Science.gov

Sample records for administrative code nac

  1. Epigenetics gets sweeter: O-GlcNAc joins the "histone code".

    PubMed

    Hanover, John A

    2010-12-22

    O-GlcNAcylation has now been added to the growing list of histone modifications making up the multifaceted "histone-code" (Sakabe et al., 2010). The sites of O-GlcNAc-histone modification hint at a role in chromatin remodeling, thus adding to mounting evidence that O-GlcNAc cycling sits atop a robust regulatory network maintaining higher-order chromatin structure and epigenetic memory.

  2. Tribal Green Building Administrative Code Example

    EPA Pesticide Factsheets

    This Tribal Green Building Administrative Code Example can be used as a template for technical code selection (i.e., building, electrical, plumbing, etc.) to be adopted as a comprehensive building code.

  3. 47 CFR 52.15 - Central office code administration.

    Code of Federal Regulations, 2010 CFR

    2010-10-01

    ... 47 Telecommunication 3 2010-10-01 2010-10-01 false Central office code administration. 52.15... (CONTINUED) NUMBERING Administration § 52.15 Central office code administration. (a) Central Office Code.... (b) Duties of the entity or entities performing central office code administration may include,...

  4. Energy Efficiency Program Administrators and Building Energy Codes

    EPA Pesticide Factsheets

    This brief explores how energy efficiency program administrators have helped advance building energy codes at federal, state, and local levels—using technical, institutional, financial, and other resources—and discusses potential next steps.

  5. The validity of ICD codes coupled with imaging procedure codes for identifying acute venous thromboembolism using administrative data.

    PubMed

    Alotaibi, Ghazi S; Wu, Cynthia; Senthilselvan, Ambikaipakan; McMurtry, M Sean

    2015-08-01

    The purpose of this study was to evaluate the accuracy of using a combination of International Classification of Diseases (ICD) diagnostic codes and imaging procedure codes for identifying deep vein thrombosis (DVT) and pulmonary embolism (PE) within administrative databases. Information from the Alberta Health (AH) inpatients and ambulatory care administrative databases in Alberta, Canada was obtained for subjects with a documented imaging study result performed at a large teaching hospital in Alberta to exclude venous thromboembolism (VTE) between 2000 and 2010. In 1361 randomly-selected patients, the proportion of patients correctly classified by AH administrative data, using both ICD diagnostic codes and procedure codes, was determined for DVT and PE using diagnoses documented in patient charts as the gold standard. Of the 1361 patients, 712 had suspected PE and 649 had suspected DVT. The sensitivities for identifying patients with PE or DVT using administrative data were 74.83% (95% confidence interval [CI]: 67.01-81.62) and 75.24% (95% CI: 65.86-83.14), respectively. The specificities for PE or DVT were 91.86% (95% CI: 89.29-93.98) and 95.77% (95% CI: 93.72-97.30), respectively. In conclusion, when coupled with relevant imaging codes, VTE diagnostic codes obtained from administrative data provide a relatively sensitive and very specific method to ascertain acute VTE.

  6. 77 FR 18716 - Transportation Security Administration Postal Zip Code Change; Technical Amendment

    Federal Register 2010, 2011, 2012, 2013, 2014

    2012-03-28

    ... Postal Zip Code Change; Technical Amendment AGENCY: Transportation Security Administration, DHS. ACTION... zip code. This rule revises existing regulations to reflect organizational changes and it has no.... Background Beginning December 17, 2008, the postal zip codes for TSA headquarters facilities in Virginia...

  7. 75 FR 56654 - RTCA NextGen Advisory Committee (NAC)

    Federal Register 2010, 2011, 2012, 2013, 2014

    2010-09-16

    ... Federal Aviation Administration RTCA NextGen Advisory Committee (NAC) AGENCY: Federal Aviation Administration (FAA), DOT. ACTION: Notice of RTCA NextGen Advisory Committee (NAC) SUMMARY: The FAA published a... public of a meeting of RTCA NextGen Advisory Committee. The Agenda in that notice has been revised....

  8. 75 FR 54221 - RTCA NextGen Advisory Committee (NAC)

    Federal Register 2010, 2011, 2012, 2013, 2014

    2010-09-03

    ...] [FR Doc No: 2010-22098] DEPARTMENT OF TRANSPORTATION Federal Aviation Administration RTCA NextGen Advisory Committee (NAC) AGENCY: Federal Aviation Administration (FAA), DOT. ACTION: Notice of RTCA NextGen... NextGen Advisory Committee (NAC). DATES: The meeting will be held September 23, 2010, from 8:30 a.m....

  9. 18 CFR 410.1 - Basin regulations-Water Code and Administrative Manual-Part III Water Quality Regulations.

    Code of Federal Regulations, 2012 CFR

    2012-04-01

    ... Code and Administrative Manual-Part III Water Quality Regulations. 410.1 Section 410.1 Conservation of... CODE AND ADMINISTRATIVE MANUAL-PART III WATER QUALITY REGULATIONS § 410.1 Basin regulations—Water Code and Administrative Manual—Part III Water Quality Regulations. (a) The Water Code of the Delaware...

  10. 18 CFR 410.1 - Basin regulations-Water Code and Administrative Manual-Part III Water Quality Regulations.

    Code of Federal Regulations, 2011 CFR

    2011-04-01

    ... Code and Administrative Manual-Part III Water Quality Regulations. 410.1 Section 410.1 Conservation of... CODE AND ADMINISTRATIVE MANUAL-PART III WATER QUALITY REGULATIONS § 410.1 Basin regulations—Water Code and Administrative Manual—Part III Water Quality Regulations. (a) The Water Code of the Delaware...

  11. 18 CFR 410.1 - Basin regulations-Water Code and Administrative Manual-Part III Water Quality Regulations.

    Code of Federal Regulations, 2013 CFR

    2013-04-01

    ... Code and Administrative Manual-Part III Water Quality Regulations. 410.1 Section 410.1 Conservation of... CODE AND ADMINISTRATIVE MANUAL-PART III WATER QUALITY REGULATIONS § 410.1 Basin regulations—Water Code and Administrative Manual—Part III Water Quality Regulations. (a) The Water Code of the Delaware...

  12. 18 CFR 410.1 - Basin regulations-Water Code and Administrative Manual-Part III Water Quality Regulations.

    Code of Federal Regulations, 2014 CFR

    2014-04-01

    ... Code and Administrative Manual-Part III Water Quality Regulations. 410.1 Section 410.1 Conservation of... CODE AND ADMINISTRATIVE MANUAL-PART III WATER QUALITY REGULATIONS § 410.1 Basin regulations—Water Code and Administrative Manual—Part III Water Quality Regulations. (a) The Water Code of the Delaware...

  13. 18 CFR 410.1 - Basin regulations-Water Code and Administrative Manual-Part III Water Quality Regulations.

    Code of Federal Regulations, 2010 CFR

    2010-04-01

    ... Code and Administrative Manual-Part III Water Quality Regulations. 410.1 Section 410.1 Conservation of... CODE AND ADMINISTRATIVE MANUAL-PART III WATER QUALITY REGULATIONS § 410.1 Basin regulations—Water Code and Administrative Manual—Part III Water Quality Regulations. (a) The Water Code of the Delaware...

  14. 76 FR 22162 - Third Meeting RTCA NextGen Advisory Committee (NAC)

    Federal Register 2010, 2011, 2012, 2013, 2014

    2011-04-20

    ... Federal Aviation Administration Third Meeting RTCA NextGen Advisory Committee (NAC) AGENCY: Federal Aviation Administration (FAA), DOT. ACTION: RTCA NextGen Advisory Committee (NAC). SUMMARY: The FAA is issuing this notice to advise the public of a meeting of RTCA NextGen Advisory Committee (NAC). DATES:...

  15. 76 FR 54526 - Fourth Meeting RTCA NextGen Advisory Committee (NAC)

    Federal Register 2010, 2011, 2012, 2013, 2014

    2011-09-01

    ... Federal Aviation Administration Fourth Meeting RTCA NextGen Advisory Committee (NAC) AGENCY: Federal Aviation Administration (FAA), DOT. ACTION: RTCA NextGen Advisory Committee (NAC). SUMMARY: The FAA is issuing this notice to advise the public of a meeting of RTCA NextGen Advisory Committee (NAC). DATES:...

  16. 76 FR 3931 - Second Meeting RTCA NextGen Advisory Committee (NAC)

    Federal Register 2010, 2011, 2012, 2013, 2014

    2011-01-21

    ... Federal Aviation Administration Second Meeting RTCA NextGen Advisory Committee (NAC) AGENCY: Federal Aviation Administration (FAA), DOT. ACTION: RTCA NextGen Advisory Committee (NAC). SUMMARY: The FAA is issuing this notice to advise the public of a meeting of RTCA NextGen Advisory Committee (NAC). DATES:...

  17. Special Education Needs: The Code of Practice and Local Administration in Northern Ireland and Britain.

    ERIC Educational Resources Information Center

    Getty, David; Gray, Marie Ann

    2001-01-01

    Study of the impact of The Code of Practice for Children with Special Education Needs on the governance and administration of local schools in Northern Ireland and Britain. Suggests methods and topics for future research. (Contains 44 references.)

  18. Nurses' attitudes toward the use of the bar-coding medication administration system.

    PubMed

    Marini, Sana Daya; Hasman, Arie; Huijer, Huda Abu-Saad; Dimassi, Hani

    2010-01-01

    This study determines nurses' attitudes toward bar-coding medication administration system use. Some of the factors underlying the successful use of bar-coding medication administration systems that are viewed as a connotative indicator of users' attitudes were used to gather data that describe the attitudinal basis for system adoption and use decisions in terms of subjective satisfaction. Only 67 nurses in the United States had the chance to respond to the e-questionnaire posted on the CARING list server for the months of June and July 2007. Participants rated their satisfaction with bar-coding medication administration system use based on system functionality, usability, and its positive/negative impact on the nursing practice. Results showed, to some extent, positive attitude, but the image profile draws attention to nurses' concerns for improving certain system characteristics. The high bar-coding medication administration system skills revealed a more negative perception of the system by the nursing staff. The reasons underlying dissatisfaction with bar-coding medication administration use by skillful users are an important source of knowledge that can be helpful for system development as well as system deployment. As a result, strengthening bar-coding medication administration system usability by magnifying its ability to eliminate medication errors and the contributing factors, maximizing system functionality by ascertaining its power as an extra eye in the medication administration process, and impacting the clinical nursing practice positively by being helpful to nurses, speeding up the medication administration process, and being user-friendly can offer a congenial settings for establishing positive attitude toward system use, which in turn leads to successful bar-coding medication administration system use.

  19. Implementing a bar-coded bedside medication administration system.

    PubMed

    Yates, Cindy

    2007-01-01

    Hospitals across the nation are struggling with implementing electronic medication administration and reporting (eMAR) systems as part of patient safety programs. St Luke's Hospital in Chesterfield, Mo, initiated their eMAR initiative in June 2003, initiating program start-up in September 2004. This case study documents how the project was approached, its overall success, and what was learned along the way. Also included is a recent update highlighting the expansion of St Luke's patient safety initiative, adapting eMAR to two specialty units: dialysis and laboratory processes.

  20. Stroke Code Improves Intravenous Thrombolysis Administration in Acute Ischemic Stroke

    PubMed Central

    Chen, Chih-Hao; Tang, Sung-Chun; Tsai, Li-Kai; Hsieh, Ming-Ju; Yeh, Shin-Joe; Huang, Kuang-Yu; Jeng, Jiann-Shing

    2014-01-01

    Background and Purpose Timely intravenous (IV) thrombolysis for acute ischemic stroke is associated with better clinical outcomes. Acute stroke care implemented with “Stroke Code” (SC) may increase IV tissue plasminogen activator (tPA) administration. The present study aimed to investigate the impact of SC on thrombolysis. Methods The study period was divided into the “pre-SC era” (January 2006 to July 2010) and “SC era” (August 2010 to July 2013). Demographics, critical times (stroke symptom onset, presentation to the emergency department, neuroimaging, thrombolysis), stroke severity, and clinical outcomes were recorded and compared between the two eras. Results During the study period, 5957 patients with acute ischemic stroke were admitted; of these, 1301 (21.8%) arrived at the emergency department within 3 h of stroke onset and 307 (5.2%) received IV-tPA. The number and frequency of IV-tPA treatments for patients with an onset-to-door time of <3 h increased from the pre-SC era (n = 91, 13.9%) to the SC era (n = 216, 33.3%) (P<0.001). SC also improved the efficiency of IV-tPA administration; the median door-to-needle time decreased (88 to 51 min, P<0.001) and the percentage of door-to-needle times ≤60 min increased (14.3% to 71.3%, P<0.001). The SC era group tended to have more patients with good outcome (modified Rankin Scale ≤2) at discharge (49.5 vs. 39.6%, P = 0.11), with no difference in symptomatic hemorrhage events or in-hospital mortality. Conclusion The SC protocol increases the percentage of acute ischemic stroke patients receiving IV-tPA and decreases door-to-needle time. PMID:25111200

  1. Results from the Veterans Health Administration ICD-10-CM/PCS Coding Pilot Study.

    PubMed

    Weems, Shelley; Heller, Pamela; Fenton, Susan H

    2015-01-01

    The Veterans Health Administration (VHA) of the US Department of Veterans Affairs has been preparing for the October 1, 2015, conversion to the International Classification of Diseases, Tenth Revision, Clinical Modification and Procedural Coding System (ICD-10-CM/PCS) for more than four years. The VHA's Office of Informatics and Analytics ICD-10 Program Management Office established an ICD-10 Learning Lab to explore expected operational challenges. This study was conducted to determine the effects of the classification system conversion on coding productivity. ICD codes are integral to VHA business processes and are used for purposes such as clinical studies, performance measurement, workload capture, cost determination, Veterans Equitable Resource Allocation (VERA) determination, morbidity and mortality classification, indexing of hospital records by disease and operations, data storage and retrieval, research purposes, and reimbursement. The data collection for this study occurred in multiple VHA sites across several months using standardized methods. It is commonly accepted that coding productivity will decrease with the implementation of ICD-10-CM/PCS. The findings of this study suggest that the decrease will be more significant for inpatient coding productivity (64.5 percent productivity decrease) than for ambulatory care coding productivity (6.7 percent productivity decrease). This study reveals the following important points regarding ICD-10-CM/PCS coding productivity: 1. Ambulatory care ICD-10-CM coding productivity is not expected to decrease as significantly as inpatient ICD-10-CM/PCS coding productivity. 2. Coder training and type of record (inpatient versus outpatient) affect coding productivity. 3. Inpatient coding productivity is decreased when a procedure requiring ICD-10-PCS coding is present. It is highly recommended that organizations perform their own analyses to determine the effects of ICD-10-CM/PCS implementation on coding productivity.

  2. The National Astronomy Consortium (NAC)

    NASA Astrophysics Data System (ADS)

    Von Schill, Lyndele; Ivory, Joyce

    2017-01-01

    The National Astronomy Consortium (NAC) program is designed to increase the number of underrepresented minority students into STEM and STEM careers by providing unique summer research experiences followed by long-term mentoring and cohort support. Hallmarks of the NAC program include: research or internship opportunities at one of the NAC partner sites, a framework to continue research over the academic year, peer and faculty mentoring, monthly virtual hangouts, and much more. NAC students also participate in two professional travel opportunities each year: the annual NAC conference at Howard University and poster presentation at the annual AAS winter meeting following their summer internship.The National Astronomy Consortium (NAC) is a program led by the National Radio Astronomy Consortium (NRAO) and Associated Universities, Inc. (AUI), in partnership with the National Society of Black Physicist (NSBP), along with a number of minority and majority universities.

  3. Patient safety with blood products administration using wireless and bar-code technology.

    PubMed

    Porcella, Aleta; Walker, Kristy

    2005-01-01

    Supported by a grant from the Agency for Healthcare Research and Quality, a University of Iowa Hospitals and Clinics interdisciplinary research team created an online data-capture-response tool utilizing wireless mobile devices and bar code technology to track and improve blood products administration process. The tool captures 1) sample collection, 2) sample arrival in the blood bank, 3) blood product dispense from blood bank, and 4) administration. At each step, the scanned patient wristband ID bar code is automatically compared to scanned identification barcode on requisition, sample, and/or product, and the system presents either a confirmation or an error message to the user. Following an eight-month, 5 unit, staged pilot, a 'big bang,' hospital-wide implementation occurred on February 7, 2005. Preliminary results from pilot data indicate that the new barcode process captures errors 3 to 10 times better than the old manual process.

  4. Banana NAC transcription factor MusaNAC042 is positively associated with drought and salinity tolerance.

    PubMed

    Tak, Himanshu; Negi, Sanjana; Ganapathi, T R

    2017-03-01

    Banana is an important fruit crop and its yield is hampered by multiple abiotic stress conditions encountered during its growth. The NAC (NAM, ATAF, and CUC) transcription factors are involved in plant response to biotic and abiotic stresses. In the present study, we studied the induction of banana NAC042 transcription factor in drought and high salinity conditions and its overexpression in transgenic banana to improve drought and salinity tolerance. MusaNAC042 expression was positively associated with stress conditions like salinity and drought and it encoded a nuclear localized protein. Transgenic lines of banana cultivar Rasthali overexpressing MusaNAC042 were generated by Agrobacterium-mediated transformation of banana embryogenic cells and T-DNA insertion was confirmed by PCR and Southern blot analysis. Our results using leaf disc assay indicated that transgenic banana lines were able to tolerate drought and high salinity stress better than the control plants and retained higher level of total chlorophyll and lower level of MDA content (malondialdehyde). Transgenic lines analyzed for salinity (250 mM NaCl) and drought (Soil gravimetric water content 0.15) tolerance showed higher proline content, better Fv/Fm ratio, and lower levels of MDA content than control suggesting that MusaNAC042 may be involved in responses to higher salinity and drought stresses in banana. Expression of several abiotic stress-related genes like those coding for CBF/DREB, LEA, and WRKY factors was altered in transgenic lines indicating that MusaNAC042 is an efficient modulator of abiotic stress response in banana.

  5. Challenges implementing bar-coded medication administration in the emergency room in comparison to medical surgical units.

    PubMed

    Glover, Nancy

    2013-03-01

    Bar-coded medication administration has been successfully implemented and utilized to decrease medication errors at a number of hospitals in recent years. The purpose of this article was to discuss the varying success in utilization of bar-coded medication administration on medical-surgical units and in the emergency department. Utilization reports were analyzed to better understand the challenges between the units. Many factors negatively impacted utilization in the emergency department, including the inability to use bar-coded medication administration for verbal orders or to document medications distributed by the prescribing providers, unique aspects of emergency department nursing workflow, additional steps to chart when using bar-coded medication administration, and alert fatigue. Hardware problems affected all users. Bar-coded medication administration in its current form is more suitable for use on medical-surgical floors than in the emergency department. New solutions should be developed for bar-coded medication administration in the emergency department, keeping in mind requirements to chart medications when there is no order in the system, document medications distributed by prescribing providers, adapt to unpredictable nursing workflow, minimize steps to chart with bar-coded medication administration, limit alerts to those that are clinically meaningful, and choose reliable hardware with adequate bar-code scanning capability.

  6. 78 FR 54509 - Tenth Meeting: RTCA Next Gen Advisory Committee (NAC)

    Federal Register 2010, 2011, 2012, 2013, 2014

    2013-09-04

    ... Federal Aviation Administration Tenth Meeting: RTCA Next Gen Advisory Committee (NAC) AGENCY: Federal Aviation Administration (FAA), U.S. Department of Transportation (DOT). ACTION: Notice of RTCA NextGen... of the RTCA NextGen Advisory Committee (NAC). DATES: The meeting will be held September 19, 2013...

  7. 78 FR 5860 - Eighth Meeting: RTCA Next Gen Advisory Committee (NAC)

    Federal Register 2010, 2011, 2012, 2013, 2014

    2013-01-28

    ... Federal Aviation Administration Eighth Meeting: RTCA Next Gen Advisory Committee (NAC) AGENCY: Federal Aviation Administration (FAA), U.S. Department of Transportation (DOT). ACTION: Notice of RTCA NextGen... meeting of the RTCA NextGen Advisory Committee (NAC). DATES: The meeting will be held February 7,...

  8. 78 FR 28940 - Ninth Meeting: RTCA Next Gen Advisory Committee (NAC)

    Federal Register 2010, 2011, 2012, 2013, 2014

    2013-05-16

    ... Federal Aviation Administration Ninth Meeting: RTCA Next Gen Advisory Committee (NAC) AGENCY: Federal Aviation Administration (FAA), U.S. Department of Transportation (DOT). ACTION: Notice of RTCA NextGen... of the RTCA NextGen Advisory Committee (NAC). DATES: The meeting will be held June 4, 2013 from...

  9. Analysis of the technology acceptance model in examining hospital nurses' behavioral intentions toward the use of bar code medication administration.

    PubMed

    Song, Lunar; Park, Byeonghwa; Oh, Kyeung Mi

    2015-04-01

    Serious medication errors continue to exist in hospitals, even though there is technology that could potentially eliminate them such as bar code medication administration. Little is known about the degree to which the culture of patient safety is associated with behavioral intention to use bar code medication administration. Based on the Technology Acceptance Model, this study evaluated the relationships among patient safety culture and perceived usefulness and perceived ease of use, and behavioral intention to use bar code medication administration technology among nurses in hospitals. Cross-sectional surveys with a convenience sample of 163 nurses using bar code medication administration were conducted. Feedback and communication about errors had a positive impact in predicting perceived usefulness (β=.26, P<.01) and perceived ease of use (β=.22, P<.05). In a multiple regression model predicting for behavioral intention, age had a negative impact (β=-.17, P<.05); however, teamwork within hospital units (β=.20, P<.05) and perceived usefulness (β=.35, P<.01) both had a positive impact on behavioral intention. The overall bar code medication administration behavioral intention model explained 24% (P<.001) of the variance. Identified factors influencing bar code medication administration behavioral intention can help inform hospitals to develop tailored interventions for RNs to reduce medication administration errors and increase patient safety by using this technology.

  10. Indications for spine surgery: validation of an administrative coding algorithm to classify degenerative diagnoses

    PubMed Central

    Lurie, Jon D.; Tosteson, Anna N.A.; Deyo, Richard A.; Tosteson, Tor; Weinstein, James; Mirza, Sohail K.

    2014-01-01

    Study Design Retrospective analysis of Medicare claims linked to a multi-center clinical trial. Objective The Spine Patient Outcomes Research Trial (SPORT) provided a unique opportunity to examine the validity of a claims-based algorithm for grouping patients by surgical indication. SPORT enrolled patients for lumbar disc herniation, spinal stenosis, and degenerative spondylolisthesis. We compared the surgical indication derived from Medicare claims to that provided by SPORT surgeons, the “gold standard”. Summary of Background Data Administrative data are frequently used to report procedure rates, surgical safety outcomes, and costs in the management of spinal surgery. However, the accuracy of using diagnosis codes to classify patients by surgical indication has not been examined. Methods Medicare claims were link to beneficiaries enrolled in SPORT. The sensitivity and specificity of three claims-based approaches to group patients based on surgical indications were examined: 1) using the first listed diagnosis; 2) using all diagnoses independently; and 3) using a diagnosis hierarchy based on the support for fusion surgery. Results Medicare claims were obtained from 376 SPORT participants, including 21 with disc herniation, 183 with spinal stenosis, and 172 with degenerative spondylolisthesis. The hierarchical coding algorithm was the most accurate approach for classifying patients by surgical indication, with sensitivities of 76.2%, 88.1%, and 84.3% for disc herniation, spinal stenosis, and degenerative spondylolisthesis cohorts, respectively. The specificity was 98.3% for disc herniation, 83.2% for spinal stenosis, and 90.7% for degenerative spondylolisthesis. Misclassifications were primarily due to codes attributing more complex pathology to the case. Conclusion Standardized approaches for using claims data to accurately group patients by surgical indications has widespread interest. We found that a hierarchical coding approach correctly classified over 90

  11. [Identification and analysis of the NAC transcription factor family in Triticum urartu].

    PubMed

    Jianhui, Ma; Doudou, Tong; Wenli, Zhang; Daijing, Zhang; Yun, Shao; Yun, Yang; Lina, Jiang

    2016-03-01

    NAC transcription factors are one of plant-specific gene families with diverse functions, and they regulate plant development, organ formation and stress responses. Currently, the researches about NAC transcription factors mainly focus on model plants, Arabidopsis and rice, whereas such studies are hardly reported in wheat and other plants. In this study, the full-length coding sequences (CDS) of NAC transcription factors from Triticum urartu (TuNAC) were identified through bioinformatic analysis. Their biological function, evolutionary relationship, gene duplication and chromosomal locations were further predicted and analyzed. The quantitative real-time PCR (qRT-PCR) assay was used to verify the expression pattern of abiotic-related TuNAC transcription factors. A total of 87 TuNAC transcription factors with full-length CDS were identified, which were divided into seven subgroups through phylogenetic analysis. Thirty-nine TuNAC transcription factors were located on seven chromosomes, and five pairs of TuNAC transcription factors were duplicated. The expression of four TuNAC transcription factors was consistently increased under diverse abiotic stress by qRT-PCR assay. Our study thus provides basis for further functional investigations of TuNAC transcription factors.

  12. Kombucha brewing under the Food and Drug Administration model Food Code: risk analysis and processing guidance.

    PubMed

    Nummer, Brian A

    2013-11-01

    Kombucha is a fermented beverage made from brewed tea and sugar. The taste is slightly sweet and acidic and it may have residual carbon dioxide. Kombucha is consumed in many countries as a health beverage and it is gaining in popularity in the U.S. Consequently, many retailers and food service operators are seeking to brew this beverage on site. As a fermented beverage, kombucha would be categorized in the Food and Drug Administration model Food Code as a specialized process and would require a variance with submission of a food safety plan. This special report was created to assist both operators and regulators in preparing or reviewing a kombucha food safety plan.

  13. Validation of ICD-9 Code 787.2 for identification of individuals with dysphagia from administrative databases.

    PubMed

    González-Fernández, Marlís; Gardyn, Michael; Wyckoff, Shamolie; Ky, Paul K S; Palmer, Jeffrey B

    2009-12-01

    The aim of this study was to determine the accuracy of dysphagia coding using the International Classification of Diseases version 9 (ICD-9) code 787.2. We used the administrative database of a tertiary hospital and sequential videofluorographic swallowing study (VFSS) reports for patients admitted to the same hospital from January to June 2007. The VFSS reports were abstracted and the hospital's database was queried to abstract the coding associated with the admission during which the VFSS was performed. The VFSS and administrative data were merged for data analysis. Dysphagia was coded (using code 787.2) in 36 of 168 cases that had a VFSS. Of these, 34 had dysphagia diagnosed by VFSS (our gold standard) and one had a prior history of dysphagia. Code 787.2 had sensitivity of 22.8, specificity of 89.5, and positive and negative predictive values of 94.4 and 12.9, respectively. Dysphagia was largely undercoded in this database, but when the code was present those individuals were very likely to be dysphagic. Selection of dysphagic cases using the ICD-9 code is appropriate for within-group comparisons. Absence of the code, however, is not a good predictor of the absence of dysphagia.

  14. 77 FR 54648 - Seventh Meeting: RTCA NextGen Advisory Committee (NAC)

    Federal Register 2010, 2011, 2012, 2013, 2014

    2012-09-05

    ... Meeting: RTCA NextGen Advisory Committee (NAC) AGENCY: Federal Aviation Administration (FAA), U.S. Department of Transportation (DOT). ACTION: Meeting Notice of RTCA NextGen Advisory Committee (NAC). SUMMARY: The FAA is issuing this notice to advise the public of the seventh meeting of the RTCA...

  15. NAC Off-Vehicle Brake Testing Project

    DTIC Science & Technology

    2007-05-01

    Supporting the Objective Force – NAC Off-vehicle Brake Testing Project -Version: 01 May 2007 FinalR1 UNCLAS: Dist A. Approved for public release NAC ...Project Officer (TIPO) US Army National Automotive Center ( NAC ) Warren, MI Report Documentation Page Form ApprovedOMB No. 0704-0188 Public reporting burden... NAC Off-vehicle Brake Testing Project 5a. CONTRACT NUMBER 5b. GRANT NUMBER 5c. PROGRAM ELEMENT NUMBER 6. AUTHOR(S) Miller, Leo 5d. PROJECT NUMBER

  16. Modeling nurses' acceptance of bar coded medication administration technology at a pediatric hospital

    PubMed Central

    Brown, Roger L; Scanlon, Matthew C; Karsh, Ben-Tzion

    2012-01-01

    Objective To identify predictors of nurses' acceptance of bar coded medication administration (BCMA). Design Cross-sectional survey of registered nurses (N=83) at an academic pediatric hospital that recently implemented BCMA. Methods Surveys assessed seven BCMA-related perceptions: ease of use; usefulness for the job; social influence from non-specific others to use BCMA; training; technical support; usefulness for patient care; and social influence from patients/families. An all possible subset regression procedure with five goodness-of-fit indicators was used to identify which set of perceptions best predicted BCMA acceptance (intention to use, satisfaction). Results Nurses reported a moderate perceived ease of use and low perceived usefulness of BCMA. Nurses perceived moderate-or-higher social influence to use BCMA and had moderately positive perceptions of BCMA-related training and technical support. Behavioral intention to use BCMA was high, but satisfaction was low. Behavioral intention to use was best predicted by perceived ease of use, perceived social influence from non-specific others, and perceived usefulness for patient care (56% of variance explained). Satisfaction was best predicted by perceived ease of use, perceived usefulness for patient care, and perceived social influence from patients/families (76% of variance explained). Discussion Variation in and low scores on ease of use and usefulness are concerning, especially as these variables often correlate with acceptance, as found in this study. Predicting acceptance benefited from using a broad set of perceptions and adapting variables to the healthcare context. Conclusion Success with BCMA and other technologies can benefit from assessing end-user acceptance and elucidating the factors promoting acceptance and use. PMID:22661559

  17. A NAC for regulating metabolism: the nitrogen assimilation control protein (NAC) from Klebsiella pneumoniae.

    PubMed

    Bender, Robert A

    2010-10-01

    The nitrogen assimilation control protein (NAC) is a LysR-type transcriptional regulator (LTTR) that is made under conditions of nitrogen-limited growth. NAC's synthesis is entirely dependent on phosphorylated NtrC from the two-component Ntr system and requires the unusual sigma factor σ54 for transcription of the nac gene. NAC activates the transcription of σ70-dependent genes whose products provide the cell with ammonia or glutamate. NAC represses genes whose products use ammonia and also represses its own transcription. In addition, NAC also subtly adjusts other cellular functions to keep pace with the supply of biosynthetically available nitrogen.

  18. An evaluation process for an electronic bar code medication administration information system in an acute care unit.

    PubMed

    Bargren, Michelle; Lu, Der-Fa

    2009-01-01

    The purpose of this case study is to present an evaluation process and recommendations for addressing the gaps found with the implementation of a new bar code medication administration (BCMA) technology in a busy acute care hospital unit. The case study analyzes workflow procedures associated with administration of medications in an inpatient labor and delivery care unit before and one year after implementation of BCMA technology. The comparison reveals a twofold increase in workflow procedures for nursing staff because of the new technology. System gaps are identified from a nursing user's perspective, and recommendations are offered to close those gaps.

  19. NAC Aftermarket Brake Components Project (Secondary Items)

    DTIC Science & Technology

    2006-09-25

    NAC Aftermarket Brake Components Project (Secondary Items) SAE Paper #2006-01-3192 25 September 2006, Grapevine Version R4 (Final) Report...REPORT TYPE N/A 3. DATES COVERED - 4. TITLE AND SUBTITLE NAC Aftermarket Brake Components Project (Secondary Items) 5a. CONTRACT NUMBER 5b...PAGE unclassified Standard Form 298 (Rev. 8-98) Prescribed by ANSI Std Z39-18 NAC Aftermarket Brake Components Project By: Leo Miller, USA

  20. NAC Aftermarket Brake Components Project (Secondary Items)

    DTIC Science & Technology

    2007-02-06

    Supporting the Objective Force – NAC Aftermarket Brake Components Project Version: 06 February 2007 Final UNCLAS: Dist A. Approved for public...release NAC Aftermarket Brake Components Project (Secondary Items) Version: 06 February 2007 Final UNCLAS: Dist A. Approved for public release Leo Miller...Technology Insertion Project Officer (TIPO) US Army National Automotive Center ( NAC ) Warren, MI Report Documentation Page Form ApprovedOMB No. 0704

  1. Molecular characterization of pig alpha2,3-Gal-beta1,3-GalNAc-alpha2,6-sialyltransferase (pST6GalNAc IV) gene specific for Neu5Acalpha2-3Galbeta1-3GalNAc trisaccharide structure.

    PubMed

    Ko, Hyun-Kwon; Song, Kwon-Ho; Jin, Un-Ho; Seong, Hwan-Hoo; Chang, Young-Chae; Kim, Nam-Hyung; Kim, Dong-Soo; Lee, Young-Choon; Kim, Cheorl-Ho

    2010-04-01

    Sialic acids of glycoconjugates play crucial roles in various biological processes, such as cell-cell communication and cell-substrate interaction. A sisalyltransferase, ST6GalNAc IV (Neu5Ac-alpha2,3-Gal-beta1,3-GalNAc-alpha2,6-sialyltransferase), catalyzes the formation of alpha2-6-linkages onto GalNAc residues of O-glycosidically linked Ser/Thr of proteins. In this study, we cloned the pig ST6GalNAc IV (pST6GalNAc IV) and investigated its functional characterization. pST6GalNAc IV cDNA has been isolated from pig liver tissues and it contains an entire open reading frame (ORF, 906 bp) coding for 302 amino acid residues. Entire ORF of pST6GalNAc IV containing sialylmotif 'L'-(Large), 'S'-(Small) and '-VS' (Very small) has a high degree of sequence similarity with Homo sapiens (90%), Pan troglodytes (91%) and Mus musculus (87%). Expression of pST6GalNAc IV mRNA in various pig tissues was identified by reverse transcription polymerase chain reaction (RT-PCR) analysis. pST6GalNAc IV mRNA was highly expressed in tongue, muscle and heart, whereas it was not expressed in pancreas. For functional characterization of pST6GalNAc IV gene in pig kidney PK15 cells, we have also established pST6GalNAc IV-transfected PK15 cells, which are stably expressing the pST6GalNAc IV gene. The glycosylation pattern of pST6GalNAc IV-transfected PK15 cells was detected by flow cytometry and immunofluorescence analysis with Maackia amurensis agglutinin (MAA), Maackia amurensis hemagglutinin (MAL II), Sambucus nigra agglutinin (SNA) and peanut agglutinin (PNA) lectins. The specific carbohydrate structures of Neu5Acalpha2-3Galbeta1-3(Neu5Acalpha2-6)GalNAc tetrasaccharide or Neu5Acalpha2-6GalNAc disaccharide recognized by MAL-II and SNA were revealed to be newly synthesized by pST6GalNAc IV. From the results, it was suggested that the pig pST6GalNAc IV gene is capable of synthesizing Neu5Acalpha2-3Galbeta1-3(Neu5Acalpha2-6)GalNAc tetrasaccharide structures on O-glycoproteins.

  2. Describing and Explaining the Personal and Professional Moral Codes Considered by Administrators as They Make Decisions

    ERIC Educational Resources Information Center

    Phillips, David E.

    2011-01-01

    Every administrative action a principal will take is reduced to a decision. These decisions are made in an arena of overlapping moralities stemming from the organizational morality in concert with his/her personal morality. As Barnard stated, it is impossible to divorce one from the other. The purpose of this study was to attempt to describe and…

  3. Effect of oral N-acetylcysteine (NAC) on volume and albumin content of respiratory tract fluid but not on epithelial secretory cell number in "smoking" rats.

    PubMed

    Robinson, N; Brattsand, R; Dahlbäck, M

    1990-03-01

    This study was designed to look at the effect of N-acetylcysteine (NAC) on epithelial secretory cells and the respiratory tract fluid volume and albumin content from the lower airways of "bronchitic" rats. Rats were exposed either to tobacco smoke (TS), TS and NAC, or NAC alone. TS caused a significant increase in epithelial secretory cell number which was not reduced by concomitant NAC administration; NAC alone had no effect on cell numbers. TS increased respiratory tract fluid volume and albumin content by a small but non-significant amount, whereas TS and NAC increased the volume and albumin content by a greater and significant amount; NAC alone was also shown to significantly increase both fluid volume and albumin content.

  4. HIPAA administrative simplification: modifications to medical data code set standards to adopt ID-10-CM and ICD-10-PCS. Final rule.

    PubMed

    2009-01-16

    This final rule adopts modifications to two of the code set standards adopted in the Transactions and Code Sets final rule published in the Federal Register pursuant to certain provisions of the Administrative Simplification subtitle of the Health Insurance Portability and Accountability Act of 1996 (HIPAA). Specifically, this final rule modifies the standard medical data code sets (hereinafter "code sets") for coding diagnoses and inpatient hospital procedures by concurrently adopting the International Classification of Diseases, 10th Revision, Clinical Modification (ICD-10-CM) for diagnosis coding, including the Official ICD-10-CM Guidelines for Coding and Reporting, as maintained and distributed by the U.S. Department of Health and Human Services (HHS), hereinafter referred to as ICD-10-CM, and the International Classification of Diseases, 10th Revision, Procedure Coding System (ICD-10-PCS) for inpatient hospital procedure coding, including the Official ICD-10-PCS Guidelines for Coding and Reporting, as maintained and distributed by the HHS, hereinafter referred to as ICD-10-PCS. These new codes replace the International Classification of Diseases, 9th Revision, Clinical Modification, Volumes 1 and 2, including the Official ICD-9-CM Guidelines for Coding and Reporting, hereinafter referred to as ICD-9-CM Volumes 1 and 2, and the International Classification of Diseases, 9th Revision, Clinical Modification, Volume 3, including the Official ICD-9-CM Guidelines for Coding and Reporting, hereinafter referred to as ICD-9-CM Volume 3, for diagnosis and procedure codes, respectively.

  5. UDP-GlcNAc: Gal beta 3GalNAc-mucin: (GlcNAc----GalNAc) beta 6-N-acetylglucosaminyltransferase and UDP-GlcNAc: Gal beta 3(GlcNAc beta 6) GalNAc-mucin (GlcNAc----Gal)beta 3-N-acetylglucosaminyltransferase from swine trachea epithelium.

    PubMed

    Sangadala, S; Sivakami, S; Mendicino, J

    1991-03-13

    Two specific beta-N-acetylglucosaminyltransferases involved in the branching and elongation of mucin oligosaccharide chains, namely, a beta 1,6 N-acetylglucosaminylsaminyltransferase that transfers N-acetylglucosamine from UDP-N-acetylglucosamine to Gal beta 3GalNAc-mucin to yield Gal beta 3(GlcNAc beta 6)GalNAc-Mucin and a beta 3-N-acetylglucosaminyl transferase that transfers N-acetylglucosamine from UDP-N-acetylglucosamine to Gal beta 3(GlcNAc beta 6)GalNAc-mucin to yield GlcNAc beta 3Gal beta 3 (GlcNAc beta 6)GalNAc-Mucin were purified from the microsomal fraction of swine trachea epithelium. The beta 1,6-N-acetylglucosaminyltransferase was purified about 21,800-fold by procedures which included affinity chromatography on DEAE columns containing bound asialo Cowper's gland mucin glycoprotein with Gal beta 1,3GalNAc side chains. The apparent molecular weight estimated by gel filtration was found to be about 60 Kd. The purified enzyme showed a high specificity for Gal beta 1,3GalNAc chains and the most active substrates were mucin glycoproteins containing these chains. The apparent Km of the beta 6-glucosaminyltrans-ferase for Cowper's gland mucin glycoprotein containing Gal beta 1,3GalNAc chains was 0.53 microM; for UDP-N-acetylglucosamine, 12 microM; and for Gal beta 1,3GalNAc alpha NO2 phi, 4 mM. The activity of the beta 6-glucosaminyltransferase was dependent on the extent of glycosylation of the Gal beta 3GalNAc chains in Cowper's gland mucin glycoprotein. The best substrate for the partially purified beta 3-Glucosaminyltransferase was Cowper's gland mucin glycoprotein containing Gal beta 1,3(GlcNAc beta 6)GalNAc side chains. This enzyme showed little or no activity with intact sialylated Cowper's gland mucin glycoprotein or derivatives of this glycoprotein containing GalNAc or Gal beta 1,3GalNAc side chains. The radioactive oligosaccharides formed by these enzymes in large scale reaction mixtures were released from the mucin glycoproteins by treatment with

  6. OGA inhibition by GlcNAc-selenazoline.

    PubMed

    Kim, Eun Ju; Love, Dona C; Darout, Etzer; Abdo, Mohannad; Rempel, Brian; Withers, Stephen G; Rablen, Paul R; Hanover, John A; Knapp, Spencer

    2010-10-01

    The title compound, which differs from the powerful O-GlcNAcase (OGA) inhibitor GlcNAc-thiazoline only at the chalcogen atom (Se for S), is a much weaker inhibitor in a direct OGA assay. In human cells, however, the selenazoline shows comparable ability to induce hyper-O-GlcNAc-ylation, and the two show similar reduction of insulin-stimulated translocation of glucose transporter 4 in differentiated 3T3 adipocytes.

