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Trunk, Thomas, Michael A. Casasanta, Christopher C. Yoo, Daniel J. Slade, and Jack C. Leo. "Comparison of type 5d autotransporter phospholipases demonstrates a correlation between high activity and intracellular pathogenic lifestyle." Biochemical Journal 476, no. 18 (September 24, 2019): 2657–76. http://dx.doi.org/10.1042/bcj20190136.
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Abstract Autotransporters, or type 5 secretion systems, are widespread surface proteins of Gram-negative bacteria often associated with virulence functions. Autotransporters consist of an outer membrane β-barrel domain and an exported passenger. In the poorly studied type 5d subclass, the passenger is a patatin-like lipase. The prototype of this secretion pathway is PlpD of Pseudomonas aeruginosa, an opportunistic human pathogen. The PlpD passenger is a homodimer with phospholipase A1 (PLA1) activity. Based on sequencing data, PlpD-like proteins are present in many bacterial species. We characterized the enzymatic activity, specific lipid binding and oligomeric status of PlpD homologs from Aeromonas hydrophila (a fish pathogen), Burkholderia pseudomallei (a human pathogen) and Ralstonia solanacearum (a plant pathogen) and compared these with PlpD. We demonstrate that recombinant type 5d-secreted patatin domains have lipase activity and form dimers or higher-order oligomers. However, dimerization is not necessary for lipase activity; in fact, by making monomeric variants of PlpD, we show that enzymatic activity slightly increases while protein stability decreases. The lipases from the intracellular pathogens A. hydrophila and B. pseudomallei display PLA2 activity in addition to PLA1 activity. Although the type 5d-secreted lipases from the animal pathogens bound to intracellular lipid targets, phosphatidylserine and phosphatidylinositol phosphates, hydrolysis of these lipids could only be observed for FplA of Fusobacterium nucleatum. Yet, we noted a correlation between high lipase activity in type 5d autotransporters and intracellular lifestyle. We hypothesize that type 5d phospholipases are intracellularly active and function in modulation of host cell signaling events.
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Lim, K. P., Lisa F. P. Ng, and D. X. Liu. "Identification of a Novel Cleavage Activity of the First Papain-Like Proteinase Domain Encoded by Open Reading Frame 1a of the Coronavirus Avian Infectious Bronchitis Virus and Characterization of the Cleavage Products." Journal of Virology 74, no. 4 (February 15, 2000): 1674–85. http://dx.doi.org/10.1128/jvi.74.4.1674-1685.2000.
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ABSTRACT The coronavirus Avian infectious bronchitis virus (IBV) employs polyprotein processing as a strategy to express its gene products. Previously we identified the first cleavage event as proteolysis at the Gly673-Gly674 dipeptide bond mediated by the first papain-like proteinase domain (PLPD-1) to release an 87-kDa mature protein. In this report, we demonstrate a novel cleavage activity of PLPD-1. Expression, deletion, and mutagenesis studies showed that the product encoded between nucleotides 2548 and 8865 was further cleaved by PLPD-1 at the Gly2265-Gly2266 dipeptide bond to release an N-terminal 195-kDa and a C-terminal 41-kDa cleavage product. Characterization of the cleavage activity revealed that the proteinase is active on this scissile bond when expressed in vitro in rabbit reticulocyte lysates and can act on the same substrate intrans when expressed in intact cells. Both the N- and C-terminal cleavage products were detected in virus-infected cells and were found to be physically associated. Glycosidase digestion and site-directed mutagenesis studies of the 41-kDa protein demonstrated that it is modified by N-linked glycosylation at the Asn2313 residue encoded by nucleotides 7465 to 7467. By using a region-specific antiserum raised against the IBV sequence encoded by nucleotides 8865 to 9786, we also demonstrated that a 33-kDa protein, representing the 3C-like proteinase (3CLP), was specifically immunoprecipitated from the virus-infected cells. Site-directed mutagenesis and expression studies showed that a previously predicted cleavage site (Q2583-G2584) located within the 41-kDa protein-encoding region was not utilized by 3CLP, supporting the conclusion that the 41-kDa protein is a mature viral product.
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Lee, KiYoung, Dae-Won Kim, DoKyun Na, Kwang H. Lee, and Doheon Lee. "PLPD: reliable protein localization prediction from imbalanced and overlapped datasets." Nucleic Acids Research 34, no. 17 (September 11, 2006): 4655–66. http://dx.doi.org/10.1093/nar/gkl638.
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Lawlor, P. G., C. L. Nekolaichuk, S. S. Lowe, A. Kelly, R. L. Fainsinger, S. Watanabe, and E. D. Bruera. "Pre-admission escalation rate of daily opioid consumption (PERDOC), and total morphine equivalent daily dose on the first complete day of admission (D1-MEDD) to a tertiary-level palliative care unit (TPCU): Correlates and predictors in patients with advan." Journal of Clinical Oncology 25, no. 18_suppl (June 20, 2007): 9065. http://dx.doi.org/10.1200/jco.2007.25.18_suppl.9065.
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9065 Background: Although animal laboratory studies attest to opioid tolerance (OT), it can be difficult in clinical practice to determine whether substantive escalation in opioid dose (average of >5% per day between initial daily dose and maximum daily dose to date) is due to disease progression (DP) or decreased opioid responsiveness, which in turn may be due to OT or other factors. Our study aims were to determine (1) the frequency of PERDOC>5%, (2) the correlates and predictors of PERDOC>5% and D1-MEDD. Methods: We retrospectively examined TPCU patient database records for demographics, physician rating of PERDOC in the Edmonton Staging System (ESS) for cancer pain classification, Edmonton Symptom Assessment System (ESAS) scores, and D1-MEDD. Consecutive 1st admission data on patients surviving >3 days were included in the initial analysis. Using complete data, logistic regression and multiple regression models were created with PERDOC>5% and logn D1-MEDD, respectively, as dependent variables. Results: From 1,351 patients who met the initial descriptive analysis eligibility criteria, 1212 (90%) had an ESS rating for PERDOC. The prevalence of PERDOC>5% was 274/1212 (19.3%). Bivariate analysis (N=969, complete data) showed that PERDOC>5% was positively associated (p<0.05) with younger age, neuropathic pain component (NPC), a pathological level of psychological distress (PLPD), substance abuse, higher D1-MEDD, and higher ESAS pain score (ESAS-P). In the multivariate analysis, NPC (Odds ratio: 2.1, 95% confidence interval: 1.5–2.9), PLPD (1.7, 1.2–2.6), and higher D1-MEDD (2.2, 1.03–4.7) were the strongest independent positive predictors, and ESAS-P (1.01, 1.003–1.02) remained as a weaker predictor. In the D1-MEDD regression model, positive predictors (p<0.05) were younger age, NPC, incident pain, PERDOC>5%, PLPD, ESAS-P and ESAS anxiety scores. Conclusions: Aside from OT and DP, the multiple predictors identified for PERDOC>5% and D1-MEDD underscore the need for a systematic multidimensional assessment of cancer pain that incorporates psychological and physical characteristics. No significant financial relationships to disclose.
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Canioni, Danielle, Nizar Mahlaoui, Chantal Andriamanga, Catherine Dubois d'Enghien, Jean-Philippe Jais, Alain Fischer, Olivier Hermine, Nicole Brousse, Dominique Stoppa-Lyonnet, and Felipe Suarez. "Histological Characteristics of Ataxia Telangiectasia Associated Lymphoproliferative Diseases. Results of the French Registry of Primary Immune Deficiencies." Blood 124, no. 21 (December 6, 2014): 1634. http://dx.doi.org/10.1182/blood.v124.21.1634.1634.
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Abstract Introduction Ataxia-telangiectasia (A-T) is a rare autosomal recessive disorder associated with mutations in the ATMgene and characterized by cerebellar ataxia, telangiectasia, immune defect, and a high incidence of lymphoid and solid cancers. We conducted a retrospective study of the patients with AT enrolled in the registry of the French National Reference Center for Primary Immune Deficiencies, in order to describe the incidence, subtypes, and outcomes of cancer and mainly of lymphoproliferative diseases (LPD) occurring in AT. Most of the LPD of this study were centrally reviewed by 2 expert hematopathologists. Patients & Results Sixty nine patients with cancers were identified among the 279 patients with AT of our cohort. Eight patients developed carcinomas, 8 acute leukemias, 3 T-cell prolymphocytic leukemias and 50 developed lymphomas. Among the lymphomas, 12 were classical Hodgkin's lymphomas (cHL), and 38 high-grade non-Hodgkin lymphomas (NHL, 26 of B-cell type, 4 of T-cell type, and 8 not phenotyped). We obtained a centralized histopathology review in 31 cases classified by pathology reports as cHL (n=6) and high-grade NHL (n=25). Cases were reviewed according to the WHO classification by H&E staining and immunohistochemistry. The presence of EBV was analyzed using antibodies to LMP and in situ hybridization for EBER. Concordance between the diagnosis established on pathology reports and the centralized review was excellent. All 6 cases of cHL were confirmed by the pathology review. The 25 cases initially diagnosed as high-grade NHL based on pathology reports fell into several WHO classification categories. Six corresponded to Burkitt's lymphomas (BL) and 12 to diffuse large B-cell lymphomas (DLBCL). Among the latter, 10 could be further classified according to cell-of-origin by the Hans algorithm as germinal center (GC, 2) and non-GC (8). Seven cases displayed polymorphic histological features reminiscent of post-transplant lymphoproliferative disorders (LPD), 5 polymorphic B cell LPD (pLPD), 1 with features of infectious mononucleosis (IM), another with features of plasmacytic hyperplasia LPD. EBV could be evaluated in 28 cases. All 6 cHL, 4 out of 11 DLBCL, all 5 pLPD, and the case of IM-like LPD were EBV positive by LMP and/or EBER staining. The 5 cases of BL that were evaluated were all EBV negative. Median age at diagnosis was 7.8 years [range 3 – 24], 14.9 [5.8 – 17.1], 12.2 [5.4 – 29] and 11 [6.3 – 17.7] for pLPD, cHL, BL and DLBCL respectively (p=ns). Median survival after diagnosis of lymphoma was 35, 8.6, 6 and 8 months for pLPD, cHL, BL and DLBCL respectively (p=ns). ATM mutation analysis was available for 20 cases (8 hypomorphic mutations, 12 loss-of-function mutations). There were no differences in age at diagnosis of lymphoma or survival according to the ATM mutation class or the EBV status. Conclusion B-cell malignancies including cHL and B-cell NHL are the most frequent malignancies in A-T and can be further classified as DLBCL, BL and cases with polymorphic features resembling post-transplant LPD. EBV seems to be associated with all cHL, approximately 50% of DLBCL and polymorphic LPD, but not with BL. The majority of DLBCL are non-GC type by immunohistochemistry. On this series of 31 patients, ATM mutation type was not associated with differences in type of lymphoma or outcome. Disclosures No relevant conflicts of interest to declare.
