The Anaphase-Promoting Complex (APC) ubiquitin ligase affects chemosensory behavior in \u3cem\u3eC. elegans\u3c/em\u3e

The regulation of fundamental aspects of neurobiological function has been linked to the ubiquitin signaling system (USS), which regulates the degradation and activity of proteins and is catalyzed by E1, E2, and E3 enzymes. The Anaphase-Promoting Complex (APC) is a multi-subunit E3 ubiquitin ligase that controls diverse developmental and signaling processes in post-mitotic neurons; however, potential roles for the APC in sensory function have yet to be explored. In this study, we examined the effect of the APC ubiquitin ligase on chemosensation in Caenorhabditis elegans by testing chemotaxis to the volatile odorants, diacetyl, pyrazine, and isoamyl alcohol, to which wild-type worms are attracted. Animals with loss of function mutations in either of two alleles (g48 and ye143) of the gene encoding the APC subunit EMB-27 APC6 showed increased chemotaxis towards diacetyl and pyrazine, odorants sensed by AWA neurons, but exhibited normal chemotaxis to isoamyl alcohol, which is sensed by AWC neurons. The statistically significant increase in chemotaxis in the emb-27 APC6 mutants suggests that the APC inhibits AWA-mediated chemosensation in C. elegans. Increased chemotaxis to pyrazine was also seen with mutants lacking another essential APC subunit, MAT-2 APC1; however, mat-2 APC1 mutants exhibited wild type responses to diacetyl. The difference in responsiveness of these two APC subunit mutants may be due to differential strength of these hypomorphic alleles or may indicate the presence of functional sub-complexes of the APC at work in this process. These findings are the first evidence for APC-mediated regulation of chemosensation and lay the groundwork for further studies aimed at identifying the expression levels, function, and targets of the APC in specific sensory neurons. Because of the similarity between human and C. elegans nervous systems, the role of the APC in sensory neurons may also advance our understanding of human sensory function and disease

Flow Field Evolution of a Decaying Sunspot

We study the evolution of the flows and horizontal proper motions in and around a decaying follower sunspot based on time sequences of two-dimensional spectroscopic observations in the visible and white light imaging data obtained over six days from June~7 to~12, 2005. During this time period the sunspot decayed gradually to a pore. The spectroscopic observations were obtained with the Fabry-P\'{e}rot based Visible-Light Imaging Magnetograph (VIM) in conjunction with the high-order adaptive optics (AO) system operated at the 65 cm vacuum reflector of the Big Bear Solar Observatory (BBSO). We apply local correlation tracking (LCT) to the speckle reconstructed time sequences of white-light images around 600 nm to infer horizontal proper motions while the Doppler shifts of the scanned \FeI line at 630.15 nm are used to calculate line-of-sight (LOS) velocities with sub-arcsecond resolution. We find that the dividing line between radial inward and outward proper motions in the inner and outer penumbra, respectively, survives the decay phase. In particular the moat flow is still detectable after the penumbra disappeared. Based on our observations three major processes removed flux from the sunspot: (a) fragmentation of the umbra, (b) flux cancelation of moving magnetic features (MMFs; of the same polarity as the sunspot) that encounter the leading opposite polarity network and plages areas, and (c) flux transport by MMFs (of the same polarity as the sunspot) to the surrounding network and plage regions that have the same polarity as the sunspot.Comment: 9 pages, 7 figures, The Astrophysical Journal, accepted September, 200

SRRM2, a Potential Blood Biomarker Revealing High Alternative Splicing in Parkinson's Disease