  7. Protocol for validating cardiovascular and cerebrovascular ICD-9-CM codes in healthcare administrative databases: the Umbria Data Value Project

    PubMed Central

    Cozzolino, Francesco; Orso, Massimiliano; Mengoni, Anna; Cerasa, Maria Francesca; Eusebi, Paolo; Ambrosio, Giuseppe; Montedori, Alessandro

    2017-01-01

    Introduction Administrative healthcare databases can provide a comprehensive assessment of the burden of diseases in terms of major outcomes, such as mortality, hospital readmissions and use of healthcare resources, thus providing answers to a wide spectrum of research questions. However, a crucial issue is the reliability of information gathered. Aim of this protocol is to validate International Classification of Diseases, 9th Revision—Clinical Modification (ICD-9-CM) codes for major cardiovascular diseases, including acute myocardial infarction (AMI), heart failure (HF), atrial fibrillation (AF) and stroke. Methods and analysis Data from the centralised administrative database of the entire Umbria Region (910 000 residents, located in Central Italy) will be considered. Patients with a first hospital discharge for AMI, HF, AF or stroke, between 2012 and 2014, will be identified in the administrative database using the following groups of ICD-9-CM codes located in primary position: (1) 410.x for AMI; (2) 427.31 for AF; (3) 428 for HF; (4) 433.x1, 434 (excluding 434.x0), 436 for ischaemic stroke, 430 and 431 for haemorrhagic stroke (subarachnoid haemorrhage and intracerebral haemorrhage). A random sample of cases, and of non-cases, will be selected, and the corresponding medical charts retrieved and reviewed for validation by pairs of trained, independent reviewers. For each condition considered, case adjudication of disease will be based on symptoms, laboratory and diagnostic tests, as available in medical charts. Divergences will be resolved by consensus. Sensitivity and specificity with 95% CIs will be calculated. Ethics and dissemination Research protocol has been granted approval by the Regional Ethics Committee. Study results will be disseminated widely through peer-reviewed publications and presentations at national and international conferences. PMID:28360241

  8. Overexpression of GalNAc-transferase GalNAc-T3 Promotes Pancreatic Cancer Cell Growth

    PubMed Central

    Taniuchi, Keisuke; Cerny, Ronald L.; Tanouchi, Aki; Kohno, Kimitoshi; Kotani, Norihiro; Honke, Koichi; Saibara, Toshiji; Hollingsworth, Michael A.

    2011-01-01

    O-linked glycans of secreted and membrane bound proteins play an important role in the pathogenesis of pancreatic cancer by modulating immune responses, inflammation, and tumorigenesis. A critical aspect of O-glycosylation, the position at which proteins are glycosylated with N-acetyl-galactosamine on serine and threonine residues, is regulated by the substrate specificity of UDP-GalNAc: polypeptide N-acetylgalactosaminyl-transferases (GalNAc-Ts). Thus, GalNAc-Ts regulate the first committed step in O-glycosylated protein biosynthesis, determine sites of O-glycosylation on proteins, and are important for understanding normal and carcinoma-associated O-glycosylation. We have found that one of these enzymes, GalNAc-T3, is overexpressed in human pancreatic cancer tissues, and suppression of GalNAc-T3 significantly attenuates growth of pancreatic cancer cells in vitro and in vivo. In addition, suppression of GalNAc-T3 induces apoptosis of pancreatic cancer cells. Our results indicate that GalNAc-T3 is likely to be involved in pancreatic carcinogenesis. Modification of cellular glycosylation occurs in nearly all types of cancer as a result of alterations in the expression levels of glycosyltransferases. We report guanine nucleotide binding protein, alpha transducing activity polypeptide 1 (GNAT1) as a possible substrate protein of GalNAc-T3. GalNAc-T3 is associated with O-glycosylation of GNAT1, and affects the subcellular distribution of GNAT1. Knocking down endogenous GNAT1 significantly suppresses the growth/survival of PDAC cells. Our results imply that GalNAc-T3 contributes to the function of O-glycosylated proteins and thereby affects the growth and survival of pancreatic cancer cells. Thus, substrate proteins of GalNAc-T3 should serve as important therapeutic targets for pancreatic cancers. PMID:21625220

  9. Overexpression of GalNAc-transferase GalNAc-T3 promotes pancreatic cancer cell growth.

    PubMed

    Taniuchi, K; Cerny, R L; Tanouchi, A; Kohno, K; Kotani, N; Honke, K; Saibara, T; Hollingsworth, M A

    2011-12-08

    O-linked glycans of secreted and membrane-bound proteins have an important role in the pathogenesis of pancreatic cancer by modulating immune responses, inflammation and tumorigenesis. A critical aspect of O-glycosylation, the position at which proteins are glycosylated with N-acetyl-galactosamine on serine and threonine residues, is regulated by the substrate specificity of UDP-GalNAc:polypeptide N-acetylgalactosaminyl-transferases (GalNAc-Ts). Thus, GalNAc-Ts regulate the first committed step in O-glycosylated protein biosynthesis, determine sites of O-glycosylation on proteins and are important for understanding normal and carcinoma-associated O-glycosylation. We have found that one of these enzymes, GalNAc-T3, is overexpressed in human pancreatic cancer tissues and suppression of GalNAc-T3 significantly attenuates the growth of pancreatic cancer cells in vitro and in vivo. In addition, suppression of GalNAc-T3 induces apoptosis of pancreatic cancer cells. Our results indicate that GalNAc-T3 is likely involved in pancreatic carcinogenesis. Modification of cellular glycosylation occurs in nearly all types of cancer as a result of alterations in the expression levels of glycosyltransferases. We report guanine the nucleotide-binding protein, α-transducing activity polypeptide-1 (GNAT1) as a possible substrate protein of GalNAc-T3. GalNAc-T3 is associated with O-glycosylation of GNAT1 and affects the subcellular distribution of GNAT1. Knocking down endogenous GNAT1 significantly suppresses the growth/survival of PDAC cells. Our results imply that GalNAc-T3 contributes to the function of O-glycosylated proteins and thereby affects the growth and survival of pancreatic cancer cells. Thus, substrate proteins of GalNAc-T3 should serve as important therapeutic targets for pancreatic cancers.

  10. The Miscanthus NAC transcription factor MlNAC9 enhances abiotic stress tolerance in transgenic Arabidopsis.

    PubMed

    Zhao, Xun; Yang, Xuanwen; Pei, Shengqiang; He, Guo; Wang, Xiaoyu; Tang, Qi; Jia, Chunlin; Lu, Ying; Hu, Ruibo; Zhou, Gongke

    2016-07-15

    NAC (NAM, ATAF1/2, and CUC2) transcription factors are known to play important roles in responses to abiotic stresses in plants. Currently, little information regarding the functional roles of NAC genes in stress tolerance is available in Miscanthus lutarioriparius, a promising bioenergy plant for cellulosic ethanol production. In this study, we carried out the functional characterization of MlNAC9 in abiotic stresses. MlNAC9 was shown to act as a nuclear localized transcription activator with the activation domain in its C-terminus. The overexpression of MlNAC9 in Arabidopsis conferred hypersensitivity to abscisic acid (ABA) at seed germination and root elongation stages. In addition, the overexpression of MlNAC9 led to increased seed germination rate and root growth under salt (NaCl) treatment. Meanwhile, the transgenic Arabidopsis overexpressing MlNAC9 showed enhanced tolerance to drought and cold stresses. The expression of stress-responsive marker genes was significantly increased in MlNAC9 overexpression lines compared to that of WT under ABA, drought, salt, and cold stresses. Correspondingly, the activities of antioxidant enzymes superoxide dismutase (SOD), peroxidase (POD), and catalase (CAT) were significantly increased and the malondialdehyde (MDA) content was lower accumulated in MlNAC9 overexpression lines under drought and salt treatments. These results indicated that the overexpression of MlNAC9 improved the tolerance to abiotic stresses via an ABA-dependent pathway, and the enhanced tolerance of transgenic plants was mainly attributed to the increased expression of stress-responsive genes and the enhanced scavenging capability of reactive oxygen species (ROS).

  11. The National Astronomy Consortium (NAC) - Overview

    NASA Astrophysics Data System (ADS)

    Sheth, Kartik; Mills, Elisabeth A. C.; Hooper, Eric; National Astronomy Consortium

    2015-01-01

    The National Astronomy Consortium (NAC; see https://sites.google.com/site/nraonac/) is a growing national partnership between majority and minority universities and institutions with the goal of increasing the numbers of under-represented minorities and students who might otherwise be overlooked by the traditional academic pipeline into STEM, or related, careers. The NAC model is based on the successful 'Posse Foundation' model for undergraduate success and incorporates all its major components: pre-training of cohorts to prepare them for the research experience, joint weekly cohort activities throughout the research summer, peer- and multiple mentoring, weekly discussion of various aspects of professional and career development, continued engagement of students in science after return to home institution and lifelong mentoring. The mentors also form a cohort, exchanging information and learning from each other. With its partner institutions, the NAC aims to build a complete pipeline from undergraduate through career for the next generation of scientists and engineers. Our annual goal is to create two to three cohorts of four to five students at each site (currently NRAO-Charlottesville, NRAO-Socorro and U. Wisconsin - Madison). Recruitment occurs in the fall semester with seminars and colloquia in partnership with faculty at the minority serving institutions and the GRAD-MAP program at the University of Maryland. In this talk we describe in detail all the components of the NAC and report on our progress. We are keen to interact and partner with new universities and institutions and encourage them to contact the NAC at nac4stem@googlegroups.com.

  12. Automation and adaptation: Nurses' problem-solving behavior following the implementation of bar coded medication administration technology.

    PubMed

    Holden, Richard J; Rivera-Rodriguez, A Joy; Faye, Héléne; Scanlon, Matthew C; Karsh, Ben-Tzion

    2013-08-01

    The most common change facing nurses today is new technology, particularly bar coded medication administration technology (BCMA). However, there is a dearth of knowledge on how BCMA alters nursing work. This study investigated how BCMA technology affected nursing work, particularly nurses' operational problem-solving behavior. Cognitive systems engineering observations and interviews were conducted after the implementation of BCMA in three nursing units of a freestanding pediatric hospital. Problem-solving behavior, associated problems, and goals, were specifically defined and extracted from observed episodes of care. Three broad themes regarding BCMA's impact on problem solving were identified. First, BCMA allowed nurses to invent new problem-solving behavior to deal with pre-existing problems. Second, BCMA made it difficult or impossible to apply some problem-solving behaviors that were commonly used pre-BCMA, often requiring nurses to use potentially risky workarounds to achieve their goals. Third, BCMA created new problems that nurses were either able to solve using familiar or novel problem-solving behaviors, or unable to solve effectively. Results from this study shed light on hidden hazards and suggest three critical design needs: (1) ecologically valid design; (2) anticipatory control; and (3) basic usability. Principled studies of the actual nature of clinicians' work, including problem solving, are necessary to uncover hidden hazards and to inform health information technology design and redesign.

  13. Automation and adaptation: Nurses’ problem-solving behavior following the implementation of bar coded medication administration technology

    PubMed Central

    Holden, Richard J.; Rivera-Rodriguez, A. Joy; Faye, Héléne; Scanlon, Matthew C.; Karsh, Ben-Tzion

    2012-01-01

    The most common change facing nurses today is new technology, particularly bar coded medication administration technology (BCMA). However, there is a dearth of knowledge on how BCMA alters nursing work. This study investigated how BCMA technology affected nursing work, particularly nurses’ operational problem-solving behavior. Cognitive systems engineering observations and interviews were conducted after the implementation of BCMA in three nursing units of a freestanding pediatric hospital. Problem-solving behavior, associated problems, and goals, were specifically defined and extracted from observed episodes of care. Three broad themes regarding BCMA’s impact on problem solving were identified. First, BCMA allowed nurses to invent new problem-solving behavior to deal with pre-existing problems. Second, BCMA made it difficult or impossible to apply some problem-solving behaviors that were commonly used pre-BCMA, often requiring nurses to use potentially risky workarounds to achieve their goals. Third, BCMA created new problems that nurses were either able to solve using familiar or novel problem-solving behaviors, or unable to solve effectively. Results from this study shed light on hidden hazards and suggest three critical design needs: (1) ecologically valid design; (2) anticipatory control; and (3) basic usability. Principled studies of the actual nature of clinicians’ work, including problem solving, are necessary to uncover hidden hazards and to inform health information technology design and redesign. PMID:24443642

  14. Novel roles for GlcNAc in cell signaling.

    PubMed

    Naseem, Shamoon; Parrino, Salvatore M; Buenten, Dane M; Konopka, James B

    2012-03-01

    N-acetylglucosamine (GlcNAc) has long been known to play important roles in cell surface structure. Recent studies are now revealing new functions for GlcNAc in cell signaling. Exposure to GlcNAc regulates virulence functions in the human fungal pathogen Candida albicans and in pathogenic bacteria. These signaling pathways sense exogenous GlcNAc and are distinct from the O-GlcNAc signaling pathways in mammalian cells in which increased levels of intracellular GlcNAc synthesis leads to post-translational modification of proteins by attachment of O-GlcNAc. The novel roles of GlcNAc in cell signaling will be the subject of this mini-review.

  15. Novel roles for GlcNAc in cell signaling

    PubMed Central

    Naseem, Shamoon; Parrino, Salvatore M.; Buenten, Dane M.; Konopka, James B.

    2012-01-01

    N-acetylglucosamine (GlcNAc) has long been known to play important roles in cell surface structure. Recent studies are now revealing new functions for GlcNAc in cell signaling. Exposure to GlcNAc regulates virulence functions in the human fungal pathogen Candida albicans and in pathogenic bacteria. These signaling pathways sense exogenous GlcNAc and are distinct from the O-GlcNAc signaling pathways in mammalian cells in which increased levels of intracellular GlcNAc synthesis leads to post-translational modification of proteins by attachment of O-GlcNAc. The novel roles of GlcNAc in cell signaling will be the subject of this mini-review. PMID:22808320

  16. First comprehensive in silico analysis of the functional and structural consequences of SNPs in human GalNAc-T1 gene.

    PubMed

    Mohamoud, Hussein Sheikh Ali; Hussain, Muhammad Ramzan Manwar; El-Harouni, Ashraf A; Shaik, Noor Ahmad; Qasmi, Zaheer Ulhaq; Merican, Amir Feisal; Baig, Mukhtiar; Anwar, Yasir; Asfour, Hani; Bondagji, Nabeel; Al-Aama, Jumana Yousuf

    2014-01-01

    GalNAc-T1, a key candidate of GalNac-transferases genes family that is involved in mucin-type O-linked glycosylation pathway, is expressed in most biological tissues and cell types. Despite the reported association of GalNAc-T1 gene mutations with human disease susceptibility, the comprehensive computational analysis of coding, noncoding and regulatory SNPs, and their functional impacts on protein level, still remains unknown. Therefore, sequence- and structure-based computational tools were employed to screen the entire listed coding SNPs of GalNAc-T1 gene in order to identify and characterize them. Our concordant in silico analysis by SIFT, PolyPhen-2, PANTHER-cSNP, and SNPeffect tools, identified the potential nsSNPs (S143P, G258V, and Y414D variants) from 18 nsSNPs of GalNAc-T1. Additionally, 2 regulatory SNPs (rs72964406 and #x26; rs34304568) were also identified in GalNAc-T1 by using FastSNP tool. Using multiple computational approaches, we have systematically classified the functional mutations in regulatory and coding regions that can modify expression and function of GalNAc-T1 enzyme. These genetic variants can further assist in better understanding the wide range of disease susceptibility associated with the mucin-based cell signalling and pathogenic binding, and may help to develop novel therapeutic elements for associated diseases.

  17. First Comprehensive In Silico Analysis of the Functional and Structural Consequences of SNPs in Human GalNAc-T1 Gene

    PubMed Central

    Ali Mohamoud, Hussein Sheikh; Manwar Hussain, Muhammad Ramzan; El-Harouni, Ashraf A.; Shaik, Noor Ahmad; Qasmi, Zaheer Ulhaq; Merican, Amir Feisal; Baig, Mukhtiar; Anwar, Yasir; Asfour, Hani; Bondagji, Nabeel; Al-Aama, Jumana Yousuf

    2014-01-01

    GalNAc-T1, a key candidate of GalNac-transferases genes family that is involved in mucin-type O-linked glycosylation pathway, is expressed in most biological tissues and cell types. Despite the reported association of GalNAc-T1 gene mutations with human disease susceptibility, the comprehensive computational analysis of coding, noncoding and regulatory SNPs, and their functional impacts on protein level, still remains unknown. Therefore, sequence- and structure-based computational tools were employed to screen the entire listed coding SNPs of GalNAc-T1 gene in order to identify and characterize them. Our concordant in silico analysis by SIFT, PolyPhen-2, PANTHER-cSNP, and SNPeffect tools, identified the potential nsSNPs (S143P, G258V, and Y414D variants) from 18 nsSNPs of GalNAc-T1. Additionally, 2 regulatory SNPs (rs72964406 and #x26; rs34304568) were also identified in GalNAc-T1 by using FastSNP tool. Using multiple computational approaches, we have systematically classified the functional mutations in regulatory and coding regions that can modify expression and function of GalNAc-T1 enzyme. These genetic variants can further assist in better understanding the wide range of disease susceptibility associated with the mucin-based cell signalling and pathogenic binding, and may help to develop novel therapeutic elements for associated diseases. PMID:24723968

  18. Code of conduct for the International Space Station Crew. National Aeronautics and Space Administration (NASA). Interim final rule.

    PubMed

    2000-12-21

    NASA is issuing new regulations entitled "International Space Station Crew," to implement certain provisions of the International Space Station (ISS) Intergovernmental Agreement (IGA) regarding ISS crewmembers' observance of an ISS Code of Conduct.

  19. ZmNAC55, a maize stress-responsive NAC transcription factor, confers drought resistance in transgenic Arabidopsis.

    PubMed

    Mao, Hude; Yu, Lijuan; Han, Ran; Li, Zhanjie; Liu, Hui

    2016-08-01

    Abiotic stress has been shown to significantly limit the growth and productivity of crops. NAC transcription factors play essential roles in response to various abiotic stresses. However, only little information regarding stress-related NAC genes is available in maize. Here, we cloned a maize NAC transcription factor ZmNAC55 and identified its function in drought stress. Transient expression and transactivation assay demonstrated that ZmNAC55 was localized in the nucleus and had transactivation activity. Expression analysis of ZmNAC55 in maize showed that this gene was induced by drought, high salinity and cold stresses and by abscisic acid (ABA). Promoter analysis demonstrated that multiple stress-related cis-acting elements exist in promoter region of ZmNAC55. Overexpression of ZmNAC55 in Arabidopsis led to hypersensitivity to ABA at the germination stage, but enhanced drought resistence compared to wild-type seedlings. Transcriptome analysis identified a number of differentially expressed genes between 35S::ZmNAC55 transgenic and wild-type plants, and many of which are involved in stress response, including twelve qRT-PCR confirmed well-known drought-responsive genes. These results highlight the important role of ZmNAC55 in positive regulates of drought resistence, and may have potential applications in transgenic breeding of drought-tolerant crops.

  20. The nac (nitrogen assimilation control) gene from Klebsiella aerogenes.

    PubMed Central

    Schwacha, A; Bender, R A

    1993-01-01

    The Klebsiella aerogenes nac gene, whose product is necessary for nitrogen regulation of a number of operons, was identified and its DNA sequence determined. The nac sequence predicted a protein a 305 amino acids with a strong similarity to members of the LysR family of regulatory proteins, especially OxyR from Escherichia coli. Analysis of proteins expressed in minicells showed that nac is a single-gene operon whose product has an apparent molecular weight of about 32 kDa as measured in sodium dodecyl sulfate-polyacrylamide gel electrophoresis. Immediately downstream from nac is a two-gene operon, the first gene of which encodes another member of the LysR family. Upstream from nac is a tRNAAsn gene transcribed divergently from nac. About 60 bp upstream from the nac open reading frame lies a sequence nearly identical to the consensus for sigma 54-dependent promoters, with the conserved GG and GC nucleotides at -26 and -14 relative to the start of transcription. About 130 bp farther upstream (at -153 relative to the start of transcription) is a sequence nearly identical to the transcriptional activator NTRC-responsive enhancer consensus. Another weaker NTRC-binding site is located adjacent to this site (at -133 relative to the start of transcription). Thus, we propose that nac is transcribed by RNA polymerase carrying sigma 54 in response to the nitrogen regulatory (NTR) system. A transposon located between the promoter and the nac ORF prevented NTR-mediated expression of nac, supporting this identification of the promoter sequence. The insertion of over 5 kb of transposon DNA between the enhancer and its target promoter had only a weak effect on enhancer-mediated regulation, suggesting that enhancers may be able to act at a considerable distance on the bacterial chromosome. Images PMID:8458853

  1. Validity of ICD-9-CM codes for breast, lung and colorectal cancers in three Italian administrative healthcare databases: a diagnostic accuracy study protocol

    PubMed Central

    Abraha, Iosief; Serraino, Diego; Giovannini, Gianni; Stracci, Fabrizio; Casucci, Paola; Alessandrini, Giuliana; Bidoli, Ettore; Chiari, Rita; Cirocchi, Roberto; De Giorgi, Marcello; Franchini, David; Vitale, Maria Francesca; Fusco, Mario; Montedori, Alessandro

    2016-01-01

    Introduction Administrative healthcare databases are useful tools to study healthcare outcomes and to monitor the health status of a population. Patients with cancer can be identified through disease-specific codes, prescriptions and physician claims, but prior validation is required to achieve an accurate case definition. The objective of this protocol is to assess the accuracy of International Classification of Diseases Ninth Revision—Clinical Modification (ICD-9-CM) codes for breast, lung and colorectal cancers in identifying patients diagnosed with the relative disease in three Italian administrative databases. Methods and analysis Data from the administrative databases of Umbria Region (910 000 residents), Local Health Unit 3 of Napoli (1 170 000 residents) and Friuli-Venezia Giulia Region (1 227 000 residents) will be considered. In each administrative database, patients with the first occurrence of diagnosis of breast, lung or colorectal cancer between 2012 and 2014 will be identified using the following groups of ICD-9-CM codes in primary position: (1) 233.0 and (2) 174.x for breast cancer; (3) 162.x for lung cancer; (4) 153.x for colon cancer and (5) 154.0–154.1 and 154.8 for rectal cancer. Only incident cases will be considered, that is, excluding cases that have the same diagnosis in the 5 years (2007–2011) before the period of interest. A random sample of cases and non-cases will be selected from each administrative database and the corresponding medical charts will be assessed for validation by pairs of trained, independent reviewers. Case ascertainment within the medical charts will be based on (1) the presence of a primary nodular lesion in the breast, lung or colon–rectum, documented with imaging or endoscopy and (2) a cytological or histological documentation of cancer from a primary or metastatic site. Sensitivity and specificity with 95% CIs will be calculated. Dissemination Study results will be disseminated widely through

  2. Genomic analysis of NAC transcription factors in banana (Musa acuminata) and definition of NAC orthologous groups for monocots and dicots.

    PubMed

    Cenci, Albero; Guignon, Valentin; Roux, Nicolas; Rouard, Mathieu

    2014-05-01

    Identifying the molecular mechanisms underlying tolerance to abiotic stresses is important in crop breeding. A comprehensive understanding of the gene families associated with drought tolerance is therefore highly relevant. NAC transcription factors form a large plant-specific gene family involved in the regulation of tissue development and responses to biotic and abiotic stresses. The main goal of this study was to set up a framework of orthologous groups determined by an expert sequence comparison of NAC genes from both monocots and dicots. In order to clarify the orthologous relationships among NAC genes of different species, we performed an in-depth comparative study of four divergent taxa, in dicots and monocots, whose genomes have already been completely sequenced: Arabidopsis thaliana, Vitis vinifera, Musa acuminata and Oryza sativa. Due to independent evolution, NAC copy number is highly variable in these plant genomes. Based on an expert NAC sequence comparison, we propose forty orthologous groups of NAC sequences that were probably derived from an ancestor gene present in the most recent common ancestor of dicots and monocots. These orthologous groups provide a curated resource for large-scale protein sequence annotation of NAC transcription factors. The established orthology relationships also provide a useful reference for NAC function studies in newly sequenced genomes such as M. acuminata and other plant species.

  3. Cloning, expression and gene organization of a human Neu5Ac alpha 2-3Gal beta 1-3GalNAc alpha 2,6-sialyltransferase: hST6GalNAcIV.

    PubMed Central

    Harduin-Lepers, A; Stokes, D C; Steelant, W F; Samyn-Petit, B; Krzewinski-Recchi, M A; Vallejo-Ruiz, V; Zanetta, J P; Augé, C; Delannoy, P

    2000-01-01

    On the basis of the detection of expressed sequence tag ('EST') similar to the rat N-acetylgalactosamine alpha2,6-sialyltransferase (ST6GalNAc) III cDNA, we have identified a novel member of the human ST6GalNAc family. We have isolated a cDNA clone containing an open reading frame that codes for a type II membrane protein of 302 amino acids with a seven-amino-acid cytoplasmic domain, an 18-amino-acid transmembrane domain and the smallest described catalytic domain of 277 amino acids. This predicted sialyltransferase sequence is similar to the rat ST6GalNAc III (46.6%), but was found to be even more similar to the recently reported mouse ST6GalNAc IV (88.1%) on the basis of amino acid sequence identity. Northern-blot analysis showed that the newly identified gene is expressed constitutively in various adult human tissues as a 2.2kb transcript, but was also found to be expressed at lower levels in brain, heart and skeletal muscle as a 2.5kb transcript. Expression of the hST6GalNAc IV gene was investigated by reverse transcription PCR in various human cancer cells, and was found to be present in the majority of cell types with the exception of the carcinoma cell line T47D and pro-monocyte THP cells. The transient expression in COS-7 cells of the full-length cDNA led to the production of an active enzyme sharing the acceptor specificity of the ST6GalNAc family towards Neu5Ac alpha 2-3Gal beta 1-3GalNAc alpha-O-R (where 'R' denotes H, benzyl, or a peptidic chain). Detailed analysis in vitro of substrate specificity revealed that the enzyme required the trisaccharide Neu5Ac alpha 2-3Gal beta1-3GalNAc found on O-glycans and arylglycosides. In addition, we have clarified the genomic organization of ST6GalNAc IV gene. PMID:11062056

  4. That's nice, but what does IT do? Evaluating the impact of bar coded medication administration by measuring changes in the process of care.

    PubMed

    Holden, Richard J; Brown, Roger L; Alper, Samuel J; Scanlon, Matthew C; Patel, Neal R; Karsh, Ben-Tzion

    2011-07-01

    Health information technology (IT) is widely endorsed as a way to improve key health care outcomes, particularly patient safety. Applying a human factors approach, this paper models more explicitly how health IT might improve or worsen outcomes. The human factors model specifies that health IT transforms the work system, which transforms the process of care, which in turn transforms the outcome of care. This study reports on transformations of the medication administration process that resulted from the implementation of one type of IT: bar coded medication administration (BCMA). Registered nurses at two large pediatric hospitals in the US participated in a survey administered before and after one of the hospitals implemented BCMA. Nurses' perceptions of the administration process changed at the hospital that implemented BCMA, whereas perceptions of nurses at the control hospital did not. BCMA appeared to improve the safety of the processes of matching medications to the medication administration record and checking patient identification. The accuracy, usefulness, and consistency of checking patient identification improved as well. In contrast, nurses' perceptions of the usefulness, time efficiency, and ease of the documentation process decreased post-BCMA. Discussion of survey findings is supplemented by observations and interviews at the hospital that implemented BCMA. By considering the way that IT transforms the work system and the work process a practitioner can better predict the kind of outcomes that the IT might produce. More importantly, the practitioner can achieve or prevent outcomes of interest by using design and redesign aimed at controlling work system and process transformations.

  5. A Diverse Range of Bacterial and Eukaryotic Chitinases Hydrolyzes the LacNAc (Galβ1–4GlcNAc) and LacdiNAc (GalNAcβ1–4GlcNAc) Motifs Found on Vertebrate and Insect Cells*

    PubMed Central

    Frederiksen, Rikki F.; Yoshimura, Yayoi; Storgaard, Birgit G.; Paspaliari, Dafni K.; Petersen, Bent O.; Chen, Kowa; Larsen, Tanja; Duus, Jens Ø.; Ingmer, Hanne; Bovin, Nicolai V.; Westerlind, Ulrika; Blixt, Ola; Palcic, Monica M.; Leisner, Jørgen J.

    2015-01-01

    There is emerging evidence that chitinases have additional functions beyond degrading environmental chitin, such as involvement in innate and acquired immune responses, tissue remodeling, fibrosis, and serving as virulence factors of bacterial pathogens. We have recently shown that both the human chitotriosidase and a chitinase from Salmonella enterica serovar Typhimurium hydrolyze LacNAc from Galβ1–4GlcNAcβ-tetramethylrhodamine (LacNAc-TMR (Galβ1–4GlcNAcβ(CH2)8CONH(CH2)2NHCO-TMR)), a fluorescently labeled model substrate for glycans found in mammals. In this study we have examined the binding affinities of the Salmonella chitinase by carbohydrate microarray screening and found that it binds to a range of compounds, including five that contain LacNAc structures. We have further examined the hydrolytic specificity of this enzyme and chitinases from Sodalis glossinidius and Polysphondylium pallidum, which are phylogenetically related to the Salmonella chitinase, as well as unrelated chitinases from Listeria monocytogenes using the fluorescently labeled substrate analogs LacdiNAc-TMR (GalNAcβ1–4GlcNAcβ-TMR), LacNAc-TMR, and LacNAcβ1–6LacNAcβ-TMR. We found that all chitinases examined hydrolyzed LacdiNAc from the TMR aglycone to various degrees, whereas they were less active toward LacNAc-TMR conjugates. LacdiNAc is found in the mammalian glycome and is a common motif in invertebrate glycans. This substrate specificity was evident for chitinases of different phylogenetic origins. Three of the chitinases also hydrolyzed the β1–6 bond in LacNAcβ1–6LacNAcβ-TMR, an activity that is of potential importance in relation to mammalian glycans. The enzymatic affinities for these mammalian-like structures suggest additional functional roles of chitinases beyond chitin hydrolysis. PMID:25561735

  6. Metabolomic Analysis of Blood Plasma after Oral Administration of N-acetyl-d-Glucosamine in Dogs

    PubMed Central

    Osaki, Tomohiro; Kurozumi, Seiji; Sato, Kimihiko; Terashi, Taro; Azuma, Kazuo; Murahata, Yusuke; Tsuka, Takeshi; Ito, Norihiko; Imagawa, Tomohiro; Minami, Saburo; Okamoto, Yoshiharu

    2015-01-01

    N-acetyl-d-glucosamine (GlcNAc) is a monosaccharide that polymerizes linearly through (1,4)-β-linkages. GlcNAc is the monomeric unit of the polymer chitin. GlcNAc is a basic component of hyaluronic acid and keratin sulfate found on the cell surface. The aim of this study was to examine amino acid metabolism after oral GlcNAc administration in dogs. Results showed that plasma levels of ectoine were significantly higher after oral administration of GlcNAc than prior to administration (p < 0.001). To our knowledge, there have been no reports of increased ectoine concentrations in the plasma. The mechanism by which GlcNAc administration leads to increased ectoine plasma concentration remains unclear; future studies are required to clarify this mechanism. PMID:26262626

  7. The effect of N-acetylcysteine (NAC) on liver and renal tissue inducible nitric oxide synthase (iNOS) and tissue lipid peroxidation in obstructive jaundice stimulated by lipopolysaccharide (LPS).

    PubMed

    Cağlikülekci, Mehmet; Pata, Cengiz; Apa, Duygu Dusmez; Dirlik, Musa; Tamer, Lulufer; Yaylak, Faik; Kanik, Arzu; Aydin, Suha

    2004-03-01

    Morbidity and mortality rates are very high in obstructive jaundice when it is associated with sepsis and multiple organ failure. Nitric oxide (NO) formation and increased expression of inducible nitric oxide synthase (iNOS) also take place in obstructive jaundice (OJ). N-Acetylcysteine (NAC) has a beneficial effect by demonstrating anti-inflammatory activity such as inhibits cytokine expression/release, inhibiting the adhesion molecule expression and inhibiting nuclear factor kappa B (NFkappaB). The aim of this study was to investigate the effects of NAC on liver and renal tissue iNOS, and liver tissue lipid peroxidation in lipopolysaccharide (LPS) induced obstructive jaundice. We randomized 48 rats into six groups. Group A: Sham group; group B: OJ group; group C: OJ+NAC; group D: OJ+LPS (Escherichia coli LPS serotype L-2630, 100mg, Sigma) group E: OJ+NAC+LPS; group F: OJ+LPS+NAC. NAC was started subcutaneously 100mg/kg. LPS was injected intraperitoneally and then at the tenth day we sacrificed the rats. Liver malondialdehyde (MDA) increased and liver ATPase decreased in groups B-D when compared to group A. After the administration of NAC (groups C-E), liver MDA levels decreased, tissue ATPase levels increased as compared to other groups. The liver and renal tissue iNOS expression was increased in groups B, D, and F. After the administration of NAC (groups C-E) the liver and renal tissue iNOS expression were decreased. Our results indicated that NAC prevented the deleterious effects of LPS in OJ by reducing iNOS expression via lipid peroxidation in liver and renal tissue; if it was administrated before LPS. But NAC failed to prevent the iNOS expression and lipid peroxidation if there was established endotoxemia in OJ.

  8. That’s nice, but what does IT do? Evaluating the impact of bar coded medication administration by measuring changes in the process of care

    PubMed Central

    Holden, Richard J.; Brown, Roger L.; Alper, Samuel J.; Scanlon, Matthew C.; Patel, Neal R.; Karsh, Ben-Tzion

    2011-01-01

    Health information technology (IT) is widely endorsed as a way to improve key health care outcomes, particularly patient safety. Applying a human factors approach, this paper models more explicitly how health IT might improve or worsen outcomes. The human factors model specifies that health IT transforms the work system, which transforms the process of care, which in turn transforms the outcome of care. This study reports on transformations of the medication administration process that resulted from the implementation of one type of IT: bar coded medication administration (BCMA). Registered nurses at two large pediatric hospitals in the US participated in a survey administered before and after one of the hospitals implemented BCMA. Nurses’ perceptions of the administration process changed at the hospital that implemented BCMA, whereas perceptions of nurses at the control hospital did not. BCMA appeared to improve the safety of the processes of matching medications to the medication administration record and checking patient identification. The accuracy, usefulness, and consistency of checking patient identification improved as well. In contrast, nurses’ perceptions of the usefulness, time efficiency, and ease of the documentation process decreased post-BCMA. Discussion of survey findings is supplemented by observations and interviews at the hospital that implemented BCMA. By considering the way that IT transforms the work system and the work process a practitioner can better predict the kind of outcomes that the IT might produce. More importantly, the practitioner can achieve or prevent outcomes of interest by using design and redesign aimed at controlling work system and process transformations. PMID:21686318

  9. Targeting Protein O-GlcNAc Modifications in Breast Cancer

    DTIC Science & Technology

    2009-09-01

    transport system. Role of hexosamine biosynthesis in the induction of insulin resistance . J Biol Chem 266:4706-12. 17. Myatt, S. S., and E. W. Lam. 2008...Wells, M. D. Lane, and G. W. Hart. 2002. Elevated nucleocytoplasmic glycosylation by O-GlcNAc results in insulin resistance associated with defects...G., K. A. Robinson, B. A. Marshall, R. C. Hresko, and M. M. Mueckler. 2002. Enhanced O-GlcNAc protein modification is associated with insulin

  10. Metabolic glycoengineering through the mammalian GalNAc salvage pathway.

    PubMed

    Pouilly, Sabrina; Piller, Véronique; Piller, Friedrich

    2012-02-01

    GalNAc is the initial sugar of mucin-type O-glycans, and is a component of several tumor antigens. The aim of this work was to determine whether synthetic GalNAc analogs could be taken up from the medium and incorporated into complex cellular O-glycans. The cell line employed was CHO ldlD, which can only use GalNAc and Gal present in the medium for the synthesis of its glycans. All GalNAc analogs with modified N-acyl groups (N-formyl, N-propionyl, N-glycolyl, N-azidoacetyl, N-bromoacetyl, and N-chloroacetyl) were incorporated into cellular O-glycans, although to different extents. The GalNAc analogs linked to Ser or Thr could be extended by the β3-galactosyltransferase glycoprotein-N-acetylgalactosamine 3β-galactosyl transferase 1 in vitro and in vivo and by α6-sialyltransferase α-N-acetylgalactosaminide-α-2,6-sialyltransferase 1. At the surface of CHO ldlD cells, all analogs were incorporated into sialylated O-glycan structures like those present on wild-type CHO cells, indicating that the GalNAc analogs do not change the overall structure of core-1 O-glycans. In addition, this study shows that the unnatural synthetic GalNAc analogs can be incorporated into human tumor cells, and that a tumor antigen modified by an analog can be readily detected by a specific antiserum. GalNAc analogs are therefore potential targets for tumor immunotherapy.

  11. Emissions Inventory Report Summary Reporting Requirements for the New Mexico Administrative Code, Title 20, Chapter 2, Part 73 (20 NMAC 2.73) for Calendar Year 1998

    SciTech Connect

    Air Quality Group, ESH-17

    1999-09-01

    Los Alamos National Laboratory (the Laboratory) is subject to emissions reporting requirements for regulated air contaminants under Title 20 of the New Mexico Administrative Code, Chapter 2, Part 73 (20 NMAC 2.73), Notice of Intent and Emissions Inventory Requirements. The Laboratory has the potential to emit 100 tons per year of suspended particulate matter, nitrogen oxides, carbon monoxide, sulfur oxides, and volatile organic compounds. For 1998, combustion products from the industrial sources contributed the greatest amount of criteria air pollutants from the Laboratory. Research and development activities contributed the greatest amount of volatile organic compounds. Emissions of beryllium and aluminum were reported for activities permitted under 20 NMAC 2.72 Construction Permits.

  12. Emissions Inventory Report Summary: Reporting Requirements for the New Mexico Administrative code, Title 20, Chapter 2, Part 73 (20 NMAC 2.73) for Calendar Year 1997

    SciTech Connect

    1999-01-01

    Los Alamos National Laboratory (the Laboratory) is subject to emissions reporting requirements for regulated air contaminants under Title 20 of the New Mexico Administrative Code, Chapter 2, Part 73, (20 NMAC 2.73), Notice of Intent and Emissions Inventory Requirements. The Laboratory has the potential to emit 100 tons per year of suspended particulate matter (PM), nitrogen oxides (NO{sub x}), carbon monoxide (CO), and volatile organic compounds (VOCs). For 1997, combustion products from the industrial sources contributed the greatest amount of regulated air emissions from the Laboratory. Research and development activities contributed the greatest amount of VOCs. Emissions of beryllium and aluminum were reported for activities permitted under 20 NMAC 2.72, Construction Permits.

  13. Emissions Inventory Report Summary: Reporting Requirements for the New Mexico Administrative Code, Title 20, Chapter 2, Part 73 (20 NMAC 2.73) for Calendar Year 2001

    SciTech Connect

    Margorie Stockton

    2003-04-01

    Los Alamos National Laboratory is subject to annual emissions-reporting requirements for regulated air contaminants under Title 20 of the New Mexico Administrative Code, Chapter 2, Part 73 (20.2.73 NMAC), Notice of Intent and Emissions Inventory Requirements. The applicability of the requirements is based on the Laboratory's potential to emit 100 tons per year of suspended particulate matter, nitrogen oxides, carbon monoxide, sulfur oxides, or volatile organic compounds. For calendar year 2001, the Technical Area 3 steam plant was the primary source of criteria air pollutants from the Laboratory, while research and development activities were the primary source of volatile organic compounds. Emissions of beryllium and aluminum were reported for activities permitted under 20.2.72 NMAC. Hazardous air pollutant emissions from chemical use for research and development activities were also reported.

  14. A practical tool for public health surveillance: Semi-automated coding of short injury narratives from large administrative databases using Naïve Bayes algorithms.

    PubMed

    Marucci-Wellman, Helen R; Lehto, Mark R; Corns, Helen L

    2015-11-01

    Public health surveillance programs in the U.S. are undergoing landmark changes with the availability of electronic health records and advancements in information technology. Injury narratives gathered from hospital records, workers compensation claims or national surveys can be very useful for identifying antecedents to injury or emerging risks. However, classifying narratives manually can become prohibitive for large datasets. The purpose of this study was to develop a human-machine system that could be relatively easily tailored to routinely and accurately classify injury narratives from large administrative databases such as workers compensation. We used a semi-automated approach based on two Naïve Bayesian algorithms to classify 15,000 workers compensation narratives into two-digit Bureau of Labor Statistics (BLS) event (leading to injury) codes. Narratives were filtered out for manual review if the algorithms disagreed or made weak predictions. This approach resulted in an overall accuracy of 87%, with consistently high positive predictive values across all two-digit BLS event categories including the very small categories (e.g., exposure to noise, needle sticks). The Naïve Bayes algorithms were able to identify and accurately machine code most narratives leaving only 32% (4853) for manual review. This strategy substantially reduces the need for resources compared with manual review alone.