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Zhong, Zhi-Rong, Zhi-rong Zhang, Ji Liu, Yong Deng, Hong-wei Zhang, Yao Fu, Qing-guo Song, and Qin He. "Characteristics comparison before and after lyophilization of transferrin modified procationic- liposome- protamine- DNA complexes (Tf- PLPD)." Archives of Pharmacal Research 30, no. 1 (January 2007): 102–8. http://dx.doi.org/10.1007/bf02977785.
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Chen, Zhongbin, Yanhua Wang, Kiira Ratia, Andrew D. Mesecar, Keith D. Wilkinson, and Susan C. Baker. "Proteolytic Processing and Deubiquitinating Activity of Papain-Like Proteases of Human Coronavirus NL63." Journal of Virology 81, no. 11 (March 28, 2007): 6007–18. http://dx.doi.org/10.1128/jvi.02747-06.
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ABSTRACT Human coronavirus NL63 (HCoV-NL63), a common human respiratory pathogen, is associated with both upper and lower respiratory tract disease in children and adults. Currently, no antiviral drugs are available to treat CoV infections; thus, potential drug targets need to be identified and characterized. Here, we identify HCoV-NL63 replicase gene products and characterize two viral papain-like proteases (PLPs), PLP1 and PLP2, which process the viral replicase polyprotein. We generated polyclonal antisera directed against two of the predicted replicase nonstructural proteins (nsp3 and nsp4) and detected replicase proteins from HCoV-NL63-infected LLC-MK2 cells by immunofluorescence, immunoprecipitation, and Western blot assays. We found that HCoV-NL63 replicase products can be detected at 24 h postinfection and that these proteins accumulate in perinuclear sites, consistent with membrane-associated replication complexes. To determine which viral proteases are responsible for processing these products, we generated constructs representing the amino-terminal end of the HCoV-NL63 replicase gene and established protease cis-cleavage assays. We found that PLP1 processes cleavage site 1 to release nsp1, whereas PLP2 is responsible for processing both cleavage sites 2 and 3 to release nsp2 and nsp3. We expressed and purified PLP2 and used a peptide-based assay to identify the cleavage sites recognized by this enzyme. Furthermore, by using K48-linked hexa-ubiquitin substrate and ubiquitin-vinylsulfone inhibitor specific for deubiquitinating enzymes (DUBs), we confirmed that, like severe acute respiratory syndrome (SARS) CoV PLpro, HCoV-NL63 PLP2 has DUB activity. The identification of the replicase products and characterization of HCoV-NL63 PLP DUB activity will facilitate comparative studies of CoV proteases and aid in the development of novel antiviral reagents directed against human pathogens such as HCoV-NL63 and SARS-CoV.
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Gadlage, Mark J., and Mark R. Denison. "Exchange of the Coronavirus Replicase Polyprotein Cleavage Sites Alters Protease Specificity and Processing." Journal of Virology 84, no. 13 (April 28, 2010): 6894–98. http://dx.doi.org/10.1128/jvi.00752-10.
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ABSTRACT Coronavirus nonstructural proteins 1 to 3 are processed by one or two papain-like proteases (PLP1 and PLP2) at specific cleavage sites (CS1 to -3). Murine hepatitis virus (MHV) PLP2 and orthologs recognize and cleave at a position following a p4-Leu-X-Gly-Gly-p1 tetrapeptide, but it is unknown whether these residues are sufficient to result in processing by PLP2 at sites normally cleaved by PLP1. We demonstrate that exchange of CS1 and/or CS2 with the CS3 p4-p1 amino acids in engineered MHV mutants switches specificity from PLP1 to PLP2 at CS2, but not at CS1, and results in altered protein processing and virus replication. Thus, the p4-p1 residues are necessary for PLP2 processing but require a specific protein or cleavage site context for optimal PLP recognition and cleavage.
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Kanjanahaluethai, Amornrat, Dalia Jukneliene, and Susan C. Baker. "Identification of the Murine Coronavirus MP1 Cleavage Site Recognized by Papain-Like Proteinase 2." Journal of Virology 77, no. 13 (July 1, 2003): 7376–82. http://dx.doi.org/10.1128/jvi.77.13.7376-7382.2003.
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ABSTRACT The replicase polyprotein of murine coronavirus is extensively processed by three proteinases, two papain-like proteinases (PLPs), termed PLP1 and PLP2, and a picornavirus 3C-like proteinase (3CLpro). Previously, we established a trans-cleavage assay and showed that PLP2 cleaves the replicase polyprotein between p210 and membrane protein 1 (MP1) (A. Kanjanahaluethai and S. C. Baker, J. Virol. 74:7911-7921, 2000). Here, we report the results of our studies identifying and characterizing this cleavage site. To determine the approximate position of the cleavage site, we expressed constructs that extended various distances upstream from the previously defined C-terminal end of MP1. We found that the construct extending from the putative PLP2 cleavage site at glycine 2840-alanine 2841 was most similar in size to the processed MP1 replicase product generated in a trans-cleavage assay. To determine which amino acids are critical for PLP2 recognition and processing, we generated 14 constructs with amino acid substitutions upstream and downstream of the putative cleavage site and assessed the effects of the mutations in the PLP2 trans-cleavage assay. We found that substitutions at phenylalanine 2835, glycine 2839, or glycine 2840 resulted in a reduction in cleavage of MP1. Finally, to unequivocally identify this cleavage site, we isolated radiolabeled MP1 protein and determined the position of [35S]methionine residues released by Edman degradation reaction. We found that the amino-terminal residue of MP1 corresponds to alanine 2841. Therefore, murine coronavirus PLP2 cleaves the replicase polyprotein between glycine 2840 and alanine 2841, and the critical determinants for PLP2 recognition and processing occupy the P6, P2, and P1 positions of the cleavage site. This study is the first report of the identification and characterization of a cleavage site recognized by murine coronavirus PLP2 activity.
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Durie, Ian A., John V. Dzimianski, Courtney M. Daczkowski, Jack McGuire, Kay Faaberg, and Scott D. Pegan. "Structural insights into the interaction of papain-like protease 2 from the alphacoronavirus porcine epidemic diarrhea virus and ubiquitin." Acta Crystallographica Section D Structural Biology 77, no. 7 (June 18, 2021): 943–53. http://dx.doi.org/10.1107/s205979832100509x.
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Porcine epidemic diarrhea is a devastating porcine disease that is caused by the alphacoronavirus porcine epidemic diarrhea virus (PEDV). Like other members of the Coronaviridae family, PEDV encodes a multifunctional papain-like protease 2 (PLP2) that has the ability to process the coronavirus viral polyprotein to aid in RNA replication and antagonize the host innate immune response through cleavage of the regulatory proteins ubiquitin (Ub) and/or interferon-stimulated gene product 15 (ISG15) (deubiquitination and deISGylation, respectively). Because Betacoronavirus PLPs have been well characterized, it was sought to determine how PLP2 from the alphacoronavirus PEDV differentiates itself from its related counterparts. PEDV PLP2 was first biochemically characterized, and a 3.1 Å resolution crystal structure of PEDV PLP2 bound to Ub was then solved, providing insight into how Alphacoronavirus PLPs bind to their preferred substrate, Ub. It was found that PEDV PLP2 is a deubiquitinase and readily processes a variety of di-Ub linkages, in comparison with its Betacoronavirus counterparts, which have a narrower range of di-Ub activity but process both Ub and ISG15.
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Dunn, John, Nicholas Kusnezov, Elizabeth Polfer, Justin Orr, Miguel Pirela-Cruz, Justin Mitchell, and Logan Koehler. "Perilunate Dislocations and Perilunate Fracture Dislocations in the U.S. Military." Journal of Wrist Surgery 07, no. 01 (June 28, 2017): 057–65. http://dx.doi.org/10.1055/s-0037-1603932.
