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Author Rajaraman, K.; Godthi, V.; Pratap, R.; Balakrishnan, R. url  openurl
  Title A novel acoustic-vibratory multimodal duet Type Journal Article
  Year 2015 Publication Abbreviated Journal J. Exp. Biol.  
  Volume 218 Issue 19 Pages (down) 3042  
  Keywords  
  Abstract The communication strategy of most crickets and bushcrickets typically consists of males broadcasting loud acoustic calling songs, while females perform phonotaxis, moving towards the source of the call. Males of the pseudophylline bushcricket species Onomarchus uninotatus produce an unusually low-pitched call, and we found that the immediate and most robust response of females to the male acoustic call was a bodily vibration, or tremulation, following each syllable of the call. We hypothesized that these bodily oscillations might send out a vibrational signal along the substrate on which the female stands, which males could use to localize her position. We quantified these vibrational signals using a laser vibrometer and found a clear phase relationship of alternation between the chirps of the male acoustic call and the female vibrational response. This system therefore constitutes a novel multimodal duet with a reliable temporal structure. We also found that males could localize the source of vibration but only if both the acoustic and vibratory components of the duet were played back. This unique multimodal duetting system may have evolved in response to higher levels of bat predation on searching bushcricket females than calling males, shifting part of the risk associated with partner localization onto the male. This is the first known example of bushcricket female tremulation in response to a long-range male acoustic signal and the first known example of a multimodal duet among animals.  
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  Call Number CES @ dilipnaidu.gt @ Serial 43000  
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Author Wright, A.A.; Cronin, A.; Milne, D.E.; Bookman, M.A.; Burger, R.A.; Cohn, D.E.; Cristea, M.C.; Griggs, J.J.; Keating, N.L.; Levenback, C.F.; Mantia-Smaldone, G.; Matulonis, U.A.; Meyer, L.A.; Niland, J.C.; Weeks, J.C.; O’Malley, D.M. url  openurl
  Title Use and Effectiveness of Intraperitoneal Chemotherapy for Treatment of Ovarian Cancer Type Journal Article
  Year 2015 Publication Abbreviated Journal J Clin Oncol  
  Volume 33 Issue 26 Pages (down) 2841-2847  
  Keywords  
  Abstract PURPOSE: A 2006 randomized trial demonstrated a 16-month survival benefit with intraperitoneal and intravenous (IP/IV) chemotherapy administered to patients who had ovarian cancer, compared with IV chemotherapy alone, but more treatment-related toxicities. The objective of this study was to examine the use and effectiveness of IP/IV chemotherapy in clinical practice. PATIENTS AND METHODS: Prospective cohort study of 823 women with stage III, optimally cytoreduced ovarian cancer diagnosed at six National Comprehensive Cancer Network institutions. We examined IP/IV chemotherapy use in all patients diagnosed between 2003 and 2012 (N = 823), and overall survival and treatment-related toxicities with Cox regression and logistic regression, respectively, in a propensity score-matched sample (n = 402) of patients diagnosed from 2006 to 2012, excluding trial participants, to minimize selection bias. RESULTS: Use of IP/IV chemotherapy increased from 0% to 33% between 2003 and 2006, increased to 50% from 2007 to 2008, and plateaued thereafter. Between 2006 and 2012, adoption of IP/IV chemotherapy varied by institution from 4% to 67% (P <.001) and 43% of patients received modified IP/IV regimens at treatment initiation. In the propensity score-matched sample, IP/IV chemotherapy was associated with significantly improved overall survival (3-year overall survival, 81% v 71%; hazard ratio, 0.68; 95% CI, 0.47 to 0.99), compared with IV chemotherapy, but also more frequent alterations in chemotherapy delivery route (adjusted rates discontinuation or change, 20.4% v 10.0%; adjusted odds ratio, 2.83; 95% CI, 1.47 to 5.47). CONCLUSION: Although the use of IP/IV chemotherapy increased significantly at National Comprehensive Cancer Network centers between 2003 and 2012, fewer than 50% of eligible patients received it. Increasing IP/IV chemotherapy use in clinical practice may be an important and underused strategy to improve ovarian cancer outcomes.  