  15. Veterans Health Administration

    MedlinePlus

    ... code here VA » Veterans Health Administration Veterans Health Administration Marine Continues to Serve by Serving Veterans David ... Read more » VA Medical Centers The Veterans Health Administration is home to the United States’ largest integrated ...

  16. Biofuel Potential of Plants Transformed Genetically with NAC Family Genes

    PubMed Central

    Singh, Sadhana; Grover, Atul; Nasim, M.

    2016-01-01

    NAC genes contribute to enhance survivability of plants under conditions of environmental stress and in secondary growth of the plants, thereby building biomass. Thus, genetic transformation of plants using NAC genes provides a possibility to tailor biofuel plants. Over-expression studies have indicated that NAC family genes can provide tolerance to various biotic and abiotic stresses, either by physiological or biochemical changes at the cellular level, or by affecting visible morphological and anatomical changes, for example, by development of lateral roots in a number of plants. Over-expression of these genes also work as triggers for development of secondary cell walls. In our laboratory, we have observed a NAC gene from Lepidium latifolium contributing to both enhanced biomass as well as cold stress tolerance of model plants tobacco. Thus, we have reviewed all the developments of genetic engineering using NAC genes which could enhance the traits required for biofuel plants, either by enhancing the stress tolerance or by enhancing the biomass of the plants. PMID:26858739

  17. Getting a Knack for NAC: N-Acetyl-Cysteine.

    PubMed

    Sansone, Randy A; Sansone, Lori A

    2011-01-01

    N-acetyl-cysteine, N-acetylcysteine, N-acetyl cysteine, and N-acetyl-L-cysteine are all designations for the same compound, which is abbreviated as NAC. NAC is a precursor to the amino acid cysteine, which ultimately plays two key metabolic roles. Through its metabolic contribution to glutathione production, cysteine participates in the general antioxidant activities of the body. Through its role as a modulator of the glutamatergic system, cysteine influences the reward-reinforcement pathway. Because of these functions, NAC may exert a therapeutic effect on psychiatric disorders allegedly related to oxidative stress (e.g., schizophrenia, bipolar disorder) as well as psychiatric syndromes characterized by impulsive/compulsive symptoms (e.g., trichotillomania, pathological nail biting, gambling, substance misuse). While the dosages, pharmacological strategies (monotherapy versus augmentation), and long-term risks are not fully evident, NAC appears to be a promising, relatively low-risk intervention. If so, NAC might be an ideal treatment strategy for a variety of psychiatric conditions in both psychiatric and primary care settings.

  18. X-inactivation normalizes O-GlcNAc transferase levels and generates an O-GlcNAc-depleted Barr body

    PubMed Central

    Olivier-Van Stichelen, Stéphanie; Hanover, John A.

    2014-01-01

    O-GlcNAc Transferase (OGT) catalyzes protein O-GlcNAcylation, an abundant and dynamic nuclear and cytosolic modification linked to epigenetic regulation of gene expression. The steady-state levels of O-GlcNAc are influenced by extracellular glucose concentrations suggesting that O-GlcNAcylation may serve as a metabolic sensor. Intriguingly, human OGT is located on the X-chromosome (Xq13) close to the X-inactivation center (XIC), suggesting that OGT levels may be controlled by dosage compensation. In human female cells, dosage compensation is accomplished by X-inactivation. Long noncoding RNAs and polycomb repression act together to produce an inactive X chromosome, or Barr body. Given that OGT has an established role in polycomb repression, it is uniquely poised to auto-regulate its own expression through X-inactivation. In this study, we examined OGT expression in male, female and triple-X female human fibroblasts, which differ in the number of inactive X chromosomes (Xi). We demonstrate that OGT is subjected to random X-inactivation in normal female and triple X cells to regulate OGT RNA levels. In addition, we used chromatin isolation by RNA purification (ChIRP) and immunolocalization to examine O-GlcNAc levels in the Xi/Barr body. Despite the established role of O-GlcNAc in polycomb repression, OGT and target proteins bearing O-GlcNAc are largely depleted from the highly condensed Barr body. Thus, while O-GlcNAc is abundantly present elsewhere in the nucleus, its absence from the Barr body suggests that the transcriptional quiescence of the Xi does not require OGT or O-GlcNAc. PMID:25136351

  19. Two recently duplicated maize NAC transcription factor paralogs are induced in response to Colletotrichum graminicola infection

    PubMed Central

    2013-01-01

    Background NAC transcription factors belong to a large family of plant-specific transcription factors with more than 100 family members in monocot and dicot species. To date, the majority of the studied NAC proteins are involved in the response to abiotic stress, to biotic stress and in the regulation of developmental processes. Maize NAC transcription factors involved in the biotic stress response have not yet been identified. Results We have found that two NAC transcription factors, ZmNAC41 and ZmNAC100, are transcriptionally induced both during the initial biotrophic as well as the ensuing necrotrophic colonization of maize leaves by the hemibiotrophic ascomycete fungus C. graminicola. ZmNAC41 transcripts were also induced upon infection with C. graminicola mutants that are defective in host penetration, while the induction of ZmNAC100 did not occur in such interactions. While ZmNAC41 transcripts accumulated specifically in response to jasmonate (JA), ZmNAC100 transcripts were also induced by the salicylic acid analog 2,6-dichloroisonicotinic acid (INA). To assess the phylogenetic relation of ZmNAC41 and ZmNAC100, we studied the family of maize NAC transcription factors based on the recently annotated B73 genome information. We identified 116 maize NAC transcription factor genes that clustered into 12 clades. ZmNAC41 and ZmNAC100 both belong to clade G and appear to have arisen by a recent gene duplication event. Including four other defence-related NAC transcription factors of maize and functionally characterized Arabidopsis and rice NAC transcription factors, we observed an enrichment of NAC transcription factors involved in host defense regulation in clade G. In silico analyses identified putative binding elements for the defence-induced ERF, Myc2, TGA and WRKY transcription factors in the promoters of four out of the six defence-related maize NAC transcription factors, while one of the analysed maize NAC did not contain any of these potential binding sites

  20. Uncertainty Analysis of LROC NAC Derived Elevation Models

    NASA Astrophysics Data System (ADS)

    Burns, K.; Yates, D. G.; Speyerer, E.; Robinson, M. S.

    2012-12-01

    One of the primary objectives of the Lunar Reconnaissance Orbiter Camera (LROC) [1] is to gather stereo observations with the Narrow Angle Camera (NAC) to generate digital elevation models (DEMs). From an altitude of 50 km, the NAC acquires images with a pixel scale of 0.5 meters, and a dual NAC observation covers approximately 5 km cross-track by 25 km down-track. This low altitude was common from September 2009 to December 2011. Images acquired during the commissioning phase and those acquired from the fixed orbit (after 11 December 2011) have pixel scales that range from 0.35 meters at the south pole to 2 meters at the north pole. Alimetric observations obtained by the Lunar Orbiter Laser Altimeter (LOLA) provide measurements of ±0.1 m between the spacecraft and the surface [2]. However, uncertainties in the spacecraft positioning can result in offsets (±20m) between altimeter tracks over many orbits. The LROC team is currently developing a tool to automatically register alimetric observations to NAC DEMs [3]. Using a generalized pattern search (GPS) algorithm, the new automatic registration adjusts the spacecraft position and pointing information during times when NAC images, as well as LOLA measurements, of the same region are acquired to provide an absolute reference frame for the DEM. This information is then imported into SOCET SET to aide in creating controlled NAC DEMs. For every DEM, a figure of merit (FOM) map is generated using SOCET SET software. This is a valuable tool for determining the relative accuracy of a specific pixel in a DEM. Each pixel in a FOM map is given a value to determine its "quality" by determining if the specific pixel was shadowed, saturated, suspicious, interpolated/extrapolated, or successfully correlated. The overall quality of a NAC DEM is a function of both the absolute and relative accuracies. LOLA altimetry provides the most accurate absolute geodetic reference frame with which the NAC DEMs can be compared. Offsets

  1. Overexpression of the Eggplant (Solanum melongena) NAC Family Transcription Factor SmNAC Suppresses Resistance to Bacterial Wilt

    PubMed Central

    Na, Chen; Shuanghua, Wu; Jinglong, Fu; Bihao, Cao; Jianjun, Lei; Changming, Chen; Jin, Jiang

    2016-01-01

    Bacterial wilt (BW) is a serious disease that affects eggplant (Solanum melongena) production. Although resistance to this disease has been reported, the underlying mechanism is unknown. In this study, we identified a NAC family transcription factor (SmNAC) from eggplant and characterized its expression, its localization at the tissue and subcellular levels, and its role in BW resistance. To this end, transgenic eggplant lines were generated in which the expression of SmNAC was constitutively up regulated or suppressed using RNAi. The results indicated that overexpression of SmNAC decreases resistance to BW. Moreover, SmNAC overexpression resulted in the reduced accumulation of the plant immune signaling molecule salicylic acid (SA) and reduced expression of ICS1 (a gene that encode isochorismate synthase 1, which is involved in SA biosynthesis). We propose that reduced SA content results in increased bacterial wilt susceptibility in the transgenic lines. Our results provide important new insights into the regulatory mechanisms of bacterial wilt resistance in eggplant. PMID:27528282

  2. Overexpression of the Eggplant (Solanum melongena) NAC Family Transcription Factor SmNAC Suppresses Resistance to Bacterial Wilt.

    PubMed

    Na, Chen; Shuanghua, Wu; Jinglong, Fu; Bihao, Cao; Jianjun, Lei; Changming, Chen; Jin, Jiang

    2016-08-16

    Bacterial wilt (BW) is a serious disease that affects eggplant (Solanum melongena) production. Although resistance to this disease has been reported, the underlying mechanism is unknown. In this study, we identified a NAC family transcription factor (SmNAC) from eggplant and characterized its expression, its localization at the tissue and subcellular levels, and its role in BW resistance. To this end, transgenic eggplant lines were generated in which the expression of SmNAC was constitutively up regulated or suppressed using RNAi. The results indicated that overexpression of SmNAC decreases resistance to BW. Moreover, SmNAC overexpression resulted in the reduced accumulation of the plant immune signaling molecule salicylic acid (SA) and reduced expression of ICS1 (a gene that encode isochorismate synthase 1, which is involved in SA biosynthesis). We propose that reduced SA content results in increased bacterial wilt susceptibility in the transgenic lines. Our results provide important new insights into the regulatory mechanisms of bacterial wilt resistance in eggplant.

  3. Targeting Protein O-GlcNAc Modifications In Breast Cancer

    DTIC Science & Technology

    2010-09-30

    vivo (months 6-12, PI:Reginato): Preliminary studies indicate elevated O-GlcNAc in ERBB2 transformed cells, and suggest that lowering O-GlcNAc levels...proteins (with OGT RNAi or OGT inhibitor) inhibits oncogenic phenotypes in vivo (months 6-12, PI:Reginato): Preliminary studies indicate elevated O...agar) of ERBB2 expressing MCF-10A cells and breast cancer cell lines (SKBR3 and MDA-MB-453). (months 1-3) Our studies completed Breast cancer cell

  4. Emissions Inventory Report Summary: Reporting Requirements for the New Mexico Administrative Code, Title 20, Chapter 2, Part 73 (20.2.73 NMAC) for Calendar Year 2003

    SciTech Connect

    M. Stockton

    2005-01-01

    Los Alamos National Laboratory is subject to annual emissions-reporting requirements for regulated air pollutants under Title 20 of the New Mexico Administrative Code, Chapter 2, Part 73 (20.2.73 NMAC), Notice of Intent and Emissions Inventory Requirements. The applicability of the requirements is based on the Laboratory's potential to emit 100 tons per year of suspended particulate matter, nitrogen oxides, carbon monoxide, sulfur oxides, or volatile organic compounds. For calendar year 2003, the Technical Area 3 steam plant and the air curtain destructors were the primary sources of criteria air pollutants from the Laboratory, while the air curtain destructors and chemical use associated with research and development activities were the primary sources of volatile organic compounds and hazardous air pollutants. Emissions of beryllium and aluminum were reported for activities permitted under 20.2.72 NMAC. Hazardous air pollutant emissions were reported from chemical use as well as from all combustion sources. In addition, estimates of particulate matter with diameter less than 2.5 micrometers and ammonia were provided as requested by the New Mexico Environment Department, Air Quality Bureau.

  5. Cell cycle-dependent alteration in NAC1 nuclear body dynamics and morphology

    NASA Astrophysics Data System (ADS)

    Wu, Pei-Hsun; Hung, Shen-Hsiu; Ren, Tina; Shih, Ie-Ming; Tseng, Yiider

    2011-02-01

    NAC1, a BTB/POZ family member, has been suggested to participate in maintaining the stemness of embryonic stem cells and has been implicated in the pathogenesis of human cancer. In ovarian cancer, NAC1 upregulation is associated with disease aggressiveness and with the development of chemoresistance. Like other BTB/POZ proteins, NAC1 forms discrete nuclear bodies in non-dividing cells. To investigate the biological role of NAC1 nuclear bodies, we characterized the expression dynamics of NAC1 nuclear bodies during different phases of the cell cycle. Fluorescence recovery after photobleaching assays revealed that NAC1 was rapidly exchanged between the nucleoplasm and NAC1 nuclear bodies in interphase cells. The number of NAC1 bodies significantly increased and their size decreased in the S phase as compared to the G0/G1 and G2 phases. NAC1 nuclear bodies disappeared and NAC1 became diffuse during mitosis. NAC1 nuclear bodies reappeared immediately after completion of mitosis. These results indicate that a cell cycle-dependent regulatory mechanism controls NAC1 body formation in the nucleus and suggest that NAC1 body dynamics are associated with mitosis or cytokinesis.

  6. Antioxidant N-acetyl-L-cysteine (NAC) supplementation reduces reactive oxygen species (ROS)-mediated hepatocellular tumor promotion of indole-3-carbinol (I3C) in rats.

    PubMed

    Shimamoto, Keisuke; Hayashi, Hitomi; Taniai, Eriko; Morita, Reiko; Imaoka, Masako; Ishii, Yuji; Suzuki, Kazuhiko; Shibutani, Makoto; Mitsumori, Kunitoshi

    2011-01-01

    Indole-3-carbinol (I3C) has a liver tumor promoting activity in rats, and is also known as a cytochrome p450 1A (CYP1A) inducer. The generation of reactive oxygen species (ROS) resulting from CYP1A induction due to I3C, is probably involved in the tumor promotion. To clarify whether ROS generation contributes to I3C's induction of hepatocellular altered foci, partially hepatectomized rats were fed a diet containing 0.5% of I3C for 8 weeks with or without 0.3% N-acetyl-L-cysteine (NAC), an antioxidant, in their drinking water after N-diethylnitrosamine (DEN) initiation. Immunohistochemical analysis showed that the glutathione-S-transferase placental form (GST-P) positive foci promoted by I3C were suppressed by the administration of NAC. The mRNAs of members of the phase II nuclear factor, erythroid derived 2, like 2 (Nrf2) gene batteries, whose promoter region is called as antioxidant response element (ARE), were down-regulated in the DEN-I3C-NAC group compared to the DEN-I3C group, but Cyp1a1 was not suppressed in the DEN-I3C-NAC group compared to the DEN-I3C group. There was no marked difference in production of microsomal ROS and genomic 8-hydroxy-2'-deoxygunosine (8-OHdG) as an oxidative DNA marker between the DEN-I3C-NAC and DEN-I3C groups, while mapkapk3 and Myc were decreased by the NAC treatment. These results indicate that oxidative stress plays an important role for I3C's tumor promotion, and NAC suppresses induction of hepatocellular altered foci with suppressed cytoplasmic oxidative stress.

  7. The Stress-Induced Soybean NAC Transcription Factor GmNAC81 Plays a Positive Role in Developmentally Programmed Leaf Senescence.

    PubMed

    Pimenta, Maiana Reis; Silva, Priscila Alves; Mendes, Giselle Camargo; Alves, Janaína Roberta; Caetano, Hanna Durso Neves; Machado, Joao Paulo Batista; Brustolini, Otavio José Bernardes; Carpinetti, Paola Avelar; Melo, Bruno Paes; Silva, José Cleydson Ferreira; Rosado, Gustavo Leão; Ferreira, Márcia Flores Silva; Dal-Bianco, Maximillir; Picoli, Edgard Augusto de Toledo; Aragao, Francisco José Lima; Ramos, Humberto Josué Oliveira; Fontes, Elizabeth Pacheco Batista

    2016-05-01

    The onset of leaf senescence is a highly regulated developmental change that is controlled by both genetics and the environment. Senescence is triggered by massive transcriptional reprogramming, but functional information about its underlying regulatory mechanisms is limited. In the current investigation, we performed a functional analysis of the soybean (Glycine max) osmotic stress- and endoplasmic reticulum (ER) stress-induced NAC transcription factor GmNAC81 during natural leaf senescence using overexpression studies and reverse genetics. GmNAC81-overexpressing lines displayed accelerated flowering and leaf senescence but otherwise developed normally. The precocious leaf senescence of GmNAC81-overexpressing lines was associated with greater Chl loss, faster photosynthetic decay and higher expression of hydrolytic enzyme-encoding GmNAC81 target genes, including the vacuolar processing enzyme (VPE), an executioner of vacuole-triggered programmed cell death (PCD). Conversely, virus-induced gene silencing-mediated silencing of GmNAC81 delayed leaf senescence and was associated with reductions in Chl loss, lipid peroxidation and the expression of GmNAC81 direct targets. Promoter-reporter studies revealed that the expression pattern of GmNAC81 was associated with senescence in soybean leaves. Our data indicate that GmNAC81 is a positive regulator of age-dependent senescence and may integrate osmotic stress- and ER stress-induced PCD responses with natural leaf senescence through the GmNAC81/VPE regulatory circuit.

  8. O-GlcNAc processing enzymes: catalytic mechanisms, substrate specificity, and enzyme regulation.

    PubMed

    Vocadlo, David J

    2012-12-01

    The addition of N-acetylglucosamine (GlcNAc) O-linked to serine and threonine residues of proteins is known as O-GlcNAc. This post-translational modification is found within multicellular eukaryotes on hundreds of nuclear and cytoplasmic proteins. O-GlcNAc transferase (OGT) installs O-GlcNAc onto target proteins and O-GlcNAcase (OGA) removes O-GlcNAc. Their combined action makes O-GlcNAc reversible and serves to regulate cellular O-GlcNAc levels. Here I review select recent literature on the catalytic mechanism of these enzymes and studies on the molecular basis by which these enzymes identify and process their substrates. Molecular level understanding of how these enzymes work, and the basis for their specificity, should aid understanding how O-GlcNAc contributes to diverse cellular processes ranging from cellular signaling through to transcriptional regulation.

  9. A computational and experimental study of O-glycosylation. Catalysis by human UDP-GalNAc polypeptide:GalNAc transferase-T2†

    PubMed Central

    Gómez, Hansel; Rojas, Raúl; Patel, Divya; Lluch, José M.

    2016-01-01

    It is estimated that >50% of proteins are glycosylated with sugar tags that can modulate protein activity through what has been called the sugar code. Here we present the first QM/MM calculations of human GalNAc-T2, a retaining glycosyltransferase, which initiates the biosynthesis of mucin-type O-glycans. Importantly, we have characterized a hydrogen bond between the β-phosphate of UDP and the backbone amide group from the Thr7 of the sugar acceptor (EA2 peptide) that promotes catalysis and that we propose could be a general catalytic strategy used in peptide O-glycosylation by retaining glycosyltransferases. Additional important substrate–substrate interactions have been identified, for example, between the β-phosphate of UDP with the attacking hydroxyl group from the acceptor substrate and with the substituent at the C2′ position of the transferred sugar. Our results support a front-side attack mechanism for this enzyme, with a barrier height of ~20 kcal mol−1 at the QM(M05-2X/TZVP//BP86/SVP)/CHARMM22 level, in reasonable agreement with the experimental kinetic data. Experimental and in silico mutations show that transferase activity is very sensitive to changes in residues Glu334, Asn335 and Arg362. Additionally, our calculations for different donor substrates suggest that human GalNAc-T2 would be inactive if 2′-deoxy-Gal or 2′-oxymethyl-Gal were used, while UDP-Gal is confirmed as a valid sugar donor. Finally, the analysis herein presented highlights that both the substrate–substrate and the enzyme–substrate interactions are mainly concentrated on stabilizing the negative charge developing at the UDP leaving group as the transition state is approached, identifying this as a key aspect of retaining glycosyltransferases catalysis. PMID:24643241

  10. Isolation and expression of NAC genes during persimmon fruit postharvest astringency removal.

    PubMed

    Min, Ting; Wang, Miao-Miao; Wang, Hongxun; Liu, Xiaofen; Fang, Fang; Grierson, Donald; Yin, Xue-Ren; Chen, Kun-Song

    2015-01-15

    NAC genes have been characterized in numerous plants, where they are involved in responses to biotic and abiotic stress, including low oxygen stress. High concentration of CO2 is one of the most effective treatments to remove astringency of persimmon fruit owing to the action of the accumulated anoxia metabolite acetaldehyde. In model plants, NAC genes have been identified as being responsive to low oxygen. However, the possible relationship between NAC transcription factors and persimmon astringency removal remains unexplored. In the present research, treatment with a high concentration of CO2 (95%) effectively removed astringency of "Mopan" persimmon fruit by causing decreases in soluble tannin. Acetaldehyde content increased in response to CO2 treatment concomitantly with astringency removal. Using RNA-seq and Rapid amplification of cDNA ends (RACE), six DkNAC genes were isolated and studied. Transcriptional analysis indicated DkNAC genes responded differentially to CO2 treatment; DkNAC1, DkNAC3, DkNAC5 and DkNAC6 were transiently up-regulated, DkNAC2 was abundantly expressed 3 days after treatment, while the DkNAC4 was suppressed during astringency removal. It is proposed that DkNAC1/3/5/6 could be important candidates as regulators of persimmon astringency removal and the roles of other member are also discussed.

  11. Molecular characterization and function analysis of SlNAC2 in Suaeda liaotungensis K.

    PubMed

    Yang, Xing; Hu, Yu-Xin; Li, Xiao-Lan; Yu, Xiao-Dong; Li, Qiu-Li

    2014-06-15

    The plant-specific NAC (NAM, ATAF1/2, and CUC) transcription factors have diverse roles in plant development and stress responses. In this study, a stress-responsive NAC gene, SlNAC2, was isolated and characterized from high-throughput Solexa sequencing of Suaeda liaotungensis. SlNAC2 showed high similarity to other NACs, especially ATAF subgroup members. Transcripts of SlNAC2 appeared in many Suaeda tissues including leaves, stems and roots. In particular, SlNAC2 was strongly expressed in leaves. Expression analysis showed that SlNAC2 was highly induced during salt and low temperature stress in leaves. Subcellular localization showed that the SlNAC2 protein localized to the nucleus. A transactivation assay in yeast demonstrated that SlNAC2 activated the expression of a reporter gene. To test its function, SlNAC2 was transformed into Arabidopsis under the control of the CaMV-35S promoter. Functional analysis showed that its overexpression resulted in enhanced tolerance to salinity stress. Therefore, SlNAC2 is a multifunctional regulatory factor in plants, and might be a good candidate gene for genetic improvement to produce stress tolerant plants.

  12. Soybean NAC transcription factors promote abiotic stress tolerance and lateral root formation in transgenic plants.

    PubMed

    Hao, Yu-Jun; Wei, Wei; Song, Qing-Xin; Chen, Hao-Wei; Zhang, Yu-Qin; Wang, Fang; Zou, Hong-Feng; Lei, Gang; Tian, Ai-Guo; Zhang, Wan-Ke; Ma, Biao; Zhang, Jin-Song; Chen, Shou-Yi

    2011-10-01

    NAC transcription factors play important roles in plant growth, development and stress responses. Previously, we identified multiple NAC genes in soybean (Glycine max). Here, we identify the roles of two genes, GmNAC11 and GmNAC20, in stress responses and other processes. The two genes were differentially induced by multiple abiotic stresses and plant hormones, and their transcripts were abundant in roots and cotyledons. Both genes encoded proteins that localized to the nucleus and bound to the core DNA sequence CGT[G/A]. In the protoplast assay system, GmNAC11 acts as a transcriptional activator, whereas GmNAC20 functions as a mild repressor; however, the C-terminal end of GmANC20 has transcriptional activation activity. Over-expression of GmNAC20 enhances salt and freezing tolerance in transgenic Arabidopsis plants; however, GmNAC11 over-expression only improves salt tolerance. Over-expression of GmNAC20 also promotes lateral root formation. GmNAC20 may regulate stress tolerance through activation of the DREB/CBF-COR pathway, and may control lateral root development by altering auxin signaling-related genes. GmNAC11 probably regulates DREB1A and other stress-related genes. The roles of the two GmNAC genes in stress tolerance were further analyzed in soybean transgenic hairy roots. These results provide a basis for genetic manipulation to improve the agronomic traits of important crops.

  13. Barley plants over-expressing the NAC transcription factor gene HvNAC005 show stunting and delay in development combined with early senescence

    PubMed Central

    Christiansen, Michael W.; Matthewman, Colette; Podzimska-Sroka, Dagmara; O’Shea, Charlotte; Lindemose, Søren; Møllegaard, Niels Erik; Holme, Inger B.; Hebelstrup, Kim; Skriver, Karen; Gregersen, Per L.

    2016-01-01

    The plant-specific NAC transcription factors have attracted particular attention because of their involvement in stress responses, senescence, and nutrient remobilization. The HvNAC005 gene of barley encodes a protein belonging to subgroup NAC-a6 of the NAC family. This study shows that HvNAC005 is associated with developmental senescence. It was significantly up-regulated following ABA treatment, supported by ABA-responsive elements in its promoter, but it was not up-regulated during dark-induced senescence. The C-termini of proteins closely related to HvNAC005 showed overall high divergence but also contained conserved short motifs. A serine- and leucine-containing central motif was essential for transcriptional activity of the HvNAC005 C-terminus in yeast. Over-expression of HvNAC005 in barley resulted in a strong phenotype with delayed development combined with precocious senescence. The over-expressing plants showed up-regulation of genes involved with secondary metabolism, hormone metabolism, stress, signalling, development, and transport. Up-regulation of senescence markers and hormone metabolism and signalling genes supports a role of HvNAC005 in the cross field of different hormone and signalling pathways. Binding of HvNAC005 to promoter sequences of putative target genes containing the T[G/A]CGT core motif was shown by direct protein–DNA interactions of HvNAC005 with promoters for two of the up-regulated genes. In conclusion, HvNAC005 was shown to be a strong positive regulator of senescence and so is an obvious target for the fine-tuning of gene expression in future attempts to improve nutrient remobilization related to the senescence process in barley. PMID:27436280

  14. RhNAC3, a stress-associated NAC transcription factor, has a role in dehydration tolerance through regulating osmotic stress-related genes in rose petals.

    PubMed

    Jiang, Xinqiang; Zhang, Changqing; Lü, Peitao; Jiang, Guimei; Liu, Xiaowei; Dai, Fanwei; Gao, Junping

    2014-01-01

    Petal cell expansion depends on cell wall metabolism, changes in cell turgor pressure and restructuring of the cytoskeleton, and recovery ability of petal cell expansion is defined as an indicator of dehydration tolerance in flowers. We previously reported that RhNAC2, a development-related NAC domain transcription factor, confers dehydration tolerance through regulating cell wall-related genes in rose petals. Here, we identify RhNAC3, a novel rose SNAC gene, and its expression in petals induced by dehydration, wounding, exogenous ethylene and abscisic acid (ABA). Expression studies in Arabidopsis protoplasts and yeast show that RhNAC3 has transactivation activity along its full length and in the carboxyl-terminal domain. Silencing RhNAC3 in rose petals by virus-induced gene silencing (VIGS) significantly decreased the cell expansion of rose petals under rehydration conditions. In total, 24 of 27 osmotic stress-related genes were down-regulated in RhNAC3-silenced rose petals, while only 4 of 22 cell expansion-related genes were down-regulated. Overexpression of RhNAC3 in Arabidopsis gave improved drought tolerance, with lower water loss of leaves in transgenic plants. Arabidopsis ATH1 microarray analysis showed that RhNAC3 regulated the expression of stress-responsive genes in overexpressing lines, and further analysis revealed that most of the RhNAC3-up-regulated genes were involved in the response to osmotic stress. Comparative analysis revealed that different transcription regulation existed between RhNAC3 and RhNAC2. Taken together, these data indicate that RhNAC3, as a positive regulator, confers dehydration tolerance of rose petals mainly through regulating osmotic adjustment-associated genes.

  15. A Tale of Two Disability Coding Systems: The Veterans Administration Schedule for Rating Disabilities (VASRD) vs. Diagnostic Coding Using the International Classification of Diseases, 9th Edition, Clinical Modification (ICD-9-CM)

    DTIC Science & Technology

    2008-01-01

    It is also not clear how the VASRD codes will relate to clinical diagnoses and treatment in hospitalizations and outpatient clinics for injuries and...Veterans Affairs (VA) facility treatment costs for Army Soldiers with a medical discharge between 1986 and 1995 were estimated at $124 million in...these VASRD codes will relate to clinical diagnoses and treatment in hospitalizations and outpatient clinics for injuries and diseases occurring

  16. O-GlcNAc inhibits interaction between Sp1 and Elf-1 transcription factors

    SciTech Connect

    Lim, Kihong; Chang, Hyo-Ihl

    2009-03-13

    The novel protein modification, O-linked N-acetylglucosamine (O-GlcNAc), plays an important role in various aspects of cell regulation. Although most of nuclear transcription regulatory factors are modified by O-GlcNAc, O-GlcNAc effects on transcription remain largely undefined yet. In this study, we show that O-GlcNAc inhibits a physical interaction between Sp1 and Elf-1 transcription factors, and negatively regulates transcription of placenta and embryonic expression oncofetal protein gene (Pem). These findings suggest that O-GlcNAc inhibits Sp1-mediated gene transcription possibly by interrupting Sp1 interaction with its cooperative factor.

  17. NAC-1 cask dose rate calculations for LWR spent fuel

    SciTech Connect

    CARLSON, A.B.

    1999-02-24

    A Nuclear Assurance Corporation nuclear fuel transport cask, NAC-1, is being considered as a transport and storage option for spent nuclear fuel located in the B-Cell of the 324 Building. The loaded casks will be shipped to the 200 East Area Interim Storage Area for dry interim storage. Several calculations were performed to assess the photon and neutron dose rates. This report describes the analytical methods, models, and results of this investigation.

  18. Photoassociation spectroscopy of ultracold highly excited NaCs molecules

    NASA Astrophysics Data System (ADS)

    Jayaseelan, Maitreyi; Haruza, Marek; Bigelow, Nicholas

    2013-05-01

    We report on our spectroscopic investigations of translationally ultracold NaCs molecules. Photoassociation from laser cooled mixtures of ground state sodium and excited cesium atoms creates molecules in excited states detuned from the Na(3s) + Cs(6d) dissociation asymptote. This is an as yet unexplored asymptote for molecule formation. We infer properties of the scattering wave from the PA spectra, and investigate the populated ground states using photoionization and depletion spectroscopy.

  19. O-GlcNAc and the cardiovascular system.

    PubMed

    Dassanayaka, Sujith; Jones, Steven P

    2014-04-01

    The cardiovascular system is capable of robust changes in response to physiologic and pathologic stimuli through intricate signaling mechanisms. The area of metabolism has witnessed a veritable renaissance in the cardiovascular system. In particular, the post-translational β-O-linkage of N-acetylglucosamine (O-GlcNAc) to cellular proteins represents one such signaling pathway that has been implicated in the pathophysiology of cardiovascular disease. This highly dynamic protein modification may induce functional changes in proteins and regulate key cellular processes including translation, transcription, and cell death. In addition, its potential interplay with phosphorylation provides an additional layer of complexity to post-translational regulation. The hexosamine biosynthetic pathway generally requires glucose to form the nucleotide sugar, UDP-GlcNAc. Accordingly, O-GlcNAcylation may be altered in response to nutrient availability and cellular stress. Recent literature supports O-GlcNAcylation as an autoprotective response in models of acute stress (hypoxia, ischemia, oxidative stress). Models of sustained stress, such as pressure overload hypertrophy, and infarct-induced heart failure, may also require protein O-GlcNAcylation as a partial compensatory mechanism. Yet, in models of Type II diabetes, O-GlcNAcylation has been implicated in the subsequent development of vascular, and even cardiac, dysfunction. This review will address this apparent paradox and discuss the potential mechanisms of O-GlcNAc-mediated cardioprotection and cardiovascular dysfunction. This discussion will also address potential targets for pharmacologic interventions and the unique considerations related to such targets.

  20. O-GlcNAc profiling: from proteins to proteomes

    PubMed Central

    2014-01-01

    O-linked β-D-N-acetylglucosamine (O-GlcNAc) modification (O-GlcNAcylation) onto serine and threonine residues of proteins is an important post-translational modification (PTM), which is involved in many crucial biological processes including transcription, translation, proteasomal degradation, and signal transduction. Aberrant protein O-GlcNAcylation is directly linked to the pathological progression of chronic diseases including diabetes, cancer, and neurodegenerative disorders. Identification, site mapping, and quantification of O-GlcNAc proteins are a prerequisite to decipher their functions. In this review, we mainly focus on technological developments regarding O-GlcNAc protein profiling. Specifically, on one hand, we show how these techniques are being used for the comprehensive characterization of certain targeted proteins in which biologists are most interested. On the other hand, we present several newly developed approaches for O-GlcNAcomic profiling as well as how they provide us with a systems perspective to crosstalk amongst different PTMs and complicated biological events. Promising technical trends are also highlighted to evoke more efforts by diverse laboratories, which would further expand our understanding of the physiological and pathological roles of protein O-GlcNAcylation in chronic diseases. PMID:24593906

  1. The rose (Rosa hybrida) NAC transcription factor 3 gene, RhNAC3, involved in ABA signaling pathway both in rose and Arabidopsis.

    PubMed

    Jiang, Guimei; Jiang, Xinqiang; Lü, Peitao; Liu, Jitao; Gao, Junping; Zhang, Changqing

    2014-01-01

    Plant transcription factors involved in stress responses are generally classified by their involvement in either the abscisic acid (ABA)-dependent or the ABA-independent regulatory pathways. A stress-associated NAC gene from rose (Rosa hybrida), RhNAC3, was previously found to increase dehydration tolerance in both rose and Arabidopsis. However, the regulatory mechanism involved in RhNAC3 action is still not fully understood. In this study, we isolated and analyzed the upstream regulatory sequence of RhNAC3 and found many stress-related cis-elements to be present in the promoter, with five ABA-responsive element (ABRE) motifs being of particular interest. Characterization of Arabidopsis thaliana plants transformed with the putative RhNAC3 promoter sequence fused to the β-glucuronidase (GUS) reporter gene revealed that RhNAC3 is expressed at high basal levels in leaf guard cells and in vascular tissues. Moreover, the ABRE motifs in the RhNAC3 promoter were observed to have a cumulative effect on the transcriptional activity of this gene both in the presence and absence of exogenous ABA. Overexpression of RhNAC3 in A. thaliana resulted in ABA hypersensitivity during seed germination and promoted leaf closure after ABA or drought treatments. Additionally, the expression of 11 ABA-responsive genes was induced to a greater degree by dehydration in the transgenic plants overexpressing RhNAC3 than control lines transformed with the vector alone. Further analysis revealed that all these genes contain NAC binding cis-elements in their promoter regions, and RhNAC3 was found to partially bind to these putative NAC recognition sites. We further found that of 219 A. thaliana genes previously shown by microarray analysis to be regulated by heterologous overexpression RhNAC3, 85 are responsive to ABA. In rose, the expression of genes downstream of the ABA-signaling pathways was also repressed in RhNAC3-silenced petals. Taken together, we propose that the rose RhNAC3 protein

  2. An Arabidopsis NAC transcription factor NAC4 promotes pathogen-induced cell death under negative regulation by microRNA164.

    PubMed

    Lee, Myoung-Hoon; Jeon, Hwi Seong; Kim, Hye Gi; Park, Ohkmae K

    2017-04-01

    Hypersensitive response (HR) is a form of programmed cell death (PCD) and the primary immune response that prevents pathogen invasion in plants. Here, we show that a microRNAmiR164 and its target gene NAC4 (At5g07680), encoding a NAC transcription factor, play essential roles in the regulation of HR PCD in Arabidopsis thaliana. Cell death symptoms were noticeably enhanced in NAC4-overexpressing (35S:NAC4) and mir164 mutant plants in response to avirulent bacterial pathogens. NAC4 expression was induced by pathogen infection and negatively regulated by miR164 expression. NAC4-binding DNA sequences were determined by in vitro binding site selection using random oligonucleotide sequences. Microarray, chromatin immunoprecipitation and quantitative real time polymerase chain reaction (qRT-PCR) analyses, followed by cell death assays in protoplasts, led to the identification of NAC4 target genes LURP1, WRKY40 and WRKY54, which act as negative regulators of cell death. Our results suggest that NAC4 promotes hypersensitive cell death by suppressing its target genes and this immune process is fine-tuned by the negative action of miR164.

  3. Production of O-GlcNAc Modified Recombinant Tau in E. coli and Detection of Ser400 O-GlcNAc Tau In Vivo.

    PubMed

    Yuzwa, Scott A; Vocadlo, David J

    2017-01-01

    Assembly of the microtubule-associated protein tau (tau) into paired helical filaments that ultimately give rise to neurofibrillary tangles (NFTs) makes up one half of the two hallmark pathologies of Alzheimer's disease (AD). Tau has been shown to be modified with O-linked N-acetylglucosamine residues (O-GlcNAc), which is the modification of serine and threonine residues of nucleocytoplasmic proteins with N-acetyl-D-glucosamine (GlcNAc) moieties. Increasing O-GlcNAc in mouse models of tauopathy has been shown to hinder the progression of symptoms in these mice and impair the aggregation of tau into NFTs. In order to study how O-GlcNAc on tau may contribute to the protective effects observed in tauopathy mouse models, it is beneficial to study O-GlcNAc modified tau in vitro. Here we describe a method for producing, purifying and enriching recombinant tau that is O-GlcNAc modified. These methods have enabled the identification of O-GlcNAc modification sites on tau including Ser400. We further describe the detection of Ser400 O-GlcNAc on tau from brain lysates.

  4. Overexpression of horsegram (Macrotyloma uniflorum Lam.Verdc.) NAC transcriptional factor (MuNAC4) in groundnut confers enhanced drought tolerance.

    PubMed

    Pandurangaiah, Merum; Lokanadha Rao, G; Sudhakarbabu, O; Nareshkumar, A; Kiranmai, K; Lokesh, U; Thapa, Ganesh; Sudhakar, Chinta

    2014-08-01

    The NAC family being the largest plant-specific transcription factors functions in diverse and vital physiological processes during development. NAC proteins are known to be crucial in imparting tolerance to plants against abiotic stresses, such as drought and salinity, but the functions of most of them are still elusive. In this study, we report for the first time expression of the MuNAC4, a member of NAC transcription factor from horsegram (Macrotyloma uniflorum) conferring drought tolerance. The groundnut (Arachis hypogaea) transgenics were generated using recombinant MuNAC4 binary vector transformation approach. Molecular analysis of these transgenic lines confirmed the stable gene integration and expression of the MuNAC4 gene. Twelve lines of T5 generation exhibited significantly enhanced tolerance to drought stress with proliferated lateral root growth as compared to wild types. Transgenics exposed to long-term desiccation stress assays showed increased lateral roots and greenish growth. The physiological parameters analysis also suggests that overexpression of MuNAC4 plays a significant role in improving the water stress tolerance of transgenic groundnut, reducing the damage to membrane structures and enhancing osmotic adjustment and antioxidative enzyme regulation under stress. This study validates MuNAC4 as an important candidate gene for future phytoengineering approaches for drought tolerance in crop plants.

