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Author Andeen, N.K.; Nguyen, T.Q.; Steegh, F.; Hudkins, K.L.; Najafian, B.; Alpers, C.E. url  openurl
  Title The phenotypes of podocytes and parietal epithelial cells may overlap in diabetic nephropathy Type Journal Article
  Year 2015 Publication Abbreviated Journal Kidney Int  
  Volume 88 Issue 5 Pages (down) 1099-1107  
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  Abstract Reversal of diabetic nephropathy (DN) has been achieved in humans and mice, but only rarely and under special circumstances. As progression of DN is related to podocyte loss, reversal of DN requires restoration of podocytes. Here, we identified and quantified potential glomerular progenitor cells that could be a source for restored podocytes. DN was identified in 31 human renal biopsy cases and separated into morphologically early or advanced lesions. Markers of podocytes (WT-1, p57), parietal epithelial cells (PECs) (claudin-1), and cell proliferation (Ki-67) were identified by immunohistochemistry. Podocyte density was progressively reduced with DN. Cells marking as podocytes (p57) were present infrequently on Bowman’s capsule in controls, but significantly increased in histologically early DN. Ki-67-expressing cells were identified on the glomerular tuft and Bowman’s capsule in DN, but rarely in controls. Cells marking as PECs were present on the glomerular tuft, particularly in morphologically advanced DN. These findings show evidence of phenotypic plasticity in podocyte and PEC populations and are consistent with studies in the BTBR ob/ob murine model in which reversibility of DN occurs with podocytes potentially regenerating from PEC precursors. Thus, our findings support, but do not prove, that podocytes may regenerate from PEC progenitors in human DN. If so, progression of DN may represent a modifiable net balance between podocyte loss and regeneration.  
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  ISSN 0085-2538 ISBN Medium  
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  Notes Approved no  
  Call Number UofT @ mathieu.lemaire @ Serial 45953  
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Author Schölz, C.; Lyon, D.; Refsgaard, J.C.; Jensen, L.J.; Choudhary, C.; Weinert, B.T. url  openurl
  Title Avoiding abundance bias in the functional annotation of post-translationally modified proteins Type Journal Article
  Year 2015 Publication Abbreviated Journal Nat Methods  
  Volume 12 Issue 11 Pages (down) 1003-1004  
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  Notes Approved no  
  Call Number UofT @ ankit.sinha @ Serial 45272  
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Author Masterson, J.E.; Schwartz, S.D. doi  openurl
  Title Evolution Alters the Enzymatic Reaction Coordinate of Dihydrofolate Reductase Type Journal Article
  Year 2015 Publication Abbreviated Journal The Journal of Physical Chemistry B  
  Volume 119 Issue 3 Pages (down) 989-996  
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  Abstract How evolution has affected enzyme function is a topic of great interest in the field of biophysical chemistry. Evolutionary changes from Escherichia coli dihydrofolate reductase (ecDHFR) to human dihydrofolate reductase (hsDHFR) have resulted in increased catalytic efficiency and an altered dynamic landscape in the human enzyme. Here, we show that a subpicosecond protein motion is dynamically coupled to hydride transfer catalyzed by hsDHFR but not ecDHFR. This motion propagates through residues that correspond to mutational events along the evolutionary path from ecDHFR to hsDHFR. We observe an increase in the variability of the transition states, reactive conformations, and times of barrier crossing in the human system. In the hsDHFR active site, we detect structural changes that have enabled the coupling of fast protein dynamics to the reaction coordinate. These results indicate a shift in the DHFR family to a form of catalysis that incorporates rapid protein dynamics and a concomitant shift to a more flexible path through reactive phase space.  