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  Notes Approved no  
  Call Number UofT @ ankit.sinha @ Serial 45060  
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Author Choi, Y.; Chan, A.P. openurl 
  Title PROVEAN web server: a tool to predict the functional effect of amino acid substitutions and indels Type Journal Article
  Year 2015 Publication Abbreviated Journal Bioinformatics  
  Volume 31 Issue 16 Pages (down) 2745--2747  
  Keywords bioinformatics,variant assessment,in silico tool  
  Abstract Summary: We present a web server to predict the functional effect of single or multiple amino acid substitutions, insertions and deletions using the prediction tool PROVEAN. The server provides rapid analysis of protein variants from any organisms, and also supports high-throughput analysis for human and mouse variants at both the genomic and protein levels.Availability and implementation: The web server is freely available and open to all users with no login requirements at http://provean.jcvi.org.Contact:achan@jcvi.orgSupplementary information:Supplementary data are available at Bioinformatics online.  
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  Series Volume Series Issue Edition  
  ISSN 1367-4803 ISBN Medium  
  Area Expedition Conference  
  Notes Approved no  
  Call Number AG @ matthewjvarga @ Serial 47017  
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Author Cajigas, I.; Leib, D.E.; Cochrane, J.; Luo, H.; Swyter, K.R.; Chen, S.; Clark, B.S.; Thompson, J.; Yates, J.R.; Kingston, R.E.; Kohtz, J.D. openurl 
  Title Evf2 lncRNA/BRG1/DLX1 interactions reveal RNA-dependent inhibition of chromatin remodeling Type Journal Article
  Year 2015 Publication Abbreviated Journal Development (Cambridge, England)  
  Volume 142 Issue 15 Pages (down) 2641--2652  
  Keywords  
  Abstract Transcription-regulating long non-coding RNAs (lncRNAs) have the potential to control the site-specific expression of thousands of target genes. Previously, we showed that Evf2, the first described ultraconserved lncRNA, increases the association of transcriptional activators (DLX homeodomain proteins) with key DNA enhancers but represses gene expression. In this report, mass spectrometry shows that the Evf2-DLX1 ribonucleoprotein (RNP) contains the SWI/SNF-related chromatin remodelers Brahma-related gene 1 (BRG1, SMARCA4) and Brahma-associated factor (BAF170, SMARCC2) in the developing mouse forebrain. Evf2 RNA colocalizes with BRG1 in nuclear clouds and increases BRG1 association with key DNA regulatory enhancers in the developing forebrain. While BRG1 directly interacts with DLX1 and Evf2 through distinct binding sites, Evf2 directly inhibits BRG1 ATPase and chromatin remodeling activities. In vitro studies show that both RNA-BRG1 binding and RNA inhibition of BRG1 ATPase/remodeling activity are promiscuous, suggesting that context is a crucial factor in RNA-dependent chromatin remodeling inhibition. Together, these experiments support a model in which RNAs convert an active enhancer to a repressed enhancer by directly inhibiting chromatin remodeling activity, and address the apparent paradox of RNA-mediated stabilization of transcriptional activators at enhancers with a repressive outcome. The importance of BRG1/RNA and BRG1/homeodomain interactions in neurodevelopmental disorders is underscored by the finding that mutations in Coffin-Siris syndrome, a human intellectual disability disorder, localize to the BRG1 RNA-binding and DLX1-binding domains.  