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Background Perilunate dislocations and perilunate fracture dislocations (PLDs/PLFDs) are rare and often associated with poor outcomes. Heretofore, these outcomes have not been evaluated in a high-demand military population. Questions/Purpose The purpose of this study was to evaluate the outcomes in a young, active population after sustaining PLD/PLFD injuries. Patients and Methods We retrospectively reviewed the U.S. military service members who underwent surgical treatment for a PLD/PLFD (Current Procedural Terminology codes 25695 and 25685) between June 1, 2010, and June 1, 2014 through the Military Health System Management Analysis and Reporting Tool (M2) database, capturing patients with a minimum 2-year follow-up. Patient characteristics and outcomes were gathered; however, radiographic analysis was not possible. Results In this study, 40 patients (40 wrists) were included with an average follow-up of 47.8 months. The average age was 28.8 years. Twenty-two injuries (55%) were PLFD and 22 (55%) cases involved the nondominant extremity. On initial presentation, 11 (27.5%) were missed and 50% of patients were presented with acute carpal tunnel syndrome. Range of motion (ROM) was 74% and grip strength was 65% compared with the contralateral wrist; 78% reported pain with activity and only 55% remained on active duty status at final follow-up. Injuries to the nondominant extremity were significantly more likely to experience a good to excellent outcome and regained a more ROM. Patients with ligamentous PLD had less pain at rest and were more likely to return to sport. Conclusion Worse outcomes can be expected for PLD/PLFD of the dominant extremity, transscaphoid PLFD, greater arc injuries, and those undergoing pinning alone. A high-demand patient may expect worse functional results with a higher degree of limitation postoperatively. Level of Evidence The level of evidence is therapeutic IV.
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Heishman, Aaron, Keldon Peak, Ryan Miller, Brady Brown, Bryce Daub, Eduardo Freitas, and Michael Bemben. "Associations Between Two Athlete Monitoring Systems Used to Quantify External Training Loads in Basketball Players." Sports 8, no. 3 (March 11, 2020): 33. http://dx.doi.org/10.3390/sports8030033.
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Monitoring external training load (eTL) has become popular for team sport for managing fatigue, optimizing performance, and guiding return-to-play protocols. During indoor sports, eTL can be measured via inertial measurement units (IMU) or indoor positioning systems (IPS). Though each device provides unique information, the relationships between devices has not been examined. Therefore, the purpose of this study was to assess the association of eTL between an IMU and IPS used to monitor eTL in team sport. Retrospective analyses were performed on 13 elite male National Collegiate Athletic Association (NCAA) Division I basketball players (age: 20.2 ± 1.2 years, height: 201.1 ± 7.6 cm, mass: 96.8 ± 8.8 kg) from three practices during the off-season training phase. A one-way analysis of variance was used to test differences in eTL across practices. Pearson’s correlation examined the association between the Distance traveled during practice captured by IPS compared to PlayerLoad (PL), PlayerLoad per Minute (PL/Min), 2-Dimensional PlayerLoad (PL2D), 1-Dimensional PlayerLoad Forward (PL1D-FWD), Side (PL1D-SIDE), and Up (PL1D-UP) captured from the IMU. Regression analyses were performed to predict PL from Distance traveled. The eTL characteristics during Practice 1: PL = 420.4 ± 102.9, PL/min = 5.8 ± 1.4, Distance = 1645.9 ± 377.0 m; Practice 2: PL = 472.8 ± 109.5, PL/min = 5.1 ± 1.2, Distance = 1940.0 ± 436.3 m; Practice 3: PL = 295.1 ± 57.8, PL/min = 5.3 ± 1.0, Distance = 1198.2 ± 219.2 m. Significant (p ≤ 0.05) differences were observed in PL, PL2D, PL1D-FWD, PL1D-SIDE, PL1D-UP, and Distance across practices. Significant correlations (p ≤ 0.001) existed between Distance and PL parameters (Practice 1: r = 0.799–0.891; Practice 2: r = 0.819–0.972; and Practice 3: 0.761–0.891). Predictive models using Distance traveled accounted for 73.5–89.7% of the variance in PL. Significant relationships and predictive capacities exists between systems. Nonetheless, each system also appears to capture unique information that may still be useful to performance practitioners regarding the understanding of eTL.
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Flanary, Paul L., Paul R. DiBello, Paula Estrada, and Henrik G. Dohlman. "Functional Analysis of Plp1 and Plp2, Two Homologues of Phosducin in Yeast." Journal of Biological Chemistry 275, no. 24 (April 3, 2000): 18462–69. http://dx.doi.org/10.1074/jbc.m002163200.
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Graham, Rachel L., and Mark R. Denison. "Replication of Murine Hepatitis Virus Is Regulated by Papain-Like Proteinase 1 Processing of Nonstructural Proteins 1, 2, and 3." Journal of Virology 80, no. 23 (September 13, 2006): 11610–20. http://dx.doi.org/10.1128/jvi.01428-06.
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ABSTRACT Coronaviruses are positive-strand RNA viruses that translate their genome RNA into polyproteins that are co- and posttranslationally processed into intermediate and mature replicase nonstructural proteins (nsps). In murine hepatitis virus (MHV), nsps 1, 2, and 3 are processed by two papain-like proteinase activities within nsp3 (PLP1 and PLP2) to yield nsp1, an nsp2-3 intermediate, and mature nsp2 and nsp3. To determine the role in replication of processing between nsp2 and nsp3 at cleavage site 2 (CS2) and PLP1 proteinase activity, mutations were engineered into the MHV genome at CS2, at CS1 and CS2, and at the PLP1 catalytic site, alone and in combination. Mutant viruses with abolished cleavage at CS2 were delayed in growth and RNA synthesis but grew to wild-type titers of >107 PFU/ml. Mutant viruses with deletion of both CS1 and CS2 exhibited both a delay in growth and a decrease in peak viral titer to ∼104 PFU/ml. Inactivation of PLP1 catalytic residues resulted in a mutant virus that did not process at either CS1 or CS2 and was severely debilitated in growth, achieving only 102 PFU/ml. However, when both CS1 and CS2 were deleted in the presence of inactivated PLP1, the growth of the resulting mutant virus was partially compensated, comparable to that of the CS1 and CS2 deletion mutant. These results demonstrate that interactions of PLP1 with CS1 and CS2 are critical for protein processing and suggest that the interactions play specific roles in regulation of the functions of nsp1, 2, and 3 in viral RNA synthesis.
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Kanjanahaluethai, Amornrat, and Susan C. Baker. "Identification of Mouse Hepatitis Virus Papain-Like Proteinase 2 Activity." Journal of Virology 74, no. 17 (September 1, 2000): 7911–21. http://dx.doi.org/10.1128/jvi.74.17.7911-7921.2000.
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ABSTRACT Mouse hepatitis virus (MHV) is a 31-kb positive-strand RNA virus that is replicated in the cytoplasm of infected cells by a viral RNA-dependent RNA polymerase, termed the replicase. The replicase is encoded in the 5′-most 22 kb of the genomic RNA, which is translated to produce a polyprotein of >800 kDa. The replicase polyprotein is extensively processed by viral and perhaps cellular proteinases to give rise to a functional replicase complex. To date, two of the MHV replicase-encoded proteinases, papain-like proteinase 1 (PLP1) and the poliovirus 3C-like proteinase (3CLpro), have been shown to process the replicase polyprotein. In this report, we describe the cloning, expression, and activity of the third MHV proteinase domain, PLP2. We show that PLP2 cleaves a substrate encoding the first predicted membrane-spanning domain (MP1) of the replicase polyprotein. Cleavage of MP1 and release of a 150-kDa intermediate, p150, are likely to be important for embedding the replicase complex in cellular membranes. Using an antiserum (anti-D11) directed against the C terminus of the MP1 domain, we verified that p150 encompasses the MP1 domain and identified a 44-kDa protein (p44) as a processed product of p150. Pulse-chase experiments showed that p150 is rapidly generated in MHV-infected cells and that p44 is processed from the p150 precursor. Protease inhibitor studies revealed that unlike 3CLpro activity, PLP2 activity is not sensitive to cysteine protease inhibitor E64d. Furthermore, coexpression studies using the PLP2 domain and a substrate encoding the MP1 cleavage site showed that PLP2 acts efficiently intrans. Site-directed mutagenesis studies confirmed the identification of cysteine 1715 as a catalytic residue of PLP2. This study is the first to report enzymatic activity of the PLP2 domain and to demonstrate that three distinct viral proteinase activities process the MHV replicase polyprotein.
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Hurst-Hess, Kelley R., Lili Kuo, and Paul S. Masters. "Dissection of Amino-Terminal Functional Domains of Murine Coronavirus Nonstructural Protein 3." Journal of Virology 89, no. 11 (March 25, 2015): 6033–47. http://dx.doi.org/10.1128/jvi.00197-15.