  5. Expression of Vitis amurensis NAC26 in Arabidopsis enhances drought tolerance by modulating jasmonic acid synthesis

    PubMed Central

    Fang, Linchuan; Su, Lingye; Sun, Xiaoming; Li, Xinbo; Sun, Mengxiang; Karungo, Sospeter Karanja; Fang, Shuang; Chu, Jinfang; Li, Shaohua; Xin, Haiping

    2016-01-01

    The growth and fruit quality of grapevines are widely affected by abnormal climatic conditions such as water deficits, but many of the precise mechanisms by which grapevines respond to drought stress are still largely unknown. Here, we report that VaNAC26, a member of the NAC transcription factor family, was upregulated dramatically during cold, drought and salinity treatments in Vitis amurensis, a cold and drought-hardy wild Vitis species. Heterologous overexpression of VaNAC26 enhanced drought and salt tolerance in transgenic Arabidopsis. Higher activities of antioxidant enzymes and lower concentrations of H2O2 and O2 − were found in VaNAC26-OE lines than in wild type plants under drought stress. These results indicated that scavenging by reactive oxygen species (ROS) was enhanced by VaNAC26 in transgenic lines. Microarray-based transcriptome analysis revealed that genes related to jasmonic acid (JA) synthesis and signaling were upregulated in VaNAC26-OE lines under both normal and drought conditions. VaNAC26 showed a specific binding ability on the NAC recognition sequence (NACRS) motif, which broadly exists in the promoter regions of upregulated genes in transgenic lines. Endogenous JA content significantly increased in the VaNAC26-OE lines 2 and 3. Our data suggest that VaNAC26 responds to abiotic stresses and may enhance drought tolerance by transcriptional regulation of JA synthesis in Arabidopsis. PMID:27162276

  6. Global Analysis of O-GlcNAc Glycoproteins in Activated Human T Cells

    PubMed Central

    Lund, Peder J.; Elias, Joshua E.

    2016-01-01

    T cell activation in response to Ag is largely regulated by protein posttranslational modifications. Although phosphorylation has been extensively characterized in T cells, much less is known about the glycosylation of serine/threonine residues by O-linked N-acetylglucosamine (O-GlcNAc). Given that O-GlcNAc appears to regulate cell signaling pathways and protein activity similarly to phosphorylation, we performed a comprehensive analysis of O-GlcNAc during T cell activation to address the functional importance of this modification and to identify the modified proteins. Activation of T cells through the TCR resulted in a global elevation of O-GlcNAc levels and in the absence of O-GlcNAc, IL-2 production and proliferation were compromised. T cell activation also led to changes in the relative expression of O-GlcNAc transferase (OGT) isoforms and accumulation of OGT at the immunological synapse of murine T cells. Using a glycoproteomics approach, we identified >200 O-GlcNAc proteins in human T cells. Many of the identified proteins had a functional relationship to RNA metabolism, and consistent with a connection between O-GlcNAc and RNA, inhibition of OGT impaired nascent RNA synthesis upon T cell activation. Overall, our studies provide a global analysis of O-GlcNAc dynamics during T cell activation and the first characterization, to our knowledge, of the O-GlcNAc glycoproteome in human T cells. PMID:27655845

  7. A NAC Transcription Factor Represses Putrescine Biosynthesis and Affects Drought Tolerance.

    PubMed

    Wu, Hao; Fu, Bing; Sun, Peipei; Xiao, Chang; Liu, Ji-Hong

    2016-11-01

    Arginine decarboxylase (ADC)-mediated putrescine biosynthesis plays an important role in plant stress responses, but the transcriptional regulation of ADC in response to abiotic stress is not well understood. We isolated a NAM, ATAF1/2, and CUC (NAC) domain-containing transcription factor, PtrNAC72, from trifoliate orange (Poncirus trifoliata) by yeast one-hybrid screening. PtrNAC72, localized to the nucleus, binds specifically to the promoter of PtADC and acts as a transcriptional repressor. PtrNAC72 expression was induced by cold, drought, and abscisic acid. ADC messenger RNA abundance and putrescine levels were decreased in transgenic tobacco (Nicotiana nudicaulis) plants overexpressing PtrNAC72 but increased, compared with the wild type, in an Arabidopsis (Arabidopsis thaliana) transfer DNA insertion mutant, nac72 While transgenic tobacco lines overexpressing PtrNAC72 were more sensitive to drought, plants of the Arabidopsis nac72 mutant exhibited enhanced drought tolerance, consistent with the accumulation of reactive oxygen species in the tested genotypes. In addition, exogenous application of putrescine to the overexpression lines restored drought tolerance, while treatment with d-arginine, an ADC inhibitor, compromised the drought tolerance of nac72 Taken together, these results demonstrate that PtrNAC72 is a repressor of putrescine biosynthesis and may negatively regulate the drought stress response, at least in part, via the modulation of putrescine-associated reactive oxygen species homeostasis.

  8. Expression of Vitis amurensis NAC26 in Arabidopsis enhances drought tolerance by modulating jasmonic acid synthesis.

    PubMed

    Fang, Linchuan; Su, Lingye; Sun, Xiaoming; Li, Xinbo; Sun, Mengxiang; Karungo, Sospeter Karanja; Fang, Shuang; Chu, Jinfang; Li, Shaohua; Xin, Haiping

    2016-04-01

    The growth and fruit quality of grapevines are widely affected by abnormal climatic conditions such as water deficits, but many of the precise mechanisms by which grapevines respond to drought stress are still largely unknown. Here, we report that VaNAC26, a member of the NAC transcription factor family, was upregulated dramatically during cold, drought and salinity treatments in Vitis amurensis, a cold and drought-hardy wild Vitis species. Heterologous overexpression of VaNAC26 enhanced drought and salt tolerance in transgenic Arabidopsis. Higher activities of antioxidant enzymes and lower concentrations of H2O2 and O2 (-) were found in VaNAC26-OE lines than in wild type plants under drought stress. These results indicated that scavenging by reactive oxygen species (ROS) was enhanced by VaNAC26 in transgenic lines. Microarray-based transcriptome analysis revealed that genes related to jasmonic acid (JA) synthesis and signaling were upregulated in VaNAC26-OE lines under both normal and drought conditions. VaNAC26 showed a specific binding ability on the NAC recognition sequence (NACRS) motif, which broadly exists in the promoter regions of upregulated genes in transgenic lines. Endogenous JA content significantly increased in the VaNAC26-OE lines 2 and 3. Our data suggest that VaNAC26 responds to abiotic stresses and may enhance drought tolerance by transcriptional regulation of JA synthesis in Arabidopsis.

  9. Dynamic behaviors of vimentin induced by interaction with GlcNAc molecules.

    PubMed

    Komura, Kenta; Ise, Hirohiko; Akaike, Toshihiro

    2012-12-01

    The cytoskeleton protein vimentin is dramatically altered following pathological events such as fibrosis and tumorigenesis. Vimentin binds to multivalent N-acetylglucosamine (GlcNAc) molecules at the cell surface and interacts with O-linked β-GlcNAc proteins. Moreover, dying cells can be engulfed by neighboring cells through surface interactions between vimentin and many O-GlcNAc proteins in cell debris. Here, we show that vimentin was altered by its interaction with GlcNAc-bearing molecules such as GlcNAc-bearing polymers. The interaction with GlcNAc-bearing polymers promoted the cell surface recruitment of vimentin followed by the phosphorylation of vimentin serine 71 and the increase in tetrameric vimentin disassembled from vimentin filaments in HeLa cells. Moreover, it was found that GlcNAc-bearing polymers and O-GlcNAc proteins from dying cells promoted vimentin expression and cell migration in the Madin-Darby canine kidney and Michigan Cancer Foundation-7 cells. These results suggest that interactions between surface vimentin and GlcNAc molecules, including the O-GlcNAc proteins from dying cells, may play a pivotal role in vimentin expression and the migration of cancer cells. We propose new mechanisms of vimentin expression in cancer cells.

  10. NAC Transcription Factors in Senescence: From Molecular Structure to Function in Crops

    PubMed Central

    Podzimska-Sroka, Dagmara; O’Shea, Charlotte; Gregersen, Per L.; Skriver, Karen

    2015-01-01

    Within the last decade, NAC transcription factors have been shown to play essential roles in senescence, which is the focus of this review. Transcriptome analyses associate approximately one third of Arabidopsis NAC genes and many crop NAC genes with senescence, thereby implicating NAC genes as important regulators of the senescence process. The consensus DNA binding site of the NAC domain is used to predict NAC target genes, and protein interaction sites can be predicted for the intrinsically disordered transcription regulatory domains of NAC proteins. The molecular characteristics of these domains determine the interactions in gene regulatory networks. Emerging local NAC-centered gene regulatory networks reveal complex molecular mechanisms of stress- and hormone-regulated senescence and basic physiological steps of the senescence process. For example, through molecular interactions involving the hormone abscisic acid, ArabidopsisNAP promotes chlorophyll degradation, a hallmark of senescence. Furthermore, studies of the functional rice ortholog, OsNAP, suggest that NAC genes can be targeted to obtain specific changes in lifespan control and nutrient remobilization in crop plants. This is also exemplified by the wheat NAM1 genes which promote senescence and increase grain zinc, iron, and protein content. Thus, NAC genes are promising targets for fine-tuning senescence for increased yield and quality. PMID:27135336

  11. Novel poly-GalNAcbeta1-4GlcNAc (LacdiNAc) and fucosylated poly-LacdiNAc N-glycans from mammalian cells expressing beta1,4-N-acetylgalactosaminyltransferase and alpha1,3-fucosyltransferase.

    PubMed

    Kawar, Ziad S; Haslam, Stuart M; Morris, Howard R; Dell, Anne; Cummings, Richard D

    2005-04-01

    Glycans containing the GalNAcbeta1-4GlcNAc (LacdiNAc or LDN) motif are expressed by many invertebrates, but this motif also occurs in vertebrates and is found on several mammalian glycoprotein hormones. This motif contrasts with the more commonly occurring Galbeta1-4GlcNAc (LacNAc or LN) motif. To better understand LDN biosynthesis and regulation, we stably expressed the cDNA encoding the Caenorhabditis elegans beta1,4-N-acetylgalactosaminyltransferase (GalNAcT), which generates LDN in vitro, in Chinese hamster ovary (CHO) Lec8 cells, to establish L8-GalNAcT CHO cells. The glycan structures from these cells were determined by mass spectrometry and linkage analysis. The L8-GalNAcT cell line produces complex-type N-glycans quantitatively bearing LDN structures on their antennae. Unexpectedly, most of these complex-type N-glycans contain novel "poly-LDN" structures consisting of repeating LDN motifs (-3GalNAcbeta1-4GlcNAcbeta1-)n. These novel structures are in contrast to the well known poly-LN structures consisting of repeating LN motifs (-3Galbeta1-4GlcNAcbeta1-)n. We also stably expressed human alpha1,3-fucosyltransferase IX in the L8-GalNAcT cells to establish a new cell line, L8-GalNAcT-FucT. These cells produce complex-type N-glycans with alpha1,3-fucosylated LDN (LDNF) GalNAcbeta1-4(Fucalpha1-3)GlcNAcbeta1-R as well as novel "poly-LDNF" structures (-3GalNAcbeta1-4(Fucalpha 1-3)GlcNAcbeta1-)n. The ability of these cell lines to generate glycoprotein hormones with LDN-containing N-glycans was studied by expressing a recombinant form of the common alpha-subunit in L8-GalNAcT cells. The alpha-subunit N-glycans carried LDN structures, which were further modified by co-expression of the human GalNAc 4-sulfotransferase I, which generates SO4-4GalNAcbeta1-4GlcNAc-R. Thus, the generation of these stable mammalian cells will facilitate future studies on the biological activities and properties of LDN-related structures in glycoproteins.

  12. O-GlcNAc Signaling in the Cardiovascular System

    PubMed Central

    Ngoh, Gladys A.; Facundo, Heberty T.; Zafir, Ayesha; Jones, Steven P.

    2010-01-01

    Cardiovascular function is regulated at multiple levels. Some of the most important aspects of such regulation involve alterations in an ever-growing list of post-translational modifications. One such modification orchestrates input from numerous metabolic cues to modify proteins and alter their localization and/or function. Known as the beta-O-linkage of N-acetylglucosamine (i.e. O-GlcNAc) to cellular proteins, this unique monosaccharide is involved in a diverse array of physiologic and pathologic functions. This Review will introduce readers to the general concepts related to O-GlcNAc, the regulation of this modification, and its role in primary pathophysiology. Much of the existing literature regarding the role of O-GlcNAcylation in disease addresses the protracted elevations in O-GlcNAcylation observed during diabetes. In this Review, we will focus on the emerging evidence of its involvement in the cardiovascular system. In particular, we will highlight evidence of protein O-GlcNAcylation as an autoprotective alarm or stress response. We will discuss recent literature supporting the idea that promoting O-GlcNAcylation improves cell survival during acute stress (e.g. hypoxia, ischemia, oxidative stress), whereas limiting O-GlcNAcylation exacerbates cell damage in similar models. In addition to addressing the potential mechanisms of O-GlcNAc-mediated cardioprotection, we will discuss technical issues related to studying protein O-GlcNAcylation in biological systems. The reader should gain an understanding of what protein O-GlcNAcylation is, and, that its roles in the acute and chronic disease settings appear distinct. PMID:20651294

  13. O-GlcNAc signaling in the cardiovascular system.

    PubMed

    Ngoh, Gladys A; Facundo, Heberty T; Zafir, Ayesha; Jones, Steven P

    2010-07-23

    Cardiovascular function is regulated at multiple levels. Some of the most important aspects of such regulation involve alterations in an ever-growing list of posttranslational modifications. One such modification orchestrates input from numerous metabolic cues to modify proteins and alter their localization and/or function. Known as the beta-O-linkage of N-acetylglucosamine (ie, O-GlcNAc) to cellular proteins, this unique monosaccharide is involved in a diverse array of physiological and pathological functions. This review introduces readers to the general concepts related to O-GlcNAc, the regulation of this modification, and its role in primary pathophysiology. Much of the existing literature regarding the role of O-GlcNAcylation in disease addresses the protracted elevations in O-GlcNAcylation observed during diabetes. In this review, we focus on the emerging evidence of its involvement in the cardiovascular system. In particular, we highlight evidence of protein O-GlcNAcylation as an autoprotective alarm or stress response. We discuss recent literature supporting the idea that promoting O-GlcNAcylation improves cell survival during acute stress (eg, hypoxia, ischemia, oxidative stress), whereas limiting O-GlcNAcylation exacerbates cell damage in similar models. In addition to addressing the potential mechanisms of O-GlcNAc-mediated cardioprotection, we discuss technical issues related to studying protein O-GlcNAcylation in biological systems. The reader should gain an understanding of what protein O-GlcNAcylation is and that its roles in the acute and chronic disease settings appear distinct.

  14. Identification of an NAC Transcription Factor Family by Deep Transcriptome Sequencing in Onion (Allium cepa L.)

    PubMed Central

    Zhu, Siyuan; Dai, Qiuzhong; Liu, Touming

    2016-01-01

    Although onion has been used extensively in the past for cytogenetic studies, molecular analysis has been lacking because the availability of genetic resources is limited. NAM, ATAF, and CUC (NAC) transcription factors (TFs) are plant-specific proteins, and they play key roles in plant growth, development, and stress tolerance. However, none of the onion NAC (CepNAC) genes had been identified thus far. In this study, the transcriptome of onion leaves was analyzed by Illumina paired-end sequencing. Approximately 102.9 million clean sequence reads were produced and used for de novo assembly, which generated 117,189 non-redundant transcripts. Of these transcripts, 39,472 were annotated for their function. In order to mine the CepNAC TFs, CepNAC genes were searched from the transcripts assembled, resulting in the identification of all 39 CepNAC genes. These 39 CepNAC proteins were subjected to phylogenetic analysis together with 47 NAC proteins of known function that were previously identified in other species. The results showed that they can be divided into five groups (NAC-I–V). Interestingly, the NAC-IV and -V groups were found to be likely related to the processes of secondary wall synthesis and stress response, respectively. The transcriptome analysis generated a substantial amount of transcripts, which will aid immensely in identifying important genes and accelerating our understanding of onion growth and development. Moreover, the discovery of 39 CepNAC TFs and the identification of the sequence conservation between them and NAC proteins published will provide a basis for further characterization and validation of their functions in the future. PMID:27331904

  15. Genome-Wide Analysis of the NAC Gene Family in Physic Nut (Jatropha curcas L.).

    PubMed

    Wu, Zhenying; Xu, Xueqin; Xiong, Wangdan; Wu, Pingzhi; Chen, Yaping; Li, Meiru; Wu, Guojiang; Jiang, Huawu

    2015-01-01

    The NAC proteins (NAM, ATAF1/2 and CUC2) are plant-specific transcriptional regulators that have a conserved NAM domain in the N-terminus. They are involved in various biological processes, including both biotic and abiotic stress responses. In the present study, a total of 100 NAC genes (JcNAC) were identified in physic nut (Jatropha curcas L.). Based on phylogenetic analysis and gene structures, 83 JcNAC genes were classified as members of, or proposed to be diverged from, 39 previously predicted orthologous groups (OGs) of NAC sequences. Physic nut has a single intron-containing NAC gene subfamily that has been lost in many plants. The JcNAC genes are non-randomly distributed across the 11 linkage groups of the physic nut genome, and appear to be preferentially retained duplicates that arose from both ancient and recent duplication events. Digital gene expression analysis indicates that some of the JcNAC genes have tissue-specific expression profiles (e.g. in leaves, roots, stem cortex or seeds), and 29 genes differentially respond to abiotic stresses (drought, salinity, phosphorus deficiency and nitrogen deficiency). Our results will be helpful for further functional analysis of the NAC genes in physic nut.

  16. Roles of NAC transcription factors in the regulation of biotic and abiotic stress responses in plants

    PubMed Central

    Nuruzzaman, Mohammed; Sharoni, Akhter M.; Kikuchi, Shoshi

    2013-01-01

    NAC transcription factors are one of the largest families of transcriptional regulators in plants, and members of the NAC gene family have been suggested to play important roles in the regulation of the transcriptional reprogramming associated with plant stress responses. A phylogenetic analysis of NAC genes, with a focus on rice and Arabidopsis, was performed. Herein, we present an overview of the regulation of the stress responsive NAC SNAC/(IX) group of genes that are implicated in the resistance to different stresses. SNAC factors have important roles for the control of biotic and abiotic stresses tolerance and that their overexpression can improve stress tolerance via biotechnological approaches. We also review the recent progress in elucidating the roles of NAC transcription factors in plant biotic and abiotic stresses. Modification of the expression pattern of transcription factor genes and/or changes in their activity contribute to the elaboration of various signaling pathways and regulatory networks. However, a single NAC gene often responds to several stress factors, and their protein products may participate in the regulation of several seemingly disparate processes as negative or positive regulators. Additionally, the NAC proteins function via auto-regulation or cross-regulation is extensively found among NAC genes. These observations assist in the understanding of the complex mechanisms of signaling and transcriptional reprogramming controlled by NAC proteins. PMID:24058359

  17. The Making of a Sweet Modification: Structure and Function of O-GlcNAc Transferase*

    PubMed Central

    Janetzko, John; Walker, Suzanne

    2014-01-01

    O-GlcNAc transferase is an essential mammalian enzyme responsible for transferring a single GlcNAc moiety from UDP-GlcNAc to specific serine/threonine residues of hundreds of nuclear and cytoplasmic proteins. This modification is dynamic and has been implicated in numerous signaling pathways. An unexpected second function for O-GlcNAc transferase as a protease involved in cleaving the epigenetic regulator HCF-1 has also been reported. Recent structural and biochemical studies that provide insight into the mechanism of glycosylation and HCF-1 cleavage will be described, with outstanding questions highlighted. PMID:25336649

  18. Molecular characterization of banana NAC transcription factors and their interactions with ethylene signalling component EIL during fruit ripening

    PubMed Central

    Shan, Wei; Kuang, Jian-fei; Chen, Jian-ye; Lu, Wang-jin

    2012-01-01

    The plant-specific NAC (NAM, ATAF1/2, and CUC2) transcription factors (TFs) play important roles in plant growth, development, and stress responses. However, the precise role of NAC TFs in relation to fruit ripening is poorly understood. In this study, six NAC genes, designated MaNAC1–MaNAC6, were isolated and characterized from banana fruit. Subcellular localization showed that MaNAC1–MaNAC5 proteins localized preferentially to the nucleus, while MaNAC6 was distributed throughout the entire cell. A transactivation assay in yeast demonstrated that MaNAC4 and MaNAC6, as well as their C-terminal regions, possessed trans-activation activity. Gene expression profiles in fruit with four different ripening characteristics, including natural, ethylene-induced, 1-methylcyclopropene (1-MCP)-delayed, and a combination of 1-MCP with ethylene treatment, revealed that the MaNAC genes were differentially expressed in peel and pulp during post-harvest ripening. MaNAC1 and MaNAC2 were apparently upregulated by ethylene in peel and pulp, consistent with the increase in ethylene production. In contrast, MaNAC3 in peel and pulp and MaNAC5 in peel were constitutively expressed, and transcripts of MaNAC4 in peel and pulp and MaNAC6 in peel decreased, while MaNAC5 or MaNAC6 in pulp increased slightly during fruit ripening. Furthermore, the MaNAC2 promoter was activated after ethylene application, further enhancing the involvement of MaNAC2 in fruit ripening. More importantly, yeast two-hybrid and bimolecular fluorescence complementation analyses confirmed that MaNAC1/2 physically interacted with a downstream component of ethylene signalling, ethylene insensitive 3 (EIN3)-like protein, termed MaEIL5, which was downregulated during ripening. Taken together, these results suggest that MaNACs such as MaNAC1/MaNAC2, may be involved in banana fruit ripening via interaction with ethylene signalling components. PMID:22888129

  19. Polar Codes

    DTIC Science & Technology

    2014-12-01

    density parity check (LDPC) code, a Reed–Solomon code, and three convolutional codes. iii CONTENTS EXECUTIVE SUMMARY...the most common. Many civilian systems use low density parity check (LDPC) FEC codes, and the Navy is planning to use LDPC for some future systems...other forward error correction methods: a turbo code, a low density parity check (LDPC) code, a Reed–Solomon code, and three convolutional codes

  20. O-GlcNAcase Expression is Sensitive to Changes in O-GlcNAc Homeostasis.

    PubMed

    Zhang, Zhen; Tan, Ee Phie; VandenHull, Nicole J; Peterson, Kenneth R; Slawson, Chad

    2014-01-01

    O-linked N-acetylglucosamine (O-GlcNAc) is a post-translational modification involving an attachment of a single β-N-acetylglucosamine moiety to serine or threonine residues in nuclear and cytoplasmic proteins. Cellular O-GlcNAc levels are regulated by two enzymes: O-GlcNAc transferase (OGT) and O-GlcNAcase (OGA), which add and remove the modification, respectively. The levels of O-GlcNAc can rapidly change in response to fluctuations in the extracellular environment; however, O-GlcNAcylation returns to a baseline level quickly after stimulus removal. This process termed O-GlcNAc homeostasis appears to be critical to the regulation of many cellular functions including cell cycle progress, stress response, and gene transcription. Disruptions in O-GlcNAc homeostasis are proposed to lead to the development of diseases, such as cancer, diabetes, and Alzheimer's disease. O-GlcNAc homeostasis is correlated with the expression of OGT and OGA. We reason that alterations in O-GlcNAc levels affect OGA and OGT transcription. We treated several human cell lines with Thiamet-G (TMG, an OGA inhibitor) to increase overall O-GlcNAc levels resulting in decreased OGT protein expression and increased OGA protein expression. OGT transcript levels slightly declined with TMG treatment, but OGA transcript levels were significantly increased. Pretreating cells with protein translation inhibitor cycloheximide did not stabilize OGT or OGA protein expression in the presence of TMG; nor did TMG stabilize OGT and OGA mRNA levels when cells were treated with RNA transcription inhibitor actinomycin D. Finally, we performed RNA Polymerase II chromatin immunoprecipitation at the OGA promoter and found that RNA Pol II occupancy at the transcription start site was lower after prolonged TMG treatment. Together, these data suggest that OGA transcription was sensitive to changes in O-GlcNAc homeostasis and was potentially regulated by O-GlcNAc.

  1. Translocation of HSP27 into liver cancer cell nucleus may be associated with phosphorylation and O-GlcNAc glycosylation.

    PubMed

    Guo, Kun; Gan, Lin; Zhang, Shu; Cui, Feng Jie; Cun, Wang; Li, Yan; Kang, Nan Xiao; Gao, Mei Dong; Liu, Kun Yin

    2012-08-01

    It has been reported that the dynamic interplay between O-GlcNAcylation and O-phosphorylation is responsible for altering the activity or localization of heat-shock proteins. The aim of this study was to determine whether dynamic interplay between O-GlcNAcylation and O-phosphorylation of HSP27 in hepatocellular cancer (HCC) cells affect its entry into the nucleus. We demonstrate that the entry of HSP27 into the nucleus correlated with its phosphorylation through transfecting HCC cells with plasmids coding for wild-type HSP27 (HSP27-WT), its non-phosphorylatable (HSP27-3A) and pseudophosphorylated (HSP27-3D) mutants, however, not all of the endogenous or exogenous nuclear HSP27 was modified by phosphorylation. We observed that HSP27 was modified with O-GlcNAc glycosylation in HCC cells and report that at conserved Ser residues of HSP27, alternative phosphorylation and O-GlcNAc modification can be predicted by the YinOYang 1.2 method. Furthermore, after P79350 or combined SB203580 and PUGNAc treatment, increased nuclear import of HSP27-WT and HSP27-3D implied that the entry of HSP27 into the nucleus was not only correlated with phosphorylation, but also with O-GlcNAc glycosylation. Collectively, O-GlcNAcylation of HSP27 in HCC cells may be a novel regulatory mode of HSP27 function, particularly for its entry into the nucleus. Crosstalk or interplay between glycosylation and phosphorylation of HSP27 could regulate its subcellular localization and biological functions in liver cancer.

  2. Experimental Studies of Interacting Electronic States in NaCs

    NASA Astrophysics Data System (ADS)

    Faust, Carl E.

    This dissertation describes methods and results of spectroscopic studies of the NaCs molecule. NaCs is of particular interest in many labs where experimental studies of ultra-cold molecules are being conducted. Data obtained in the present work will also be useful as benchmarks for various theoretical calculations. Our goals in studying this molecule were to map out high lying electronic states and to understand how these states interact with one another. Sodium and cesium metal were heated in a heat-pipe oven to form a vapor of NaCs molecules. These molecules were excited using narrow band, continuous wave (cw), tunable lasers. We employed the optical-optical double resonance (OODR) technique to obtain Doppler-free spectra of transitions to rotational and vibrational levels of high lying electronic states. One state of particular interest was the 12(0+) electronic state. Rovibrational level energies corresponding to this state were measured and used to generate a potential energy curve using computer programs to implement both the Rydberg-Klein-Rees (RKR) method and the inverted perturbation approach (IPA). By observing fluorescence from the 12(0+) state resolved as a function of wavelength, we determined that this state interacts with the nearby 11(0+) electronic state, which was previously mapped out by Ashman et al. A two-stage coupling model was devised to describe the resolved fluorescence originating from these two interacting states. The electronic states interact via spin-orbit coupling, while the individual rovibrational levels interact via a second mechanism, likely nonadiabatic coupling. This two-stage coupling between the levels of these states causes quantum interference between fluorescence pathways associated with different components of the wavefunctions describing these levels. This interference results in more complicated resolved fluorescence spectra. The model was used to fit parameters describing these interactions so that the resolved

  3. The NAC-type transcription factor OsNAC2 regulates ABA-dependent genes and abiotic stress tolerance in rice

    PubMed Central

    Shen, Jiabin; Lv, Bo; Luo, Liqiong; He, Jianmei; Mao, Chanjuan; Xi, Dandan; Ming, Feng

    2017-01-01

    Plants can perceive environmental changes and respond to external stressors. Here, we show that OsNAC2, a member of the NAC transcription factor family, was strongly induced by ABA and osmotic stressors such as drought and high salt. With reduced yields under drought conditions at the flowering stage, OsNAC2 overexpression lines had lower resistance to high salt and drought conditions. RNAi plants showed enhanced tolerance to high salinity and drought stress at both the vegetative and flowering stages. Furthermore, RNAi plants had improved yields after drought stress. A microarray assay indicated that many ABA-dependent stress-related genes were down-regulated in OsNAC2 overexpression lines. We further confirmed that OsNAC2 directly binds the promoters of LATE EMBRYOGENESIS ABUNDANT 3 (OsLEA3) and Stress-Activated Protein Kinases 1 (OsSAPK1), two marker genes in the abiotic stress and ABA response pathways, respectively. Our results suggest that in rice OsNAC2 regulates both abiotic stress responses and ABA-mediated responses, and acts at the junction between the ABA and abiotic stress pathways. PMID:28074873

  4. Structural, evolutionary and functional analysis of the NAC domain protein family in Eucalyptus.

    PubMed

    Hussey, Steven G; Saïdi, Mohammed N; Hefer, Charles A; Myburg, Alexander A; Grima-Pettenati, Jacqueline

    2015-06-01

    NAC domain transcription factors regulate many developmental processes and stress responses in plants and vary widely in number and family structure. We analysed the characteristics and evolution of the NAC gene family of Eucalyptus grandis, a fast-growing forest tree in the rosid order Myrtales. NAC domain genes identified in the E. grandis genome were subjected to amino acid sequence, phylogenetic and motif analyses. Transcript abundance in developing tissues and abiotic stress conditions in E. grandis and E. globulus was quantified using RNA-seq and reverse transcription quantitative PCR (RT-qPCR). One hundred and eighty-nine E. grandis NAC (EgrNAC) proteins, arranged into 22 subfamilies, are extensively duplicated in subfamilies associated with stress response. Most EgrNAC genes form tandem duplicate arrays that frequently carry signatures of purifying selection. Sixteen amino acid motifs were identified in EgrNAC proteins, eight of which are enriched in, or unique to, Eucalyptus. New candidates for the regulation of normal and tension wood development and cold responses were identified. This first description of a Myrtales NAC domain family reveals an unique history of tandem duplication in stress-related subfamilies that has likely contributed to the adaptation of eucalypts to the challenging Australian environment. Several new candidates for the regulation of stress, wood formation and tree-specific development are reported.

  5. Vimentin and desmin possess GlcNAc-binding lectin-like properties on cell surfaces.

    PubMed

    Ise, Hirohiko; Kobayashi, Satoshi; Goto, Mitsuaki; Sato, Takao; Kawakubo, Masatomo; Takahashi, Masafumi; Ikeda, Uichi; Akaike, Toshihiro

    2010-07-01

    Vimentin and desmin are intermediate filament proteins found in various mesenchymal and skeletal muscle cells, respectively. These proteins play an important role in the stabilization of the cytoplasmic architecture. Here, we found, using artificial biomimicking glycopolymers, that vimentin and desmin possess N-acetylglucosamine (GlcNAc)-binding lectin-like properties on the cell surfaces of various vimentin- and desmin-expressing cells such as cardiomyocytes and vascular smooth muscle cells. The rod II domain of these proteins was demonstrated to be localized to the cell surface and to directly bind to the artificial biomimicking GlcNAc-bearing polymer, by confocal laser microscopy and surface plasmon resonance analysis. These glycopolymers strongly interact with lectins and are useful tools for the analysis of lectin-carbohydrate interactions, since glycopolymers binding to lectins can induce the clustering of lectins due to multivalent glycoside ligand binding. Moreover, immunocytochemistry and pull-down assay with His-tagged vimentin-rod II domain protein showed that the vimentin-rod II domain interacts with O-GlcNAc proteins. These results suggest that O-GlcNAc proteins might be one candidate for physiological GlcNAc-bearing ligands with which vimentin and desmin interact. These findings demonstrate a novel function of vimentin and desmin that does not involve stabilization of the cytoplasmic architecture by which these proteins interact with physiological GlcNAc-bearing ligands such as O-GlcNAc proteins on the cell surface through their GlcNAc-binding lectin-like properties.

  6. [Cloning and characterization of a transcription factor ZmNAC1 in maize (Zea mays)].

    PubMed

    Liu, Zhan-Ji; Shao, Feng-Xia; Tang, Gui-Ying; Shan, Lei; Bi, Yu-Ping

    2009-02-01

    NAC transcription factors are a family of functionally diverse proteins. They are unique to plants and play an important role in regulation of plant growth and development, hormone regulation and responses to various stresses. A cDNA encoding the NAC-like gene homologue was isolated from maize (Zea mays L.) by RT-PCR and designated ZmNAC1 (GenBank Accession No. EU224278). Sequence analysis showed that cDNA of ZmNAC1 was 1,029 bp long and contained a single open reading frame (ORF, 26 to approximately 907 bp). The predicted ZmNAC1 protein has 293 amino acids with an estimated molecular mass of 32.3 kDa and an isoelectric point of 8.65. RT-PCR analysis showed that the expression of ZmNAC1 was induced by low temperature, PEG, salt, and ABA, respectively. These results suggest that ZmNAC1 may play important roles in biotic and abiotic resistance pathways. This is the first NAC-like gene reported in maize.

  7. Clinical coding. Code breakers.

    PubMed

    Mathieson, Steve

    2005-02-24

    --The advent of payment by results has seen the role of the clinical coder pushed to the fore in England. --Examinations for a clinical coding qualification began in 1999. In 2004, approximately 200 people took the qualification. --Trusts are attracting people to the role by offering training from scratch or through modern apprenticeships.

  8. Plant development. Arabidopsis NAC45/86 direct sieve element morphogenesis culminating in enucleation.

    PubMed

    Furuta, Kaori Miyashima; Yadav, Shri Ram; Lehesranta, Satu; Belevich, Ilya; Miyashima, Shunsuke; Heo, Jung-ok; Vatén, Anne; Lindgren, Ove; De Rybel, Bert; Van Isterdael, Gert; Somervuo, Panu; Lichtenberger, Raffael; Rocha, Raquel; Thitamadee, Siripong; Tähtiharju, Sari; Auvinen, Petri; Beeckman, Tom; Jokitalo, Eija; Helariutta, Ykä

    2014-08-22

    Photoassimilates such as sugars are transported through phloem sieve element cells in plants. Adapted for effective transport, sieve elements develop as enucleated living cells. We used electron microscope imaging and three-dimensional reconstruction to follow sieve element morphogenesis in Arabidopsis. We show that sieve element differentiation involves enucleation, in which the nuclear contents are released and degraded in the cytoplasm at the same time as other organelles are rearranged and the cytosol is degraded. These cellular reorganizations are orchestrated by the genetically redundant NAC domain-containing transcription factors, NAC45 and NAC86 (NAC45/86). Among the NAC45/86 targets, we identified a family of genes required for enucleation that encode proteins with nuclease domains. Thus, sieve elements differentiate through a specialized autolysis mechanism.

  9. A little sugar goes a long way: The cell biology of O-GlcNAc

    PubMed Central

    2015-01-01

    Unlike the complex glycans decorating the cell surface, the O-linked β-N-acetyl glucosamine (O-GlcNAc) modification is a simple intracellular Ser/Thr-linked monosaccharide that is important for disease-relevant signaling and enzyme regulation. O-GlcNAcylation requires uridine diphosphate–GlcNAc, a precursor responsive to nutrient status and other environmental cues. Alternative splicing of the genes encoding the O-GlcNAc cycling enzymes O-GlcNAc transferase (OGT) and O-GlcNAcase (OGA) yields isoforms targeted to discrete sites in the nucleus, cytoplasm, and mitochondria. OGT and OGA also partner with cellular effectors and act in tandem with other posttranslational modifications. The enzymes of O-GlcNAc cycling act preferentially on intrinsically disordered domains of target proteins impacting transcription, metabolism, apoptosis, organelle biogenesis, and transport. PMID:25825515

  10. BnNAC485 is involved in abiotic stress responses and flowering time in Brassica napus.

    PubMed

    Ying, Lu; Chen, Haiying; Cai, Weiming

    2014-06-01

    NAC domain proteins are plant-specific transcription factors that play important roles in plant growth and development. In this present study, we isolated BnNAC485 from Brassica napus L. (cv. HuYou15) and found that it showed high homology (84% at the amino acid level) with a NAC protein called AtRD26/ANAC072. BnNAC485 was specifically expressed in cotyledons and leaves of young seedlings, and expression was induced by abiotic stress and abscisic acid (ABA) treatment. The BnNAC485 protein localized to the nucleus. Over-expression of BnNAC485 enhanced tolerance to abiotic stress compared with wild-type plants in both B. napus and Arabidopsis thaliana. Furthermore, under exogenous ABA stress, BnNAC485 over-expression lines showed hypersensitivity to this treatment compared with wild-type B. napus and A. thaliana plants. Moreover, exogenous ABA treatment enhanced stomatal closing in B. napus plants over-expressing BnNAC485. Real-time RT-PCR assays showed that some abiotic- or ABA-responsive genes were up-regulated in A. thaliana plants over-expressing BnNAC485. Additionally, the transgenic lines flowered earlier than the wild-type B. napus and A. thaliana plants and the expression patterns of certain circadian clock genes were found to have changed. These results suggest that BnNAC485 acts in response to abiotic stress in plants via an ABA-mediated pathway and this gene can also alter plant flowering time.

  11. The NAC family transcription factor OsNAP confers abiotic stress response through the ABA pathway.

    PubMed

    Chen, Xu; Wang, Yaofeng; Lv, Bo; Li, Jie; Luo, Liqiong; Lu, Songchong; Zhang, Xuan; Ma, Hong; Ming, Feng

    2014-03-01

    Plants respond to environmental stresses by altering gene expression, and several genes have been found to mediate stress-induced expression, but many additional factors are yet to be identified. OsNAP is a member of the NAC transcription factor family; it is localized in the nucleus, and shows transcriptional activator activity in yeast. Analysis of the OsNAP transcript levels in rice showed that this gene was significantly induced by ABA and abiotic stresses, including high salinity, drought and low temperature. Rice plants overexpressing OsNAP did not show growth retardation, but showed a significantly reduced rate of water loss, enhanced tolerance to high salinity, drought and low temperature at the vegetative stage, and improved yield under drought stress at the flowering stage. Microarray analysis of transgenic plants overexpressing OsNAP revealed that many stress-related genes were up-regulated, including OsPP2C06/OsABI2, OsPP2C09, OsPP2C68 and OsSalT, and some genes coding for stress-related transcription factors (OsDREB1A, OsMYB2, OsAP37 and OsAP59). Our data suggest that OsNAP functions as a transcriptional activator that plays a role in mediating abiotic stress responses in rice.

  12. IRIG Serial Time Code Formats

    DTIC Science & Technology

    2016-08-01

    TELECOMMUNICATIONS AND TIMING GROUP IRIG STANDARD 200-16 IRIG SERIAL TIME CODE FORMATS DISTRIBUTION A: APPROVED FOR...ARNOLD ENGINEERING DEVELOPMENT COMPLEX NATIONAL AERONAUTICS AND SPACE ADMINISTRATION This page intentionally left blank. IRIG SERIAL TIME CODE ...Serial Time Code Formats, RCC 200-16, August 2016 v Table of Contents Preface

  13. NAC-1, a potential stem cell pluripotency factor, contributes to paclitaxel resistance in ovarian cancer through inactivating Gadd45 pathway.

    PubMed

    Jinawath, N; Vasoontara, C; Yap, K-L; Thiaville, M M; Nakayama, K; Wang, T-L; Shih, I-M

    2009-05-07

    Nucleus accumbens-1 (Nac1 or NAC-1) belongs to the BTB/POZ (Pox virus and Zinc finger/Bric-a-brac Tramtrack Broad complex) transcription factor family and is a novel protein that potentially participates in self-renewal and pluripotency in embryonic stem cells. In human cancer, NAC-1 is upregulated in several types of neoplasms, but particularly in recurrent chemoresistant ovarian carcinomas, suggesting a biological role for NAC-1 in the development of drug resistance in ovarian cancer. We have assessed this possibility and shown a correlation between NAC-1 expression and ex vivo paclitaxel resistance in ovarian serous carcinoma tissues and cell lines. We found that expression of Gadd45-gamma-interacting protein 1 (Gadd45gip1), a downstream target negatively regulated by NAC-1, was reduced in paclitaxel-resistant cells. Ectopic expression of NAC-1 or knockdown of Gadd45gip1 conferred paclitaxel resistance, whereas NAC-1 knockdown or ectopic expression of Gadd45gip1 increased paclitaxel sensitivity. Furthermore, silencing NAC-1 expression or disrupting NAC-1 homodimerization by a dominant negative NAC-1 protein that contained only the BTB/POZ domain induced the expression of Gadd45gamma, which interacted with Gadd45gip1. Reducing Gadd45gamma expression by small hairpin RNAs partially enhanced paclitaxel resistance. Thus, this study provides new evidence that NAC-1 upregulation and homodimerization contribute to tumor recurrence by equipping ovarian cancer cells with the paclitaxel-resistant phenotype through negative regulation of the Gadd45 pathway.