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  Series Volume Series Issue Edition  
  ISSN 1477-9129 ISBN Medium  
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  Notes Approved no  
  Call Number AG @ matthewjvarga @ Serial 47024  
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Author Blume-Jensen, P.; Berman, D.M.; Rimm, D.L.; Shipitsin, M.; Putzi, M.; Nifong, T.P.; Small, C.; Choudhury, S.; Capela, T.; Coupal, L.; Ernst, C.; Hurley, A.; Kaprelyants, A.; Chang, H.; Giladi, E.; Nardone, J.; Dunyak, J.; Loda, M.; Klein, E.A.; Magi-Galluzzi, C.; Latour, M.; Epstein, J.I.; Kantoff, P.; Saad, F. url  openurl
  Title Development and clinical validation of an in situ biopsy-based multimarker assay for risk stratification in prostate cancer Type Journal Article
  Year 2015 Publication Abbreviated Journal Clin Cancer Res  
  Volume 21 Issue 11 Pages (down) 2591-2600  
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  Abstract PURPOSE: Prostate cancer aggressiveness and appropriate therapy are routinely determined following biopsy sampling. Current clinical and pathologic parameters are insufficient for accurate risk prediction leading primarily to overtreatment and also missed opportunities for curative therapy. EXPERIMENTAL DESIGN: An 8-biomarker proteomic assay for intact tissue biopsies predictive of prostate pathology was defined in a study of 381 patient biopsies with matched prostatectomy specimens. A second blinded study of 276 cases validated this assay’s ability to distinguish “favorable” versus “nonfavorable” pathology independently and relative to current risk classification systems National Comprehensive Cancer Network (NCCN and D’Amico). RESULTS: A favorable biomarker risk score of ≤0.33, and a nonfavorable risk score of >0.80 (possible range between 0 and 1) were defined on “false-negative” and “false-positive” rates of 10% and 5%, respectively. At a risk score ≤0.33, predictive values for favorable pathology in very low-risk and low-risk NCCN and low-risk D’Amico groups were 95%, 81.5%, and 87.2%, respectively, higher than for these current risk classification groups themselves (80.3%, 63.8%, and 70.6%, respectively). The predictive value for nonfavorable pathology was 76.9% at biomarker risk scores >0.8 across all risk groups. Increased biomarker risk scores correlated with decreased frequency of favorable cases across all risk groups. The validation study met its two coprimary endpoints, separating favorable from nonfavorable pathology (AUC, 0.68; P < 0.0001; OR, 20.9) and GS-6 versus non-GS-6 pathology (AUC, 0.65; P < 0.0001; OR, 12.95). CONCLUSIONS: The 8-biomarker assay provided individualized, independent prognostic information relative to current risk stratification systems, and may improve the precision of clinical decision making following prostate biopsy.  
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  Call Number UofT @ ankit.sinha @ Serial 45258  
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Author Zhuo, Y.; Cano, K.E.; Wang, L.; Ilangovan, U.; Hinck, A.P.; Sousa, R.; Lafer, E.M. url  openurl
  Title Nuclear Magnetic Resonance Structural Mapping Reveals Promiscuous Interactions between Clathrin-Box Motif Sequences and the N-Terminal Domain of the Clathrin Heavy Chain Type Journal Article
  Year 2015 Publication Abbreviated Journal Biochemistry  
  Volume 54 Issue 16 Pages (down) 2571-2580  
  Keywords JHU, CME, clathrin box  
  Abstract The recruitment and organization of clathrin at endocytic sites first to form coated pits and then clathrin-coated vesicles depend on interactions between the clathrin N-terminal domain (TD) and multiple clathrin binding sequences on the cargo adaptor and accessory proteins that are concentrated at such sites. Up to four distinct protein binding sites have been proposed to be present on the clathrin TD, with each site proposed to interact with a distinct clathrin binding motif. However, an understanding of how such interactions contribute to clathrin coat assembly must take into account observations that any three of these four sites on clathrin TD can be mutationally ablated without causing loss of clathrin-mediated endocytosis. To take an unbiased approach to mapping binding sites for clathrin-box motifs on clathrin TD, we used isothermal titration calorimetry (ITC) and nuclear magnetic resonance spectroscopy. Our ITC experiments revealed that a canonical clathrin-box motif peptide from the AP-2 adaptor binds to clathrin TD with a stoichiometry of 3:1. Assignment of 90% of the total visible amide resonances in the TROSY-HSQC spectrum of (13)C-, (2)H-, and (15)N-labeled TD40 allowed us to map these three binding sites by analyzing the chemical shift changes as clathrin-box motif peptides were titrated into clathrin TD. We found that three different clathrin-box motif peptides can each simultaneously bind not only to the previously characterized clathrin-box site but also to the W-box site and the β-arrestin splice loop site on a single TD. The promiscuity of these binding sites can help explain why their mutation does not lead to larger effects on clathrin function and suggests a mechanism by which clathrin may be transferred between different proteins during the course of an endocytic event.  