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ABSTRACTCoronaviruses, the largest RNA viruses, have a complex program of RNA synthesis that entails genome replication and transcription of subgenomic mRNAs. RNA synthesis by the prototype coronavirus mouse hepatitis virus (MHV) is carried out by a replicase-transcriptase composed of 16 nonstructural protein (nsp) subunits. Among these, nsp3 is the largest and the first to be inserted into the endoplasmic reticulum. nsp3 comprises multiple structural domains, including two papain-like proteases (PLPs) and a highly conserved ADP-ribose-1″-phosphatase (ADRP) macrodomain. We have previously shown that the ubiquitin-like domain at the amino terminus of nsp3 is essential and participates in a critical interaction with the viral nucleocapsid protein early in infection. In the current study, we exploited atypical expression schemes to uncouple PLP1 from the processing of nsp1 and nsp2 in order to investigate the requirements of nsp3 domains for viral RNA synthesis. In the first strategy, a mutant was created in which replicase polyprotein translation initiated with nsp3, thereby establishing that complete elimination of nsp1 and nsp2 does not abolish MHV viability. In the second strategy, a picornavirus autoprocessing element was used to separate a truncated nsp1 from nsp3. This provided a platform for further dissection of amino-terminal domains of nsp3. From this, we found that catalytic mutation of PLP1 or complete deletion of PLP1 and the adjacent ADRP domain was tolerated by the virus. These results showed that neither the PLP1 domain nor the ADRP domain of nsp3 provides integral activities essential for coronavirus genomic or subgenomic RNA synthesis.IMPORTANCEThe largest component of the coronavirus replicase-transcriptase complex, nsp3, contains multiple modules, many of which do not have clearly defined functions in genome replication or transcription. These domains may play direct roles in RNA synthesis, or they may have evolved for other purposes, such as to combat host innate immunity. We initiated a dissection of MHV nsp3 aimed at identifying those activities or structures in this huge molecule that are essential to replicase activity. We found that both PLP1 and ADRP could be entirely deleted, provided that the requirement for proteolytic processing by PLP1 was offset by an alternative mechanism. This demonstrated that neither PLP1 nor ADRP plays an essential role in coronavirus RNA synthesis.
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Choy, Daniel S. J. "Repeat PLDD." Photomedicine and Laser Surgery 24, no. 5 (October 2006): 660. http://dx.doi.org/10.1089/pho.2006.24.660.
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Ali, M. Y., J. Md Sarwar, and Muhd M. Rahman. "O41 Percutaneous laser disc decompression (PLDD) with 970 nm wavelength laser: a minimal invasive surgery for PLID, first time in Bangladesh." Photodiagnosis and Photodynamic Therapy 7 (July 2010): S19. http://dx.doi.org/10.1016/s1572-1000(10)70056-9.
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Pecl, Jakub, Petr Jabandžiev, Tereza Pinkasová, and Markéta Veverková. "Constipation in the paediatric practice." Pediatrie pro praxi 18, no. 5 (November 1, 2017): 276–81. http://dx.doi.org/10.36290/ped.2017.054.
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Regis, Stefano, Serena Grossi, Fabio Corsolini, Roberta Biancheri, and Mirella Filocamo. "PLP1 gene duplication causes overexpression and alteration of the PLP/DM20 splicing balance in fibroblasts from Pelizaeus–Merzbacher disease patients." Biochimica et Biophysica Acta (BBA) - Molecular Basis of Disease 1792, no. 6 (June 2009): 548–54. http://dx.doi.org/10.1016/j.bbadis.2009.04.002.
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Hadeli, Hadeli, and Nana Sepriyanti. "The Effectiveness of in-service Teacher Training Program at Faculty of Islamic Education and Teacher Training IAIN Imam Bonjol Padang." Al-Ta lim Journal 22, no. 3 (December 10, 2015): 195–202. http://dx.doi.org/10.15548/jt.v22i3.120.
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The purpose of this research is to reveal: 1. The influence of in-service Teacher Training Program (PLPG) towards the teacher competency as participant of PLPG; 2. The correlation between gender (X1) towards the teachers’ competency as participant of PLPG; .3. The correlation between Age (X2) towards the teachers’ competency as participant of PLPG; 4. The correlation between years of service towards the teachers’ competency as participant of PLPG; 5. The correlation between the number of training followed (X4) towards teachers’ competency as participant of PLPG; and 6. This research used quantitative method. The population of this research is 1.300 teachers of PLPG in 2013. By using Yamane formulation, there are 220 teachers taken as the sample. The data was analyzed by using t test and correlation analysis. The findings of the study suggested that: 1. There is a positive influence of PLPG implementation towards teachers’ competency as PLPG participant; 2. There is no significant correlation between gender (X1) and teachers’ competency as PLPG participant; 3. There is a significant correlation between Age (X2) towards teachers’ competency of PLPG; 4. There is no significant correlation between the Years of Service (X3) towards teachers’ competency as the participant of PLPG; 5. There is a significant correlation between the number of Diklat followed (X4) towards teachers’ competency as the participant of PLPG; and 6. There is a significant correlation between the effectiveness of PLPG (X5) towards teachers’ competency as the participant of PLPG. Keywords: PLPG, LPTK, teacher certificationCopyright © 2015 by Al-Ta'lim All right reserved
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CHAMBERS, R. ALAN, JOHN A. BOTSFORD, and ELIZABETH FANELLI. "The PLDD Registry." Journal of Clinical Laser Medicine & Surgery 13, no. 3 (June 1995): 215–19. http://dx.doi.org/10.1089/clm.1995.13.215.
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Argon, E., I. L. Chang, G. Gunaratna, D. K. Kahaner, and M. A. Reed. "Mathematical software: Plod." IEEE Micro 8, no. 4 (August 1988): 56–61. http://dx.doi.org/10.1109/40.7772.
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Lanzafame, Raymond J., and Chukura S. Enwemeka. "PLDD in 2004." Photomedicine and Laser Surgery 22, no. 5 (October 2004): 391. http://dx.doi.org/10.1089/pho.2004.22.391.
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Pandis, Ippokratis, Pinar Tözün, Ryan Johnson, and Anastasia Ailamaki. "PLP." Proceedings of the VLDB Endowment 4, no. 10 (July 2011): 610–21. http://dx.doi.org/10.14778/2021017.2021019.
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McGinley, Kathleen F., Xizi Sun, Lauren E. Howard, William J. Aronson, Martha K. Terris, Christopher J. Kane, Christopher L. Amling, Matthew R. Cooperberg, and Stephen J. Freedland. "Utilization and impact of surgical technique on the performance of pelvic lymph node dissection at radical prostatectomy: Results from the SEARCH database." Journal of Clinical Oncology 33, no. 7_suppl (March 1, 2015): 73. http://dx.doi.org/10.1200/jco.2015.33.7_suppl.73.
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73 Background: Performance of a pelvic lymph node dissection (PLND) with radical prostatectomy (RP) is critical for staging and treatment of high-risk prostate cancer (PC). Conversely, performance of a PLND in low-risk PC contributes to morbidity with minimal benefit. Robot-assisted laparoscopic RP (RARP) is associated with decreased PLND use. We evaluated PLND use over time, stratified by PC risk group and surgical technique. Methods: We used SEARCH to identify men who had open RP (ORP) or RARP from 2006-2013 with complete data. Univariable logistic regression was used to test the association between age, race, BMI, number of positive cores, AUA risk group, year, center, and surgical technique on PLND use. Multivariable logistic analysis was used to examine surgical technique and PLND performance stratified by AUA risk-group. Spearman correlation was used to examine temporal changes in PLND utilization stratified by risk-group and surgical technique. Results: 1,439 men met inclusion criteria. Of these, 66% had a PLND. On univariable analysis, age, year, number of positive cores, AUA risk group, center, and surgical technique were significantly associated with PLND performance (all p<0.02). On multivariable analysis, when adjusted for age, race, BMI, number of positive cores, year, and center, RARP was associated with a 89% decreased use of PLND in the low-risk group, 85% decreased in intermediate risk, and 86% decreased in high risk men (all p≤0.002). Over time, PLND was increasingly used with RARP in low-risk patients (p=0.022); a trend of increased PLND performance with RARP in high risk men was noted (p=0.077) reaching ~85% in 2012-2013 vs. ~95% in ORP. For ORP, PLND use did not significantly change over time except a trend of fewer PLND in low-risk men which decreased to ~35% (p=0.064) in 2012-2013. Conclusions: Regardless of risk group, PLND is markedly less likely to be performed when a RARP is done. While improved over time, PLND remains over-utilized in low-risk men and under-utilized in high risk men regardless of surgical technique.
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Elzayat, Ehab A., and Ali A. Al-Zahrani. "Pelvic Lymphadenectomy in the Treatment of Invasive Bladder Cancer: Literature Review." Advances in Urology 2011 (2011): 1–8. http://dx.doi.org/10.1155/2011/701481.
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The standard surgical treatment of invasive bladder cancer is the radical cystectomy and pelvic lymph node dissection (PLND). Up to one-third of patients with invasive bladder cancer have lymph node metastasis. Thus, PLND has important therapeutic and prognostic benefits. The number of lymph nodes that should be removed and the extent of the PLND are still a controversial issue. Recently, the trend of PLND increased toward more extended PLND. Several prognostic factors related to PLND were reported in the literature. In this paper, we will discuss the different PLND templates, number of lymph nodes that should be resected, lymph node density, lymphovascular invasion, tumor burden, extracapsular extension, and the aggregate lymph node metastasis diameter.
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Kojima, Seiji, Takuro Yoneda, Wakako Morimoto, and Michio Homma. "Effect of PlzD, a YcgR homologue of c-di-GMP-binding protein, on polar flagellar motility in Vibrio alginolyticus." Journal of Biochemistry 166, no. 1 (February 18, 2019): 77–88. http://dx.doi.org/10.1093/jb/mvz014.
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AbstractYcgR, a cyclic diguanylate (c-di-GMP)-binding protein expressed in Escherichia coli, brakes flagellar rotation by binding to the motor in a c-di-GMP dependent manner and has been implicated in triggering biofilm formation. Vibrio alginolyticus has a single polar flagellum and encodes YcgR homologue, PlzD. When PlzD or PlzD-GFP was highly over-produced in nutrient-poor condition, the polar flagellar motility of V. alginolyticus was reduced. This inhibitory effect is c-di-GMP independent as mutants substituting putative c-di-GMP-binding residues retain the effect. Moderate over-expression of PlzD-GFP allowed its localization at the flagellated cell pole. Truncation of the N-terminal 12 or 35 residues of PlzD abolished the inhibitory effect and polar localization, and no inhibitory effect was observed by deleting plzD or expressing an endogenous level of PlzD-GFP. Subcellular fractionation showed that PlzD, but not its N-terminally truncated variants, was precipitated when over-produced. Moreover, immunoblotting and N-terminal sequencing revealed that endogenous PlzD is synthesized from Met33. These results suggest that an N-terminal extension allows PlzD to localize at the cell pole but causes aggregation and leads to inhibition of motility. In V. alginolyticus, PlzD has a potential property to associate with the polar flagellar motor but this interaction is too weak to inhibit rotation.