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  Series Volume Series Issue Edition  
  ISSN 1520-6106 ISBN Medium  
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  Notes NULL Times cited: 12 Approved no  
  Call Number AG @ matthewjvarga @ Serial 46517  
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Author Butterfield, L.H. url  openurl
  Title Cancer vaccines Type Journal Article
  Year 2015 Publication Abbreviated Journal Bmj  
  Volume 350 Issue Pages (down) h988  
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  Abstract Cancer vaccines are designed to promote tumor specific immune responses, particularly cytotoxic CD8 positive T cells that are specific to tumor antigens. The earliest vaccines, which were developed in 1994-95, tested non-mutated, shared tumor associated antigens that had been shown to be immunogenic and capable of inducing clinical responses in a minority of people with late stage cancer. Technological developments in the past few years have enabled the investigation of vaccines that target mutated antigens that are patient specific. Several platforms for cancer vaccination are being tested, including peptides, proteins, antigen presenting cells, tumor cells, and viral vectors. Standard of care treatments, such as surgery and ablation, chemotherapy, and radiotherapy, can also induce antitumor immunity, thereby having cancer vaccine effects. The monitoring of patients’ immune responses at baseline and after standard of care treatment is shedding light on immune biomarkers. Combination therapies are being tested in clinical trials and are likely to be the best approach to improving patient outcomes.  
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  Notes Approved no  
  Call Number UofT @ ankit.sinha @ Serial 45100  
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Author Wu, H.; Zeng, H.; Lam, R.; Tempel, W.; Kerr, I.D.; Min, J. url  openurl
  Title Structure of the human MLH1 N-terminus: implications for predisposition to Lynch syndrome Type Journal Article
  Year 2015 Publication Abbreviated Journal Acta Crystallogr F Struct Biol Commun  
  Volume 71 Issue 26249686 Pages (down) 981--985  
  Keywords structural biology,variant assessment,pdb  
  Abstract Mismatch repair prevents the accumulation of erroneous insertions/deletions and non-Watson-Crick base pairs in the genome. Pathogenic mutations in the MLH1 gene are associated with a predisposition to Lynch and Turcot’s syndromes. Although genetic testing for these mutations is available, robust classification of variants requires strong clinical and functional support. Here, the first structure of the N-terminus of human MLH1, determined by X-ray crystallography, is described. The structure shares a high degree of similarity with previously determined prokaryotic MLH1 homologs; however, this structure affords a more accurate platform for the classification of MLH1 variants.  
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  Series Volume Series Issue Edition  
  ISSN 2053-230x ISBN Medium  
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  Notes Approved no  
  Call Number AG @ matthewjvarga @ Serial 47007  
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Author Defrin, R.; Schreiber, S.; Ginzburg, K. url  doi
openurl 
  Title Paradoxical Pain Perception in Posttraumatic Stress Disorder: The Unique Role of Anxiety and Dissociation Type Journal Article
  Year 2015 Publication The Journal of Pain : Official Journal of the American Pain Society Abbreviated Journal J Pain  
  Volume 16 Issue 10 Pages (down) 961-970  
  Keywords Chronic pain; anxiety; dissociation; hyperresponsiveness; hypoalgesia; posttraumatic stress disorder; psychophysics  
  Abstract Posttraumatic stress disorder (PTSD) and chronic pain often co-occur and exacerbate each other. Elucidating the mechanism of this co-occurrence therefore has clinical importance. Previously, patients with PTSD with chronic pain were found to demonstrate a unique paradoxical pain profile: hyperresponsiveness together with hyposensitivity to pain. Our aim was to examine whether 2 seemingly paradoxical facets of PTSD (anxiety and dissociation) underlie this paradoxical profile. Patients with PTSD (n = 32) and healthy control individuals (n = 43) underwent psychophysical testing and completed questionnaires. Patients with PTSD had higher pain thresholds and higher pain ratings to suprathreshold stimuli than control individuals. Pain thresholds were positively associated with dissociation levels and negatively associated with anxiety sensitivity levels. Experimental pain ratings were positively associated with anxiety sensitivity and negatively related to dissociation levels. Chronic pain intensity was associated with anxiety, anxiety sensitivity, and pain catastrophizing. It appears that reduced conscious attention toward incoming stimuli, resulting from dissociation, causes delayed response in pain threshold measurement, whereas biases toward threatening stimuli and decreased inhibition, possibly caused by increased anxiety, are responsible for the intensification of experimental and chronic pain. The paradoxical facets of PTSD and their particular influences over pain perception seem to reinforce the coexistence of PTSD and chronic pain, and should be considered when treating traumatized individuals. PERSPECTIVE: This article provides new information regarding the underlying mechanism of the coexistence of PTSD and chronic pain. This knowledge could help to provide better management of PTSD and chronic pain among individuals in the aftermath of trauma.  