  14. Systematic analysis and identification of stress-responsive genes of the NAC gene family in Brachypodium distachyon.

    PubMed

    You, Jun; Zhang, Lihua; Song, Bo; Qi, Xiaoquan; Chan, Zhulong

    2015-01-01

    Plant-specific NAC proteins are one of the largest families of transcription factors in plants, and members of this family have been characterized with roles in the regulation of diverse biological processes, including development and stress responses. In the present study, we identified 101 putative NAC domain-encoding genes (BdNACs) through systematic sequence analysis in Brachypodium distachyon, a new model plant of family Poaceae. BdNAC proteins were phylogenetically clustered into 13 groups, and each group possesses similar motif compositions. Phylogenetic analysis using known stress-related NACs from Arabidopsis and rice as query sequences identified 18 BdNACs as putative stress-responsive genes. In silico promoter analysis showed that almost all BdNAC genes contain putative stress-related cis-elements in their promoter regions. Expression profile of BdNAC genes in response to abiotic stresses and phytohormones was analyzed by quantitative real-time RT-PCR. Several putative stress-responsive BdNAC genes, including BdNAC003 and BdNAC044 which is ortholog of known stress-responsive rice gene SNAC1 and SNAC2, respectively, were highly regulated by multiple abiotic stresses and stress-related phytohormone treatments. Taken together, our results presented here would be helpful in laying the foundation for understanding of the complex mechanisms of NAC mediated abiotic stress signaling transduction pathways in B. distachyon.

  15. The influence of intravesical administration of resiniferatoxin (RTX) on the chemical coding of sympathetic chain ganglia (SChG) neurons supplying the porcine urinary bladder.

    PubMed

    Lepiarczyk, Ewa; Majewski, Mariusz; Bossowska, Agnieszka

    2015-11-01

    Resiniferatoxin (RTX) is used as an experimental drug in therapy of neurogenic urinary bladder disorders. The present study investigated the chemical coding of sympathetic chain ganglia (SChG) neurons supplying porcine urinary bladder after intravesical RTX instillation. The SChG neurons were visualized with retrograde tracing method and their chemical profile was disclosed with double-labeling immunohistochemistry using antibodies against dopamine β-hydroxylase (DβH; marker of noradrenergic neurons), neuropeptide Y (NPY), vasoactive intestinal polypeptide (VIP), somatostatin (SOM), galanin, Leu(5)-enkephalin and neuronal nitric oxide synthase (nNOS). It was found that in both the control (n = 5) and RTX-treated pigs (n = 5), the vast majority (90.4 ± 2.8 and 89.7 ± 2.3%, respectively) of FB-positive (FB+) nerve cells were DβH+. RTX instillation caused a decrease in the number of FB+/DβH+ neurons immunopositive to NPY (71.1 ± 12.1 vs 43.2 ± 6.7%), VIP (21.3 ± 10.7 vs 5.3 ± 4.3%) or SOM (16.5 ± 4.6 vs 2.3 ± 2.6%) and a distinct increase in the number of FB+/DβH+ neurons immunoreactive to nNOS (0.8 ± 1 vs 5.3 ± 1.9 %). The present study for the first time has provided some information that therapeutic effects of RTX on the mammalian urinary bladder can be partly mediated by SChG neurons.

  16. NAC transcription factors in plant multiple abiotic stress responses: progress and prospects

    PubMed Central

    Shao, Hongbo; Wang, Hongyan; Tang, Xiaoli

    2015-01-01

    Abiotic stresses adversely affect plant growth and agricultural productivity. According to the current climate prediction models, crop plants will face a greater number of environmental stresses, which are likely to occur simultaneously in the future. So it is very urgent to breed broad-spectrum tolerant crops in order to meet an increasing demand for food productivity due to global population increase. As one of the largest families of transcription factors (TFs) in plants, NAC TFs play vital roles in regulating plant growth and development processes including abiotic stress responses. Lots of studies indicated that many stress-responsive NAC TFs had been used to improve stress tolerance in crop plants by genetic engineering. In this review, the recent progress in NAC TFs was summarized, and the potential utilization of NAC TFs in breeding abiotic stress tolerant transgenic crops was also be discussed. In view of the complexity of field conditions and the specificity in multiple stress responses, we suggest that the NAC TFs commonly induced by multiple stresses should be promising candidates to produce plants with enhanced multiple stress tolerance. Furthermore, the field evaluation of transgenic crops harboring NAC genes, as well as the suitable promoters for minimizing the negative effects caused by over-expressing some NAC genes, should be considered. PMID:26579152

  17. Molecular Evolution and Expansion Analysis of the NAC Transcription Factor in Zea mays

    PubMed Central

    Fan, Kai; Wang, Ming; Miao, Ying; Ni, Mi; Bibi, Noreen; Yuan, Shuna; Li, Feng; Wang, Xuede

    2014-01-01

    NAC (NAM, ATAF1, 2 and CUC2) family is a plant-specific transcription factor and it controls various plant developmental processes. In the current study, 124 NAC members were identified in Zea mays and were phylogenetically clustered into 13 distinct subfamilies. The whole genome duplication (WGD), especially an additional WGD event, may lead to expanding ZmNAC members. Different subfamily has different expansion rate, and NAC subfamily preference was found during the expansion in maize. Moreover, the duplication events might occur after the divergence of the lineages of Z. mays and S. italica, and segmental duplication seemed to be the dominant pattern for the gene duplication in maize. Furthermore, the expansion of ZmNAC members may be also related to gain and loss of introns. Besides, the restriction of functional divergence was discovered after most of the gene duplication events. These results could provide novel insights into molecular evolution and expansion analysis of NAC family in maize, and advance the NAC researches in other plants, especially polyploid plants. PMID:25369196

  18. O-GlcNAc signaling is essential for NFAT-mediated transcriptional reprogramming during cardiomyocyte hypertrophy

    PubMed Central

    Facundo, Heberty T.; Brainard, Robert E.; Watson, Lewis J.; Ngoh, Gladys A.; Hamid, Tariq; Prabhu, Sumanth D.

    2012-01-01

    The regulation of cardiomyocyte hypertrophy is a complex interplay among many known and unknown processes. One specific pathway involves the phosphatase calcineurin, which regulates nuclear translocation of the essential cardiac hypertrophy transcription factor, nuclear factor of activated T-cells (NFAT). Although metabolic dysregulation is frequently described during cardiac hypertrophy, limited insights exist regarding various accessory pathways. One metabolically derived signal, beta-O-linked N-acetylglucosamine (O-GlcNAc), has emerged as a highly dynamic posttranslational modification of serine and threonine residues regulating physiological and stress processes. Given the metabolic dysregulation during hypertrophy, we hypothesized that NFAT activation is dependent on O-GlcNAc signaling. Pressure overload-induced hypertrophy (via transverse aortic constriction) in mice or treatment of neonatal rat cardiac myocytes with phenylephrine significantly enhanced global O-GlcNAc signaling. NFAT-luciferase reporter activity revealed O-GlcNAc-dependent NFAT activation during hypertrophy. Reversal of enhanced O-GlcNAc signaling blunted cardiomyocyte NFAT-induced changes during hypertrophy. Taken together, these results demonstrate a critical role of O-GlcNAc signaling in NFAT activation during hypertrophy and provide evidence that O-GlcNAc signaling is coordinated with the onset and progression of cardiac hypertrophy. This represents a potentially significant and novel mechanism of cardiac hypertrophy, which may be of particular interest in future in vivo studies of hypertrophy. PMID:22408028

  19. Intracellular protein O-GlcNAc modification integrates nutrient status with transcriptional and metabolic regulation.

    PubMed

    Nagel, Alexis K; Ball, Lauren E

    2015-01-01

    The inducible, nutrient-sensitive posttranslational modification of protein Ser/Thr residues with O-linked β-N-acetylglucosamine (O-GlcNAc) occurs on histones, transcriptional regulators, metabolic enzymes, oncogenes, tumor suppressors, and many critical intermediates of growth factor signaling. Cycling of O-GlcNAc modification on and off of protein substrates is catalyzed by the actions of O-GlcNAc transferase (OGT) and O-GlcNAcase (OGA), respectively. To date, there are less than 150 publications addressing the role of O-GlcNAc modification in cancer and over half were published in the last 2 years. These studies have clearly established that increased expression of OGT and hyper-O-GlcNAcylation is common to human cancers of breast, prostate, colon, lung, and pancreas. Furthermore, attenuating OGT activity reduces tumor growth in vitro and metastasis in vivo. This chapter discusses the structure and function of the O-GlcNAc cycling enzymes, mechanisms by which protein O-GlcNAc modification sense changes in nutrient status, the influence of O-GlcNAc cycling enzymes on glucose metabolism, and provides an overview of recent observations regarding the role of O-GlcNAcylation in cancer.

  20. An NAC transcription factor controls ethylene-regulated cell expansion in flower petals.

    PubMed

    Pei, Haixia; Ma, Nan; Tian, Ji; Luo, Jing; Chen, Jiwei; Li, Jing; Zheng, Yi; Chen, Xiang; Fei, Zhangjun; Gao, Junping

    2013-10-01

    Cell expansion is crucial for plant growth. It is well known that the phytohormone ethylene functions in plant development as a key modulator of cell expansion. However, the role of ethylene in the regulation of this process remains unclear. In this study, 2,189 ethylene-responsive transcripts were identified in rose (Rosa hybrida) petals using transcriptome sequencing and microarray analysis. Among these transcripts, an NAC (for no apical meristem [NAM], Arabidopsis transcription activation factor [ATAF], and cup-shaped cotyledon [CUC])-domain transcription factor gene, RhNAC100, was rapidly and dramatically induced by ethylene in the petals. Interestingly, accumulation of the RhNAC100 transcript was modulated by ethylene via microRNA164-dependent posttranscriptional regulation. Overexpression of RhNAC100 in Arabidopsis (Arabidopsis thaliana) substantially reduced the petal size by repressing petal cell expansion. By contrast, silencing of RhNAC100 in rose petals using virus-induced gene silencing significantly increased petal size and promoted cell expansion in the petal abaxial subepidermis (P < 0.05). Expression analysis showed that 22 out of the 29 cell expansion-related genes tested exhibited changes in expression in RhNAC100-silenced rose petals. Moreover, of those genes, one cellulose synthase and two aquaporin genes (Rosa hybrida Cellulose Synthase2 and R. hybrida Plasma Membrane Intrinsic Protein1;1/2;1) were identified as targets of RhNAC100. Our results suggest that ethylene regulates cell expansion by fine-tuning the microRNA164/RhNAC100 module and also provide new insights into the function of NAC transcription factors.

  1. Chemo-enzymatic synthesis of glycosylated insulin using a GlcNAc tag.

    PubMed

    Tomabechi, Yusuke; Suzuki, Rena; Haneda, Katsuji; Inazu, Toshiyuki

    2010-02-01

    Artificial insulin with an N-linked oligosaccharide was synthesized by a chemo-enzymatic method using endo-beta-N-acetylglucosaminidase from Mucor hiemalis (Endo-M). GlcNAc-modified insulin was prepared by the reaction of the carboxymethyl glycoside of GlcNAc and 3 amino groups of bovine insulin using a dimethylphosphinothioic mixed anhydride (Mpt-MA) method. A transglycosylation reaction of the GlcNAc-modified insulin using Endo-M gave mono-transglycosylated insulin predominantly. We determined the transglycosylation site of the mono-transglycosylated insulin.

  2. Rheological properties of the product slurry of the Nitrate to Ammonia and Ceramic (NAC) process

    SciTech Connect

    Muguercia, I.; Yang, G.; Ebadian, M.A.; Lee, D.D.; Mattus, A.J.; Hunt, R.D.

    1995-03-01

    The Nitrate to Ammonia and Ceramic (NAC) process is an innovative technology for immobilizing the liquid from Low Level radioactive Waste (LLW). An experimental study was conducted to measure the rheological properties of the pipe flow of the NAC product slurry. Test results indicate that the NAC product slurry has a profound rheological behavior. At low solids concentration, the slurry exhibits a typical dilatant fluid (or shear thinning)fluid. The transition from dilatant fluid to pseudo-plastic fluid will occur at between 25% to 30% solids concentration in temperature ranges of 50--80{degree}C. Correlation equations are developed based on the test data.

  3. The computer-based control system of the NAC accelerator

    NASA Astrophysics Data System (ADS)

    Burdzik, G. F.; Bouckaert, R. F. A.; Cloete, I.; Dutoit, J. S.; Kohler, I. H.; Truter, J. N. J.; Visser, K.; Wikner, V. C. S. J.

    The National Accelerator Center (NAC) of the CSIR is building a two-stage accelerator which will provide charged-particle beams for use in medical and research applications. The control system for this accelerator is based on three mini-computers and a CAMAC interfacing network. Closed-loop control is being relegated to the various subsystems of the accelerators, and the computers and CAMAC network will be used in the first instance for data transfer, monitoring and servicing of the control consoles. The processing power of the computers will be utilized for automating start-up and beam-change procedures, for providing flexible and convenient information at the control consoles, for fault diagnosis and for beam-optimizing procedures. Tasks of a localized or dedicated nature are being off-loaded onto microcomputers, which are being used either in front-end devices or as slaves to the mini-computers. On the control consoles only a few instruments for setting and monitoring variables are being provided, but these instruments are universally-linkable to any appropriate machine variable.

  4. Wood reinforcement of poplar by rice NAC transcription factor.

    PubMed

    Sakamoto, Shingo; Takata, Naoki; Oshima, Yoshimi; Yoshida, Kouki; Taniguchi, Toru; Mitsuda, Nobutaka

    2016-01-27

    Lignocellulose, composed of cellulose, hemicellulose, and lignin, in the secondary cell wall constitutes wood and is the most abundant form of biomass on Earth. Enhancement of wood accumulation may be an effective strategy to increase biomass as well as wood strength, but currently only limited research has been undertaken. Here, we demonstrated that OsSWN1, the orthologue of the rice NAC Secondary-wall Thickening factor (NST) transcription factor, effectively enhanced secondary cell wall formation in the Arabidopsis inflorescence stem and poplar (Populus tremula×Populus tremuloides) stem when expressed by the Arabidopsis NST3 promoter. Interestingly, in transgenic Arabidopsis and poplar, ectopic secondary cell wall deposition in the pith area was observed in addition to densification of the secondary cell wall in fiber cells. The cell wall content or density of the stem increased on average by up to 38% and 39% in Arabidopsis and poplar, respectively, without causing growth inhibition. As a result, physical strength of the stem increased by up to 57% in poplar. Collectively, these data suggest that the reinforcement of wood by NST3pro:OsSWN1 is a promising strategy to enhance wood-biomass production in dicotyledonous plant species.

  5. Wood reinforcement of poplar by rice NAC transcription factor

    PubMed Central

    Sakamoto, Shingo; Takata, Naoki; Oshima, Yoshimi; Yoshida, Kouki; Taniguchi, Toru; Mitsuda, Nobutaka

    2016-01-01

    Lignocellulose, composed of cellulose, hemicellulose, and lignin, in the secondary cell wall constitutes wood and is the most abundant form of biomass on Earth. Enhancement of wood accumulation may be an effective strategy to increase biomass as well as wood strength, but currently only limited research has been undertaken. Here, we demonstrated that OsSWN1, the orthologue of the rice NAC Secondary-wall Thickening factor (NST) transcription factor, effectively enhanced secondary cell wall formation in the Arabidopsis inflorescence stem and poplar (Populus tremula×Populus tremuloides) stem when expressed by the Arabidopsis NST3 promoter. Interestingly, in transgenic Arabidopsis and poplar, ectopic secondary cell wall deposition in the pith area was observed in addition to densification of the secondary cell wall in fiber cells. The cell wall content or density of the stem increased on average by up to 38% and 39% in Arabidopsis and poplar, respectively, without causing growth inhibition. As a result, physical strength of the stem increased by up to 57% in poplar. Collectively, these data suggest that the reinforcement of wood by NST3pro:OsSWN1 is a promising strategy to enhance wood-biomass production in dicotyledonous plant species. PMID:26812961

  6. Bivalent Carbohydrate Binding Is Required for Biological Activity of Clitocybe nebularis Lectin (CNL), the N,N′-Diacetyllactosediamine (GalNAcβ1–4GlcNAc, LacdiNAc)-specific Lectin from Basidiomycete C. nebularis*

    PubMed Central

    Pohleven, Jure; Renko, Miha; Magister, Špela; Smith, David F.; Künzler, Markus; Štrukelj, Borut; Turk, Dušan; Kos, Janko; Sabotič, Jerica

    2012-01-01

    Lectins are carbohydrate-binding proteins that exert their biological activity by binding to specific cell glycoreceptors. We have expressed CNL, a ricin B-like lectin from the basidiomycete Clitocybe nebularis in Escherichia coli. The recombinant lectin, rCNL, agglutinates human blood group A erythrocytes and is specific for the unique glycan N,N′-diacetyllactosediamine (GalNAcβ1–4GlcNAc, LacdiNAc) as demonstrated by glycan microarray analysis. We here describe the crystal structures of rCNL in complex with lactose and LacdiNAc, defining its interactions with the sugars. CNL is a homodimeric lectin, each of whose monomers consist of a single ricin B lectin domain with its β-trefoil fold and one carbohydrate-binding site. To study the mode of CNL action, a nonsugar-binding mutant and nondimerizing monovalent CNL mutants that retain carbohydrate-binding activity were prepared. rCNL and the mutants were examined for their biological activities against Jurkat human leukemic T cells and the hypersensitive nematode Caenorhabditis elegans mutant strain pmk-1. rCNL was toxic against both, although the mutants were inactive. Thus, the bivalent carbohydrate-binding property of homodimeric CNL is essential for its activity, providing one of the rare pieces of evidence that certain activities of lectins are associated with their multivalency. PMID:22298779

  7. The emerging link between O-GlcNAc and Alzheimer disease.

    PubMed

    Zhu, Yanping; Shan, Xiaoyang; Yuzwa, Scott A; Vocadlo, David J

    2014-12-12

    Regional glucose hypometabolism is a defining feature of Alzheimer disease (AD). One emerging link between glucose hypometabolism and progression of AD is the nutrient-responsive post-translational O-GlcNAcylation of nucleocytoplasmic proteins. O-GlcNAc is abundant in neurons and occurs on both tau and amyloid precursor protein. Increased brain O-GlcNAcylation protects against tau and amyloid-β peptide toxicity. Decreased O-GlcNAcylation occurs in AD, suggesting that glucose hypometabolism may impair the protective roles of O-GlcNAc within neurons and enable neurodegeneration. Here, we review how O-GlcNAc may link cerebral glucose hypometabolism to progression of AD and summarize data regarding the protective role of O-GlcNAc in AD models.

  8. 75 FR 42339 - List of Approved Spent Fuel Storage Casks: NAC-MPC System, Revision 6

    Federal Register 2010, 2011, 2012, 2013, 2014

    2010-07-21

    ..., Whistleblowing. For the reasons set out in the preamble and under the authority of the Atomic Energy Act of 1954.... Certificate Expiration Date: April 10, 2020. Model Number: NAC-MPC. * * * * * Dated at Rockville,...

  9. Extended O-GlcNAc on HLA Class-I-Bound Peptides.

    PubMed

    Marino, Fabio; Bern, Marshall; Mommen, Geert P M; Leney, Aneika C; van Gaans-van den Brink, Jacqueline A M; Bonvin, Alexandre M J J; Becker, Christopher; van Els, Cécile A C M; Heck, Albert J R

    2015-09-02

    We report unexpected mass spectrometric observations of glycosylated human leukocyte antigen (HLA) class I-bound peptides. Complemented by molecular modeling, in vitro enzymatic assays, and oxonium ion patterns, we propose that the observed O-linked glycans carrying up to five monosaccharides are extended O-GlcNAc's rather than GalNAc-initiated O-glycans. A cytosolic O-GlcNAc modification is normally terminal and does not extend to produce a polysaccharide, but O-GlcNAc on an HLA peptide presents a special case because the loaded HLA class I complex traffics through the endoplasmic reticulum and Golgi apparatus on its way to the cell membrane and is hence exposed to glycosyltransferases. We also report for the first time natural HLA class I presentation of O- and N-linked glycopeptides derived from membrane proteins. HLA class I peptides with centrally located oligosaccharides have been shown to be immunogenic and may thus be important targets for immune surveillance.

  10. N-acetylcysteine (NAC) in neurological disorders: mechanisms of action and therapeutic opportunities

    PubMed Central

    Bavarsad Shahripour, Reza; Harrigan, Mark R; Alexandrov, Andrei V

    2014-01-01

    Background There is an expanding field of research investigating the benefits of medicines with multiple mechanisms of action across neurological disorders. N-acetylcysteine (NAC), widely known as an antidote to acetaminophen overdose, is now emerging as treatment of vascular and nonvascular neurological disorders. NAC as a precursor to the antioxidant glutathione modulates glutamatergic, neurotrophic, and inflammatory pathways. Aim and discussion Most NAC studies up to date have been carried out in animal models of various neurological disorders with only a few studies completed in humans. In psychiatry, NAC has been tested in over 20 clinical trials as an adjunctive treatment; however, this topic is beyond the scope of this review. Herein, we discuss NAC molecular, intracellular, and systemic effects, focusing on its potential applications in neurodegenerative diseases including spinocerebellar ataxia, Parkinson's disease, tardive dyskinesia, myoclonus epilepsy of the Unverricht–Lundbor type as well as multiple sclerosis, amyotrophic lateral sclerosis, and Alzheimer's disease. Conclusion Finally, we review the potential applications of NAC to facilitate recovery after traumatic brain injury, cerebral ischemia, and in treatment of cerebrovascular vasospasm after subarachnoid hemorrhage. PMID:24683506

  11. Administrators: Nursing Home Administrator

    ERIC Educational Resources Information Center

    Kahl, Anne

    1976-01-01

    Responsibilities, skills needed, training needed, earnings, employment outlook, and sources of additional information are outlined for the administrator who holds the top management job in a nursing home. (JT)

  12. Ethical coding.

    PubMed

    Resnik, Barry I

    2009-01-01

    It is ethical, legal, and proper for a dermatologist to maximize income through proper coding of patient encounters and procedures. The overzealous physician can misinterpret reimbursement requirements or receive bad advice from other physicians and cross the line from aggressive coding to coding fraud. Several of the more common problem areas are discussed.

  13. Distinct Effects of Enriched Environment on Dopamine Clearance in Nucleus Accumbens Shell and Core Following Systemic Nicotine Administration

    PubMed Central

    ZHU, JUN; BARDO, MICHAEL T.; DWOSKIN, LINDA P.

    2013-01-01

    Environmental enrichment during development may reduce drug abuse liability by modulating dopamine transporter (DAT) function. Nucleus accumbens (NAc) shell and core respond differentially to regulate the rewarding properties and locomotor stimulant effects of psychostimulants. The current study evaluated dopamine (DA) clearance (CLDA) in the NAc shell and core using in vivo voltammetry in rats raised in an enriched condition (EC) or an impoverished condition (IC) and determined the effect of nicotine (0.4 mg/kg) on CLDA. Baseline CLDA in NAc shell and core was not different between EC and IC rats. In the saline control group, CLDA in NAc shell was greater across time in IC when compared with EC rats, whereas CLDA in NAc core was greater in EC rats when compared with IC rats. Consistent with these findings, opposite effects of enrichment on DA clearance in shell and core were obtained following acute nicotine administration. In NAc shell, nicotine increased CLDA in EC rats, but not in IC rats. Conversely, in NAc core, nicotine increased CLDA in IC rats, but not in EC rats. The current results demonstrate that environmental enrichment differentially regulates the response to nicotine in NAc shell and core via alterations in DAT function, which may explain how environmental enrichment reduces the behavioral response to nicotine. PMID:23065942

  14. Transcriptome-Wide Identification and Expression Analysis of the NAC Gene Family in Tea Plant [Camellia sinensis (L.) O. Kuntze

    PubMed Central

    Wang, Yong-Xin; Liu, Zhi-Wei; Wu, Zhi-Jun; Li, Hui; Zhuang, Jing

    2016-01-01

    In plants, the NAC (NAM-ATAF1/2-CUC) family of proteins constitutes several transcription factors and plays vital roles in diverse biological processes, such as growth, development, and adaption to adverse factors. Tea, as a non-alcoholic drink, is known for its bioactive ingredients and health efficacy. Currently, knowledge about NAC gene family in tea plant remains very limited. In this study, a total of 45 CsNAC genes encoding NAC proteins including three membrane-bound members were identified in tea plant through transcriptome analysis. CsNAC factors and Arabidopsis counterparts were clustered into 17 subgroups after phylogenetic analysis. Conserved motif analysis revealed that CsNAC proteins with a close evolutionary relationship possessed uniform or similar motif compositions. The distribution of NAC family MTFs (membrane-associated transcription factors) among higher plants of whose genome-wide has been completed revealed that the existence of doubled TMs (transmembrane motifs) may be specific to fabids. Transcriptome analysis exhibited the expression profiles of CsNAC genes in different tea plant cultivars under non-stress conditions. Nine CsNAC genes, including the predicted stress-related and membrane-bound genes, were examined through qRT-PCR (quantitative real time polymerase chain reaction) in two tea plant cultivars, namely, ‘Huangjinya’ and ‘Yingshuang’. The expression patterns of these genes were investigated in different tissues (root, stem, mature leaf, young leaf and bud) and under diverse environmental stresses (drought, salt, heat, cold and abscisic acid). Several CsNAC genes, including CsNAC17 and CsNAC30 that are highly orthologous to known stress-responsive ANAC072/RD26 were identified as highly responsive to abiotic stress. This study provides a global survey of tea plant NAC proteins, and would be helpful for the improvement of stress resistance in tea plant via genetic engineering. PMID:27855193

  15. Co-administration of N-Acetylcysteine and Acetaminophen Efficiently Blocks Acetaminophen Toxicity.

    PubMed

    Owumi, Solomon E; Andrus, James P; Herzenberg, Leonard A; Herzenberg, Leonore A

    2015-08-01

    Preclinical Research Although acetaminophen (APAP) is an effective analgesic and anti-pyretic, APAP overdose is the most frequent cause of serious, often lethal, drug-induced hepatotoxicity. Administration of N-acetyl cysteine (NAC) within 8 hours of APAP overdose effectively mitigates APAP-induced hepatotoxicity. Thus, preventing APAP toxicity before it occurs by formulating APAP with NAC is logical and, as we show here in a mouse model, is effective in preventing APAP toxicity. Thus, toxic oral APAP doses sufficient to cause severe widespread liver damage do not cause significant damage when administered concurrently with equal amounts of NAC, that is, in the NAC-APAP treated animals, hepatic transaminases increase only marginally and liver architecture remains fully intact. Thus, we conclude that concomitant oral dosing with APAP and NAC can provide a convenient and effective way of preventing toxicity associated with large dosage of APAP. From a public health perspective, these findings support the concept that a co-formulation of APAP plus NAC is a viable over-the-counter (OTC) alternative to the current practice of providing APAP OTC and treating APAP toxicity if/when it occurs. In essence, our findings indicate that replacing the current OTC APAP with a safe and functional APAP/NAC formulation could prevent the accidental and intentional APAP toxicity that occurs today.

  16. Dress Codes. Legal Brief.

    ERIC Educational Resources Information Center

    Zirkel, Perry A.

    2000-01-01

    As illustrated by two recent decisions, the courts in the past decade have demarcated wide boundaries for school officials considering dress codes, whether in the form of selective prohibitions or required uniforms. Administrators must warn the community, provide legitimate justification and reasonable clarity, and comply with state law. (MLH)

  17. Modulation of cytokines and chemokines expression by NAC in cadmium chloride treated human lung cells.

    PubMed

    Odewumi, Caroline O; Latinwo, Lekan M; Ruden, Michael L; Badisa, Veera L D; Fils-Aime, Sheila; Badisa, Ramesh B

    2016-11-01

    Cadmium (Cd), is one of the most hazardous metals found in the environment. Cd exposure through inhalation has been linked to various diseases in lungs. It was shown that Cd induces proinflammatory cytokines through oxidative stress mechanism. In this report, we studied the immunomodulatory effect of a well known antioxidant, N-acetylcysteine (NAC) on cadmium chloride (CdCl2 ) treated human lung A549 cells through human cytokine array 6. The lung cells were treated with 0 or 75 µM CdCl2 alone, 2.5 mM NAC alone, or co-treated with 2.5 mM NAC and 75 µM CdCl2 for 24 h. The viability of cells was measured by crystal violet dye. The array results were validated by human IL-1alpha enzyme- linked immunosorbent assay (ELISA) kit. The viability of the 75 µM CdCl2 alone treated cells was decreased to 44.5%, while the viability of the co-treated cells with 2.5 mM NAC was increased to 84.1% in comparison with untreated cells. In the cell lysate of CdCl2 alone treated cells, 19 and 8 cytokines were up and down-regulated, while in the medium 15 and 3 cytokines were up and downregulated in comparison with the untreated cells. In the co-treated cells, all these cytokines expression was modulated by the NAC treatment. The IL-1α ELISA result showed the same pattern of cytokine expression as the cytokine array. This study clearly showed the modulatory effect of NAC on cytokines and chemokines expression in CdCl2- treated cells and suggests the use of NAC as protective agent against cadmium toxicity. © 2015 Wiley Periodicals, Inc. Environ Toxicol 31: 1612-1619, 2016.

  18. N-acetyl cysteine (NAC) treatment reduces mercury-induced neurotoxicity in the developing rat hippocampus

    PubMed Central

    Falluel-Morel, Anthony; Lin, Lulu; Sokolowski, Katie; McCandlish, Elizabeth; Buckley, Brian; DiCicco-Bloom, Emanuel

    2011-01-01

    Mercury is an environmental toxicant that can disrupt brain development. However, while progress has been made in defining its neurotoxic effects, we know far less about available therapies that can effectively protect brain in exposed individuals. We previously developed an animal model in which we defined the sequence of events underlying neurotoxicity: Methylmercury (MeHg) injection in postnatal rat acutely induced inhibition of mitosis and stimulated apoptosis in the hippocampus, that later resulted in intermediate term deficits in structure size and cell number. NAC is the N-acetyl derivative of L-cysteine used clinically for treatment of drug intoxication. Here, based on its known efficacy in promoting MeHg urinary excretion, we evaluated NAC for protective effects in the developing brain. In immature neurons and precursors MeHg (3µM) induced a >50% decrease in DNA synthesis at 24hr, an effect that was completely blocked by NAC co-incubation. In vivo, injection of MeHg (5µg/gbw) into 7 day-old rats induced a 22% decrease in DNA synthesis in whole hippocampus and a 4-fold increase in activated caspase-3 immunoreactive cells at 24hr, and reduced total cell numbers by 13% at 3 weeks. Treatment of MeHg exposed rats with repeated injections of NAC abolished MeHg toxicity. NAC prevented the reduction in DNA synthesis and the marked increase in caspase-3 immunoreactivity. Moreover, the intermediate term decrease in hippocampal cell number provoked by MeHg was fully blocked by NAC. Altogether, these results suggest that MeHg toxicity in the perinatal brain can be ameliorated by using NAC, opening potential avenues for therapeutic intervention. PMID:22420031

  19. O-GlcNAc modification of PPAR{gamma} reduces its transcriptional activity

    SciTech Connect

    Ji, Suena; Park, Sang Yoon; Roth, Juergen; Kim, Hoe Suk; Cho, Jin Won

    2012-01-27

    Highlights: Black-Right-Pointing-Pointer We found that PPAR{gamma} is modified by O-GlcNAc in 3T3-L1 adipocytes. Black-Right-Pointing-Pointer The Thr54 of PPAR{gamma}1 is the major O-GlcNAc site. Black-Right-Pointing-Pointer Transcriptional activity of PPAR{gamma}1 was decreased on treatment with the OGA inhibitor. -- Abstract: The peroxisome proliferator-activated receptor {gamma} (PPAR{gamma}), a member of the nuclear receptor superfamily, is a key regulator of adipogenesis and is important for the homeostasis of the adipose tissue. The {beta}-O-linked N-acetylglucosamine (O-GlcNAc) modification, a posttranslational modification on various nuclear and cytoplasmic proteins, is involved in the regulation of protein function. Here, we report that PPAR{gamma} is modified by O-GlcNAc in 3T3-L1 adipocytes. Mass spectrometric analysis and mutant studies revealed that the threonine 54 of the N-terminal AF-1 domain of PPAR{gamma} is the major O-GlcNAc site. Transcriptional activity of wild type PPAR{gamma} was decreased 30% by treatment with the specific O-GlcNAcase (OGA) inhibitor, but the T54A mutant of PPAR{gamma} did not respond to inhibitor treatment. In 3T3-L1 cells, an increase in O-GlcNAc modification by OGA inhibitor reduced PPAR{gamma} transcriptional activity and terminal adipocyte differentiation. Our results suggest that the O-GlcNAc state of PPAR{gamma} influences its transcriptional activity and is involved in adipocyte differentiation.

  20. Molecular genetics of blood-fleshed peach reveals activation of anthocyanin biosynthesis by NAC transcription factors.

    PubMed

    Zhou, Hui; Lin-Wang, Kui; Wang, Huiliang; Gu, Chao; Dare, Andrew P; Espley, Richard V; He, Huaping; Allan, Andrew C; Han, Yuepeng

    2015-04-01

    Anthocyanin pigmentation is an important consumer trait in peach (Prunus persica). In this study, the genetic basis of the blood-flesh trait was investigated using the cultivar Dahongpao, which shows high levels of cyanidin-3-glucoside in the mesocarp. Elevation of anthocyanin levels in the flesh was correlated with the expression of an R2R3 MYB transcription factor, PpMYB10.1. However, PpMYB10.1 did not co-segregate with the blood-flesh trait. The blood-flesh trait was mapped to a 200-kb interval on peach linkage group (LG) 5. Within this interval, a gene encoding a NAC domain transcription factor (TF) was found to be highly up-regulated in blood-fleshed peaches when compared with non-red-fleshed peaches. This NAC TF, designated blood (BL), acts as a heterodimer with PpNAC1 which shows high levels of expression in fruit at late developmental stages. We show that the heterodimer of BL and PpNAC1 can activate the transcription of PpMYB10.1, resulting in anthocyanin pigmentation in tobacco. Furthermore, silencing the BL gene reduces anthocyanin pigmentation in blood-fleshed peaches. The transactivation activity of the BL-PpNAC1 heterodimer is repressed by a SQUAMOSA promoter-binding protein-like TF, PpSPL1. Low levels of PpMYB10.1 expression in fruit at early developmental stages is probably attributable to lower levels of expression of PpNAC1 plus the presence of high levels of repressors such as PpSPL1. We present a mechanism whereby BL is the key gene for the blood-flesh trait in peach via its activation of PpMYB10.1 in maturing fruit. Partner TFs such as basic helix-loop-helix proteins and NAC1 are required, as is the removal of transcriptional repressors.

  1. The Arabidopsis Transcription Factor NAC016 Promotes Drought Stress Responses by Repressing AREB1 Transcription through a Trifurcate Feed-Forward Regulatory Loop Involving NAP[OPEN

    PubMed Central

    Sakuraba, Yasuhito; Kim, Ye-Sol; Han, Su-Hyun; Lee, Byoung-Doo; Paek, Nam-Chon

    2015-01-01

    Drought and other abiotic stresses negatively affect plant growth and development and thus reduce productivity. The plant-specific NAM/ATAF1/2/CUC2 (NAC) transcription factors have important roles in abiotic stress-responsive signaling. Here, we show that Arabidopsis thaliana NAC016 is involved in drought stress responses; nac016 mutants have high drought tolerance, and NAC016-overexpressing (NAC016-OX) plants have low drought tolerance. Using genome-wide gene expression microarray analysis and MEME motif searches, we identified the NAC016-specific binding motif (NAC16BM), GATTGGAT[AT]CA, in the promoters of genes downregulated in nac016-1 mutants. The NAC16BM sequence does not contain the core NAC binding motif CACG (or its reverse complement CGTG). NAC016 directly binds to the NAC16BM in the promoter of ABSCISIC ACID-RESPONSIVE ELEMENT BINDING PROTEIN1 (AREB1), which encodes a central transcription factor in the stress-responsive abscisic acid signaling pathway and represses AREB1 transcription. We found that knockout mutants of the NAC016 target gene NAC-LIKE, ACTIVATED BY AP3/PI (NAP) also exhibited strong drought tolerance; moreover, NAP binds to the AREB1 promoter and suppresses AREB1 transcription. Taking these results together, we propose that a trifurcate feed-forward pathway involving NAC016, NAP, and AREB1 functions in the drought stress response, in addition to affecting leaf senescence in Arabidopsis. PMID:26059204

  2. The Arabidopsis Transcription Factor NAC016 Promotes Drought Stress Responses by Repressing AREB1 Transcription through a Trifurcate Feed-Forward Regulatory Loop Involving NAP.

    PubMed

    Sakuraba, Yasuhito; Kim, Ye-Sol; Han, Su-Hyun; Lee, Byoung-Doo; Paek, Nam-Chon

    2015-06-01

    Drought and other abiotic stresses negatively affect plant growth and development and thus reduce productivity. The plant-specific NAM/ATAF1/2/CUC2 (NAC) transcription factors have important roles in abiotic stress-responsive signaling. Here, we show that Arabidopsis thaliana NAC016 is involved in drought stress responses; nac016 mutants have high drought tolerance, and NAC016-overexpressing (NAC016-OX) plants have low drought tolerance. Using genome-wide gene expression microarray analysis and MEME motif searches, we identified the NAC016-specific binding motif (NAC16BM), GATTGGAT[AT]CA, in the promoters of genes downregulated in nac016-1 mutants. The NAC16BM sequence does not contain the core NAC binding motif CACG (or its reverse complement CGTG). NAC016 directly binds to the NAC16BM in the promoter of ABSCISIC ACID-RESPONSIVE ELEMENT BINDING PROTEIN1 (AREB1), which encodes a central transcription factor in the stress-responsive abscisic acid signaling pathway and represses AREB1 transcription. We found that knockout mutants of the NAC016 target gene NAC-LIKE, ACTIVATED BY AP3/PI (NAP) also exhibited strong drought tolerance; moreover, NAP binds to the AREB1 promoter and suppresses AREB1 transcription. Taking these results together, we propose that a trifurcate feed-forward pathway involving NAC016, NAP, and AREB1 functions in the drought stress response, in addition to affecting leaf senescence in Arabidopsis.

  3. LacdiNAc-glycans constitute a parasite pattern for galectin-3-mediated immune recognition.

    PubMed

    van den Berg, Timo K; Honing, Henk; Franke, Niels; van Remoortere, Alexandra; Schiphorst, Wietske E C M; Liu, Fu-Tong; Deelder, André M; Cummings, Richard D; Hokke, Cornelis H; van Die, Irma

    2004-08-01

    Although Gal beta 1-4GlcNAc (LacNAc) moieties are the most common constituents of N-linked glycans on vertebrate proteins, GalNAc beta 1-4GlcNAc (LacdiNAc, LDN)-containing glycans are widespread in invertebrates, such as helminths. We postulated that LDN might be a molecular pattern for recognition of helminth parasites by the immune system. Using LDN-based affinity chromatography and mass spectrometry, we have identified galectin-3 as the major LDN-binding protein in macrophages. By contrast, LDN binding was not observed with galectin-1. Surface plasmon resonance (SPR) analysis and a solid phase binding assay demonstrated that galectin-3 binds directly to neoglycoconjugates carrying LDN glycans. In addition, galectin-3 bound to Schistosoma mansoni soluble egg Ags and a mAb against the LDN glycan inhibited this binding, suggesting that LDN glycans within S. mansoni soluble egg Ags contribute to galectin-3 binding. Immunocytochemistry demonstrated high levels of galectin-3 in liver granulomas of S. mansoni-infected hamsters, and a colocalization of galectin-3 and LDN glycans was observed on the parasite eggshells. Finally, we demonstrate that galectin-3 can mediate recognition and phagocytosis of LDN-coated particles by macrophages. These findings provide evidence that LDN-glycans constitute a parasite pattern for galectin-3-mediated immune recognition.

  4. The CENP-A NAC/CAD kinetochore complex controls chromosome congression and spindle bipolarity.

    PubMed

    McClelland, Sarah E; Borusu, Satyarebala; Amaro, Ana C; Winter, Jennifer R; Belwal, Mukta; McAinsh, Andrew D; Meraldi, Patrick

    2007-12-12

    Kinetochores are complex protein machines that link chromosomes to spindle microtubules and contain a structural core composed of two conserved protein-protein interaction networks: the well-characterized KMN (KNL1/MIND/NDC80) and the recently identified CENP-A NAC/CAD. Here we show that the CENP-A NAC/CAD subunits can be assigned to one of two different functional classes; depletion of Class I proteins (Mcm21R(CENP-O) and Fta1R(CENP-L)) causes a failure in bipolar spindle assembly. In contrast, depletion of Class II proteins (CENP-H, Chl4R(CENP-N), CENP-I and Sim4R(CENP-K)) prevents binding of Class I proteins and causes chromosome congression defects, but does not perturb spindle formation. Co-depletion of Class I and Class II proteins restores spindle bipolarity, suggesting that Class I proteins regulate or counteract the function of Class II proteins. We also demonstrate that CENP-A NAC/CAD and KMN regulate kinetochore-microtubule attachments independently, even though CENP-A NAC/CAD can modulate NDC80 levels at kinetochores. Based on our results, we propose that the cooperative action of CENP-A NAC/CAD subunits and the KMN network drives efficient chromosome segregation and bipolar spindle assembly during mitosis.

  5. Decreased UDP-GlcNAc levels abrogate proliferation control in EMeg32-deficient cells

    PubMed Central

    Boehmelt, Guido; Wakeham, Andrew; Elia, Andrew; Sasaki, Takehiko; Plyte, Sue; Potter, Julia; Yang, Yingju; Tsang, Eric; Ruland, Jürgen; Iscove, Norman N.; Dennis, James W.; Mak, Tak W.