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Suarez-Ibarrola, Rodrigo, Mario Basulto-Martinez, August Sigle, Mohammad Abufaraj, Christian Gratzke, and Arkadiusz Miernik. "Is There an Oncological Benefit of Performing Bilateral Pelvic Lymph Node Dissection in Patients with Penile Cancer and Inguinal Lymph Node Metastasis?" Journal of Clinical Medicine 10, no. 4 (February 13, 2021): 754. http://dx.doi.org/10.3390/jcm10040754.
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We aim to review the literature for studies investigating the oncological outcomes of patients with penile cancer (PC) undergoing bilateral pelvic lymph node dissection (PLND) in the presence of inguinal lymph node metastasis (LNM) who are at risk of harboring pelvic metastasis. A search of English language literature was performed using the PubMed-MEDLINE database up to 3 December 2020 to identify articles addressing bilateral PLND in PC patients. Eight articles investigating bilateral PLND met our inclusion criteria. Patients with pelvic LNM have a dismal prognosis and, therefore, PLND has an important role in both the staging and treatment of PC patients. Ipsilateral PLND is recommended in the presence of ≥2 positive inguinal nodes and/or extranodal extension (ENE). Significant survival improvements were observed with a higher pelvic lymph node yield, in patients with pN2 disease, and in men treated with bilateral PLND as opposed to ipsilateral PLND. Nevertheless, the role of bilateral PLND for unilateral inguinal LNM remains unclear. Although the EAU guidelines state that pelvic nodal disease does not occur without ipsilateral inguinal LNM, metastatic spread from one inguinal side to the contralateral pelvic side has been reported in a number of studies. Further studies are needed to clarify the disseminative pattern of LNM, in order to establish PLND templates according to patients’ risk profiles and to investigate the benefit of performing bilateral PLND for unilateral inguinal disease.
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No, Sutris. "Efektivitas Penilaian Sertifikasi Guru Kelas MI melalui Kegiatan PLPG Kuota Tambahan Tahun 2013." MUDARRISA: Jurnal Kajian Pendidikan Islam 8, no. 2 (December 13, 2016): 283. http://dx.doi.org/10.18326/mdr.v8i2.283-312.
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Tulisan ini bertujuan untuk memaparkan tentang evektivitas penilaian sertifikasi guru kelas MI melalui kegiatan PLPG. Penelitian ini menggunakan metode deskriptif analitis dengan mengkaji referensi yang bersumber dari perpustakaan. Dalam penelitian ini didapatkan beberapa kesimpulan kesimpulan: pertama, proses dan intstrumen penilaian sertifikasi guru kelas MI melalui PLPG pada guru kelas MI se-kecamatan Mejobo kabupaten Kudus yang telah mengikuti PLPG sudah terlaksanakan dengan baik dan sesuai dengan peraturan pemerintah; kedua, pandangan guru kelas MI se-kecamatan Mejobo kabupaten Kudus yang telah mengikuti PLPG terhadap penilaian sertifikasi guru kelas MI melalui PLPG sudah baik, karena banyak guru yang pada awal datangnya terlihat pasif kemudian menjadi aktif dan kreatif; ketiga, ketercapaian penilaian sertifikasi guru melalui kegiatan PLPG dapat dilihat melalui meningkatnya motivasi para guru dalam mengajar, membangun mental positif para guru dalam melaksanakan pembelajaran, meningkatkan kompetensi guru, guru terdidik melaksanakan tugas dengan sepenuh hati, dan guru dapat melaksanakan pembelajaran aktif; keempat, kurang efektifnya penilaian sertifikasi guru melalui kegiatan PLPG di LPTK Rayon 232 IAIN terkendala pada sisi teknis waktu pelaksanaan PLPG yang singkat sehingga berimbas pada kedalaman pemahaman guru terhadap materi yang diberikan.This paper aims to describe the effectiveness of assessment of MI (Madrasah Ibtidaiyah: Indonesian State Islamic Primary School) teacher certification through PLPG activities. This research uses descriptive analytical method to assess references from the library. In this study, as the first conclusion, the processes and the assessment instrument of certification in PLPG LPTK Rayon 232 IAIN Surakarta (additional quota of 2013) for the teachers of District Mejobo, Kudus has properly fulfilled the standard in accordance with the regulations and operational guidelines as directed by the government. Secondly, from the teachers’ point of view, the assessment of MI teachers certification through PLPG is already good because many teachers look passive initially then becomes active and creative at last. Thirdly, the assessment of teacher achievement, to be certified through PLPG activities, basically aims to increase the motivation of teachers in their teaching implementation. Fourthly, the ineffective assessment of teacher certification through PLPG is due to the “short time” (the length of time) allotted for the PLPG which brings about the effect on the deepness of the teachers' understanding on the materials supplied.
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Pandher, Karamjeet, Anthony W. Confer, and George L. Murphy. "Genetic and Immunologic Analyses of PlpE, a Lipoprotein Important in Complement-Mediated Killing of Pasteurella haemolytica Serotype 1." Infection and Immunity 66, no. 12 (December 1, 1998): 5613–19. http://dx.doi.org/10.1128/iai.66.12.5613-5619.1998.
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ABSTRACT Pasteurella haemolytica serotype 1 is the bacterium most commonly associated with bovine shipping fever. The presence of antibodies against P. haemolytica outer membrane proteins (OMPs) correlates statistically with resistance to experimentalP. haemolytica challenge in cattle. Until now, specificP. haemolytica OMPs which elicit antibodies that function in host defense mechanisms have not been identified. In this study, we have cloned and sequenced the gene encoding one such protein, PlpE. Analysis of the deduced amino acid sequence revealed that PlpE is a lipoprotein and that it is similar to an Actinobacillus pleuropneumoniae lipoprotein, OmlA. Affinity-purified, anti-PlpE antibodies recognize a protein in all serotypes of P. haemolytica except serotype 11. We found that intact P. haemolytica and recombinant E. coli expressing PlpE are capable of absorbing anti-PlpE antibodies from bovine immune serum, indicating that PlpE is surface exposed in P. haemolyticaand assumes a similar surface-exposed conformation in E. coli. In complement-mediated killing assays, we observed a significant reduction in killing of P. haemolytica when bovine immune serum that was depleted of anti-PlpE antibodies was used as the source of antibody. Our data suggest that PlpE is surface exposed and immunogenic in cattle and that antibodies against PlpE contribute to host defense against P. haemolytica.
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Frank, Lori. "Research Engagement With Persons Living With Dementia: Putting Lessons Learned Into Practice." Innovation in Aging 4, Supplement_1 (December 1, 2020): 728. http://dx.doi.org/10.1093/geroni/igaa057.2585.
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Abstract In the US few research initiatives actively engage persons living with dementia (PLWD) as partners in the research. The 2017 Summit actively engaged multiple types of stakeholder groups, including one for Persons Living with Dementia (PLWD), and was the first large-scale US research meeting to actively engage PLWD in planning and conduct of the meeting. The PLWD conducted a self-evaluation of their work that yielded best practices, meeting the need for guidelines for engaging with PLWD. The 2020 Summit presented the opportunity to test best practices. Some were implemented by the group conveners, like use of video-enabled meetings. Others were implemented with the PLWD, including decisions about governance structure for the group. The use of learnings from the first Summit in engaging with PLWD in the following Summit supported refinement of some engagement practices, yielding a list of recommendations for future work.
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Bai, Hua, Yudi Zhu, Peipei Xu, and Bing Chen. "PLP2 Expression as a Prognostic and Therapeutic Indicator in High-Risk Multiple Myeloma." BioMed Research International 2020 (June 10, 2020): 1–8. http://dx.doi.org/10.1155/2020/4286101.
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Multiple myeloma (MM) is a devastating cancer with a highly heterogeneous outcome. Because of the heterogeneity of myeloma cells, risk stratification is important for making therapeutic regimens. Nevertheless, no immunohistochemical predictive and prognostic marker has been constructed yet. In the present study, we explored the prognostic value of proteolipid protein 2 (PLP2) in MM patients using immunohistochemistry (IHC). We assessed PLP2 expression in bone marrow (BM) biopsy specimens obtained from 87 newly diagnosed MM (NDMM) patients. Correlations between PLP2 expression and clinicopathological features were analyzed. PLP2 expression was present in high-risk MM patients, which was increased with disease progression and poor prognosis. PLP2 was increasing in parallel with high beta-2 microglobulin (β2-MG) and lactate dehydrogenase (LDH). Furthermore, MM patients with low PLP2 expression could achieve a favorable treatment response. PLP2 may be a novel biomarker for prognostic prediction and a therapeutic target for anti-MM treatments.
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Deligiorgi, Maria V., Mihalis I. Panayiotidis, and Dimitrios T. Trafalis. "Prophylactic lymph node dissection in clinically N0 differentiated thyroid carcinoma: example of personalized treatment." Personalized Medicine 17, no. 4 (July 1, 2020): 317–38. http://dx.doi.org/10.2217/pme-2019-0119.