Parkinson's disease (PD) is a progressive neurodegenerative disorder that affects about five million people worldwide. Diagnosis remains clinical, based on phenotypic patterns. The discovery of laboratory markers that will enhance diagnostic accuracy, allow pre-clinical detection and tracking of disease progression is critically needed. These biomarkers may include transcripts with different isoforms.We performed extensive analysis on 3 PD microarray experiments available through GEO and found that the RNA splicing gene SRRM2 (or SRm300), sereine/arginine repetitive matrix 2, was the only gene differentially upregulated among all the three PD experiments. SRRM2 expression was not changed in the blood of other neurological diseased patients versus the healthy controls. Using real-time PCR, we report that the shorter transcript of SRRM2 was 1.7 fold (p = 0.008) upregulated in the substantia nigra of PDs vs controls while the longer transcript was 0.4 downregulated in both the substantia nigra (p = 0.03) and amygdala (p = 0.003). To validate our results and test for the possibility of alternative splicing in PD, we performed independent microarray scans, using Affymetrix Exon_ST1 arrays, from peripheral blood of 28 individuals (17 PDs and 11 Ctrls) and found a significant upregulation of the upstream (5') exons of SRRM2 and a downregulation of the downstream exons, causing a total of 0.7 fold down regulation (p = 0.04) of the long isoform. In addition, we report novel information about hundreds of genes with significant alternative splicing (differential exonic expression) in PD blood versus controls.The consistent dysregulation of the RNA splicing factor SRRM2 in two different PD neuronal sources and in PD blood but not in blood of other neurologically diseased patients makes SRRM2 a strong candidate gene for PD and draws attention to the role of RNA splicing in the disease

Automated Fidelity Assessment for Strategy Training in Inpatient Rehabilitation using Natural Language Processing

Strategy training is a multidisciplinary rehabilitation approach that teaches skills to reduce disability among those with cognitive impairments following a stroke. Strategy training has been shown in randomized, controlled clinical trials to be a more feasible and efficacious intervention for promoting independence than traditional rehabilitation approaches. A standardized fidelity assessment is used to measure adherence to treatment principles by examining guided and directed verbal cues in video recordings of rehabilitation sessions. Although the fidelity assessment for detecting guided and directed verbal cues is valid and feasible for single-site studies, it can become labor intensive, time consuming, and expensive in large, multi-site pragmatic trials. To address this challenge to widespread strategy training implementation, we leveraged natural language processing (NLP) techniques to automate the strategy training fidelity assessment, i.e., to automatically identify guided and directed verbal cues from video recordings of rehabilitation sessions. We developed a rule-based NLP algorithm, a long-short term memory (LSTM) model, and a bidirectional encoder representation from transformers (BERT) model for this task. The best performance was achieved by the BERT model with a 0.8075 F1-score. This BERT model was verified on an external validation dataset collected from a separate major regional health system and achieved an F1 score of 0.8259, which shows that the BERT model generalizes well. The findings from this study hold widespread promise in psychology and rehabilitation intervention research and practice.Comment: Accepted at the AMIA Informatics Summit 202

Deep learning network to correct axial and coronal eye motion in 3D OCT retinal imaging

Optical Coherence Tomography (OCT) is one of the most important retinal imaging technique. However, involuntary motion artifacts still pose a major challenge in OCT imaging that compromises the quality of downstream analysis, such as retinal layer segmentation and OCT Angiography. We propose deep learning based neural networks to correct axial and coronal motion artifacts in OCT based on a single volumetric scan. The proposed method consists of two fully-convolutional neural networks that predict Z and X dimensional displacement maps sequentially in two stages. The experimental result shows that the proposed method can effectively correct motion artifacts and achieve smaller error than other methods. Specifically, the method can recover the overall curvature of the retina, and can be generalized well to various diseases and resolutions

Constructing Kinetically Controlled Denaturation Isotherms of Folded Proteins Using Denaturant-Pulse Chaperonin Binding

Methods to assess the kinetic stability of proteins, particularly those that are aggregation prone, are very useful in establishing ligand induced stabilizing effects. Because aggregation prone proteins are by nature difficult to work with, most solution based methods are compromised by this inherent instability. Here, we describe a label-free method that examines the denaturation of immobilized proteins where the dynamic unfolded protein populations are captured and detected by chaperonin binding

Mapping genomic and transcriptomic alterations spatially in epithelial cells adjacent to human breast carcinoma.

Almost all genomic studies of breast cancer have focused on well-established tumours because it is technically challenging to study the earliest mutational events occurring in human breast epithelial cells. To address this we created a unique dataset of epithelial samples ductoscopically obtained from ducts leading to breast carcinomas and matched samples from ducts on the opposite side of the nipple. Here, we demonstrate that perturbations in mRNA abundance, with increasing proximity to tumour, cannot be explained by copy number aberrations. Rather, we find a possibility of field cancerization surrounding the primary tumour by constructing a classifier that evaluates where epithelial samples were obtained relative to a tumour (cross-validated micro-averaged AUC = 0.74). We implement a spectral co-clustering algorithm to define biclusters. Relating to over-represented bicluster pathways, we further validate two genes with tissue microarrays and in vitro experiments. We highlight evidence suggesting that bicluster perturbation occurs early in tumour development