    2000-01-01

    The hexosamine pathway provides UDP-N-acetylhexosamine donor substrates used in cytosolic and Golgi-mediated glycosylation of proteins and for formation of glycosylphosphatidylinositol (GPI) anchors, which tether proteins to the outer plasma membrane. We have recently identified the murine glucosamine-6-phosphate (GlcN6P) acetyltransferase, EMeg32, as a developmentally regulated enzyme on the route to UDP-N-acetylglucosamine (UDP-GlcNAc). Here we describe embryos and cells that have the EMeg32 gene inactivated by homologous recombination. Homozygous mutant embryos die at around embryonic day (E) 7.5 with a general proliferative delay of development. In vitro differentiated EMeg32–/– ES cells show reduced proliferation. Mouse embryonic fibroblasts (MEFs) deficient for EMeg32 exhibit defects in proliferation and adhesiveness, which could be complemented by stable re-expression of EMeg32 or by nutritional restoration of intracellular UDP-GlcNAc levels. Reduced UDP-GlcNAc levels predominantly translated into decreased O-GlcNAc modifications of cytosolic and nuclear proteins. Interestingly, growth-impaired EMeg32–/– MEFs withstand a number of apoptotic stimuli and express activated PKB/AKT. Thus, EMeg32-dependent UDP-GlcNAc levels influence cell cycle progression and susceptibility to apoptotic stimuli. PMID:11013212

  6. N-Acetyl Cysteine (NAC)-Directed Detoxification of Methacryloxylethyl Cetyl Ammonium Chloride (DMAE-CB).

    PubMed

    Jiao, Yang; Ma, Sai; Li, Jing; Shan, Lequn; Wang, Yingjie; Tian, Min; Yang, Yanwei; Sun, Jinlong; Ban, Jinghao; Chen, Jihua

    2015-01-01

    Methacryloxylethyl cetyl ammonium chloride (DMAE-CB) is a polymerizable antibacterial monomer and has been proved as an effective strategy to achieve bioactive bonding with reliable bacterial inhibitory effects. However, the toxicity of DMAE-CB may hamper its wide application in clinical situations. Thus, this study was designed to investigate the toxicity of DMAE-CB and explore the possible protective effects of N-acetyl cysteine (NAC). High performance liquid chromatography (HPLC) and liquid chromatography-mass spectrometry (LC-MS) analysis showed that chemical binding of NAC and DMAE-CB occurred in a time dependent manner. Pre-incubation of fourty-eight hours is required for adequate reaction between DMAE-CB and NAC. DMAE-CB reduced human dental pulp cells (hDPCs) viability in a dose-dependent manner. The toxic effects of DMAE-CB were accompanied by increased reactive oxygen species (ROS) level and reduced glutathione (GSH) content. NAC alleviated DMAE-CB-induced oxidative stress. Annexin V/ Propidium Iodide (PI) staining and Hoechst 33342 staining indicated that DMAE-CB induced apoptosis. Collapsed mitochondrial membrane potential (MMP) and activation of caspase-3 were also observed after DMAE-CB treatment. NAC rescued hDPCs from DMAE-CB-induced apoptosis, accompanied by lower level of MMP loss and caspase-3 activity. This study assists to elucidate the mechanism underlying the cytotoxic effects of DMAE-CB and provides theoretical supports for the searching of effective strategies to reduce toxicity of quaternary ammonium dental monomers.

  7. Characterization of a novel Medicago sativa NAC transcription factor gene involved in response to drought stress.

    PubMed

    Wang, Yong Xin

    2013-11-01

    Relying on the regulation of transcription factors, plants resist to various abiotic and biotic stresses. NAC (NAM, ATAF1/2, CUC2) are one of the largest families of plant-specific transcription factors and known to play important roles in plant development and response to environmental stresses. A new NAC gene was cloned on the basis of 503 bp EST fragment from the SSH cDNA library of Medicago sativa. It was 1,115 bp including an 816 bp ORF and encodes 271 amino acids. A highly conserved region is located from the 7th amino acid to the 315th amino acid in its N-terminal domain. The NAC protein is subcellularly localized in the nucleus of onion epidemical cells and possible functions as a transcription factor. The relative quantitative real-time RT-PCR was performed at different stress time. The results revealed that the transcription expression of NAC gene could be induced by drought, high salinity and ABA. The transgenic Arabidopsis with NAC gene has the drought tolerance better than the wild-type.

  8. Sharing code.

    PubMed

    Kubilius, Jonas

    2014-01-01

    Sharing code is becoming increasingly important in the wake of Open Science. In this review I describe and compare two popular code-sharing utilities, GitHub and Open Science Framework (OSF). GitHub is a mature, industry-standard tool but lacks focus towards researchers. In comparison, OSF offers a one-stop solution for researchers but a lot of functionality is still under development. I conclude by listing alternative lesser-known tools for code and materials sharing.

  9. Bidirectional Synaptic Structural Plasticity after Chronic Cocaine Administration Occurs through Rap1 Small GTPase Signaling.

    PubMed

    Cahill, Michael E; Bagot, Rosemary C; Gancarz, Amy M; Walker, Deena M; Sun, HaoSheng; Wang, Zi-Jun; Heller, Elizabeth A; Feng, Jian; Kennedy, Pamela J; Koo, Ja Wook; Cates, Hannah M; Neve, Rachael L; Shen, Li; Dietz, David M; Nestler, Eric J

    2016-02-03

    Dendritic spines are the sites of most excitatory synapses in the CNS, and opposing alterations in the synaptic structure of medium spiny neurons (MSNs) of the nucleus accumbens (NAc), a primary brain reward region, are seen at early versus late time points after cocaine administration. Here we investigate the time-dependent molecular and biochemical processes that regulate this bidirectional synaptic structural plasticity of NAc MSNs and associated changes in cocaine reward in response to chronic cocaine exposure. Our findings reveal key roles for the bidirectional synaptic expression of the Rap1b small GTPase and an associated local synaptic protein translation network in this process. The transcriptional mechanisms and pathway-specific inputs to NAc that regulate Rap1b expression are also characterized. Collectively, these findings provide a precise mechanism by which nuclear to synaptic interactions induce "metaplasticity" in NAc MSNs, and we reveal the specific effects of this plasticity on reward behavior in a brain circuit-specific manner.

  10. Genome-wide characterization and expression profiling of the NAC genes under abiotic stresses in Cucumis sativus.

    PubMed

    Zhang, Xiao Meng; Yu, Hong Jun; Sun, Chao; Deng, Jie; Zhang, Xue; Liu, Peng; Li, Yun Yun; Li, Qiang; Jiang, Wei Jie

    2017-04-01

    The NAC (standing for no apical meristem [NAM], Arabidopsis transcription activation factor [ATAF] and cup-shaped cotyledon [CUC]) proteins pertain to one of the plant-specific transcription factor families that play important roles in plant development, abiotic stress resistance and signalling transduction. In the present study, the genomic features of the NAC genes in cucumber were analysed in depth using in silico tools. To reveal a tissue-specific, abiotic stress and hormone-responsive expression profile of CsNAC genes, RT-qPCR was performed under different treatments. Phylogenetic analyses and genome-wide annotation indicated that 82 high-confidence CsNAC genes were clustered into 13 sub-groups with uneven distribution in the cucumber genome. Furthermore, the CsNAC genes exhibited different tissue-specific expression patterns in 10 tissues under normal growth conditions, while 13 (16%) and 28 (34%) genes displayed preferential expression in roots and flowers, respectively. Moreover, CsNAC genes were more sensitive to salinity than other stresses; however, their responses were relatively rapid and transient to nutrition deprivation. Several CsNAC genes, including CsNAC35, which is an orthologue of the known stress-responsive Arabidopsis RD26, were identified as highly responsive to abiotic stresses and hormones. Overall, our findings revealed the genomic landscape and expression profiling of the CsNAC genes in response to multiple stresses and hormones, offering clues for further function analyses and molecular breeding.

  11. Initiation of protein O glycosylation by the polypeptide GalNAcT-1 in vascular biology and humoral immunity.

    PubMed

    Tenno, Mari; Ohtsubo, Kazuaki; Hagen, Fred K; Ditto, David; Zarbock, Alexander; Schaerli, Patrick; von Andrian, Ulrich H; Ley, Klaus; Le, Dzung; Tabak, Lawrence A; Marth, Jamey D

    2007-12-01

    Core-type protein O glycosylation is initiated by polypeptide N-acetylgalactosamine (GalNAc) transferase (ppGalNAcT) activity and produces the covalent linkage of serine and threonine residues of proteins. More than a dozen ppGalNAcTs operate within multicellular organisms, and they differ with respect to expression patterns and substrate selectivity. These distinctive features imply that each ppGalNAcT may differentially modulate regulatory processes in animal development, physiology, and perhaps disease. We found that ppGalNAcT-1 plays key roles in cell and glycoprotein selective functions that modulate the hematopoietic system. Loss of ppGalNAcT-1 activity in the mouse results in a bleeding disorder which tracks with reduced plasma levels of blood coagulation factors V, VII, VIII, IX, X, and XII. ppGalNAcT-1 further supports leukocyte trafficking and residency in normal homeostatic physiology as well as during inflammatory responses, in part by providing a scaffold for the synthesis of selectin ligands expressed by neutrophils and endothelial cells of peripheral lymph nodes. Animals lacking ppGalNAcT-1 are also markedly impaired in immunoglobulin G production, coincident with increased germinal center B-cell apoptosis and reduced levels of plasma B cells. These findings reveal that the initiation of protein O glycosylation by ppGalNAcT-1 provides a distinctive repertoire of advantageous functions that support vascular responses and humoral immunity.

  12. Preclinical and Clinical Advances of GalNAc-Decorated Nucleic Acid Therapeutics.

    PubMed

    Huang, Yuanyu

    2017-03-17

    A main challenge in realizing the full potential of nucleic acid therapeutics is efficient delivery of them into targeted tissues and cells. N-acetylgalactosamine (GalNAc) is a well-defined liver-targeted moiety benefiting from its high affinity with asialoglycoprotein receptor (ASGPR). By conjugating it directly to the oligonucleotides or decorating it to a certain delivery system as a targeting moiety, GalNAc has achieved compelling successes in the development of nucleic acid therapeutics in recent years. Several oligonucleotide modalities are undergoing pivotal clinical studies, followed by a blooming pipeline in the preclinical stage. This review covers the progress of GalNAc-decorated oligonucleotide drugs, including siRNAs, anti-miRs, and ASOs, which provides a panorama for this field.

  13. Residual mucin and response after neoadjuvant chemotherapy (NAC) in breast cancer.

    PubMed

    Jove, Maria; Verghese, Eldo; Sharma, Nisha; Lane, Sally

    2016-05-06

    Neoadjuvant chemotherapy (NAC) is the standard of care for patients with breast cancer with inoperable disease or smaller tumours who might benefit from a conservative surgery after downstaging of their disease. Nevertheless, evidence shows that preoperative and postoperative chemotherapy are equivalent in terms of long-term survival. Response and histological changes after NAC have been widely studied in invasive ductal carcinoma not otherwise specified, but there is a paucity of characterisation of patterns of response to chemotherapy in less frequent histological types. We report extensive residual mucin deposits after chemotherapy in a woman with locally advanced breast cancer and a prominent mucinous component at diagnosis. Interestingly, residual mucin was co-located with the initial tumour, in the breast as well as in the axillary lymph nodes. The distribution of mucin may be a valuable marker of the extent of mucinous carcinomas prior to NAC.

  14. The Early Metazoan Trichoplax adhaerens Possesses a Functional O-GlcNAc System*

    PubMed Central

    Selvan, Nithya; Mariappa, Daniel; van den Toorn, Henk W. P.; Heck, Albert J. R.; Ferenbach, Andrew T.; van Aalten, Daan M. F.

    2015-01-01

    Protein O-GlcNAcylation is a reversible post-translational signaling modification of nucleocytoplasmic proteins that is essential for embryonic development in bilateria. In a search for a reductionist model to study O-GlcNAc signaling, we discovered the presence of functional O-GlcNAc transferase (OGT), O-GlcNAcase (OGA), and nucleocytoplasmic protein O-GlcNAcylation in the most basal extant animal, the placozoan Trichoplax adhaerens. We show via enzymatic characterization of Trichoplax OGT/OGA and genetic rescue experiments in Drosophila melanogaster that these proteins possess activities/functions similar to their bilaterian counterparts. The acquisition of O-GlcNAc signaling by metazoa may have facilitated the rapid and complex signaling mechanisms required for the evolution of multicellular organisms. PMID:25778404

  15. The NAC domain-containing protein, GmNAC6, is a downstream component of the ER stress- and osmotic stress-induced NRP-mediated cell-death signaling pathway

    PubMed Central

    2011-01-01

    Background The endoplasmic reticulum (ER) is a major signaling organelle, which integrates a variety of responses against physiological stresses. In plants, one such stress-integrating response is the N-rich protein (NRP)-mediated cell death signaling pathway, which is synergistically activated by combined ER stress and osmotic stress signals. Despite the potential of this integrated signaling to protect plant cells against different stress conditions, mechanistic knowledge of the pathway is lacking, and downstream components have yet to be identified. Results In the present investigation, we discovered an NAC domain-containing protein from soybean, GmNAC6 (Glycine max NAC6), to be a downstream component of the integrated pathway. Similar to NRP-A and NRP-B, GmNAC6 is induced by ER stress and osmotic stress individually, but requires both signals for full activation. Transient expression of GmNAC6 promoted cell death and hypersensitive-like responses in planta. GmNAC6 and NRPs also share overlapping responses to biotic signals, but the induction of NRPs peaked before the increased accumulation of GmNAC6 transcripts. Consistent with the delayed kinetics of GmNAC6 induction, increased levels of NRP-A and NRP-B transcripts induced promoter activation and the expression of the GmNAC6 gene. Conclusions Collectively, our results biochemically link GmNAC6 to the ER stress- and osmotic stress-integrating cell death response and show that GmNAC6 may act downstream of the NRPs. PMID:21943253

  16. Efficient and Regioselective Synthesis of β-GalNAc/GlcNAc-Lactose by a Bifunctional Transglycosylating β-N-Acetylhexosaminidase from Bifidobacterium bifidum

    PubMed Central

    Chen, Xiaodi; Xu, Li; Jin, Lan; Sun, Bin; Gu, Guofeng

    2016-01-01

    ABSTRACT β-N-Acetylhexosaminidases have attracted interest particularly for oligosaccharide synthesis, but their use remains limited by the rarity of enzyme sources , low efficiency, and relaxed regioselectivity of transglycosylation. In this work, genes of 13 β-N-acetylhexosaminidases, including 5 from Bacteroides fragilis ATCC 25285, 5 from Clostridium perfringens ATCC 13124, and 3 from Bifidobacterium bifidum JCM 1254, were cloned and heterogeneously expressed in Escherichia coli. The resulting recombinant enzymes were purified and screened for transglycosylation activity. A β-N-acetylhexosaminidase named BbhI, which belongs to glycoside hydrolase family 20 and was obtained from B. bifidum JCM 1254, possesses the bifunctional property of efficiently transferring both GalNAc and GlcNAc residues through β1-3 linkage to the Gal residue of lactose. The effects of initial substrate concentration, pH, temperature, and reaction time on transglycosylation activities of BbhI were studied in detail. With the use of 10 mM pNP-β-GalNAc or 20 mM pNP-β-GlcNAc as the donor and 400 mM lactose as the acceptor in phosphate buffer (pH 5.8), BbhI synthesized GalNAcβ1-3Galβ1-4Glc and GlcNAcβ1-3Galβ1-4Glc at maximal yields of 55.4% at 45°C and 4 h and 44.9% at 55°C and 1.5 h, respectively. The model docking of BbhI with lactose showed the possible molecular basis of strict regioselectivity of β1-3 linkage in β-N-acetylhexosaminyl lactose synthesis. IMPORTANCE Oligosaccharides play a crucial role in many biological events and therefore are promising potential therapeutic agents. However, their use is limited because large-scale production of oligosaccharides is difficult. The chemical synthesis requires multiple protecting group manipulations to control the regio- and stereoselectivity of glycosidic bonds. In comparison, enzymatic synthesis can produce oligosaccharides in one step by using glycosyltransferases and glycosidases. Given the lower price of their glycosyl

  17. Prevention of Acoustic Trauma-Induced Hearing Loss by N-acetylcysteine Administration in Rabbits

    PubMed Central

    Motalebi Kashani, Masoud; Saberi, Hamidreza; Hannani, Mitra

    2013-01-01

    Background Acoustic trauma is an injury to the hearing mechanisms in the inner ear due to excessive noise. This injury is the most prevalent cause of sensorineural hearing loss in humans, especially from occupational exposure. Previous studies have shown the essential role of free radical formation in the inner ear hearing loss caused by acoustic trauma. Objectives This study was performed to determine the effect of N-acetylcysteine (NAC) administration for reducing acute acoustic trauma in rabbits. Materials and Methods Twenty four rabbits were assigned to four groups including: control, noise plus saline, noise plus NAC administration (325 mg/kg body weight by intraperitoneal injection (IP), three days before exposure to noise and three days after noise exposure), and NAC alone. Auditory brain stem response (ABR) threshold was measured before exposure and one hour and 14 days after exposure. Results The saline plus noise group had on average a 49 decibel (dB) temporary threshold shift (TTS) and 23.9 dB permanent threshold shift (PTS) at the studied frequencies, while rabbits in the NAC administration plus noise group had a 31.5 dB TTS and 10.7 dB PTS averaged across the frequencies. Conclusions Administration of NAC can provide appropriate protection against acoustic trauma-induced hearing loss in rabbits at all studied frequencies. PMID:24396768

  18. sgs1: a neomorphic nac52 allele impairing PTGS through SGS3 down-regulation.

    PubMed

    Butel, Nicolas; Le Masson, Ivan; Bouteiller, Nathalie; Vaucheret, Hervé; Elmayan, Taline

    2017-02-16

    Post-transcriptional gene silencing (PTGS) is a defense mechanism that targets invading nucleic acids from endogenous (transposons) or exogenous (pathogens, transgenes) origins. Genetic screens based on the reactivation of silenced transgenes have long been used to identify cellular PTGS components and regulators. Here we show that the first isolated PTGS-deficient mutant, sgs1, is impaired in the transcription factor NAC52. This mutant exhibits striking similarities with a mutant impaired in the H3K4me3 demethylase JMJ14 isolated from the same genetic screen. These similarities including increased transgene promoter DNA methylation, reduced H3K4me3 and H3K36me3 levels, reduced PolII occupancy and reduced transgene mRNA accumulation. Likely, increased DNA methylation is the cause of reduced transcription because the effect of jmj14 and sgs1 on transgene transcription is suppressed by drm2, a mutation that compromises de novo DNA methylation, suggesting that the JMJ14-NAC52 module promotes transgene transcription by preventing DNA methylation. Remarkably, sgs1 has a stronger effect than jmj14 and nac52 null alleles on PTGS systems requiring siRNA amplification, and this is due to reduced SGS3 mRNA levels in sgs1. Given that the sgs1 mutation changes a conserved aminoacid of the NAC proteins involved in homodimerization, we propose that sgs1 corresponds to a neomorphic nac52 allele encoding a mutant protein that lacks wild-type NAC52 activity but promotes SGS3 down-regulation. Together, these results indicate that PTGS impairment in sgs1 is due to its dual effect on transgene transcription and SGS3 transcription, thus compromising siRNA amplification. This article is protected by copyright. All rights reserved.

  19. Changes in Metabolic Chemical Reporter Structure Yield a Selective Probe of O-GlcNAc Modification

    PubMed Central

    2015-01-01

    Metabolic chemical reporters (MCRs) of glycosylation are analogues of monosaccharides that contain bioorthogonal functionalities and enable the direct visualization and identification of glycoproteins from living cells. Each MCR was initially thought to report on specific types of glycosylation. We and others have demonstrated that several MCRs are metabolically transformed and enter multiple glycosylation pathways. Therefore, the development of selective MCRs remains a key unmet goal. We demonstrate here that 6-azido-6-deoxy-N-acetyl-glucosamine (6AzGlcNAc) is a specific MCR for O-GlcNAcylated proteins. Biochemical analysis and comparative proteomics with 6AzGlcNAc, N-azidoacetyl-glucosamine (GlcNAz), and N-azidoacetyl-galactosamine (GalNAz) revealed that 6AzGlcNAc exclusively labels intracellular proteins, while GlcNAz and GalNAz are incorporated into a combination of intracellular and extracellular/lumenal glycoproteins. Notably, 6AzGlcNAc cannot be biosynthetically transformed into the corresponding UDP sugar-donor by the canonical salvage-pathway that requires phosphorylation at the 6-hydroxyl. In vitro experiments showed that 6AzGlcNAc can bypass this roadblock through direct phosphorylation of its 1-hydroxyl by the enzyme phosphoacetylglucosamine mutase (AGM1). Taken together, 6AzGlcNAc enables the specific analysis of O-GlcNAcylated proteins, and these results suggest that specific MCRs for other types of glycosylation can be developed. Additionally, our data demonstrate that cells are equipped with a somewhat unappreciated metabolic flexibility with important implications for the biosynthesis of natural and unnatural carbohydrates. PMID:25153642

  20. Absence of intraepidermal glycosyltransferase ppGalNac-T3 expression in familial tumoral calcinosis.

    PubMed

    Topaz, Orit; Bergman, Reuven; Mandel, Ulla; Maor, Gila; Goldberg, Ruth; Richard, Gabriele; Sprecher, Eli

    2005-06-01

    Hyperphosphatemic familial tumoral calcinosis (HFTC) is a rare autosomal recessive disorder characterized by progressive, tumor-like calcifications in the dermis and subcutaneous tissues. The disease is associated with primary hyperphosphatemia due to increased renal tubular reabsorption of phosphate. We recently identified mutations in GALNT3 as the proximal cause of this metabolic disorder. GALNT3 encodes the glycosyltransferase UDP-N-acetyl-alpha-D-galactosamine:polypeptide N-acetylgalactosaminyl-transferase 3 (ppGalNAc-T3), which initiates mucin-type O-glycosylation and thus takes part in posttranslational modification and formation of mucin-type glycoproteins. A number of studies have previously described the histopathological and ultrastructural features of lesional skin in HFTC, but little is currently known about the morphology of the normal-appearing non-lesional skin. We obtained biopsies of uninvolved skin from two HFTC patients carrying a known splice site mutation in GALNT3. Light and electron microscopic examination of a biopsy of one of the two patients did not reveal abnormal findings in the epidermis or dermis. However, immunohistochemical studies of frozen skin sections of biopsies of the two patients using monoclonal antibodies directed against three ppGalNac isoforms revealed the complete absence of immunostaining for ppGalNAc-T3 while the staining pattern for ppGalNAc-T2 and -T6 was identical in skin biopsies obtained from HFTC patients and healthy control individuals. Our data provide for the first time evidence for ppGalNAc-T3 deficiency in the skin of HFTC patients and suggest that immunostaining of skin biopsy samples for ppGal-Nac-T3 might be a useful tool for the diagnosis of HFTC.

  1. 45 CFR 162.1011 - Valid code sets.

    Code of Federal Regulations, 2013 CFR

    2013-10-01

    ... 45 Public Welfare 1 2013-10-01 2013-10-01 false Valid code sets. 162.1011 Section 162.1011 Public Welfare DEPARTMENT OF HEALTH AND HUMAN SERVICES ADMINISTRATIVE DATA STANDARDS AND RELATED REQUIREMENTS ADMINISTRATIVE REQUIREMENTS Code Sets § 162.1011 Valid code sets. Each code set is valid within the...

  2. 45 CFR 162.1011 - Valid code sets.

    Code of Federal Regulations, 2012 CFR

    2012-10-01

    ... 45 Public Welfare 1 2012-10-01 2012-10-01 false Valid code sets. 162.1011 Section 162.1011 Public Welfare DEPARTMENT OF HEALTH AND HUMAN SERVICES ADMINISTRATIVE DATA STANDARDS AND RELATED REQUIREMENTS ADMINISTRATIVE REQUIREMENTS Code Sets § 162.1011 Valid code sets. Each code set is valid within the...

  3. 45 CFR 162.1011 - Valid code sets.

    Code of Federal Regulations, 2014 CFR

    2014-10-01

    ... 45 Public Welfare 1 2014-10-01 2014-10-01 false Valid code sets. 162.1011 Section 162.1011 Public Welfare Department of Health and Human Services ADMINISTRATIVE DATA STANDARDS AND RELATED REQUIREMENTS ADMINISTRATIVE REQUIREMENTS Code Sets § 162.1011 Valid code sets. Each code set is valid within the...

  4. 45 CFR 162.1011 - Valid code sets.

    Code of Federal Regulations, 2011 CFR

    2011-10-01

    ... 45 Public Welfare 1 2011-10-01 2011-10-01 false Valid code sets. 162.1011 Section 162.1011 Public Welfare DEPARTMENT OF HEALTH AND HUMAN SERVICES ADMINISTRATIVE DATA STANDARDS AND RELATED REQUIREMENTS ADMINISTRATIVE REQUIREMENTS Code Sets § 162.1011 Valid code sets. Each code set is valid within the...

  5. Use of a mutant OGA for detecting O-GlcNAc modified proteins.

    PubMed

    Chalkley, Robert J

    2015-12-01

    In the previous issue of Biochemical Journal Mariappa et al. [(2015) Biochem J. 470,: 255-262] demonstrate a new method for visualizing O-linked N-acetylglucosamine (O-GlcNAc) modified proteins by making use of a catalytically dead version of the enzyme that normally removes this modification. They show their approach has broader specificity than current antibody-based techniques and higher specificity than lectin and chemical biology-based labelling approaches. This commentary discusses methods for O-GlcNAc detection and the significance of this work for characterizing this common, but currently poorly understood regulatory modification.

  6. Prediction error as a linear function of reward probability is coded in human nucleus accumbens.

    PubMed

    Abler, Birgit; Walter, Henrik; Erk, Susanne; Kammerer, Hannes; Spitzer, Manfred

    2006-06-01

    Reward probability has been shown to be coded by dopamine neurons in monkeys. Phasic neuronal activation not only increased linearly with reward probability upon expectation of reward, but also varied monotonically across the range of probabilities upon omission or receipt of rewards, therefore modeling discrepancies between expected and received rewards. Such a discrete coding of prediction error has been suggested to be one of the basic principles of learning. We used functional magnetic resonance imaging (fMRI) to show that the human dopamine system codes reward probability and prediction error in a similar way. We used a simple delayed incentive task with a discrete range of reward probabilities from 0%-100%. Activity in the nucleus accumbens of human subjects strongly resembled the phasic responses found in monkey neurons. First, during the expectation period of the task, the fMRI signal in the human nucleus accumbens (NAc) increased linearly with the probability of the reward. Second, during the outcome phase, activity in the NAc coded the prediction error as a linear function of reward probabilities. Third, we found that the Nac signal was correlated with individual differences in sensation seeking and novelty seeking, indicating a link between individual fMRI activation of the dopamine system in a probabilistic paradigm and personality traits previously suggested to be linked with reward processing. We therefore identify two different covariates that model activity in the Nac: specific properties of a psychological task and individual character traits.

  7. Genome-wide organization and expression profiling of the NAC transcription factor family in potato (Solanum tuberosum L.).

    PubMed

    Singh, Anil Kumar; Sharma, Vishal; Pal, Awadhesh Kumar; Acharya, Vishal; Ahuja, Paramvir Singh

    2013-08-01

    NAC [no apical meristem (NAM), Arabidopsis thaliana transcription activation factor [ATAF1/2] and cup-shaped cotyledon (CUC2)] proteins belong to one of the largest plant-specific transcription factor (TF) families and play important roles in plant development processes, response to biotic and abiotic cues and hormone signalling. Our genome-wide analysis identified 110 StNAC genes in potato encoding for 136 proteins, including 14 membrane-bound TFs. The physical map positions of StNAC genes on 12 potato chromosomes were non-random, and 40 genes were found to be distributed in 16 clusters. The StNAC proteins were phylogenetically clustered into 12 subgroups. Phylogenetic analysis of StNACs along with their Arabidopsis and rice counterparts divided these proteins into 18 subgroups. Our comparative analysis has also identified 36 putative TNAC proteins, which appear to be restricted to Solanaceae family. In silico expression analysis, using Illumina RNA-seq transcriptome data, revealed tissue-specific, biotic, abiotic stress and hormone-responsive expression profile of StNAC genes. Several StNAC genes, including StNAC072 and StNAC101that are orthologs of known stress-responsive Arabidopsis RESPONSIVE TO DEHYDRATION 26 (RD26) were identified as highly abiotic stress responsive. Quantitative real-time polymerase chain reaction analysis largely corroborated the expression profile of StNAC genes as revealed by the RNA-seq data. Taken together, this analysis indicates towards putative functions of several StNAC TFs, which will provide blue-print for their functional characterization and utilization in potato improvement.

  8. An OGA-Resistant Probe Allows Specific Visualization and Accurate Identification of O-GlcNAc-Modified Proteins in Cells.

    PubMed

    Li, Jing; Wang, Jiajia; Wen, Liuqing; Zhu, He; Li, Shanshan; Huang, Kenneth; Jiang, Kuan; Li, Xu; Ma, Cheng; Qu, Jingyao; Parameswaran, Aishwarya; Song, Jing; Zhao, Wei; Wang, Peng George

    2016-11-18

    O-linked β-N-acetyl-glucosamine (O-GlcNAc) is an essential and ubiquitous post-translational modification present in nucleic and cytoplasmic proteins of multicellular eukaryotes. The metabolic chemical probes such as GlcNAc or GalNAc analogues bearing ketone or azide handles, in conjunction with bioorthogonal reactions, provide a powerful approach for detecting and identifying this modification. However, these chemical probes either enter multiple glycosylation pathways or have low labeling efficiency. Therefore, selective and potent probes are needed to assess this modification. We report here the development of a novel probe, 1,3,6-tri-O-acetyl-2-azidoacetamido-2,4-dideoxy-d-glucopyranose (Ac34dGlcNAz), that can be processed by the GalNAc salvage pathway and transferred by O-GlcNAc transferase (OGT) to O-GlcNAc proteins. Due to the absence of a hydroxyl group at C4, this probe is less incorporated into α/β 4-GlcNAc or GalNAc containing glycoconjugates. Furthermore, the O-4dGlcNAz modification was resistant to the hydrolysis of O-GlcNAcase (OGA), which greatly enhanced the efficiency of incorporation for O-GlcNAcylation. Combined with a click reaction, Ac34dGlcNAz allowed the selective visualization of O-GlcNAc in cells and accurate identification of O-GlcNAc-modified proteins with LC-MS/MS. This probe represents a more potent and selective tool in tracking, capturing, and identifying O-GlcNAc-modified proteins in cells and cell lysates.

  9. The barley HvNAC6 transcription factor affects ABA accumulation and promotes basal resistance against powdery mildew.

    PubMed

    Chen, Yan-Jun; Perera, Venura; Christiansen, Michael W; Holme, Inger B; Gregersen, Per L; Grant, Murray R; Collinge, David B; Lyngkjær, Michael F

    2013-12-01

    Barley HvNAC6 is a member of the plant-specific NAC (NAM, ATAF1,2, CUC2) transcription factor family and we have shown previously that it acts as a positive regulator of basal resistance in barley against the biotrophic pathogen Blumeria graminis f. sp. hordei (Bgh). In this study, we use a transgenic approach to constitutively silence HvNAC6 expression, using RNA interference (RNAi), to investigate the in vivo functions of HvNAC6 in basal resistance responses in barley in relation to the phytohormone ABA. The HvNAC6 RNAi plants displayed reduced HvNAC6 transcript levels and were more susceptible to Bgh than wild-type plants. Application of exogenous ABA increased basal resistance against Bgh in wild-type plants, but not in HvNAC6 RNAi plants, suggesting that ABA is a positive regulator of basal resistance which depends on HvNAC6. Silencing of HvNAC6 expression altered the light/dark rhythm of ABA levels which were, however, not influenced by Bgh inoculation. The expression of the two ABA biosynthetic genes HvNCED1 and HvNCED2 was compromised, and transcript levels of the ABA conjugating HvBG7 enzyme were elevated in the HvNAC6 RNAi lines, but this effect was not clearly associated with transgene-mediated resistance. Together, these data support a function of HvNAC6 as a regulator of ABA-mediated defence responses for maintenance of effective basal resistance against Bgh.

  10. Genome-Wide Organization and Expression Profiling of the NAC Transcription Factor Family in Potato (Solanum tuberosum L.)

    PubMed Central

    Singh, Anil Kumar; Sharma, Vishal; Pal, Awadhesh Kumar; Acharya, Vishal; Ahuja, Paramvir Singh

    2013-01-01

    NAC [no apical meristem (NAM), Arabidopsis thaliana transcription activation factor [ATAF1/2] and cup-shaped cotyledon (CUC2)] proteins belong to one of the largest plant-specific transcription factor (TF) families and play important roles in plant development processes, response to biotic and abiotic cues and hormone signalling. Our genome-wide analysis identified 110 StNAC genes in potato encoding for 136 proteins, including 14 membrane-bound TFs. The physical map positions of StNAC genes on 12 potato chromosomes were non-random, and 40 genes were found to be distributed in 16 clusters. The StNAC proteins were phylogenetically clustered into 12 subgroups. Phylogenetic analysis of StNACs along with their Arabidopsis and rice counterparts divided these proteins into 18 subgroups. Our comparative analysis has also identified 36 putative TNAC proteins, which appear to be restricted to Solanaceae family. In silico expression analysis, using Illumina RNA-seq transcriptome data, revealed tissue-specific, biotic, abiotic stress and hormone-responsive expression profile of StNAC genes. Several StNAC genes, including StNAC072 and StNAC101that are orthologs of known stress-responsive Arabidopsis RESPONSIVE TO DEHYDRATION 26 (RD26) were identified as highly abiotic stress responsive. Quantitative real-time polymerase chain reaction analysis largely corroborated the expression profile of StNAC genes as revealed by the RNA-seq data. Taken together, this analysis indicates towards putative functions of several StNAC TFs, which will provide blue-print for their functional characterization and utilization in potato improvement. PMID:23649897

  11. Accelerated urinary excretion of methylmercury following administration of its antidote N-acetylcysteine requires Mrp2/Abcc2, the apical multidrug resistance-associated protein.

    PubMed

    Madejczyk, Michael S; Aremu, David A; Simmons-Willis, Tracey A; Clarkson, Thomas W; Ballatori, Nazzareno

    2007-07-01

    N-Acetylcysteine (NAC) is a sulfhydryl-containing compound that produces a dramatic acceleration of urinary methylmercury (MeHg) excretion in poisoned mice, but the molecular mechanism for this effect is poorly defined. MeHg readily binds to NAC to form the MeHg-NAC complex, and recent studies indicate that this complex is an excellent substrate for the basolateral organic anion transporter (Oat)-1, Oat1/Slc22a6, thus potentially explaining the uptake from blood into the renal tubular cells. The present study tested the hypothesis that intracellular MeHg is subsequently transported across the apical membrane of the cells into the tubular fluid as a MeHg-NAC complex using the multidrug resistance-associated protein-2 (Mrp2/Abcc2). NAC markedly stimulated urinary [(14)C]MeHg excretion in wild-type Wistar rats, and a second dose of NAC was as effective as the first dose in stimulating MeHg excretion. In contrast with the normal Wistar rats, NAC was much less effective at stimulating urinary MeHg excretion in the Mrp2-deficient (TR-) Wistar rats. The TR- rats excreted only approximately 30% of the MeHg excreted by the wild-type animals. To directly test whether MeHg-NAC is a substrate for Mrp2, studies were carried out in plasma membrane vesicles isolated from livers of TR- and control Wistar rats. Transport of MeHg-NAC was lower in vesicles prepared from TR- rats, whereas transport of MeHg-cysteine was similar in control and TR- rats. These results indicate that Mrp2 is involved in urinary MeHg excretion after NAC administration and suggest that the transported molecule is most likely the MeHg-NAC complex.

  12. Sharing code

    PubMed Central

    Kubilius, Jonas

    2014-01-01

    Sharing code is becoming increasingly important in the wake of Open Science. In this review I describe and compare two popular code-sharing utilities, GitHub and Open Science Framework (OSF). GitHub is a mature, industry-standard tool but lacks focus towards researchers. In comparison, OSF offers a one-stop solution for researchers but a lot of functionality is still under development. I conclude by listing alternative lesser-known tools for code and materials sharing. PMID:25165519

  13. Administrative simplification: change to the compliance date for the International Classification of Diseases, 10th Revision (ICD-10-CM and ICD-10-PCS) medical data code sets. Final rule.

    PubMed

    2014-08-04

    This final rule implements section 212 of the Protecting Access to Medicare Act of 2014 by changing the compliance date for the International Classification of Diseases, 10th Revision, Clinical Modification (ICD-10-CM) for diagnosis coding, including the Official ICD-10-CM Guidelines for Coding and Reporting, and the International Classification of Diseases, 10th Revision, Procedure Coding System (ICD-10-PCS) for inpatient hospital procedure coding, including the Official ICD-10-PCS Guidelines for Coding and Reporting, from October 1, 2014 to October 1, 2015. It also requires the continued use of the International Classification of Diseases, 9th Revision, Clinical Modification, Volumes 1 and 2 (diagnoses), and 3 (procedures) (ICD-9-CM), including the Official ICD-9-CM Guidelines for Coding and Reporting, through September 30, 2015.

  14. Dynamic O-GlcNAc cycling at promoters of Caenorhabditis elegans genes regulating longevity, stress, and immunity.

    PubMed

    Love, Dona C; Ghosh, Salil; Mondoux, Michelle A; Fukushige, Tetsunari; Wang, Peng; Wilson, Mark A; Iser, Wendy B; Wolkow, Catherine A; Krause, Michael W; Hanover, John A

    2010-04-20

    Nutrient-driven O-GlcNAcylation of key components of the transcription machinery may epigenetically modulate gene expression in metazoans. The global effects of GlcNAcylation on transcription can be addressed directly in C. elegans because knockouts of the O-GlcNAc cycling enzymes are viable and fertile. Using anti-O-GlcNAc ChIP-on-chip whole-genome tiling arrays on wild-type and mutant strains, we detected over 800 promoters where O-GlcNAc cycling occurs, including microRNA loci and multigene operons. Intriguingly, O-GlcNAc-marked promoters are biased toward genes associated with PIP3 signaling, hexosamine biosynthesis, and lipid/carbohydrate metabolism. These marked genes are linked to insulin-like signaling, metabolism, aging, stress, and pathogen-response pathways in C. elegans. Whole-genome transcriptional profiling of the O-GlcNAc cycling mutants confirmed dramatic deregulation of genes in these key pathways. As predicted, the O-GlcNAc cycling mutants show altered lifespan and UV stress susceptibility phenotypes. We propose that O-GlcNAc cycling at promoters participates in a molecular program impacting nutrient-responsive pathways in C. elegans, including stress, pathogen response, and adult lifespan. The observed impact of O-GlcNAc cycling on both signaling and transcription in C. elegans has important implications for human diseases of aging, including diabetes and neurodegeneration.

  15. Conformational effects in enzyme catalysis: QM/MM free energy calculation of the 'NAC' contribution in chorismate mutase.

    PubMed

    Ranaghan, Kara E; Mulholland, Adrian J

    2004-05-21

    The controversial 'near attack conformation'(NAC) effect in the important model enzyme chorismate mutase is calculated to be 3.8-4.6 kcal mol(-1) by QM/MM free energy perturbation molecular dynamics methods, showing that the NAC effect by itself does not account for catalysis in this enzyme.

  16. GhNAC12, a neutral candidate gene, leads to early aging in cotton (Gossypium hirsutum L).

    PubMed

    Zhao, Fengli; Ma, Jianhui; Li, Libei; Fan, Shuli; Guo, Yaning; Song, Meizhen; Wei, Hengling; Pang, Chaoyou; Yu, Shuxun

    2016-01-15

    NAC (NAM, ATAF, and CUC) is one of the largest transcription factor families in plants, and its members play various roles in plant growth, development, and the response to biotic and abiotic stresses. Currently, 77 NAC genes have been reported in cotton (Gossypium hirsutum L.). And GhNAC12 showed up-regulation during leaf senescence, but its role in this process is poorly understood. In the present study, a preliminary function analysis of GhNAC12 was performed during leaf senescence. qRT-PCR analysis indicated that GhNAC12 expression increased during the early-aging process and the aging of cotyledons. Additionally, we observed that overexpression of GhNAC12 in Arabidopsis led to early senescence (early aging). Our findings suggest that GhNAC12 is a candidate gene for early aging in upland cotton cultivars. Neutrality tests suggested that there was no selection pressure imposed on GhNAC12 during the domestication of upland cotton.

  17. Comparative Genomics of NAC Transcriptional Factors in Angiosperms: Implications for the Adaptation and Diversification of Flowering Plants.