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Considering the ‘differentiated thyroid carcinoma (DTC) epidemic’, the indolent nature of DTC imposes a treatment paradigm shift toward elimination of recurrence. Lymph node metastases in cervical compartments, encountered in 20–90% of DTC, are the main culprit of recurrent disease, affecting 5–30% of patients. Personalized risk-stratified cervical prophylactic lymph node dissection (PLND) at initial thyroidectomy in DTC with no clinical, sonographic or intraoperative evidence of lymph node metastases (clinically N0) has been advocated, though not unanimously. The present review dissects the controversy over PLND. Weighing the benefit yielded from PLND up against the PLND-related morbidity is so far hampered by the inconsistent profit yielded by PLND and the challenging patient selection. Advances in tailoring PLND are anticipated to empower optimal patient care.
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Wight, Patricia A. "Effects of Intron 1 Sequences on Human PLP1 Expression: Implications for PLP1-Related Disorders." ASN Neuro 9, no. 4 (July 24, 2017): 175909141772058. http://dx.doi.org/10.1177/1759091417720583.
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Alterations in the myelin proteolipid protein gene ( PLP1) may result in rare X-linked disorders in humans such as Pelizaeus–Merzbacher disease and spastic paraplegia type 2. PLP1 expression must be tightly regulated since null mutations, as well as elevated PLP1 copy number, both lead to disease. Previous studies with Plp1-lacZ transgenic mice have demonstrated that mouse Plp1 ( mPlp1) intron 1 DNA (which accounts for slightly more than half of the gene) is required for the mPlp1 promoter to drive significant levels of reporter gene expression in brain. However not much is known about the mechanisms that control expression of the human PLP1 gene ( hPLP1). Therefore this review will focus on sequences in hPLP1 intron 1 DNA deemed important for hPLP1 gene activity as well as a couple of “human-specific” supplementary exons within the first intron which are utilized to generate novel splice variants, and the potential role that these sequences may play in PLP1-linked disorders.
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Rankin Russell, Richard. "Hopkins’s and Heaney’s ‘Plod’." Notes and Queries 66, no. 2 (April 25, 2019): 320–22. http://dx.doi.org/10.1093/notesj/gjz047.
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Hasanah, Uswatun, Zulfikar Ali As, and Maharso Maharso. "Tingkat Kebisingan Di Kawasan Permukiman Sekitar PLTD Muara Teweh." JURNAL KESEHATAN LINGKUNGAN: Jurnal dan Aplikasi Teknik Kesehatan Lingkungan 13, no. 1 (January 1, 2016): 328. http://dx.doi.org/10.31964/jkl.v13i1.30.
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Abstract: Level of Noise in the residential around muara teweh’s PLTD. Muara Teweh’s PLTD was one of the regional companied responsible for the provision of electricity serviced. The impact of the operation of the PLTD is the emergence of noise caused by the PLTD engine so that it appeared on public complainted, especially communication disordered, disordered of physiological and psychological disordered. This study aims to determine the noise level and subjective complainted felt in residential areas around Muara Teweh’s PLTD. This research was a descriptive observational describe the noise level in residential areas Muara Teweh’s PLTD. This study include cross-sectional design that aims to determine the noise until at residential areas around Muara Teweh’s PLTD and connect with public complainted in residential areas around Muara Teweh’s PLTD. The measurement resulted show noise levels in residential areas around Muara Teweh’s PLTD exceeded the NAV according KEPMEN / LH / 48/1996, which is 62.9 dBA in the North, 70.4 dBA in the Northeast, 69.3 dBA in the East , 69.4 dBA in the direction of the Southeast, 72.3 dBA in the south, 72.2 dBA in the direction of the Southwest, 78.2 in the West and 75.5 dBA in the northwest. Subjective complainted of the most widely felt in residential areas Muara Teweh’s PLTD form (45.9%), headache (56.8%), discomfort (91.9%), insomnia (83.8%) fast and emotions (40.5%). Efforts should be madeto controlnoise levelsand complaintsaregiving them the toolsnoise suppressioninengine room, thickenthe barrier, put upcurtainsat thewindows of the houseanddo notoftenopen thedoor. Keywords : Noisy environment, residential noise
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Schiffmann, Jonas, Alessandro Larcher, Maxine Sun, Zhe Tian, Jérémie Berdugo, Ion Leva, Hugues Widmer, et al. "Suboptimal use of pelvic lymph node dissection: Differences in guideline adherence between robot-assisted and open radical prostatectomy." Canadian Urological Association Journal 10, no. 7-8 (August 16, 2016): 269. http://dx.doi.org/10.5489/cuaj.3563.
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<p><strong>Introduction:</strong> Our aim was to assess adherence to National Comprehensive Cancer Network (NCCN) and American Urological Association (AUA) guidelines for pelvic lymph node dissection (PLND) at the time of either robot-assisted (RARP) or open radical prostatectomy (ORP).</p><p><strong>Methods:</strong> We relied on the Surveillance, Epidemiology, and End Results-Medicare linked database and focused on localized prostate cancer (PCa) patients who were treated with either RARP or ORP between October 2008 and December 2009. Categorical and multivariable logistic regression analyses targeted two endpoints: 1) probability of guideline-recommended PLND; and 2) probability of no PLND, when not guideline-recommended.</p><p><strong>Results:</strong> Among 5268 PCa patients, adherence to NCCN PLND guideline was 56.9% during RARP and 76.5% during ORP (odds ratio [OR] 0.4, 95% confidence interval [CI] 0.3‒0.6). AUA PLND guideline adherence was 68.1% during RARP and 82.4% during ORP (OR 0.7, 95% CI 0.5‒0.9). When PLND was not recommended, it was more frequently performed during ORP according to either NCCN (OR 3.7, 95% CI 3.5‒3.9) or AUA (OR 2.7, 95% CI 2.6‒2.8). According to the NCCN guideline, at recommended PLND in ORP patients, 6.3% harboured lymph node invasion (LNI) (number needed to treat [NNT] 16) vs. 3.2% at RARP (NNT 31). According to the AUA guideline, at recommended PLND in ORP patients, 12.3% harboured LNI (NNT 8) vs. 5.1% RARP (NNT 19).</p><p><strong>Conclusions:</strong> Adherence to NCCN and AUA PLND guidelines was lower during RARP than during ORP when PLND was recommended. The rate of non-recommended PLND was also higher during ORP than during RARP. Technical considerations may be at play.</p>
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Legge, Kevin L., Booki Min, Nicholas T. Potter, and Habib Zaghouani. "Presentation of a T Cell Receptor Antagonist Peptide by Immunoglobulins Ablates Activation of T Cells by a Synthetic Peptide or Proteins Requiring Endocytic Processing." Journal of Experimental Medicine 185, no. 6 (March 17, 1997): 1043–54. http://dx.doi.org/10.1084/jem.185.6.1043.
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T cell receptor (TCR) antagonism is being considered for inactivation of aggressive T cells and reversal of T cell–mediated autoimmune diseases. TCR antagonist peptides silence aggressive T cells and reverse experimental allergic encephalomyelitis induced with free peptides. However, it is not clear whether free antagonist peptides could reverse natural disease where the antigen is presumably available for endocytic processing and peptides gain access to newly synthesized class II MHC molecules. Using an efficient endocytic presentation system, we demonstrate that a proteolipid protein (PLP) TCR antagonist peptide (PLP-LR) presented on an Ig molecule (IgPLP-LR) abrogates the activation of T cells stimulated with free encephalitogenic PLP peptide (PLP1), native PLP, or an Ig containing PLP1 peptide (Ig-PLP1). Free PLP-LR abolishes T cell activation when the stimulator is free PLP1 peptide, but has no measurable effect when the stimulator is the native PLP or Ig-PLP1. In vivo, Ig-PLP1 induces a T cell response to PLP1 peptide. However, when coadministered with Ig-PLP-LR, the response to PLP1 peptide is markedly reduced whereas the response to PLP-LR is normal. Free PLP-LR coadministered with Ig-PLP1 has no effect on the T cell response to PLP1. These findings indicate that endocytic presentation of an antagonist peptide by Ig outcompete both external and endocytic agonist peptides whereas free antagonist hinders external but not endocytic agonist peptide. Direct contact with antagonist ligand and/or trans-regulation by PLP-LR–specific T cells may be the operative mechanism for Ig-PLP-LR–mediated downregulation of PLP1-specific T cells in vivo. Efficient endocytic presentation of antagonist peptides, which is the fundamental event for either mechanism, may be critical for reversal of spontaneous T cell–mediated autoimmune diseases where incessant endocytic antigen processing could be responsible for T cell aggressivity.
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Feng, Z., W. Zhou, J. Wang, B. Huang, A. Chen, D. Zhang, R. Bjerkvig, J. Wang, F. Thorsen, and X. Li. "P11.52 Reduced expression of proteolipid protein 2 increases ER-stress-induced apoptosis and autophagy in glioblastoma." Neuro-Oncology 21, Supplement_3 (August 2019): iii55. http://dx.doi.org/10.1093/neuonc/noz126.198.