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  ISSN 1520-4995 0006-2960 ISBN Medium  
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  Notes each CLTC.TD binds three AP2B2s w/ KD of 420 uM Approved no  
  Call Number AG @ matthewjvarga @ Serial 46732  
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Author Naslim, N.; Kemper, F.; Madden, S.C.; Hony, S.; Chu, Y.-H.; Galliano, F.; Bot, C.; Yang, Y.; Seok, J.; Oliveira, J.M.; van Loon, J.T.; Meixner, M.; Li, A.; Hughes, A.; Gordon, K.D.; Otsuka, M.; Hirashita, H.; Morata, O.; Lebouteiller, V.; Indebetouw, R.; Srinivasan, S.; Bernard, J.-P.; Reach, W.T. doi  openurl
  Title Molecular hydrogen emission in the interstellar medium of the Large Magellanic Cloud Type Journal Article
  Year 2015 Publication Mon.~Not.~R.~Astron.~Soc. Abbreviated Journal  
  Volume 446 Issue 3 Pages (down) 2490-2504  
  Keywords ISM: molecules; photodissociation region (PDR); galaxies: ISM; Magellanic Cloud; infrared: ISM  
  Abstract We present the detection and analysis of molecular hydrogen emission towards ten interstellar regions in the Large Magellanic Cloud. We examined low-resolution infrared spectral maps of 12 regions obtained with the Spitzer infrared spectrograph (IRS). The pure rotational 0-0 transitions of H2 at 28.2 and 17.1 μm are detected in the IRS spectra for 10 regions. The higher level transitions are mostly upper limit measurements except for three regions, where a 3σ detection threshold is achieved for lines at 12.2 and 8.6 μm. The excitation diagrams of the detected H2 transitions are used to determine the warm H2 gas column density and temperature. The single-temperature fits through the lower transition lines give temperatures in the range 86-137 K. The bulk of the excited H2 gas is found at these temperatures and contributes ˜5-17 per cent to the total gas mass. We find a tight correlation of the H2 surface brightness with polycyclic aromatic hydrocarbon and total infrared emission, which is a clear indication of photoelectric heating in photodissociation regions. We find the excitation of H2 by this process is equally efficient in both atomic- and molecular-dominated regions. We also present the correlation of the warm H2 physical conditions with dust properties. The warm H2 mass fraction and excitation temperature show positive correlations with the average starlight intensity, again supporting H2 excitation in photodissociation regions.  
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  Notes refereed; Owner: ciska; Added to JabRef: 2015.04.15 Approved no  
  Call Number ASIAA @ ciska @ Serial 41815  
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Author Naslim, N.; Kemper, F.; Madden, S.C.; Hony, S.; Chu, Y.-H.; Galliano, F.; Bot, C.; Yang, Y.; Seok, J.; Oliveira, J.M.; van Loon, J.T.; Meixner, M.; Li, A.; Hughes, A.; Gordon, K.D.; Otsuka, M.; Hirashita, H.; Morata, O.; Lebouteiller, V.; Indebetouw, R.; Srinivasan, S.; Bernard, J.-P.; Reach, W.T. doi  openurl
  Title Molecular hydrogen emission in the interstellar medium of the Large Magellanic Cloud Type Journal Article
  Year 2015 Publication Mon.~Not.~R.~Astron.~Soc. Abbreviated Journal  
  Volume 446 Issue 3 Pages (down) 2490-2504  
  Keywords ISM: molecules; photodissociation region (PDR); galaxies: ISM; Magellanic Cloud; infrared: ISM  
  Abstract We present the detection and analysis of molecular hydrogen emission towards ten interstellar regions in the Large Magellanic Cloud. We examined low-resolution infrared spectral maps of 12 regions obtained with the Spitzer infrared spectrograph (IRS). The pure rotational 0-0 transitions of H2 at 28.2 and 17.1 μm are detected in the IRS spectra for 10 regions. The higher level transitions are mostly upper limit measurements except for three regions, where a 3σ detection threshold is achieved for lines at 12.2 and 8.6 μm. The excitation diagrams of the detected H2 transitions are used to determine the warm H2 gas column density and temperature. The single-temperature fits through the lower transition lines give temperatures in the range 86-137 K. The bulk of the excited H2 gas is found at these temperatures and contributes ˜5-17 per cent to the total gas mass. We find a tight correlation of the H2 surface brightness with polycyclic aromatic hydrocarbon and total infrared emission, which is a clear indication of photoelectric heating in photodissociation regions. We find the excitation of H2 by this process is equally efficient in both atomic- and molecular-dominated regions. We also present the correlation of the warm H2 physical conditions with dust properties. The warm H2 mass fraction and excitation temperature show positive correlations with the average starlight intensity, again supporting H2 excitation in photodissociation regions.  