    PubMed

    Pereira-Santana, Alejandro; Alcaraz, Luis David; Castaño, Enrique; Sanchez-Calderon, Lenin; Sanchez-Teyer, Felipe; Rodriguez-Zapata, Luis

    2015-01-01

    NAC proteins constitute one of the largest groups of plant-specific transcription factors and are known to play essential roles in various developmental processes. They are also important in plant responses to stresses such as drought, soil salinity, cold, and heat, which adversely affect growth. The current knowledge regarding the distribution of NAC proteins in plant lineages comes from relatively small samplings from the available data. In the present study, we broadened the number of plant species containing the NAC family origin and evolution to shed new light on the evolutionary history of this family in angiosperms. A comparative genome analysis was performed on 24 land plant species, and NAC ortholog groups were identified by means of bidirectional BLAST hits. Large NAC gene families are found in those species that have experienced more whole-genome duplication events, pointing to an expansion of the NAC family with divergent functions in flowering plants. A total of 3,187 NAC transcription factors that clustered into six major groups were used in the phylogenetic analysis. Many orthologous groups were found in the monocot and eudicot lineages, but only five orthologous groups were found between P. patens and each representative taxa of flowering plants. These groups were called basal orthologous groups and likely expanded into more recent taxa to cope with their environmental needs. This analysis on the angiosperm NAC family represents an effort to grasp the evolutionary and functional diversity within this gene family while providing a basis for further functional research on vascular plant gene families.

  18. Synthesis of tetravalent LacNAc-glycoclusters as high-affinity cross-linker against Erythrina cristagalli agglutinin.

    PubMed

    Ogata, Makoto; Chuma, Yasushi; Yasumoto, Yoshinori; Onoda, Takashi; Umemura, Myco; Usui, Taichi; Park, Enoch Y

    2016-01-01

    Four kinds of tetravalent double-headed glycoclusters [(LacNAc)4-DHGs] were designed with linkers of varying lengths consisting of alkanedioic carboxyamido groups (C6, C12, C18 and C24) between two bi-antennary LacNAc-glycosides. These glycoclusters served as high-affinity cross-linking ligands for the LacNAc-binding lectin Erythrina cristagalli agglutinin (ECA). The binding activity and cross-linking between each ligand and ECA were characterized by a hemagglutination inhibition (HI) assay, isothermal titration calorimetry (ITC), a quantitative precipitation assay and dynamic light scattering (DLS). For the precipitation assay and DLS measurement, the synthesized (LacNAc)4-DHGs were found to be capable of binding and precipitating the ECA as multivalent ligands. ITC analysis indicated the binding of (LacNAc)4-DHGs was driven by a favorable enthalpy change. Furthermore, the entropy penalty from binding (LacNAc)4-DHGs clearly decreased in a spacer length-dependent manner. The binding affinities of flexible (LacNAc)4-DHGs (C18 and C24) with long spacers were found to be more favorable than those of the clusters having short spacers (C6 and C12). These results were supported by molecular dynamics simulations with explicit water molecules for the tetravalent glycoclusters with ECA. We concluded that the subtle modification in the epitope-presenting scaffolds exerts the significant effect in the recognition efficiency involved in the LacNAc moieties by ECA.

  19. Isolation and expression profiling of GhNAC transcription factor genes in cotton (Gossypium hirsutum L.) during leaf senescence and in response to stresses.

    PubMed

    Shah, Syed Tariq; Pang, Chaoyou; Fan, Shuli; Song, Meizhen; Arain, Saima; Yu, Shuxun

    2013-12-01

    NAC (NAM, ATAF, and CUC) is a plant-specific transcription factor family with diverse roles in plant development and stress regulation. In this report, stress-responsive NAC genes (GhNAC8-GhNAC17) isolated from cotton (Gossypium hirsutum L.) were characterised in the context of leaf senescence and stress tolerance. The characterisation of NAC genes during leaf senescence has not yet been reported for cotton. Based on the sequence characterisation, these GhNACs could be classified into three groups belonging to three known NAC sub-families. Their predicted amino acid sequences exhibited similarities to NAC genes from other plant species. Senescent leaves were the sites of maximum expression for all GhNAC genes except GhNAC10 and GhNAC13, which showed maximum expression in fibres, collected from 25 days post anthesis (DPA) plants. The ten GhNAC genes displayed differential expression patterns and levels during natural and induced leaf senescence. Quantitative RT-PCR and promoter analyses suggest that these genes are induced by ABA, ethylene, drought, salinity, cold, heat, and other hormonal treatments. These results support a role for cotton GhNAC genes in transcriptional regulation of leaf senescence, stress tolerance and other developmental stages of cotton.

  20. Identification of 7 stress-related NAC transcription factor members in maize (Zea mays L.) and characterization of the expression pattern of these genes.

    PubMed

    Lu, Min; Sun, Qing-Peng; Zhang, Deng-Feng; Wang, Tian-Yu; Pan, Jin-Bao

    2015-06-26

    NAC proteins are plant-specific transcription factors that play essential roles in plant development and various abiotic stress responses. A comprehensive analysis of maize NAC genes was performed in this study. A total of 157 non-redundant maize NAC genes including seven membrane-bound members were identified and found to be unevenly distributed on 10 maize chromosomes. Motif composition analysis indicated that the maize NAC proteins share three relatively conserved motifs in the NAC domain within the N-terminal region. Phylogenetic analysis of 157 maize NAC proteins accompanied by 117 NAC proteins from Arabidopsis and 151 from rice were presented. The NAC proteins evaluated were divided into two large groups including 18 subgroups. Gene duplication analysis indicated that gene loss occurred during maize evolution. Seven NAC members that belong to the same clade of maize NAC domain genes were isolated, and overlapping expression patterns were observed under various abiotic stresses, including low temperature, high salinity and dehydration, and phytohormone abscisic acid treatments. This suggested that NAC members function as stress-responsive transcription factors in ABA-dependent signaling pathways. Relatively higher expression levels of these selected maize NAC genes were detected in roots. The stress responsive NAC genes may have applications in molecular breeding to improve crop stress tolerance.

  1. ERK8 is a negative regulator of O-GalNAc glycosylation and cell migration

    PubMed Central

    Chia, Joanne; Tham, Keit Min; Gill, David James; Bard-Chapeau, Emilie Anne; Bard, Frederic A

    2014-01-01

    ER O-glycosylation can be induced through relocalisation GalNAc-Transferases from the Golgi. This process markedly stimulates cell migration and is constitutively activated in more than 60% of breast carcinomas. How this activation is achieved remains unclear. Here, we screened 948 signalling genes using RNAi and imaging. We identified 12 negative regulators of O-glycosylation that all control GalNAc-T sub-cellular localisation. ERK8, an atypical MAPK with high basal kinase activity, is a strong hit and is partially localised at the Golgi. Its inhibition induces the relocation of GalNAc-Ts, but not of KDEL receptors, revealing the existence of two separate COPI-dependent pathways. ERK8 down-regulation, in turn, activates cell motility. In human breast and lung carcinomas, ERK8 expression is reduced while ER O-glycosylation initiation is hyperactivated. In sum, ERK8 appears as a constitutive brake on GalNAc-T relocalisation, and the loss of its expression could drive cancer aggressivity through increased cell motility. DOI: http://dx.doi.org/10.7554/eLife.01828.001 PMID:24618899

  2. αβ'-NAC cooperates with Sam37 to mediate early stages of mitochondrial protein import.

    PubMed

    Ponce-Rojas, José Carlos; Avendaño-Monsalve, Maria Clara; Yañez-Falcón, Armando Roberto; Jaimes-Miranda, Fabiola; Garay, Erika; Torres-Quiroz, Francisco; DeLuna, Alexander; Funes, Soledad

    2017-03-01

    The mitochondrial proteome is mostly composed of nuclear-encoded proteins. Such polypeptides are synthesized with signals that guide their intracellular transport to the surface of the organelle and later within the different mitochondrial subcompartments until they reach their functional destination. It has been suggested that the nascent-polypeptide associated complex (NAC) - a cytosolic chaperone that recognizes nascent chains on translationally active ribosomes - has a role in the import of nuclear-encoded mitochondrial proteins. However, the molecular mechanisms that regulate the NAC-mediated cotranslational import are still not clear. Here, we show that a particular NAC heterodimer formed by subunits α and β' in Saccharomyces cerevisiae is specifically involved in the process of mitochondrial import and functionally cooperates with Sam37, an outer membrane protein subunit of the sorting and assembly machinery complex. Mutants in both components display growth defects, incorrectly accumulate precursor forms of mitochondrial proteins in the cytosol, and have an altered mitochondrial protein content. We propose that αβ'-NAC and Sam37 are members of the system that recognizes mitochondrial proteins at early stages of their synthesis, escorting them to the import machinery of mitochondria.

  3. O-GlcNAc reports ambient temperature and confers heat resistance on ectotherm development

    PubMed Central

    Radermacher, Pablo T.; Myachina, Faina; Bosshardt, Fritz; Pandey, Rahul; Mariappa, Daniel; Müller, H.-Arno J.; Lehner, Christian F.

    2014-01-01

    Effects of temperature on biological processes are complex. Diffusion is less affected than the diverse enzymatic reactions that have distinct individual temperature profiles. Hence thermal fluctuations pose a formidable challenge to ectothermic organisms in which body temperature is largely dictated by the ambient temperature. How cells in ectotherms cope with the myriad disruptive effects of temperature variation is poorly understood at the molecular level. Here we show that nucleocytoplasmic posttranslational modification of proteins with O-linked GlcNAc (O-GlcNAc) is closely correlated with ambient temperature during development of distantly related ectotherms ranging from the insect Drosophila melanogaster to the nematode Caenorhabditis elegans to the fish Danio rerio. Regulation seems to occur at the level of activity of the only two enzymes, O-GlcNAc transferase and O-GlcNAcase, that add and remove, respectively, this posttranslational modification in nucleus and cytoplasm. With genetic approaches in D. melanogaster and C. elegans, we demonstrate the importance of high levels of this posttranslational modification for successful development at elevated temperatures. Because many cytoplasmic and nuclear proteins in diverse pathways are O-GlcNAc targets, temperature-dependent regulation of this modification might contribute to an efficient coordinate adjustment of cellular processes in response to thermal change. PMID:24706800

  4. A Gibberellin-Mediated DELLA-NAC Signaling Cascade Regulates Cellulose Synthesis in Rice[OPEN

    PubMed Central

    Huang, Debao; Wang, Shaogan; Zhang, Baocai; Shang-Guan, Keke; Shi, Yanyun; Zhang, Dongmei; Liu, Xiangling; Wu, Kun; Xu, Zuopeng; Fu, Xiangdong; Zhou, Yihua

    2015-01-01

    Cellulose, which can be converted into numerous industrial products, has important impacts on the global economy. It has long been known that cellulose synthesis in plants is tightly regulated by various phytohormones. However, the underlying mechanism of cellulose synthesis regulation remains elusive. Here, we show that in rice (Oryza sativa), gibberellin (GA) signals promote cellulose synthesis by relieving the interaction between SLENDER RICE1 (SLR1), a DELLA repressor of GA signaling, and NACs, the top-layer transcription factors for secondary wall formation. Mutations in GA-related genes and physiological treatments altered the transcription of CELLULOSE SYNTHASE genes (CESAs) and the cellulose level. Multiple experiments demonstrated that transcription factors NAC29/31 and MYB61 are CESA regulators in rice; NAC29/31 directly regulates MYB61, which in turn activates CESA expression. This hierarchical regulation pathway is blocked by SLR1-NAC29/31 interactions. Based on the results of anatomical analysis and GA content examination in developing rice internodes, this signaling cascade was found to be modulated by varied endogenous GA levels and to be required for internode development. Genetic and gene expression analyses were further performed in Arabidopsis thaliana GA-related mutants. Altogether, our findings reveal a conserved mechanism by which GA regulates secondary wall cellulose synthesis in land plants and provide a strategy for manipulating cellulose production and plant growth. PMID:26002868

  5. Digital Elevation Models and Derived Products from Lroc Nac Stereo Observations

    NASA Astrophysics Data System (ADS)

    Burns, K. N.; Speyerer, E. J.; Robinson, M. S.; Tran, T.; Rosiek, M. R.; Archinal, B. A.; Howington-Kraus, E.; the LROC Science Team

    2012-08-01

    One of the primary objectives of the Lunar Reconnaissance Orbiter Camera (LROC) is to acquire stereo observations with the Narrow Angle Camera (NAC) to enable production of high resolution digital elevation models (DEMs). This work describes the processes and techniques used in reducing the NAC stereo observations to DEMs through a combination of USGS integrated Software for Imagers and Spectrometers (ISIS) and SOCET SET® from BAE Systems by a team at Arizona State University (ASU). LROC Science Operations Center personnel have thus far reduced 130 stereo observations to DEMs of more than 130 stereo pairs for 11 Constellation Program (CxP) sites and 53 other regions of scientific interest. The NAC DEM spatial sampling is typically 2 meters, and the vertical precision is 1-2 meters. Such high resolution provides the three-dimensional view of the lunar surface required for site selection, hazard avoidance and planning traverses that minimize resource consumption. In addition to exploration analysis, geologists can measure parameters such as elevation, slope, and volume to place constraints on composition and geologic history. The NAC DEMs are released and archived through NASA's Planetary Data System.

  6. O-GlcNAc reports ambient temperature and confers heat resistance on ectotherm development.

    PubMed

    Radermacher, Pablo T; Myachina, Faina; Bosshardt, Fritz; Pandey, Rahul; Mariappa, Daniel; Müller, H-Arno J; Lehner, Christian F

    2014-04-15

    Effects of temperature on biological processes are complex. Diffusion is less affected than the diverse enzymatic reactions that have distinct individual temperature profiles. Hence thermal fluctuations pose a formidable challenge to ectothermic organisms in which body temperature is largely dictated by the ambient temperature. How cells in ectotherms cope with the myriad disruptive effects of temperature variation is poorly understood at the molecular level. Here we show that nucleocytoplasmic posttranslational modification of proteins with O-linked GlcNAc (O-GlcNAc) is closely correlated with ambient temperature during development of distantly related ectotherms ranging from the insect Drosophila melanogaster to the nematode Caenorhabditis elegans to the fish Danio rerio. Regulation seems to occur at the level of activity of the only two enzymes, O-GlcNAc transferase and O-GlcNAcase, that add and remove, respectively, this posttranslational modification in nucleus and cytoplasm. With genetic approaches in D. melanogaster and C. elegans, we demonstrate the importance of high levels of this posttranslational modification for successful development at elevated temperatures. Because many cytoplasmic and nuclear proteins in diverse pathways are O-GlcNAc targets, temperature-dependent regulation of this modification might contribute to an efficient coordinate adjustment of cellular processes in response to thermal change.

  7. The National Astronomy Consortium (NAC) - the University of Wisconsin-Madison Cohort

    NASA Astrophysics Data System (ADS)

    Hooper, Eric; Sheth, Kartik; Mills, Elisabeth A. C.; National Astronomy Consortium

    2015-01-01

    The UW-Madison Research Experiences for Undergraduates (REU) program in astrophysics (http://www.astro.wisc.edu/undergrads/uw-madison-reu-program/) is partnering with the National Radio Astronomy Observatory, the National Society of Black Physicists, and other universities in an entity called the National Astronomy Consortium (NAC; see https://sites.google.com/site/nraonac/). The mission of the NAC is to increase the numbers of students who might otherwise be overlooked by the traditional academic pipeline into STEM, or related, careers. This begins with a cohort of students who are part of the regular REU program. In addition to working on original research projects under the mentorship of university astronomers and astrophysics, the cohort students participate in professional development seminars and join other NAC cohort sites in a diversity speaker series. The mentor-student and student-student connections continue beyond the summer, including a fall meeting of the national NAC cohorts. The UW-Madison REU program is supported by the National Science Foundation through Award AST-1004881.

  8. Three Rice NAC Transcription Factors Heteromerize and Are Associated with Seed Size

    PubMed Central

    Mathew, Iny Elizebeth; Das, Sweta; Mahto, Arunima; Agarwal, Pinky

    2016-01-01

    NACs are plant-specific transcription factors (TFs) involved in multiple aspects of development and stress. In rice, three NAC TF encoding genes, namely ONAC020, ONAC026, and ONAC023 express specifically during seed development, at extremely high levels. They exhibit significantly strong association with seed size/weight with the sequence variations located in the upstream regulatory region. Concomitantly, their expression pattern/levels during seed development vary amongst different accessions with variation in seed size. The alterations in the promoter sequences of the three genes, amongst the five rice accessions, correlate with the expression levels to a certain extent only. In terms of transcriptional properties, the three NAC TFs can activate and/or suppress downstream genes, though to different extents. Only ONAC026 is localized to the nucleus while ONAC020 and ONAC023 are targeted to the ER and cytoplasm, respectively. Interestingly, these two proteins interact with ONAC026 and the dimers localize in the nucleus. Trans-splicing between ONAC020 and ONAC026 results in three additional forms of ONAC020. The transcriptional properties including activation, repression, subcellular localization and heterodimerization of trans-spliced forms of ONAC020 and ONAC026 are different, indicating toward their role as competitors. The analysis presented in this paper helps to conclude that the three NAC genes, which are associated with seed size, have independent as well as overlapping roles during the process and can be exploited as potential targets for crop improvement. PMID:27872632

  9. Understanding the Role of O-GlcNAc Modifications in Plant Development

    SciTech Connect

    Olszewski, Neil, E.

    2011-06-16

    This project has contributed towards understanding the role of O-GlcNAc (O-linked N-acetylglucosamine) transferases (OGTs) in plants. Through analyses of single and double mutants, we have investigated the unique and overlapping functions of SECRET AGENT (SEC) and SPINDLY (SPY), the arabidopsis OGTs. This work showed that SEC functions as negative regulators of the long-day flowering pathway. SEC also has a positive role in regulation of rosette. An E. coli co-expression system that allows potential substrates to be co-expressed with and O-GlcNAc modified by SEC was developed. We showed that SEC is a bona fide OGT that modifies itself with single O-linked GlcNAc(s). Using this system, we tested a number of proteins that were hypothesized to be substrates of SEC and identified a number of substrates include GIGANTEA (GI), a component of the long day flowering pathway. The hypothesis that O-GlcNAc modification controls GI activity was tested by first mapping where E. coli-expressed SEC modifies GI and then assessing the activity of a non-modifiable mutant form of GI. The activity of the mutant form of GI was indistinguishable from that of wild type suggesting that either O-GlcNAc does not regulate GI activity or that additional modification sites exist on GI. In collaboration with Dr. Juan Antonio Garcia at Universidad Autónoma de Madrid the role of O-GlcNAc modification of the plum pox virus coat protein (PPV-CP) was investigated. SEC was shown to O-GlcNAc modify PPV-CP and the modification was shown to facilitate the infection process. E. coli-expressed SEC was shown to modify the same PPV-CP sites that are modified in plants. SEC has a large protein interaction domain called the TPR domain that has been hypothesized to have a role in determining the substrate specificity of the enzyme and/or to regulate its activity. A mutational analysis of the TPR domain did not find evidence for a role in substrate specificity but did obtain evidence that the domain regulates

  10. 45 CFR 162.1002 - Medical data code sets.

    Code of Federal Regulations, 2010 CFR

    2010-10-01

    ... 45 Public Welfare 1 2010-10-01 2010-10-01 false Medical data code sets. 162.1002 Section 162.1002... REQUIREMENTS ADMINISTRATIVE REQUIREMENTS Code Sets § 162.1002 Medical data code sets. The Secretary adopts the following maintaining organization's code sets as the standard medical data code sets: (a) For the...

  11. 45 CFR 162.1011 - Valid code sets.

    Code of Federal Regulations, 2010 CFR

    2010-10-01

    ... 45 Public Welfare 1 2010-10-01 2010-10-01 false Valid code sets. 162.1011 Section 162.1011 Public... ADMINISTRATIVE REQUIREMENTS Code Sets § 162.1011 Valid code sets. Each code set is valid within the dates specified by the organization responsible for maintaining that code set....

  12. 45 CFR 162.1002 - Medical data code sets.

    Code of Federal Regulations, 2011 CFR

    2011-10-01

    ... 45 Public Welfare 1 2011-10-01 2011-10-01 false Medical data code sets. 162.1002 Section 162.1002... REQUIREMENTS ADMINISTRATIVE REQUIREMENTS Code Sets § 162.1002 Medical data code sets. The Secretary adopts the following maintaining organization's code sets as the standard medical data code sets: (a) For the...

  13. Characterizing N-acetylcysteine (NAC) and N-acetylcysteine amide (NACA) binding for lead poisoning treatment.

    PubMed

    Chen, Weiqing; Ercal, Nuran; Huynh, Tien; Volkov, Anatoliy; Chusuei, Charles C

    2012-04-01

    Using antioxidants is an important means of treating lead poisoning. Prior in vivo studies showed marked differences between various chelator antioxidants in their ability to decrease both blood Pb(II) levels and oxidative stress resulting from lead poisoning. The comparative abilities of NAC and NACA to Pb(II) were studied in vitro, for the first time, to examine the role of the -OH/-NH(2) functional group in antioxidant binding behavior. To assay the antioxidant-divalent metal interaction, the antioxidants were probed as solid surfaces, adsorbing Pb(II) onto them. Surface characterization was carried out using X-ray photoelectron spectroscopy (XPS) analysis to quantify Pb(II) in the resulting adducts. XPS of the Pb 4f orbitals showed that more Pb(II) was chemically bound to NACA than NAC. In addition, the antioxidant surfaces probed via point-of-zero charge (PZC) measurements of NAC and NACA were obtained to gain further insight into the Pb-NAC and Pb-NACA binding, showing that Coulombic interactions played a partial role in facilitating complex formation. The data correlated well with solution analysis of metal-ligand complexation. UV-vis spectroscopy was used to probe complexation behavior. NACA was found to have the higher binding affinity as shown by free Pb(II) available in the solution after complexation from HPLC data. Electrospray ionization mass spectrometry (ESI-MS) was applied to delineate the structures of Pb-antioxidant complexes. Experimental results were further supported by density functional theory (DFT) calculations of supermolecular interaction energies (E(inter)) showing a greater interaction of Pb(II) with NACA than NAC.

  14. Molecular Characterization and Expression Profiling of NAC Transcription Factors in Brachypodium distachyon L

    PubMed Central

    Zhu, Yan; Lu, Xiaobing; Li, Xiaohui; Hu, Yingkao; Yan, Yueming

    2015-01-01

    NAC (NAM, ATAF1/2, CUC2) transcription factors are involved in regulating plant developmental processes and response to environmental stresses. Brachypodium distachyon is an emerging model system for cereals, temperate grasses and biofuel crops. In this study, a comprehensive investigation of the molecular characterizations, phylogenetics and expression profiles under various abiotic stresses of the NAC gene family in Brachypodium distachyon was performed. In total, 118 BNAC genes in B. distachyon were identified, of which 22 (18.64%) were tandemly duplicated and segmentally duplicated, respectively. The Bayesian phylogenetic inference using Markov Chain Monte Carlo (MCMC) algorithms showed that they were divided into two clades and fourteen subfamilies, supported by similar motif compositions within one subfamily. Some critical amino acids detected using DIVERGE v3.0 might contribute to functional divergence among subfamilies. The different exon-intron organizations among subfamilies revealed structural differentiation. Promoter sequence predictions showed that the BNAC genes were involved in various developmental processes and diverse stress responses. Three NAC domain-encoding genes (BNAC012, BNAC078 and BNAC108), orthologous of NAC1, were targeted by five miRNA164 (Bdi-miR164a-c, e, f), suggesting that they might function in lateral organ enlargement, floral development and the responses to abiotic stress. Eleven (~9.32%) BNAC proteins containing α-helical transmembrane motifs were identified. 23 representative BNAC genes were analyzed by quantitative real-time PCR, showing different expression patterns under various abiotic stresses, of which 18, 17 and 11 genes were up-regulated significantly under drought, H2O2 and salt stresses, respectively. Only four and two genes were up-regulated under cold and cadmium stresses, respectively. Dynamic transcriptional expression analysis revealed that six genes showed constitutive expression and period

  15. Molecular Characterization and Expression Profiling of NAC Transcription Factors in Brachypodium distachyon L.

    PubMed

    Zhu, Gengrui; Chen, Guanxing; Zhu, Jiantang; Zhu, Yan; Lu, Xiaobing; Li, Xiaohui; Hu, Yingkao; Yan, Yueming

    2015-01-01

    NAC (NAM, ATAF1/2, CUC2) transcription factors are involved in regulating plant developmental processes and response to environmental stresses. Brachypodium distachyon is an emerging model system for cereals, temperate grasses and biofuel crops. In this study, a comprehensive investigation of the molecular characterizations, phylogenetics and expression profiles under various abiotic stresses of the NAC gene family in Brachypodium distachyon was performed. In total, 118 BNAC genes in B. distachyon were identified, of which 22 (18.64%) were tandemly duplicated and segmentally duplicated, respectively. The Bayesian phylogenetic inference using Markov Chain Monte Carlo (MCMC) algorithms showed that they were divided into two clades and fourteen subfamilies, supported by similar motif compositions within one subfamily. Some critical amino acids detected using DIVERGE v3.0 might contribute to functional divergence among subfamilies. The different exon-intron organizations among subfamilies revealed structural differentiation. Promoter sequence predictions showed that the BNAC genes were involved in various developmental processes and diverse stress responses. Three NAC domain-encoding genes (BNAC012, BNAC078 and BNAC108), orthologous of NAC1, were targeted by five miRNA164 (Bdi-miR164a-c, e, f), suggesting that they might function in lateral organ enlargement, floral development and the responses to abiotic stress. Eleven (~9.32%) BNAC proteins containing α-helical transmembrane motifs were identified. 23 representative BNAC genes were analyzed by quantitative real-time PCR, showing different expression patterns under various abiotic stresses, of which 18, 17 and 11 genes were up-regulated significantly under drought, H2O2 and salt stresses, respectively. Only four and two genes were up-regulated under cold and cadmium stresses, respectively. Dynamic transcriptional expression analysis revealed that six genes showed constitutive expression and period

  16. O-GlcNAc cycling: Emerging Roles in Development and Epigenetics

    PubMed Central

    Love, Dona C.; Krause, Michael W.; Hanover, John A.

    2010-01-01

    The nutrient-sensing hexosamine signaling pathway modulates the levels of O-linked N-acetylglucosamine (O-GlcNAc) on key targets impacting cellular signaling, protein turnover and gene expression. O-GlcNAc cycling may be deregulated in neurodegenerative disease, cancer, and diabetes. Studies in model organisms demonstrate that the O-GlcNAc transferase (OGT/Sxc) is essential for Polycomb group (PcG) repression of the homeotic genes, clusters of genes responsible for the adult body plan. Surprisingly, from flies to man, the O-GlcNAcase (OGA, MGEA5) gene is embedded within the NK cluster, the most evolutionarily ancient of three homeobox gene clusters regulated by PcG repression. PcG repression also plays a key role in maintaining stem cell identity, recruiting the DNA methyltransferase machinery for imprinting, and in X-chromosome inactivation. Intriguingly, the Ogt gene resides near the Xist locus in vertebrates and is subject to regulation by PcG-dependent X-inactivation. OGT is also an enzymatic component of the human dosage compensation complex. These ‘evo-devo’ relationships linking O-GlcNAc cycling to higher order chromatin structure provide insights into how nutrient availability may influence the epigenetic regulation of gene expression. O-GlcNAc cycling at promoters and PcG repression represent concrete mechanisms by which nutritional information may be transmitted across generations in the intra-uterine environment. Thus, the nutrient-sensing hexosamine signaling pathway may be a key contributor to the metabolic deregulation resulting from prenatal exposure to famine, or the ‘vicious cycle’ observed in children of mothers with type-2 diabetes and metabolic disease. PMID:20488252

  17. Speech coding

    SciTech Connect

    Ravishankar, C., Hughes Network Systems, Germantown, MD

    1998-05-08

    Speech is the predominant means of communication between human beings and since the invention of the telephone by Alexander Graham Bell in 1876, speech services have remained to be the core service in almost all telecommunication systems. Original analog methods of telephony had the disadvantage of speech signal getting corrupted by noise, cross-talk and distortion Long haul transmissions which use repeaters to compensate for the loss in signal strength on transmission links also increase the associated noise and distortion. On the other hand digital transmission is relatively immune to noise, cross-talk and distortion primarily because of the capability to faithfully regenerate digital signal at each repeater purely based on a binary decision. Hence end-to-end performance of the digital link essentially becomes independent of the length and operating frequency bands of the link Hence from a transmission point of view digital transmission has been the preferred approach due to its higher immunity to noise. The need to carry digital speech became extremely important from a service provision point of view as well. Modem requirements have introduced the need for robust, flexible and secure services that can carry a multitude of signal types (such as voice, data and video) without a fundamental change in infrastructure. Such a requirement could not have been easily met without the advent of digital transmission systems, thereby requiring speech to be coded digitally. The term Speech Coding is often referred to techniques that represent or code speech signals either directly as a waveform or as a set of parameters by analyzing the speech signal. In either case, the codes are transmitted to the distant end where speech is reconstructed or synthesized using the received set of codes. A more generic term that is applicable to these techniques that is often interchangeably used with speech coding is the term voice coding. This term is more generic in the sense that the

  18. Binding of Abeta to alpha- and beta-synucleins: identification of segments in alpha-synuclein/NAC precursor that bind Abeta and NAC.

    PubMed Central

    Jensen, P H; Hojrup, P; Hager, H; Nielsen, M S; Jacobsen, L; Olesen, O F; Gliemann, J; Jakes, R

    1997-01-01

    NAC, a 35-residue peptide derived from the neuronal protein alpha-synuclein/NAC precursor, is tightly associated with Abeta fibrils in Alzheimer's disease amyloid, and alpha-synuclein has recently been shown to bind Abeta in vitro. We have studied the interaction between Abeta and synucleins, aiming at determining segments in alpha-synuclein that can account for the binding, as well as identifying a possible interaction between Abeta and the beta-type synuclein. We report that Abeta binds to native and recombinant alpha-synuclein, and to beta-synuclein in an SDS-sensitive interaction (IC50 approx. 20 microM), as determined by chemical cross-linking and solid-phase binding assays. alpha-Synuclein and beta-synuclein were found to stimulate Abeta-aggregation in vitro to the same extent. The synucleins also displayed Abeta-inhibitable binding of NAC and they were capable of forming dimers. Using proteolytic fragmentation of alpha-synuclein and cross-linking to 125I-Abeta, we identified two consecutive binding domains (residues 1-56 and 57-97) by Edman degradation and mass spectrometric analysis, and a synthetic peptide comprising residues 32-57 possessed Abeta-binding activity. To test further the possible significance in pathology, alpha-synuclein was biotinylated and shown to bind specifically to amyloid plaques in a brain with Alzheimer's disease. It is proposed that the multiple Abeta-binding sites in alpha-synuclein are involved in the development of amyloid plaques. PMID:9163350

  19. The Sweet Potato NAC-Domain Transcription Factor IbNAC1 Is Dynamically Coordinated by the Activator IbbHLH3 and the Repressor IbbHLH4 to Reprogram the Defense Mechanism against Wounding

    PubMed Central

    Chen, Shi-Peng; Kuo, Chih-Hsien; Lu, Hsueh-Han; Lo, Hui-Shan; Yeh, Kai-Wun

    2016-01-01

    IbNAC1 is known to activate the defense system by reprogramming a genetic network against herbivory in sweet potato. This regulatory activity elevates plant defense potential but relatively weakens plants by IbNAC1-mediated JA response. The mechanism controlling IbNAC1 expression to balance plant vitality and survival remains unclear. In this study, a wound-responsive G-box cis-element in the IbNAC1 promoter from -1484 to -1479 bp was identified. From a screen of wound-activated transcriptomic data, one transcriptional activator, IbbHLH3, and one repressor, IbbHLH4, were selected that bind to and activate or repress, respectively, the G-box motif in the IbNAC1 promoter to modulate the IbNAC1-mediated response. In the early wound response, the IbbHLH3-IbbHLH3 protein complex binds to the G-box motif to activate IbNAC1 expression. Thus, an elegant defense network is activated against wounding stress. Until the late stages of wounding, IbbHLH4 interacts with IbbHLH3, and the IbbHLH3-IbbHLH4 heterodimer competes with the IbbHLH3-IbbHLH3 complex to bind the G-box and suppress IbNAC1 expression and timely terminates the defense network. Moreover, the JAZs and IbEIL1 proteins interact with IbbHLH3 to repress the transactivation function of IbbHLH3 in non-wounded condition, but their transcription is immediately inhibited upon early wounding. Our work provides a genetic model that accurately switches the regulatory mechanism of IbNAC1 expression to adjust wounding physiology and represents a delicate defense regulatory network in plants. PMID:27780204

  20. Oxidative stress induces transient O-GlcNAc elevation and tau dephosphorylation in SH-SY5Y cells.

    PubMed

    Kátai, Emese; Pál, József; Poór, Viktor Soma; Purewal, Rupeena; Miseta, Attila; Nagy, Tamás

    2016-12-01

    O-linked β-N-acetlyglucosamine or O-GlcNAc modification is a dynamic post-translational modification occurring on the Ser/Thr residues of many intracellular proteins. The chronic imbalance between phosphorylation and O-GlcNAc on tau protein is considered as one of the main hallmarks of Alzheimer's disease. In recent years, many studies also showed that O-GlcNAc levels can elevate upon acute stress and suggested that this might facilitate cell survival. However, many consider chronic stress, including oxidative damage as a major risk factor in the development of the disease. In this study, using the neuronal cell line SH-SY5Y we investigated the dynamic nature of O-GlcNAc after treatment with 0.5 mM H2 O2 for 30 min. to induce oxidative stress. We found that overall O-GlcNAc quickly increased and reached peak level at around 2 hrs post-stress, then returned to baseline levels after about 24 hrs. Interestingly, we also found that tau protein phosphorylation at site S262 showed parallel, whereas at S199 and PHF1 sites showed inverse dynamic to O-Glycosylation. In conclusion, our results show that temporary elevation in O-GlcNAc modification after H2 O2 -induced oxidative stress is detectable in cells of neuronal origin. Furthermore, oxidative stress changes the dynamic balance between O-GlcNAc and phosphorylation on tau proteins.

  1. Dynamic interplay between catalytic and lectin domains of GalNAc-transferases modulates protein O-glycosylation

    NASA Astrophysics Data System (ADS)

    Lira-Navarrete, Erandi; de Las Rivas, Matilde; Compañón, Ismael; Pallarés, María Carmen; Kong, Yun; Iglesias-Fernández, Javier; Bernardes, Gonçalo J. L.; Peregrina, Jesús M.; Rovira, Carme; Bernadó, Pau; Bruscolini, Pierpaolo; Clausen, Henrik; Lostao, Anabel; Corzana, Francisco; Hurtado-Guerrero, Ramon

    2015-05-01

    Protein O-glycosylation is controlled by polypeptide GalNAc-transferases (GalNAc-Ts) that uniquely feature both a catalytic and lectin domain. The underlying molecular basis of how the lectin domains of GalNAc-Ts contribute to glycopeptide specificity and catalysis remains unclear. Here we present the first crystal structures of complexes of GalNAc-T2 with glycopeptides that together with enhanced sampling molecular dynamics simulations demonstrate a cooperative mechanism by which the lectin domain enables free acceptor sites binding of glycopeptides into the catalytic domain. Atomic force microscopy and small-angle X-ray scattering experiments further reveal a dynamic conformational landscape of GalNAc-T2 and a prominent role of compact structures that are both required for efficient catalysis. Our model indicates that the activity profile of GalNAc-T2 is dictated by conformational heterogeneity and relies on a flexible linker located between the catalytic and the lectin domains. Our results also shed light on how GalNAc-Ts generate dense decoration of proteins with O-glycans.

  2. Engulfment and clearance of apoptotic cells based on a GlcNAc-binding lectin-like property of surface vimentin.

    PubMed

    Ise, Hirohiko; Goto, Mitsuaki; Komura, Kenta; Akaike, Toshihiro

    2012-06-01

    The clearance of apoptotic cells is important to maintain tissue homeostasis. The engulfment of apoptotic cells is performed by professional phagocytes, such as macrophages, and also by non-professional phagocytes, such as mesenchymal cells. Here, we show that vimentin, a cytoskeletal protein, functions as an engulfment receptor on neighboring phagocytes, which recognize O-linked β-N-acetylglucosamine (O-GlcNAc)-modified proteins from apoptotic cells as "eat me" ligands. Previously, we reported that vimentin possesses a GlcNAc-binding lectin-like property on cell surface. However, the physiological relevance of the surface localization and GlcNAc-binding property of vimentin remained unclear. In the present study, we observed that O-GlcNAc proteins from apoptotic cells interacted with the surface vimentin of neighboring phagocytes and that this interaction induced serine 71-phosphorylation and recruitment of vimentin to the cell surface of the neighboring phagocytes. Moreover, tetrameric vimentin that was disassembled by serine 71-phosphorylation possessed a GlcNAc-binding activity and was localized to the cell surface. We demonstrated our findings in vimentin-expressing common cell lines such as HeLa cells. Furthermore, during normal developmental processes, the phagocytic engulfment and clearance of apoptotic footplate cells in mouse embryos was mediated by the interaction of surface vimentin with O-GlcNAc proteins. Our results suggest a common mechanism for the clearance of apoptotic cells, through the interaction of surface vimentin with O-GlcNAc-modified proteins.

  3. Dynamic interplay between catalytic and lectin domains of GalNAc-transferases modulates protein O-glycosylation

    PubMed Central

    Lira-Navarrete, Erandi; de las Rivas, Matilde; Compañón, Ismael; Pallarés, María Carmen; Kong, Yun; Iglesias-Fernández, Javier; Bernardes, Gonçalo J. L.; Peregrina, Jesús M.; Rovira, Carme; Bernadó, Pau; Bruscolini, Pierpaolo; Clausen, Henrik; Lostao, Anabel; Corzana, Francisco; Hurtado-Guerrero, Ramon

    2015-01-01

    Protein O-glycosylation is controlled by polypeptide GalNAc-transferases (GalNAc-Ts) that uniquely feature both a catalytic and lectin domain. The underlying molecular basis of how the lectin domains of GalNAc-Ts contribute to glycopeptide specificity and catalysis remains unclear. Here we present the first crystal structures of complexes of GalNAc-T2 with glycopeptides that together with enhanced sampling molecular dynamics simulations demonstrate a cooperative mechanism by which the lectin domain enables free acceptor sites binding of glycopeptides into the catalytic domain. Atomic force microscopy and small-angle X-ray scattering experiments further reveal a dynamic conformational landscape of GalNAc-T2 and a prominent role of compact structures that are both required for efficient catalysis. Our model indicates that the activity profile of GalNAc-T2 is dictated by conformational heterogeneity and relies on a flexible linker located between the catalytic and the lectin domains. Our results also shed light on how GalNAc-Ts generate dense decoration of proteins with O-glycans. PMID:25939779

  4. A Structural Basis for the Allosteric Regulatin of Non-Hydrolysing UDP-G1cNAc 2-Epimerases

    SciTech Connect

    Velloso,L.; Bhaskaran, S.; Schuch, R.; Fischetti, V.; Stebbins, C.

    2008-01-01

    The non-hydrolysing bacterial UDP-N-acetylglucosamine 2-epimerase (UDP-GlcNAc 2-epimerase) catalyses the conversion of UDP-GlcNAc into UDP-N-acetylmannosamine, an intermediate in the biosynthesis of several cell-surface polysaccharides. This enzyme is allosterically regulated by its substrate UDP-GlcNAc. The structure of the ternary complex between the Bacillus anthracis UDP-GlcNAc 2-epimerase, its substrate UDP-GlcNAc and the reaction intermediate UDP, showed direct interactions between UDP and its substrate, and between the complex and highly conserved enzyme residues, identifying the allosteric site of the enzyme. The binding of UDP-GlcNAc is associated with conformational changes in the active site of the enzyme. Kinetic data and mutagenesis of the highly conserved UDP-GlcNAc-interacting residues confirm their importance in the substrate binding and catalysis of the enzyme. This constitutes the first example to our knowledge, of an enzymatic allosteric activation by direct interaction between the substrate and the allosteric activator.