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Abstract BACKGROUND The PLP2 gene encodes for the Proteolipid protein 2 (PLP2) which is an integral ion channel membrane protein of the endoplasmic reticulum. The protein has been shown to be involved in several human cancers, but the importance of PLP2 in gliomas is poorly understood. In the present study, we therefore investigated the role of PLP2 in human glioma development. MATERIAL AND METHODS Immunohistochemistry was carried out for paraffin-embedded glioma samples, and changes in protein level were detected by western blot analysis. Small interfering RNA transfections were used for knockdown of specific genes. Cell viability and proliferation was then assessed by CCK-8 assay and EdU assay. Transmission electron microscopy was used to observe the ultrastructure of the cells and flow cytometry for the evaluation of apoptosis. Finally, U87 and U251 cells were treated with lentiviral transduction to obtain stably PLP2-knockdown cell lines, which were used for an in vivo study. RESULTS Data from publicly available datasets (Rembrandt, TCGA and CGGA) showed a correlation between up-regulation of PLP2 levels and increased malignancy. This was confirmed by IHC staining of sections from our own clinical glioma samples. Mechanistically, down-regulation of PLP2 in U87 and U251 glioma cell lines decreased the proliferation and increased apoptosis and autophagy, mediated by ER-stress. In PLP2 knockdown U87 and U251 cells, autophagy inhibition by chloroquine (CQ) augmented apoptotic cell death. Finally, orthotopic U87-shPLP2 and U251-shPLP2 intracranial xenograft models revealed that down-regulating of PLP2 inhibited glioma development in vivo. CONCLUSION In conclusion, the results indicate that PLP2 expression is related to glioma progression, and could be a potential target for future treatment strategies.
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Camera, Sylvain La, Claudine Balagué, Cornelia Göbel, Pierrette Geoffroy, Michel Legrand, Ivo Feussner, Dominique Roby, and Thierry Heitz. "The Arabidopsis Patatin-Like Protein 2 (PLP2) Plays an Essential Role in Cell Death Execution and Differentially Affects Biosynthesis of Oxylipins and Resistance to Pathogens." Molecular Plant-Microbe Interactions® 22, no. 4 (April 2009): 469–81. http://dx.doi.org/10.1094/mpmi-22-4-0469.
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We previously reported that patatin-like protein 2 (PLP2), a pathogen-induced patatin-like lipid acyl hydrolase, promotes cell death and negatively affects Arabidopsis resistance to the fungus Botrytis cinerea and to the bacteria Pseudomonas syringae. We show here that, on the contrary, PLP2 contributes to resistance to Cucumber mosaic virus, an obligate parasite inducing the hypersensitive response. These contrasted impacts on different pathosystems were also reflected by differential effects on defense gene induction. To examine a possible link between PLP2 lipolytic activity and oxylipin metabolism, gene expression profiling was performed and identified B. cinerea among these pathogens as the strongest inducer of most oxylipin biosynthetic genes. Quantitative oxylipin profiling in wild-type and PLP2-modified, Botrytis-challenged plants established the massive accumulation of oxidized fatty acid derivatives in infected leaves. Several compounds previously described as modulating plant tissue damage and issued from the α-dioxygenase pathway were found to accumulate in a PLP2-dependent manner. Finally, the contribution of PLP2 to genetically controlled cell death was evaluated using PLP2-silenced or -overexpressing plants crossed with the lesion mimic mutant vascular-associated death 1 (vad1). Phenotypic analysis of double-mutant progeny showed that PLP2 expression strongly promotes necrotic symptoms in vad1 leaves. Collectively, our data indicate that PLP2 is an integral component of the plant cell death execution machinery, possibly providing fatty acid precursors for the biosynthesis of specific oxylipins and differentially affecting resistance to pathogens with distinct lifestyles.
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Chen, Yi-Hsuan, Dueng-Yuan Hueng, and Wen-Chiuan Tsai. "Proteolipid Protein 2 Overexpression Indicates Aggressive Tumor Behavior and Adverse Prognosis in Human Gliomas." International Journal of Molecular Sciences 19, no. 11 (October 26, 2018): 3353. http://dx.doi.org/10.3390/ijms19113353.
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Proteolipid protein 2 (PLP2), a membrane protein of the endoplasmic reticulum, is related to tumor proliferation and metastasis in some human cancers, but not in gliomas. First, we performed western-blot analysis, real-time quantitative PCR and immunohistochemical stains to detect PLP2 expression in 4 glioma cell lines and human glioma tissues. In addition, we used small interfering RNA (SiPLP2) and short hairpin RNA (shPLP2) to knockdown PLP2 expression in GBM8401 and LN229 glioma cell lines. After then, the alteration of PLP2 suppressed glioma cells behavior were examined by cell proliferation, wound healing, cell invasion, and colonies formation assays. Finally, the possible mechanism of PLP2 was analyzed by detecting the expression of the proteins related to cell-cycle checkpoints, cell-proliferative signaling factors, and cell-matrix interaction. Compared with normal brain cell lysates and mRNA, all glioma cell lines displayed PLP2 protein and mRNA overexpression. Besides, higher PLP2 IHC staining significantly correlated with more advanced tumor grades and poorer prognosis in human gliomas. Both siPLP2 transfected gliomas showed a clear inhibition of glioma cell proliferation, migration, and invasion as well as down-regulating p-p38, p-ERK, MMP-2, and MMP-9 expression. In conclusion, we successfully demonstrated that PLP2 overexpression played an oncogenic role in glioma development and aggressive tumor behavior.
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Brösamle, Christian. "The myelin proteolipid DMalpha in fishes." Neuron Glia Biology 6, no. 2 (June 10, 2009): 109–12. http://dx.doi.org/10.1017/s1740925x09000131.
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Vertebrate myelin membranes are compacted and held in close apposition by three structural proteins of myelin, myelin basic protein, myelin protein zero (MPZ) and myelin proteolipid protein (PLP1/DMalpha). PLP1/DMalpha is considered to function as a scaffolding protein and play a role in intracellular trafficking in oligodendrocytes. In humans, point mutations, duplications or deletions of PLP1 are associated with Pelizaeus–Merzbacher disease and spastic paraplegia Type 2. PLP1 is highly conserved between mammals, but less so in lower vertebrates. This has led some researchers to question whether certain fish species express PLP1 orthologues at all, and to suggest that the function of PLP1/DMalpha in the central nervous system (CNS) may have been taken over by MPZ. Here, we review the evidence for the conservation of orthologues of PLP1/DMalpha in actinopterygian fishes and provide a comparison of currently available sequence data across 17 fish species. Our analysis demonstrates that orthologues of PLP1/DMalpha have been retained and are functionally expressed in many, if not all, extant species of bony fish. Many of the amino acids that, when mutated, are associated with severe CNS pathology are conserved in teleosts, demonstrating conservation of essential functions and justifying the development of novel disease models in species such as the zebrafish.
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Naim, Kurniati. "Perbandingan Sistem Proteksi Generator SWD Dengan Generator Mitsubishi Di Unit PLTD Tello." Jurnal Teknologi Elekterika 15, no. 2 (November 30, 2018): 53. http://dx.doi.org/10.31963/elekterika.v15i2.2016.
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Sistem proteksi banyak digunakan pada perangkat-perangkat kelistrikan. Sistem proteksi diharapkan dapat menjaga perangkat-perangkat dari gangguan-gangguan yang dapat mengakibatkan kesalahan kerja maupun kerusakan. PLTD Tello smenggunakan generator SWD dan generator Mitsubishi. Penelitian ini bertujuan untuk menganalisis spesifikasi rele proteksi yang digunakan pada generator SWD dan generator Mitsubishi di Unit PLTD Tello, menganalisis jenis gangguan yang sering terjadi pada sistem proteksi generator SWD dan generator Mitsubishi di PLTD Tello dan menganalisis perbandingan yang ada pada sistem proteksi generator SWD dengan generator Mitsubishi di Unit PLTD Tello.Metode penelitian yang dilakukan yaitu Data yang diperoleh akan diolah dan dianalisis. Adapun nilai yang didapatkan selama penelitian akan diolah secara matematis sesuai standar yang diperoleh dari rekomendasi sistem proteksi yang dikeluarkan oleh PT. PLN (Persero) PLTD Tello dan berlaku untuk waktu tersebut. Relay proteksi generator SWD PLTD Tello PT.PLN (Persero) terdiri dari 7 proteksi.Sedangkan pada Relay proteksi generator Mitsubishi PLTD Tello PT. PLN (Persero) terdiri dari 12 proteksi. Pada tahun 2015, terjadi gangguan pada generator Mitsubishi yang menyebabkan differensial relay bekerja. Pada tahun 2016, terjadi gangguan pada Generator SWD yang menyebabkan over voltage relay bekerja.
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Pavan, Nicola, Samarpit Rai, Nachiketh Soodana-Prakash, Raymond R. Balise, Maria Carmen Mir, Bruno Nahar, Chad Ritch, Dipen Parekh, and Mark L. Gonzalgo. "Impact of pelvic lymph node dissection during radical prostatectomy on 30-day post operative complications: Results from a large national database." Journal of Clinical Oncology 34, no. 2_suppl (January 10, 2016): 238. http://dx.doi.org/10.1200/jco.2016.34.2_suppl.238.