Overexpression of the Aspergillus nidulans histone 4 acetyltransferase EsaA increases activation of secondary metabolite production

This is the peer reviewed version of the following article: Soukup, A. A., Chiang, Y.-M., Bok, J. W., Reyes-Dominguez, Y., Oakley, B. R., Wang, C. C. C., Strauss, J. and Keller, N. P. (2012), Overexpression of the Aspergillus nidulans histone 4 acetyltransferase EsaA increases activation of secondary metabolite production. Molecular Microbiology, 86: 314–330. doi:10.1111/j.1365-2958.2012.08195.x, which has been published in final form at http://doi.org/10.1111/j.1365-2958.2012.08195.x. This article may be used for non-commercial purposes in accordance with Wiley Terms and Conditions for Self-Archiving.Regulation of secondary metabolite (SM) gene clusters in Aspergillus nidulans has been shown to occur through cluster specific transcription factors or through global regulators of chromatin structure such as histone methyltransferases, histone deacetylases, or the putative methyltransferase LaeA. A multi-copy suppressor screen for genes capable of returning SM production to the SM deficient ΔlaeA mutant resulted in identification of the essential histone acetyltransferase EsaA, able to complement an esa1 deletion in Saccharomyces cereviseae. Here we report that EsaA plays a novel role in SM cluster activation through histone 4 lysine 12 (H4K12) acetylation in four examined SM gene clusters (sterigmatocystin, penicillin, terrequinone, and orsellinic acid), in contrast to no increase in H4K12 acetylation of the housekeeping tubA promoter. This augmented SM cluster acetylation requires LaeA for full effect and correlates with both increased transcript levels and metabolite production relative to wild type. H4K12 levels may thus represent a unique indicator of relative production potential, notably of SMs

Gemini Planet Imager Observational Calibrations VI: Photometric and Spectroscopic Calibration for the Integral Field Spectrograph

The Gemini Planet Imager (GPI) is a new facility instrument for the Gemini Observatory designed to provide direct detection and characterization of planets and debris disks around stars in the solar neighborhood. In addition to its extreme adaptive optics and corona graphic systems which give access to high angular resolution and high-contrast imaging capabilities, GPI contains an integral field spectrograph providing low resolution spectroscopy across five bands between 0.95 and 2.5 $\mu$m. This paper describes the sequence of processing steps required for the spectro-photometric calibration of GPI science data, and the necessary calibration files. Based on calibration observations of the white dwarf HD 8049B we estimate that the systematic error in spectra extracted from GPI observations is less than 5%. The flux ratio of the occulted star and fiducial satellite spots within coronagraphic GPI observations, required to estimate the magnitude difference between a target and any resolved companions, was measured in the $H$-band to be $\Delta m = 9.23\pm0.06$ in laboratory measurements and $\Delta m = 9.39\pm 0.11$ using on-sky observations. Laboratory measurements for the $Y$, $J$, $K1$ and $K2$ filters are also presented. The total throughput of GPI, Gemini South and the atmosphere of the Earth was also measured in each photometric passband, with a typical throughput in $H$-band of 18% in the non-coronagraphic mode, with some variation observed over the six-month period for which observations were available. We also report ongoing development and improvement of the data cube extraction algorithm.Comment: 15 pages, 6 figures. Proceedings of the SPIE, 9147-30

Nitrogen isotope evidence for expanded ocean suboxia in the early Cenozoic

The million-year variability of the marine nitrogen cycle is poorly understood. Before 57 million years (Ma) ago, the ^(15)N/^(14)N ratio (δ^(15)N) of foraminifera shell-bound organic matter from three sediment cores was high, indicating expanded water column suboxia and denitrification. Between 57 and 50 Ma ago, δ^(15)N declined by 13 to 16 per mil in the North Pacific and by 3 to 8 per mil in the Atlantic. The decline preceded global cooling and appears to have coincided with the early stages of the Asia-India collision. Warm, salty intermediate-depth water forming along the Tethys Sea margins may have caused the expanded suboxia, ending with the collision. From 50 to 35 Ma ago, δ^(15)N was lower than modern values, suggesting widespread sedimentary denitrification on broad continental shelves. Δ^(15)N rose at 35 Ma ago, as ice sheets grew, sea level fell, and continental shelves narrowed