http://www.plosone.org/article/info:doi/10.1371/journal.pone.0031302#pone-0031302-g002" target="_blank">Figs. 2D, E</a> magnification = 4×, <a href="http://www.plosone.org/article/info:doi/10.1371/journal.pone.0031302#pone-0031302-g002" target="_blank">Figs. 2G–I</a> magnification = 10×. <a href="http://www.plosone.org/article/info:doi/10.1371/journal.pone.0031302#pone-0031302-g002" target="_blank">Fig. 2F</a> magnification = 40×.</p

Progressive spread of tauopathy to monosynaptically connected regions of the hippocampus.

<p>Young NT mice (<a href="http://www.plosone.org/article/info:doi/10.1371/journal.pone.0031302#pone-0031302-g004" target="_blank">Fig. 4A</a>) show accumulation of human tau immunolabeled with CP27 predominately in the endzones of the perforant pathway that terminate in the middle third of the molecular layer of the DG (area 3). Terminals from neurons in the LEC terminating in the outer third of the molecular layer are shown in area 4. Human tau was also seen in cells in the hilus (area 1). Granule cell layers of the DG (area 2) did not accumulate human tau at this age. Old NT mice (<a href="http://www.plosone.org/article/info:doi/10.1371/journal.pone.0031302#pone-0031302-g004" target="_blank">Fig. 4B</a>) show accumulation of human tau in cell bodies in the granule cells of the DG (area 2). Increased accumulation of human tau is seen in layers 1, 2 and 4 but the perforant pathway endzone in layer 3 was significantly depleted of tau. Magnification = 20×.</p