  Address Bob Shapell School of Social Work, Tel-Aviv University, Tel-Aviv, Israel  
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  Language English Summary Language Original Title  
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  Series Volume Series Issue Edition  
  ISSN 1526-5900 ISBN Medium  
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  Notes PMID:26168878 Approved no  
  Call Number UU @ jana.mullerova @ Serial 42177  
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Author Krishnan, A.; Ghara, M.; Kasinathan, S.; Pramanik, G.K.; Revadi, S.; Borges, R.M. doi  openurl
  Title Plant reproductive traits mediate tritrophic feedback effects within an obligate brood-site pollination mutualism Type Journal Article
  Year 2015 Publication Abbreviated Journal Oecologia  
  Volume 179 Issue 3 Pages (down) 797-809  
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  Abstract Plants, herbivores and parasitoids affect each other directly and indirectly; however, feedback effects mediated by host plant traits have rarely been demonstrated in these tritrophic interactions. Brood-site pollination mutualisms (e.g. those involving figs and fig wasps) represent specialised tritrophic communities where the progeny of mutualistic pollinators and of non-mutualistic gallers (both herbivores) together with that of their parasitoids develop within enclosed inflorescences called syconia (hence termed brood-sites or microcosms). Plant reproductive phenology (which affects temporal brood-site availability) and inflorescence size (representing brood-site size) are plant traits that could affect reproductive resources, and hence relationships between trees, pollinators and non-pollinating wasps. Analysing wasp and seed contents of syconia, we examined direct, indirect, trophic and non-trophic relationships within the interaction web of the fig–fig wasp community of Ficus racemosa in the context of brood site size and availability. We demonstrate that in addition to direct resource competition and predator–prey (host–parasitoid) interactions, these communities display exploitative or apparent competition and trait-mediated indirect interactions. Inflorescence size and plant reproductive phenology impacted plant–herbivore and plant–parasitoid associations. These plant traits also influenced herbivore–herbivore and herbivore–parasitoid relationships via indirect effects. Most importantly, we found a reciprocal effect between within-tree reproductive asynchrony and fig wasp progeny abundances per syconium that drives a positive feedback cycle within the system. The impact of a multitrophic feedback cycle within a community built around a mutualistic core highlights the need for a holistic view of plant–herbivore–parasitoid interactions in the community ecology of mutualisms.  
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  Series Volume Series Issue Edition  
  ISSN 1432-1939 ISBN Medium  
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  Notes Approved no  
  Call Number CES @ dilipnaidu.gt @ Serial 43113  
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Author Mandal, S.; Gadagkar, R. doi  openurl
  Title Homing abilities of the tropical primitively eusocial paper wasp Ropalidia marginata Type Journal Article
  Year 2015 Publication Abbreviated Journal Journal of Comparative Physiology A  
  Volume 201 Issue 8 Pages (down) 795-802  
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  Abstract Compared to our extensive knowledge about the navigation and homing abilities of ants and bees, we know rather little about these phenomena in social wasps. Here, we report the homing abilities of the tropical primitively eusocial wasp Ropalidia marginata and the factors that affect their homing success. To determine from how far these wasps can return to their nests, we transported foragers blindfold and released them at gradually increasing distances from their nests in four cardinal directions. Their homing success was determined by checking their presence on their nests on three consecutive nights. All foragers (56 individuals, 115 releases) returned back from an area of 0.73 ± 0.25 km2 on the day of release (minimal homing area), whereas 83.8 % of the foragers (217 individuals, 420 releases) returned when we enlarged the area of release to 6.22 ± 0.66 km2 around their nests (maximal homing area). Of 66 releases, no wasps returned from beyond the maximal homing area. The minimal homing area might be familiar to the foragers because they probably routinely forage in this area and the maximal homing area represents the maximum distances from which the wasps are capable of returning to their nests, with or without familiarity.  