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238 Background: Pelvic lymph node dissection (PLND) during radical prostatectomy (RP) is the most effective method for detecting lymph node metastases in patients with prostate cancer. The association between PLND during RP and morbidity, especially thromboembolic adverse events (AEs), remains unclear. We assessed the effect of PLND on 30−day postoperative AEs in patients undergoing RP using the American College of Surgeons’ National Surgical Quality Improvement Program database (NSQIP). Methods: A total of 21,895 men undergoing RP between 2006 and 2013 were classified into two groups according to surgical approach (MIS−RP vs. ORP) and whether PLND was performed. Multivariate logistic regression adjusting for approach and demographic features was performed to assess the impact of PLND for predicting two primary endpoints (overall complications and major complications defined as Clavien−Dindo ≥ 3) and for 17 types of complications. P−values were adjusted to maintain an experiment−wise p < 0.05. Results: MIS−RP and ORP was performed in 17,354 (79.3%) and 4,541 (20.7%) patients, respectively. PLND was performed in 7,579 (43.7%) and 3,597 (79.2%) patients in the MIS−RP and ORP groups, respectively. The overall postoperative complication rate was 8.7% (5.5% for MIS−RP and 21.0% for ORP). PLND was not associated with a higher risk of DVT (OR 0.99; p= 0.98) or PE (OR 1.02; p= 0.91). However, PLND was associated with a higher risk of superficial surgical site infection (OR 1.68; p = 0.013), organ space surgical site infection (OR 1.77; p = 0.02), and perioperative transfusion (OR 1.32; p = 0.002) regardless of surgical approach. PLND was not associated with overall or major AEs on multivariable analysis. ORP was associated with a significantly higher risk of overall (OR 4.64, p < 0.0001) and major (OR 1.6, p = 0.0004) AEs compared to MIS−RP. Conclusions: PLND during RP is associated with a significantly increased risk of certain types of AEs within the 30−day post−operative period. However, there appears to be no significant association between PLND and thromboembolic AEs.
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Modi, Parth K., Megan Bock, Sinae Kim, Eric A. Singer, and Rahul Parikh. "Utilization of pelvic lymph node dissection for low-risk prostate cancer." Journal of Clinical Oncology 35, no. 6_suppl (February 20, 2017): 86. http://dx.doi.org/10.1200/jco.2017.35.6_suppl.86.
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86 Background: National guidelines suggest against pelvic lymph node dissection (PLND) for patients with low-risk prostate cancer (PCa). However, the actuarial rate of PLND in this population is unknown. This study aimed to characterize the use of PLND in contemporary cohort of men with low-risk PCa undergoing robotic assisted radical prostatectomy (RARP). Methods: The National Cancer Database was queried for PCa patients who underwent RARP from 2010 to 2013. Patients who underwent PLND were identified and patient clinicodemographic and hospital characteristics were abstracted. The primary outcome measure was receipt of PLND. Secondary outcome measures included number of lymph nodes evaluated and number of lymph nodes positive for cancer. Unadjusted and multivariate regression analyses were conducted to identify predictors of receipt of PLND. Analysis of clustered data was employed to account for hospital-level correlation in utilization. Results: Of 51,971 patients with low-risk PCa who underwent RARP, 19,059 (36.7%) received PLND. Lymph node positivity was identified in 0.4% of low-risk patients and 4.6% of intermediate/high risk patients. Predictors of PLND in low-risk patients included rural residence (OR 1.157), treatment at academic institutions (OR 1.492) or high-volume (OR 1.327) facilities. Mean number of lymph nodes obtained in low-risk patients was lower than in intermediate- or high-risk patients (4.74 vs 5.86, P < 0.0001). In multivariate analysis, black race was associated with significantly fewer lymph nodes retrieved. Intermediate or high risk PCa; rural residence; and treatment at an academic, high-volume, or West region facility were independently associated with a higher yield of retrieved lymph nodes. Conclusions: PLND is performed for greater than one-third of low-risk PCa patients undergoing RARP in this large hospital-based data set. Our study demonstrated a low likelihood (0.4%) of detecting nodal metastasis in this population, thus validating the national recommendations against PLND. Rural residence and treatment at high-volume and academic centers are associated with receipt of PLND. Reasons for the variation in practice patterns should be investigated to improve the quality of PCa care.
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Gil, Heidi, Stephani Shivers, Bob Savage, Geri Taylor, Jim Taylor, Erica DeFrancesco, Maria O’Connell, and Michael Lepore. "Empowering Partnerships Among Researchers, Persons Living With Dementia, and Caregivers." Innovation in Aging 4, Supplement_1 (December 1, 2020): 729. http://dx.doi.org/10.1093/geroni/igaa057.2587.
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Abstract Conducting research collaboratively with persons living with dementia (PLWD) requires preparation. To enhance the capacity of PLWD to be engaged in research, we collaboratively developed and deployed a replicable two-day training workshop for PLWD, care partners, and professional/academic researchers. An assessment of strengths, values and experiences, and an introductory education session, served as experiential warmup activities for PLWD prior to the two-day workshop. Twelve PLWD, nine care partners, and 14 professional/academic researchers participated in the workshop. Participants identified 16 topics as highly important for research and prioritized four topics for immediate study design. Studies addressing these topics were collaboratively designed by PLWD, care partners, and professional researchers during day two of the workshop. Lessons learned from the workshop, including key preparation steps for collaboration—such as securing minimally distracting collaboration environments—are summarized, and access to a free toolkit that supports workshop replication is provided.
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Sorbera, L. A., J. Castañer, and J. Bozzo. "PLD-118." Drugs of the Future 27, no. 11 (2002): 1049. http://dx.doi.org/10.1358/dof.2002.027.11.707984.
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MICHAELSEN, ANDREW R., JOSEPH G. SEBRANEK, and JAMES S. DICKSON. "Effects of Microbial Inhibitors and Modified Atmosphere Packaging on Growth of Listeria monocytogenes and Salmonella enterica Typhimurium and on Quality Attributes of Injected Pork Chops and Sliced Cured Ham." Journal of Food Protection 69, no. 11 (November 1, 2006): 2671–80. http://dx.doi.org/10.4315/0362-028x-69.11.2671.
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This study was designed to determine the inhibitory effects of modified atmosphere packaging (MAP), both alone and in combination with potassium lactate and sodium diacetate (PLSD), on selected pathogens common to pork products. Effects of the treatments on product quality also were assessed. The hypothesis was that high-CO2 MAP would increase the effectiveness of PLSD for inhibition of pork pathogens. Fresh chops from untreated pork loins and loins that were injected with PLSD were inoculated with Salmonella enterica Typhimurium, and slices of untreated hams and hams that were injected with PLSD were inoculated with Listeria monocytogenes. The samples were subjected to vacuum packaging (VP) or MAP with high concentrations (99.5 to 100%) of CO2. Pathogens were enumerated periodically during storage at 4 and 10°C. Storage of pork chops at 4°C slowed the growth of Salmonella Typhimurium, and there was little difference in pathogen numbers between VP and MAP samples. L. monocytogenes growth on ham slices at 4°C was inhibited for up to 28 days by all of the treatments, but after 28 days, the VP-PLSD treatment had a greater inhibitory effect than did the other treatments. At 10°C, the PLSD and MAP treatments each effectively inhibited the growth of the pathogens on pork chops and ham slices when compared with controls (VP). However, the results obtained with MAP plus PLSD at 10°C were not different from those obtained with either MAP or PLSD alone. Therefore, the hypothesis was not supported; the high-CO2 atmosphere of the MAP did not increase the effectiveness of PLSD for inhibition of pathogens.
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Lynch, Kevin, Yinin Hu, Norma Farrow, Yun Song, Max Meneveau, Minyoung Kwak, Michael C. Lowe, et al. "Isolated same-basin lymph node recurrence after precision lymph node excision for clinically evident melanoma metastasis." Journal of Clinical Oncology 39, no. 15_suppl (May 20, 2021): 9576. http://dx.doi.org/10.1200/jco.2021.39.15_suppl.9576.
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9576 Background: While management of the nodal basin for melanoma has largely moved to observation for microscopic sentinel lymph node (SLN) metastasis, complete lymph node dissection (CLND) remains the current standard of care for melanoma patients with macroscopic, clinically detectable lymph node metastases (cLN). As CLND is associated with high surgical morbidity, we sought to study whether cLN may be safely managed by excision of only clinically abnormal nodes (precision lymph node dissection, PLND). Currently, a small subset of patients with cLN do not undergo CLND because of frailty or patient preference. We hypothesized that in these selected patients, PLND would provide acceptable regional control rates. Methods: Retrospective chart review was conducted at four academic tertiary care hospitals to identify melanoma patients who underwent PLND for cLN. cLN were defined as palpable or radiographically abnormal nodes. Recurrences were categorized as local/in-transit, same-basin lymph node, or distal lymph node/visceral. The primary outcome was isolated same-basin recurrence after PLND. Results: Twenty-one patients underwent PLND for cLN without synchronous distant metastases (characteristics of primary lesions summarized in Table). Reasons for forgoing CLND included patient preference (n=8), imaging indeterminate for distant metastases (n=2), comorbidities (n=4), loss to follow up (n=1), partial response to checkpoint blockade (n=1), or not reported (n=5). The inguinal node basin was the most common site (n=10), followed by the axillary (n=8) and cervical basins (n=3). A median of 2 nodes were resected at PLND, and 68% of resected nodes were positive for melanoma (median: 1, range: 1-3 nodes). Median follow-up was 23 months from PLND, and recurrence was observed in 28.6% of patients overall. Only 1 patient (4.8%) developed an isolated same-basin recurrence. The 3-year cumulative incidence of isolated same-basin recurrence was 5.3%, while risk of isolated local/in-transit recurrence or distant basin/visceral metastasis were 19.8% and 33.3%, respectively. Complications from PLND were reported in 1 patient (4.8%) and were limited to post-operative seroma and lymphedema. Conclusions: These pilot data suggest that PLND may offer acceptable regional disease control for cLN. Post-operative morbidity from PLND was also low, raising the possibility that PLND may provide adequate regional disease control without the morbidity associated with CLND. These data justify additional, prospective evaluation of PLND in selected patients.[Table: see text]