A Novel Peptide-Based SILAC Method to Identify the Posttranslational Modifications Provides Evidence for Unconventional Ubiquitination in the ER-Associated Degradation Pathway.

The endoplasmic reticulum-associated degradation (ERAD) pathway is responsible for disposing misfolded proteins from the endoplasmic reticulum by inducing their ubiquitination and degradation. Ubiquitination is conventionally observed on lysine residues and has been demonstrated on cysteine residues and protein N-termini. Ubiquitination is fundamental to the ERAD process; however, a mutant T-cell receptor α (TCRα) lacking lysine residues is targeted for the degradation by the ERAD pathway. We have shown that ubiquitination of lysine-less TCRα occurs on internal, non-lysine residues and that the same E3 ligase conjugates ubiquitin to TCRα in the presence or absence of lysine residues. Mass-spectrometry indicates that WT-TCRα is ubiquitinated on multiple lysine residues. Recent publications have provided indirect evidence that serine and threonine residues may be modified by ubiquitin. Using a novel peptide-based stable isotope labeling in cell culture (SILAC) approach, we show that specific lysine-less TCRα peptides become modified. In this study, we demonstrate that it is possible to detect both ester and thioester based ubiquitination events, although the exact linkage on lysine-less TCRα remains elusive. These findings demonstrate that SILAC can be used as a tool to identify modified peptides, even those with novel modifications that may not be detected using conventional proteomic work flows or informatics algorithms

The Copula: A Tool for Simulating Speckle Dynamics

Use of a copula for generating a sequence of correlated speckle patterns is introduced. The chief characteristic of this algorithm is that it generates a continuous speckle sequence with a specified evolution of the correlation and does so with just two arrays of random numbers. Thus, physically realistic temporally varying speckle patterns with proper first- and second-order statistics are easily realized. We illustrate use of the algorithm for generating sequences with prescribed Gaussian, exponential, and equal-interval correlations and demonstrate how correlation times can be specified independently. This approach to generating sequences of random realizations with prescribed correlations should prove useful in modeling such phenomena as dynamic light scatter, flow-dependent laser speckle contrast, and propagation of spatial coherence

Evaluation of the Lens Weight as an Aging Technique for the Cotton Rat, Sigmodon hispidus Say and Ord.

Zoolog

Notes on Captive Sea Otters

Notes on the behaviour of three yearlings kept two and a half months in 1954 in a dry environment at Amchitka in the Aleutians. Their sleeping, preening, reaction to man and feeding habits, drinking, locomotion, handling, food and sociability voice, etc., are discussed in detail. Their anatomy and environment in captivity are also discussed: water for swimming was found desirable, if not necessary. Results of physiological investigations are reported by D.E. Stullken and C.M. Kirkpatrick, q.v

Scallops, schools and scholars : reflections on the emergence of a research-oriented learning project

Peer reviewedPostprin

PIKES Analysis Reveals Response to Degraders and Key Regulatory Mechanisms of the CRL4 Network

Co-opting Cullin4 RING ubiquitin ligases (CRL4s) to inducibly degrade pathogenic proteins is emerging as a promising therapeutic strategy. Despite intense efforts to rationally design degrader molecules that co-opt CRL4s, much about the organization and regulation of these ligases remains elusive. Here, we establish protein interaction kinetics and estimation of stoichiometries (PIKES) analysis, a systematic proteomic profiling platform that integrates cellular engineering, affinity purification, chemical stabilization, and quantitative mass spectrometry to investigate the dynamics of interchangeable multiprotein complexes. Using PIKES, we show that ligase assemblies of Cullin4 with individual substrate receptors differ in abundance by up to 200-fold and that Cand1/2 act as substrate receptor exchange factors. Furthermore, degrader molecules can induce the assembly of their cognate CRL4, and higher expression of the associated substrate receptor enhances degrader potency. Beyond the CRL4 network, we show how PIKES can reveal systems level biochemistry for cellular protein networks important to drug development

J-Band Infrared Spectroscopy of a Sample of Brown Dwarfs Using Nirspec on Keck II

Near-infrared spectroscopic observations of a sample of very cool, low-mass objects are presented with higher spectral resolution than in any previous studies. Six of the objects are L-dwarfs, ranging in spectral class from L2 to L8/9, and the seventh is a methane or T-dwarf. These new observations were obtained during commissioning of NIRSPEC, the first high-resolution near-infrared cryogenic spectrograph for the Keck II 10-meter telescope on Mauna Kea, Hawaii. Spectra with a resolving power of R=2500 from 1.135 to 1.360 microns (approximately J-band) are presented for each source. At this resolution, a rich spectral structure is revealed, much of which is due to blending of unresolved molecular transitions. Strong lines due to neutral potassium (K I), and bands due to iron hydride (FeH) and steam (H2O) change significantly throughout the L sequence. Iron hydride disappears between L5 and L8, the steam bands deepen and the K I lines gradually become weaker but wider due to pressure broadening. An unidentified feature occurs at 1.22 microns which has a temperature dependence like FeH but has no counterpart in the available FeH opacity data. Because these objects are 3-6 magnitudes brighter in the near-infrared compared to the I-band, spectral classification is efficient. One of the objects studied (2MASSW J1523+3014) is the coolest L-dwarf discovered so far by the 2-Micron All-Sky Survey (2MASS), but its spectrum is still significantly different from the methane-dominated objects such as Gl229B or SDSS 1624+0029.Comment: New paper, Latex format, 2 figures, accepted to ApJ Letter

A Simple Likelihood Method for Quasar Target Selection

We present a new method for quasar target selection using photometric fluxes and a Bayesian probabilistic approach. For our purposes we target quasars using Sloan Digital Sky Survey (SDSS) photometry to a magnitude limit of g=22. The efficiency and completeness of this technique is measured using the Baryon Oscillation Spectroscopic Survey (BOSS) data, taken in 2010. This technique was used for the uniformly selected (CORE) sample of targets in BOSS year one spectroscopy to be realized in the 9th SDSS data release. When targeting at a density of 40 objects per sq-deg (the BOSS quasar targeting density) the efficiency of this technique in recovering z>2.2 quasars is 40%. The completeness compared to all quasars identified in BOSS data is 65%. This paper also describes possible extensions and improvements for this techniqueComment: Updated to accepted version for publication in the Astrophysical Journal. 10 pages, 10 figures, 3 table

Soybean cultivar UA 5213C

Disclosed a soybean cultivar designated UA 5213C. The invention relates to the seeds of this cultivar, to the plants, to the plant parts, and to methods for producing progeny of the cultivar. The invention also relates to methods for producing a soybean plant containing in its genetic material one or more transgenes and to the transgenic soybean plants and plant parts produced by those methods. The invention also relates to soybean cultivars or breeding cultivars, and plant parts derived from this cultivar, and to methods for producing other soybean cultivars, lines, or plant parts derived from it. The invention further relates to hybrid soybean seeds, plants, and plant parts produced by crossing this cultivar with another soybean cultivar