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  ISSN 1432-1351 ISBN Medium  
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  Notes Approved no  
  Call Number CES @ dilipnaidu.gt @ Serial 43021  
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Author Posor, Y.; Eichhorn-Grünig, M.; Haucke, V. url  openurl
  Title Phosphoinositides in endocytosis Type Journal Article
  Year 2015 Publication Abbreviated Journal Biochim Biophys Acta  
  Volume 1851 Issue 6 Pages (down) 794-804  
  Keywords Jhu, Cme, Pip2  
  Abstract The internalization and subsequent endosomal trafficking of proteins and membrane along the endocytic pathway is a fundamental cellular process. Over the last two decades, this pathway has emerged to be subject to extensive regulation by phosphoinositides (PIs), phosphorylated derivatives of the minor membrane phospholipid phosphatidylinositol. Clathrin-mediated endocytosis (CME) is the endocytic mechanism characterized in most detail. It now represents a prime example of a process spatiotemporally organized by the interplay of PI metabolizing enzymes. The most abundant PI, phosphatidylinositol-4,5-bisphosphate [PI(4,5)P₂], serves as a denominator of plasma membrane identity and together with cargo proteins is instrumental for the initiation of clathrin-coated pit (CCP) formation. During later stages of the process, the generation of phosphatidylinositol-3,4-bisphosphate [PI(3,4)P₂] and the dephosphorylation of PI(4,5)P₂regulate CCP maturation and vesicle uncoating. Here we provide an overview of the mechanisms by which PIs are made and consumed to regulate CME and other endocytic pathways and how conversion of PIs en route to endosomes may be accomplished. Mutations in PI converting enzymes are linked to multiple diseases ranging from mental retardation and neurodegeneration, to inherited muscle and kidney disorders suggesting that the tight control of PI levels along the endocytic pathway plays a critical role in cell physiology. This article is part of a Special Issue entitled Phosphoinositides.  
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  ISSN 0006-3002 ISBN Medium  
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  Notes Approved no  
  Call Number AG @ matthewjvarga @ Serial 46813  
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Author Pillon, Y.; Lucas, E.; Johansen, J. B.; Sakishima, T.; Hall, B.; Geib, S. M.; Stacy, E. A. url  doi
openurl 
  Title An expanded Metrosideros (Myrtaceae) to include Carpolepis and Tepualia based on nuclear genes Type Journal Article
  Year 2015 Publication Systematic Botany Abbreviated Journal  
  Volume 40 Issue 3 Pages (down) 782-790  
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  Abstract The genus Metrosideros (Myrtaceae) comprises 50-60 species, found largely across the Pacific Islands. The relationships within this genus, including the circumscriptions of the subgenera Mearnsia and Metrosideros and their relationships with the other members of the tribe Metrosidereae, namely the New Caledonian endemic genus Carpolepis and the South American Tepualia, are poorly understood. Phylogenetic analyses were carried out using previously published ITS sequences, covering most species of the tribe, and new sequences of five single-copy nuclear genes on a reduced sampling. The independent and combined analyses of the five nuclear genes using a range of approaches, including Bayesian single-gene, concatenated (MrBayes), concordance (BUCKy) and coalescent (*BEAST) analyses, yielded different topologies, indicating important conflicts among individual gene phylogenetic signals. The deep relationships within the tribe Metrosidereae remain poorly resolved, but our results indicate that the species of Carpolepis and Tepualia are likely nested in the genus Metrosideros. A broad circumscription of the genus Metrosideros is therefore adopted, and the new combinations Metrosideros laurifolia var. demonstrans, Metrosideros tardiflora and Metrosideros vitiensis are here published.  
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  Notes Approved no  
  Call Number NYBG @ sthackurdeen @ Serial 42390  
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