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  Notes refereed; Owner: ciska; Added to JabRef: 2015.04.15 Approved no  
  Call Number ASIAA @ ciska @ Serial 42038  
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Author Nicholson, A.A.; Densmore, M.; Frewen, P.A.; Theberge, J.; Neufeld, R.W.; McKinnon, M.C.; Lanius, R.A. url  doi
openurl 
  Title The Dissociative Subtype of Posttraumatic Stress Disorder: Unique Resting-State Functional Connectivity of Basolateral and Centromedial Amygdala Complexes Type Journal Article
  Year 2015 Publication Neuropsychopharmacology : Official Publication of the American College of Neuropsychopharmacology Abbreviated Journal Neuropsychopharmacology  
  Volume 40 Issue 10 Pages (down) 2317-2326  
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  Abstract Previous studies point towards differential connectivity patterns among basolateral (BLA) and centromedial (CMA) amygdala regions in patients with posttraumatic stress disorder (PTSD) as compared with controls. Here we describe the first study to compare directly connectivity patterns of the BLA and CMA complexes between PTSD patients with and without the dissociative subtype (PTSD+DS and PTSD-DS, respectively). Amygdala connectivity to regulatory prefrontal regions and parietal regions involved in consciousness and proprioception were expected to differ between these two groups based on differential limbic regulation and behavioral symptoms. PTSD patients (n=49) with (n=13) and without (n=36) the dissociative subtype and age-matched healthy controls (n=40) underwent resting-state fMRI. Bilateral BLA and CMA connectivity patterns were compared using a seed-based approach via SPM Anatomy Toolbox. Among patients with PTSD, the PTSD+DS group exhibited greater amygdala functional connectivity to prefrontal regions involved in emotion regulation (bilateral BLA and left CMA to the middle frontal gyrus and bilateral CMA to the medial frontal gyrus) as compared with the PTSD-DS group. In addition, the PTSD+DS group showed greater amygdala connectivity to regions involved in consciousness, awareness, and proprioception-implicated in depersonalization and derealization (left BLA to superior parietal lobe and cerebellar culmen; left CMA to dorsal posterior cingulate and precuneus). Differences in amygdala complex connectivity to specific brain regions parallel the unique symptom profiles of the PTSD subgroups and point towards unique biological markers of the dissociative subtype of PTSD.  
  Address Lawson Health Research Institute, Western University, London, Ontario, Canada  
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  Language English Summary Language Original Title  
  Series Editor Series Title Abbreviated Series Title  
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  ISSN 0893-133X ISBN Medium  
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  Notes PMID:25790021 Approved no  
  Call Number UU @ jana.mullerova @ Serial 42191  
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Author Al-Awqati, Q. url  openurl
  Title Kidney growth and hypertrophy: the role of mTOR and vesicle trafficking Type Journal Article
  Year 2015 Publication Abbreviated Journal J Clin Invest  
  Volume 125 Issue 6 Pages (down) 2267-2270  
  Keywords  
  Abstract The kidney, like other organs, grows in constant proportion to the rest of the body. When one kidney is removed, the remaining one hypertrophies. In a comprehensive series of studies, Chen et al. show that growth during maturation is mediated by the mTORC1 signaling pathway, which is induced by EGF-like peptides, and requires PI3K, PDK, AKT, mTORC2, and activation of mTORC1 through the combined effects of TSC and RHEB as part of a multiprotein complex localized on lysosomes. However, compensatory growth is mediated by amino acids, which act on mTORC1 independently of the previous pathway, and requires a class III PI3K (VPS34) that is known to be involved in vesicle trafficking to the lysosomes.  
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  ISSN 0021-9738 ISBN Medium  
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  Notes Approved no  
  Call Number UofT @ mathieu.lemaire @ Serial 45804  
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