  5. A dual function for chaperones SSB–RAC and the NAC nascent polypeptide–associated complex on ribosomes

    PubMed Central

    Koplin, Ansgar; Preissler, Steffen; Ilina, Yulia; Koch, Miriam; Scior, Annika; Erhardt, Marc

    2010-01-01

    The yeast Hsp70/40 system SSB–RAC (stress 70 B–ribosome-associated complex) binds to ribosomes and contacts nascent polypeptides to assist cotranslational folding. In this study, we demonstrate that nascent polypeptide–associated complex (NAC), another ribosome-tethered system, is functionally connected to SSB–RAC and the cytosolic Hsp70 network. Simultaneous deletions of genes encoding NAC and SSB caused conditional loss of cell viability under protein-folding stress conditions. Furthermore, NAC mutations revealed genetic interaction with a deletion of Sse1, a nucleotide exchange factor regulating the cytosolic Hsp70 network. Cells lacking SSB or Sse1 showed protein aggregation, which is enhanced by additional loss of NAC; however, these mutants differ in their potential client repertoire. Aggregation of ribosomal proteins and biogenesis factors accompanied by a pronounced deficiency in ribosomal particles and translating ribosomes only occurs in ssbΔ and nacΔssbΔ cells, suggesting that SSB and NAC control ribosome biogenesis. Thus, SSB–RAC and NAC assist protein folding and likewise have important functions for regulation of ribosome levels. These findings emphasize the concept that ribosome production is coordinated with the protein-folding capacity of ribosome-associated chaperones. PMID:20368618

  6. The PTH-Gαs-Protein Kinase A Cascade Controls αNAC Localization To Regulate Bone Mass

    PubMed Central

    Pellicelli, Martin; Miller, Julie A.; Arabian, Alice; Gauthier, Claude; Akhouayri, Omar; Wu, Joy Y.; Kronenberg, Henry M.

    2014-01-01

    The binding of PTH to its receptor induces Gαs-dependent cyclic AMP (cAMP) accumulation to turn on effector kinases, including protein kinase A (PKA). The phenotype of mice with osteoblasts specifically deficient for Gαs is mimicked by a mutation leading to cytoplasmic retention of the transcriptional coregulator αNAC, suggesting that Gαs and αNAC form part of a common genetic pathway. We show that treatment of osteoblasts with PTH(1–34) or the PKA-selective activator N6-benzoyladenosine cAMP (6Bnz-cAMP) leads to translocation of αNAC to the nucleus. αNAC was phosphorylated by PKA at serine 99 in vitro. Phospho-S99-αNAC accumulated in osteoblasts exposed to PTH(1–34) or 6Bnz-cAMP but not in treated cells expressing dominant-negative PKA. Nuclear accumulation was abrogated by an S99A mutation but enhanced by a phosphomimetic residue (S99D). Chromatin immunoprecipitation (ChIP) analysis showed that PTH(1–34) or 6Bnz-cAMP treatment leads to accumulation of αNAC at the Osteocalcin (Ocn) promoter. Altered gene dosages for Gαs and αNAC in compound heterozygous mice result in reduced bone mass, increased numbers of osteocytes, and enhanced expression of Sost. Our results show that αNAC is a substrate of PKA following PTH signaling. This enhances αNAC translocation to the nucleus and leads to its accumulation at target promoters to regulate transcription and affect bone mass. PMID:24550008

  7. Poly-LacNAc as an Age-Specific Ligand for Rotavirus P[11] in Neonates and Infants

    PubMed Central

    Liu, Yang; Huang, Pengwei; Jiang, Baoming; Tan, Ming; Morrow, Ardythe L.; Jiang, Xi

    2013-01-01

    Rotavirus (RV) P[11] is an unique genotype that infects neonates. The mechanism of such age-specific host restriction remains unknown. In this study, we explored host mucosal glycans as a potential age-specific factor for attachment of P[11] RVs. Using in vitro binding assays, we demonstrated that VP8* of a P[11] RV (N155) could bind saliva of infants (60.3%, N = 151) but not of adults (0%, N = 48), with a significantly negative correlation between binding of VP8* and ages of infants (P<0.01). Recognition to the infant saliva did not correlate with the ABO, secretor and Lewis histo-blood group antigens (HBGAs) but with the binding of the lectin Lycopersicon esculentum (LEA) that is known to recognize the oligomers of N-acetyllactosamine (LacNAc), a precursor of human HBGAs. Direct evidence of LacNAc involvement in P[11] binding was obtained from specific binding of VP8* with homopolymers of LacNAc in variable lengths through a glycan array analysis of 611 glycans. These results were confirmed by strong binding of VP8* to the Lec2 cell line that expresses LacNAc oligomers but not to the Lec8 cell line lacking the LacNAc. In addition, N155 VP8* and authentic P[11] RVs (human 116E and bovine B223) hemagglutinated human red blood cells that are known to express poly-LacNAc. The potential role of poly-LacNAc in host attachment and infection of RVs has been obtained by abrogation of 116E replication by the PAA-conjugated poly-LacNAc, human milk, and LEA positive infant saliva. Overall, our results suggested that the poly-LacNAc could serve as an age-specific receptor for P[11] RVs and well explained the epidemiology that P[11] RVs mainly infect neonates and young children. PMID:24244290

  8. QR Codes

    ERIC Educational Resources Information Center

    Lai, Hsin-Chih; Chang, Chun-Yen; Li, Wen-Shiane; Fan, Yu-Lin; Wu, Ying-Tien

    2013-01-01

    This study presents an m-learning method that incorporates Integrated Quick Response (QR) codes. This learning method not only achieves the objectives of outdoor education, but it also increases applications of Cognitive Theory of Multimedia Learning (CTML) (Mayer, 2001) in m-learning for practical use in a diverse range of outdoor locations. When…

  9. Iminosugar C-Glycoside Analogues of α-d-GlcNAc-1-Phosphate: Synthesis and Bacterial Transglycosylase Inhibition

    PubMed Central

    2015-01-01

    We herein describe the first synthesis of iminosugar C-glycosides of α-d-GlcNAc-1-phosphate in 10 steps starting from unprotected d-GlcNAc. A diastereoselective intramolecular iodoamination–cyclization as the key step was employed to construct the central piperidine ring of the iminosugar and the C-glycosidic structure of α-d-GlcNAc. Finally, the iminosugar phosphonate and its elongated phosphate analogue were accessed. These phosphorus-containing iminosugars were coupled efficiently with lipophilic monophosphates to give lipid-linked pyrophosphate derivatives, which are lipid II mimetics endowed with potent inhibitory properties toward bacterial transglycosylases (TGase). PMID:25137529

  10. N-acetylcysteine administration does not improve patient outcome after liver resection

    PubMed Central

    Robinson, Stuart M; Saif, Rehan; Sen, Gourab; French, Jeremy J; Jaques, Bryon C; Charnley, Richard M; Manas, Derek M; White, Steven A

    2013-01-01

    Background Post-operative hepatic dysfunction is a major cause of concern when undertaking a liver resection. The generation of reactive oxygen species (ROS) as a result of hepatic ischaemia/reperfusion (I/R) injury can result in hepatocellular injury. Experimental evidence suggests that N-acetylcysteine may ameliorate ROS-mediated liver injury. Methods A cohort of 44 patients who had undergone a liver resection and receiving peri-operative N-acetylcysteine (NAC) were compared with a further cohort of 44 patients who did not. Liver function tests were compared on post-operative days 1, 3 and 5. Peri-operative outcome data were retrieved from a prospectively maintained database within our unit. ResultsAdministration of NAC was associated with a prolonged prothrombin time on the third post-operative day (18.4 versus 16.4 s; P = 0.002). The incidence of grades B and C liver failure was lower in the NAC group although this difference did not reach statistical significance (6.9% versus 14%; P = 0.287). The overall complication rate was similar between groups (32% versus 25%; P = ns). There were two peri-operative deaths in the NAC group and one in the control group (P = NS). ConclusionIn spite of promising experimental evidence, this study was not able to demonstrate any advantage in the routine administration of peri-operative NAC in patients undergoing a liver resection. PMID:23458723

  11. Administrative Synergy

    ERIC Educational Resources Information Center

    Hewitt, Kimberly Kappler; Weckstein, Daniel K.

    2012-01-01

    One of the biggest obstacles to overcome in creating and sustaining an administrative professional learning community (PLC) is time. Administrators are constantly deluged by the tyranny of the urgent. It is a Herculean task to carve out time for PLCs, but it is imperative to do so. In this article, the authors describe how an administrative PLC…

  12. National Automotive Center (NAC) Overview & Green Technology Initiatives: Visit by Agency for Defense Development, South Korea

    DTIC Science & Technology

    2010-11-17

    infusion of commercially viable technology into military land warfare systems” TARDEC National Automotive Center (NAC) 3 Army Energy Security Goals...alternated with petroleum-derived fuel 15 Fossil Energy Feedstock (large U.S. resource) coal petcokeoil shale • Various conversion processes dependent on... feedstock • Product meeting commercial and/or military specifications • Specs evolving to address alternatively sourced hydrocarbons tallow, fats

  13. Glucokinase expression is regulated by glucose through O-GlcNAc glycosylation.

    PubMed

    Baldini, Steffi F; Steenackers, Agata; Olivier-Van Stichelen, Stéphanie; Mir, Anne-Marie; Mortuaire, Marlène; Lefebvre, Tony; Guinez, Céline

    2016-09-16

    Blood glucose fluctuates with the fasting-feeding cycle. One of the liver's functions is to maintain blood glucose concentrations within a physiological range. Glucokinase (GCK) or hexokinase IV, is the main enzyme that regulates the flux and the use of glucose in the liver leading to a compensation of hyperglycemia. In hepatocytes, GCK catalyzes the phosphorylation of glucose into glucose-6-phosphate. This critical enzymatic reaction is determinant for the metabolism of glucose in the liver which includes glycogen synthesis, glycolysis, lipogenesis and gluconeogenesis. In liver, simultaneous increase of glucose and insulin enhances GCK activity and gene expression, changes its subcellular location and interaction with regulatory proteins. The post-translational O-linked β-N-acetylglucosaminylation (O-GlcNAcylation) acts as a glucose-sensitive modification and is believed to take part in hepatic glucose sensing by modifying key regulatory proteins. Therefore, we aimed to determine whether GCK is modified by O-GlcNAcylation in the liver of mice and investigated the role that this modification plays in regulating GCK protein expression. We demonstrated that endogenous GCK expression correlated with O-GlcNAc levels in the pathophysiological model ob/ob mice. More specifically, in response to the pharmacological inhibition of O-GlcNAcase (OGA) contents of GCK increased. Using the GlcNAc specific lectin succinylated-WGA and click chemistry labeling approaches, we demonstrated that GCK is modified by O-GlcNAcylation. Further, we demonstrated that siRNA-mediated Ogt knock-down not only decreases O-GlcNAc content but also GCK protein level. Altogether, our in vivo and in vitro results demonstrate that GCK expression is regulated by nutrient-sensing O-GlcNAc cycling in liver.

  14. A NAC domain protein family contributing to the regulation of wood formation in poplar.

    PubMed

    Ohtani, Misato; Nishikubo, Nobuyuki; Xu, Bo; Yamaguchi, Masatoshi; Mitsuda, Nobutaka; Goué, Nadia; Shi, Fusun; Ohme-Takagi, Masaru; Demura, Taku

    2011-08-01

    Wood harvested from trees is one of the most widely utilized natural materials on our planet. Recent environmental issues have prompted an increase in the demand for wood, especially as a cost-effective and renewable resource for industry and energy, so it is important to understand the process of wood formation. In the present study, we focused on poplar (Populus trichocarpa) NAC domain protein genes which are homologous to well-known Arabidopsis transcription factors regulating the differentiation of xylem vessels and fiber cells. From phylogenetic analysis, we isolated 16 poplar NAC domain protein genes, and named them PtVNS (VND-, NST/SND- and SMB-related proteins) genes. Expression analysis revealed that 12 PtVNS (also called PtrWND) genes including both VND and NST groups were expressed in developing xylem tissue and phloem fiber, whereas in primary xylem vessels, only PtVNS/PtrWND genes of the VND group were expressed. By using the post-translational induction system of Arabidopsis VND7, a master regulator of xylem vessel element differentiation, many poplar genes functioning in xylem vessel differentiation downstream from NAC domain protein genes were identified. Transient expression assays showed the variation in PtVNS/PtrWND transactivation activity toward downstream genes, even between duplicate gene pairs. Furthermore, overexpression of PtVNS/PtrWND genes induced ectopic secondary wall thickening in poplar leaves as well as in Arabidopsis seedlings with different levels of induction efficiency according to the gene. These results suggest that wood formation in poplar is regulated by cooperative functions of the NAC domain proteins.

  15. Synthesis of a chitosan tetramer derivative, beta-D-GlcNAc-(1-->4)-beta-D-GlcNAc-(1-->4)-beta-D-GlcNAc-(1-->4)-D-Glc N through a partial N-acetylation reaction by chitin deacetylase.

    PubMed

    Tokuyasu, K; Ono, H; Mitsutomi, M; Hayashi, K; Mori, Y

    2000-04-20

    We have synthesized beta-D-GlcNAc-(1-->4)-beta-D-GlcNAc-(1-->4)-beta-D-GlcNAc-(1-->4)-D-GlcN (2) through a partial N-acetylation reaction of chitosan tetramer 1 by a chitin deacetylase from Colletotrichum lindemuthianum ATCC 56676. The compound was purified from the mixture of acetylation products of 1 using cation-exchange column chromatography and amine-adsorption column chromatography, and its structure was estimated by 1H NMR and FABMS analyses. The enzymatic reaction allows a regioselectivity that is hard to achieve by chemical N-acetylation.

  16. Suppression of tomato SlNAC1 transcription factor delays fruit ripening.

    PubMed

    Meng, Chen; Yang, Dongyue; Ma, Xiaocui; Zhao, Weiyang; Liang, Xiaoqing; Ma, Nana; Meng, Qingwei

    2016-04-01

    Fruit ripening is a complex process involving many physiological and biochemical changes, including those for ethylene, carotenoid, and cell wall metabolism. Tomato (Solanum lycopersicum) serves as a research model for fruit development and ripening because it possesses numerous favorable genetic features. In this study, SlNAC1 was cloned. An antisense (AS) vector was constructed and transferred to tomato to further explore the function of SlNAC1. The results showed that AS fruits exhibited delayed ripening and a deeper red appearance when these fruits were fully ripened. Fully ripened AS fruits also produced higher total carotenoid and lycopene contents than those of the wild-type (WT) line. Ethylene production of AS fruits was delayed but occurred to a higher extent than that of WT fruits. The softening of AS fruits was slower than that of WT fruits. Endogenous abscisic acid (ABA) level in AS-4 fruits was lower than that in WT fruits. Exogenous ABA accelerated the softening of AS fruits. Furthermore, AS fruits demonstrated up-regulated expression of genes related to lycopene and ethylene biosynthesis but down-regulated expression of genes related to cell wall metabolism and ABA synthesis. Therefore, SlNAC1 is likely implicated in fruit ripening.

  17. Protective effect of NAC against malathion-induced oxidative stress in freshly isolated rat hepatocytes

    PubMed Central

    Mostafalou, Sara; Abdollahi, Mohammad; Eghbal, Mohammad Ali; Saeedi Kouzehkonani, Nazli

    2012-01-01

    Purpose: Induction of oxidative stress by Organophosphate compounds (OPs) has been previously reported. In the present work, the mechanism of protective effects of N-acetylcysteine as a glutathion (GSH) prodrug against malathion–induced cell toxicity was investigated. In this work, freshly isolated rat hepatocytes were used to determine the effect of NAC on malathion-induced cytotoxicity, formation of reactive oxygen species (ROS) and mitochondrial dysfunction. Methods: Rat hepatocytes were isolated using collagenase perfusion and then cell viability, mitchondrial membrane potential (MMP) and ROS formation were determined using trypan blue exclusion, Rhodamine 123 fluorescence and fluorogenic probe, 2', 7' -dichlorofluorescin diacetate (DCFH-DA), respectively. Results: Despite the protective effect of NAC on malathion-induced cell toxicity and MMP dysfunction, its efficacy against ROS formation was not adequate to completely protect the cells. Conclusion: Cytotoxic effects of malathion regardless of its cholinergic feature, is started with gradual free radical production but, the main factor that causes cell death, is mitochondrial dysfunction, so that reduction of ROS formation alone is not sufficient for cell survival, and the maintenance of mitochondrial integrity through different mechanisms is the most ameliorative factor specially at high levels of cell damage, as NAC seemed to protect cells with various fashions apart from ROS scavenging in concentrations higher than malathion’s LC50. PMID:24312774

  18. 77 FR 15358 - National Oceanic and Atmospheric Administration

    Federal Register 2010, 2011, 2012, 2013, 2014

    2012-03-15

    ... National Oceanic and Atmospheric Administration Availability of Seats for the Monitor National Marine...), National Oceanic and Atmospheric Administration (NOAA), Department of Commerce (DOC). ACTION: Notice and..., National Ocean Service, National Oceanic and Atmospheric Administration. BILLING CODE 3510-NK-M...

  19. Functional characterization of NAC55 transcription factor from oilseed rape (Brassica napus L.) as a novel transcriptional activator modulating reactive oxygen species accumulation and cell death.

    PubMed

    Niu, Fangfang; Wang, Chen; Yan, Jingli; Guo, Xiaohua; Wu, Feifei; Yang, Bo; Deyholos, Michael K; Jiang, Yuan-Qing

    2016-09-01

    NAC transcription factors (TFs) are plant-specific and play important roles in development, responses to biotic and abiotic cues and hormone signaling. So far, only a few NAC genes have been reported to regulate cell death. In this study, we identified and characterized a NAC55 gene isolated from oilseed rape (Brassica napus L.). BnaNAC55 responds to multiple stresses, including cold, heat, abscisic acid (ABA), jasmonic acid (JA) and a necrotrophic fungal pathogen Sclerotinia sclerotiorum. BnaNAC55 has transactivation activity and is located in the nucleus. BnaNAC55 is able to form homodimers in planta. Unlike ANAC055, full-length BnaNAC55, but not either the N-terminal NAC domain or C-terminal regulatory domain, induces ROS accumulation and hypersensitive response (HR)-like cell death when expressed both in oilseed rape protoplasts and Nicotiana benthamiana. Furthermore, BnaNAC55 expression causes obvious nuclear DNA fragmentation. Moreover, quantitative reverse transcription PCR (qRT-PCR) analysis identified that the expression levels of multiple genes regulating ROS production and scavenging, defense response as well as senescence are significantly induced. Using a dual luciferase reporter assay, we further confirm that BnaNAC55 could activate the expression of a few ROS and defense-related gene expression. Taken together, our work has identified a novel NAC TF from oilseed rape that modulates ROS accumulation and cell death.

  20. Canola (Brassica napus L.) NAC103 transcription factor gene is a novel player inducing reactive oxygen species accumulation and cell death in plants.

    PubMed

    Niu, Fangfang; Wang, Boya; Wu, Feifei; Yan, Jingli; Li, Liang; Wang, Chen; Wang, Yiqiao; Yang, Bo; Jiang, Yuan-Qing

    2014-11-07

    NAC transcription factors are plant-specific and play important roles in many processes including plant development, response to biotic and abiotic stresses and hormone signaling. So far, only a few NAC genes have been identified to mediate cell death. In this study, we identified a novel NAC gene from canola (Brassica napus L.), BnaNAC103 which induces reactive oxygen species (ROS) accumulation and cell death in Nicotianabenthamiana leaves. We found that BnaNAC103 responded to multiple signalings, including cold, salicylic acid (SA) and a fungal pathogen Sclerotinia sclerotiorum. BnaNAC103 is located in the nucleus. Expression of full-length BnaNAC103, but not either the N-terminal NAC domain or C-terminal regulatory domain, was identified to induce hypersensitive response (HR)-like cell death when expressed in N. benthamiana. The cell death triggered by BnaNAC103 is preceded by accumulation of ROS, with diaminobenzidine (DAB) staining supporting this. Moreover, quantification of ion leakage and malondialdehyde (MDA) of leaf discs indicates significant cell membrane breakage and lipid peroxidation induced by BnaNAC103 expression. Taken together, our work has identified a novel NAC transcription factor gene modulating ROS level and cell death in plants.

  1. Characterization, Expression, and Functional Analysis of a Novel NAC Gene Associated with Resistance to Verticillium Wilt and Abiotic Stress in Cotton

    PubMed Central

    Wang, Weina; Yuan, Youlu; Yang, Can; Geng, Shuaipeng; Sun, Quan; Long, Lu; Cai, Chaowei; Chu, Zongyan; Liu, Xin; Wang, Guanghao; Du, Xiongming; Miao, Chen; Zhang, Xiao; Cai, Yingfan

    2016-01-01

    Elucidating the mechanism of resistance to biotic and abiotic stress is of great importance in cotton. In this study, a gene containing the NAC domain, designated GbNAC1, was identified from Gossypium barbadense L. Homologous sequence alignment indicated that GbNAC1 belongs to the TERN subgroup. GbNAC1 protein localized to the cell nucleus. GbNAC1 was expressed in roots, stems, and leaves, and was especially highly expressed in vascular bundles. Functional analysis showed that cotton resistance to Verticillium wilt was reduced when the GbNAC1 gene was silenced using the virus-induced gene silencing (VIGS) method. GbNAC1-overexpressing Arabidopsis showed enhanced resistance to Verticillium dahliae compared to wild-type. Thus, GbNAC1 is involved in the positive regulation of resistance to Verticillium wilt. In addition, analysis of GbNAC1-overexpressing Arabidopsis under different stress treatments indicated that it is involved in plant growth, development, and response to various abiotic stresses (ABA, mannitol, and NaCl). This suggests that GbNAC1 plays an important role in resistance to biotic and abiotic stresses in cotton. This study provides a foundation for further study of the function of NAC genes in cotton and other plants. PMID:27784753

  2. Characterization, Expression, and Functional Analysis of a Novel NAC Gene Associated with Resistance to Verticillium Wilt and Abiotic Stress in Cotton.

    PubMed

    Wang, Weina; Yuan, Youlu; Yang, Can; Geng, Shuaipeng; Sun, Quan; Long, Lu; Cai, Chaowei; Chu, Zongyan; Liu, Xin; Wang, Guanghao; Du, Xiongming; Miao, Chen; Zhang, Xiao; Cai, Yingfan

    2016-12-07

    Elucidating the mechanism of resistance to biotic and abiotic stress is of great importance in cotton. In this study, a gene containing the NAC domain, designated GbNAC1, was identified from Gossypium barbadense L. Homologous sequence alignment indicated that GbNAC1 belongs to the TERN subgroup. GbNAC1 protein localized to the cell nucleus. GbNAC1 was expressed in roots, stems, and leaves, and was especially highly expressed in vascular bundles. Functional analysis showed that cotton resistance to Verticillium wilt was reduced when the GbNAC1 gene was silenced using the virus-induced gene silencing (VIGS) method. GbNAC1-overexpressing Arabidopsis showed enhanced resistance to Verticillium dahliae compared to wild-type. Thus, GbNAC1 is involved in the positive regulation of resistance to Verticillium wilt. In addition, analysis of GbNAC1-overexpressing Arabidopsis under different stress treatments indicated that it is involved in plant growth, development, and response to various abiotic stresses (ABA, mannitol, and NaCl). This suggests that GbNAC1 plays an important role in resistance to biotic and abiotic stresses in cotton. This study provides a foundation for further study of the function of NAC genes in cotton and other plants.

  3. 45 CFR 162.1002 - Medical data code sets.

    Code of Federal Regulations, 2012 CFR

    2012-10-01

    ... 45 Public Welfare 1 2012-10-01 2012-10-01 false Medical data code sets. 162.1002 Section 162.1002 Public Welfare DEPARTMENT OF HEALTH AND HUMAN SERVICES ADMINISTRATIVE DATA STANDARDS AND RELATED REQUIREMENTS ADMINISTRATIVE REQUIREMENTS Code Sets § 162.1002 Medical data code sets. The Secretary adopts...

  4. 45 CFR 162.1002 - Medical data code sets.

    Code of Federal Regulations, 2014 CFR

    2014-10-01

    ... 45 Public Welfare 1 2014-10-01 2014-10-01 false Medical data code sets. 162.1002 Section 162.1002 Public Welfare Department of Health and Human Services ADMINISTRATIVE DATA STANDARDS AND RELATED REQUIREMENTS ADMINISTRATIVE REQUIREMENTS Code Sets § 162.1002 Medical data code sets. The Secretary adopts...

  5. 45 CFR 162.1002 - Medical data code sets.

    Code of Federal Regulations, 2013 CFR

    2013-10-01

    ... 45 Public Welfare 1 2013-10-01 2013-10-01 false Medical data code sets. 162.1002 Section 162.1002 Public Welfare DEPARTMENT OF HEALTH AND HUMAN SERVICES ADMINISTRATIVE DATA STANDARDS AND RELATED REQUIREMENTS ADMINISTRATIVE REQUIREMENTS Code Sets § 162.1002 Medical data code sets. The Secretary adopts...

  6. Theoretical pKa prediction of the α-phosphate moiety of uridine 5‧-diphosphate-GlcNAc

    NASA Astrophysics Data System (ADS)

    Vipperla, Bhavaniprasad; Griffiths, Thomas M.; Wang, Xingyong; Yu, Haibo

    2017-01-01

    The pKa value of the α-phosphate moiety of uridine 5‧-diphosphate-GlcNAc (UDP-GlcNAc) has been successfully calculated using density functional theory methods in conjunction with the Polarizable Continuum Models. Theoretical methods were benchmarked over a dataset comprising of alkyl phosphates. B3LYP/6-31+G(d,p) calculations using SMD solvation model provide excellent agreement with the experimental data. The predicted pKa for UDP-GlcNAc is consistent with most recent NMR studies but much higher than what it has long been thought to be. The importance of this study is evident that the predicted pKa for UDP-GlcNAc supports its potential role as a catalytic base in the substrate-assisted biocatalysis.

  7. Chemical Changes in Nonthermal Plasma-Treated N-Acetylcysteine (NAC) Solution and Their Contribution to Bacterial Inactivation

    PubMed Central

    Ercan, Utku K.; Smith, Josh; Ji, Hai-Feng; Brooks, Ari D.; Joshi, Suresh G.

    2016-01-01

    In continuation of our previous reports on the broad-spectrum antimicrobial activity of atmospheric non-thermal dielectric barrier discharge (DBD) plasma treated N-Acetylcysteine (NAC) solution against planktonic and biofilm forms of different multidrug resistant microorganisms, we present here the chemical changes that mediate inactivation of Escherichia coli. In this study, the mechanism and products of the chemical reactions in plasma-treated NAC solution are shown. UV-visible spectrometry, FT-IR, NMR, and colorimetric assays were utilized for chemical characterization of plasma treated NAC solution. The characterization results were correlated with the antimicrobial assays using determined chemical species in solution in order to confirm the major species that are responsible for antimicrobial inactivation. Our results have revealed that plasma treatment of NAC solution creates predominantly reactive nitrogen species versus reactive oxygen species, and the generated peroxynitrite is responsible for significant bacterial inactivation. PMID:26832829

  8. Chemical Changes in Nonthermal Plasma-Treated N-Acetylcysteine (NAC) Solution and Their Contribution to Bacterial Inactivation.

    PubMed

    Ercan, Utku K; Smith, Josh; Ji, Hai-Feng; Brooks, Ari D; Joshi, Suresh G

    2016-02-02

    In continuation of our previous reports on the broad-spectrum antimicrobial activity of atmospheric non-thermal dielectric barrier discharge (DBD) plasma treated N-Acetylcysteine (NAC) solution against planktonic and biofilm forms of different multidrug resistant microorganisms, we present here the chemical changes that mediate inactivation of Escherichia coli. In this study, the mechanism and products of the chemical reactions in plasma-treated NAC solution are shown. UV-visible spectrometry, FT-IR, NMR, and colorimetric assays were utilized for chemical characterization of plasma treated NAC solution. The characterization results were correlated with the antimicrobial assays using determined chemical species in solution in order to confirm the major species that are responsible for antimicrobial inactivation. Our results have revealed that plasma treatment of NAC solution creates predominantly reactive nitrogen species versus reactive oxygen species, and the generated peroxynitrite is responsible for significant bacterial inactivation.

  9. Comparative Genomics of NAC Transcriptional Factors in Angiosperms: Implications for the Adaptation and Diversification of Flowering Plants

    PubMed Central

    Pereira-Santana, Alejandro; Alcaraz, Luis David; Castaño, Enrique; Sanchez-Calderon, Lenin; Sanchez-Teyer, Felipe; Rodriguez-Zapata, Luis

    2015-01-01

    NAC proteins constitute one of the largest groups of plant-specific transcription factors and are known to play essential roles in various developmental processes. They are also important in plant responses to stresses such as drought, soil salinity, cold, and heat, which adversely affect growth. The current knowledge regarding the distribution of NAC proteins in plant lineages comes from relatively small samplings from the available data. In the present study, we broadened the number of plant species containing the NAC family origin and evolution to shed new light on the evolutionary history of this family in angiosperms. A comparative genome analysis was performed on 24 land plant species, and NAC ortholog groups were identified by means of bidirectional BLAST hits. Large NAC gene families are found in those species that have experienced more whole-genome duplication events, pointing to an expansion of the NAC family with divergent functions in flowering plants. A total of 3,187 NAC transcription factors that clustered into six major groups were used in the phylogenetic analysis. Many orthologous groups were found in the monocot and eudicot lineages, but only five orthologous groups were found between P. patens and each representative taxa of flowering plants. These groups were called basal orthologous groups and likely expanded into more recent taxa to cope with their environmental needs. This analysis on the angiosperm NAC family represents an effort to grasp the evolutionary and functional diversity within this gene family while providing a basis for further functional research on vascular plant gene families. PMID:26569117

  10. GSK-3β-dependent downregulation of γ-taxilin and αNAC merge to regulate ER stress responses

    PubMed Central

    Hotokezaka, Y; Katayama, I; van Leyen, K; Nakamura, T

    2015-01-01

    The signaling pathway leading to the endoplasmic reticulum (ER) stress responses has not been fully elucidated. Here we showed that glycogen synthase kinase-3β (GSK-3β)-dependent downregulation of γ-taxilin and nascent polypeptide-associated complex α-subunit (αNAC) mediates hypoxia-induced unfolded protein responses (UPRs) and the subsequent apoptotic and autophagic pathways. The degradation of γ-taxilin or αNAC was sufficient to initiate UPRs in normoxic cells. However, the ER stress signaling pathways initiated by γ-taxilin or αNAC were distinct, triggering different ER stress sensors and activating different downstream pathways. Hypoxia caused GSK-3β-dependent tau hyperphosphorylation and cleavage in neuronal cells, but γ-taxilin ablation induced tau hyperphosphorylation alone and αNAC ablation induced neither changes. Notably, downregulation of γ-taxilin and αNAC occurs in the brain of patients with Alzheimer's disease. These results suggest that GSK-3β-dependent downregulation of γ-taxilin and αNAC, which differently activate the UPRs, merge to regulate hypoxia-induced ER stress responses and provide a new insight into the pathogenesis of neurodegenerative diseases. PMID:25880086

  11. 28 CFR 70.42 - Codes of conduct.

    Code of Federal Regulations, 2010 CFR

    2010-07-01

    ... 28 Judicial Administration 2 2010-07-01 2010-07-01 false Codes of conduct. 70.42 Section 70.42 Judicial Administration DEPARTMENT OF JUSTICE (CONTINUED) UNIFORM ADMINISTRATIVE REQUIREMENTS FOR GRANTS...-PROFIT ORGANIZATIONS Post-Award Requirements Procurement Standards § 70.42 Codes of conduct....

  12. Pen and Pal are nucleotide-sugar dehydratases that convert UDP-GlcNAc to UDP-6-deoxy-D-GlcNAc-5,6-ene and then to UDP-4-keto-6-deoxy-L-AltNAc for CMP-pseudaminic acid synthesis in Bacillus thuringiensis.

    PubMed

    Li, Zi; Hwang, Soyoun; Ericson, Jaime; Bowler, Kyle; Bar-Peled, Maor

    2015-01-09

    CMP-pseudaminic acid is a precursor required for the O-glycosylation of flagellin in some pathogenic Gram-negative bacteria, a process known to be critical in bacterial motility and infection. However, little is known about flagellin glycosylation in Gram-positive bacteria. Here, we identified and functionally characterized an operon, named Bti_pse, in Bacillus thuringiensis israelensis ATCC 35646, which encodes seven different enzymes that together convert UDP-GlcNAc to CMP-pseudaminic acid. In contrast, Gram-negative bacteria complete this reaction with six enzymes. The first enzyme, which we named Pen, converts UDP-d-GlcNAc to an uncommon UDP-sugar, UDP-6-deoxy-D-GlcNAc-5,6-ene. Pen contains strongly bound NADP(+) and has distinct UDP-GlcNAc 4-oxidase, 5,6-dehydratase, and 4-reductase activities. The second enzyme, which we named Pal, converts UDP-6-deoxy-D-GlcNAc-5,6-ene to UDP-4-keto-6-deoxy-L-AltNAc. Pal is NAD(+)-dependent and has distinct UDP-6-deoxy-d-GlcNAc-5,6-ene 4-oxidase, 5,6-reductase, and 5-epimerase activities. We also show here using NMR spectroscopy and mass spectrometry that in B. thuringiensis, the enzymatic product of Pen and Pal, UDP-4-keto-6-deoxy-L-AltNAc, is converted to CMP-pseudaminic acid by the sequential activities of a C4″-transaminase (Pam), a 4-N-acetyltransferase (Pdi), a UDP-hydrolase (Phy), an enzyme (Ppa) that adds phosphoenolpyruvate to form pseudaminic acid, and finally a cytidylyltransferase that condenses CTP to generate CMP-pseudaminic acid. Knowledge of the distinct dehydratase-like enzymes Pen and Pal and their role in CMP-pseudaminic acid biosynthesis in Gram-positive bacteria provides a foundation to investigate the role of pseudaminic acid and flagellin glycosylation in Bacillus and their involvement in bacterial motility and pathogenicity.

  13. Dysregulation of dopamine and glutamate release in the prefrontal cortex and nucleus accumbens following methamphetamine self-administration and during reinstatement in rats.

    PubMed

    Parsegian, Aram; See, Ronald E

    2014-03-01

    Methamphetamine (meth) addicts often exhibit enduring cognitive and neural deficits that likely contribute to persistent drug seeking and the high rates of relapse. These deficits may be related to changes in the prefrontal cortex (PFC) and its glutamatergic projections to the nucleus accumbens (NAc). Here, we performed in vivo microdialysis in the PFC and NAc in rats following either meth self-administration or yoked-saline control histories to assess baseline glutamate (GLU) levels, or reinstatement-evoked GLU and dopamine (DA) efflux in both regions simultaneously under cue-induced, meth-primed, or combined cues+meth reinstatement conditions. Our results show that meth self-administration (1) reduced basal GLU levels in both the dmPFC and NAc, (2) concurrently increased dmPFC and NAc GLU efflux during reinstatement, and (3) increased DA efflux in the dmPFC, but not in the NAc, under all reinstatement conditions when compared with yoked-saline controls. These data demonstrate for the first time that a history of psychostimulant self-administration alters GLU homeostasis not only in the NAc, but also in the dmPFC, its primary GLU projection source. Furthermore, combined cues+meth-primed reinstatement conditions produced the most pronounced increases in mPFC and NAc extracellular GLU, suggesting that the cue and meth prime conditions are additive in promoting reinstatement. Finally, increased efflux of DA in the dmPFC, but not in the NAc, across reinstatement conditions suggests that DA release in the dmPFC may be an important mediator of drug seeking initiated by multiple relapse triggers.

  14. 28 CFR 36.608 - Guidance concerning model codes.

    Code of Federal Regulations, 2010 CFR

    2010-07-01

    ... 28 Judicial Administration 1 2010-07-01 2010-07-01 false Guidance concerning model codes. 36.608... Codes § 36.608 Guidance concerning model codes. Upon application by an authorized representative of a private entity responsible for developing a model code, the Assistant Attorney General may review...

  15. Rising taurine and ethanol concentrations in nucleus accumbens interact to produce dopamine release after ethanol administration.

    PubMed

    Ericson, Mia; Chau, PeiPei; Clarke, Rhona B; Adermark, Louise; Söderpalm, Bo

    2011-07-01

    We have previously demonstrated that glycine receptors in the nucleus accumbens (nAc) are involved in modulating both basal and ethanol-induced dopamine output in the same brain region. Ethanol is known to induce a release of both taurine and dopamine in the nAc, but the relationship between these two neuromodulators has not been investigated thoroughly. In vivo microdialysis was used to measure the effects of systemic ethanol diluted in isotonic (0.9% NaCl) or hypertonic (3.6% NaCl) saline on accumbal taurine and dopamine levels. We found that ethanol given in a hypertonic solution, contrary to an isotonic solution, failed to increase concentrations both of taurine and dopamine in the nAc. However, a modest, non-dopamine elevating concentration of taurine in the nAc disclosed a dopamine-elevating effect of systemic ethanol also when given in a hypertonic solution. In a second experiment, we investigated the effects of ethanol on taurine and dopamine in normal rats and rats with decreased levels of endogenous taurine. Lowering the level of taurine, approximately 40% by adding 5% β-alanine in the drinking water, did not influence taurine or dopamine output over time. We conclude that the elevations of taurine and dopamine in the nAc are closely related, and that in order for ethanol to induce dopamine release, a simultaneous increase of extracellular taurine levels in the nAc is required. These data also provide support for the notion that the nAc is the primary target for ethanol in its dopamine-activating effect after systemic administration.

  16. Hyaluronan synthase assembles chitin oligomers with -GlcNAc(α1→)UDP at the reducing end.

    PubMed

    Weigel, Paul H; West, Christopher M; Zhao, Peng; Wells, Lance; Baggenstoss, Bruce A; Washburn, Jennifer L

    2015-06-01

    Class I hyaluronan synthases (HASs) assemble a polysaccharide containing the repeating disaccharide [GlcNAc(β1,4)GlcUA(β1,3)]n-UDP and vertebrate HASs also assemble (GlcNAc-β1,4)n homo-oligomers (chitin) in the absence of GlcUA-UDP. This multi-membrane domain CAZy GT2 family glycosyltransferase, which couples HA synthesis and translocation across the cell membrane, is atypical in that monosaccharides are incrementally assembled at the reducing, rather than the non-reducing, end of the growing polymer. Using Escherichia coli membranes containing recombinant Streptococcus equisimilis HAS, we demonstrate that a prokaryotic Class I HAS also synthesizes chitin oligomers (up to 15-mers, based on MS and MS/MS analyses of permethylated products). Furthermore, chitin oligomers were found attached at their reducing end to -4GlcNAc(α1→)UDP [i.e. (GlcNAcβ1,4)nGlcNAc(α1→)UDP]. These oligomers, which contained up to at least seven HexNAc residues, consisted of β4-linked GlcNAc residues, based on the sensitivity of the native products to jack bean β-N-acetylhexosaminidase. Interestingly, these oligomers exhibited mass defects of -2, or -4 for longer oligomers, that strictly depended on conjugation to UDP, but MS/MS analyses indicate that these species result from chemical dehydrogenations occurring in the gas phase. Identification of (GlcNAc-β1,4)n-GlcNAc(α1→)UDP as HAS reaction products, made in the presence of GlcNAc(α1→)UDP only, provides strong independent confirmation for the reducing terminal addition mechanism. We conclude that chitin oligomer products made by HAS are derived from the cleavage of these novel activated oligo-chitosyl-UDP oligomers. Furthermore, it is possible that these UDP-activated chitin oligomers could serve as self-assembled primers for initiating HA synthesis and ultimately modify the non-reducing terminus of HA with a chitin cap.

  17. Overexpression of TaNAC2D Displays Opposite Responses to Abiotic Stresses between Seedling and Mature Stage of Transgenic Arabidopsis

    PubMed Central

    Huang, Quanjun; Wang, Yan

    2016-01-01

    Environmental stresses frequently affect plant growth and development, and many genes have been found to be induced by unfavorable environmental conditions. Here, we reported the biological functions of TaNAC2D, a stress-related NAC (NAM, ATAF, and CUC) gene from wheat. TaNAC2D showed transcriptional activator activity in yeast. TaNAC2D-GFP fusion protein was localized in the nucleus of wheat mesophyll protoplasts. TaNAC2D transcript abundance was significantly induced by NaCl, PEG6000, and abscisic acid (ABA) at seedling stage, and repressed by NaCl and PEG6000 at mature plant stage. When TaNAC2D was introduced into Arabidopsis, the 35-day-old soil-grown TaNAC2D-overexpression (TaNAC2D-OX) plants displayed slower stomatal closure, higher water loss rate, and more sensitivity to salt and drought stresses compared with WT plants. In contrast, TaNAC2D-OX seedlings, grown on 1/2 MS medium supplemented with different concentrations of NaCl, Mannitol, and MV, had enhanced tolerances to salt, osmotic and oxidative stresses during seed germination and post-germination periods. The opposite stress-responsive phenotypes of transgenic Arabidopsis were consistent with the expression patterns of TaNAC2D in wheat. Moreover, under high salinity and dehydration conditions, three marker genes, including NCED3, RD29A, and RD29B, were down-regulated in 35-day-old TaNAC2D-OX plants grown in soil and up-regulated in 14-day-old TaNAC2D-OX seedlings grown on 1/2 MS medium. Our results suggest that the change in growth stages and environmental conditions may regulate TaNAC2D’s function. PMID:27933076

  18. Administrative Ecology

    ERIC Educational Resources Information Center

    McGarity, Augustus C., III; Maulding, Wanda

    2007-01-01

    This article discusses how all four facets of administrative ecology help dispel the claims about the "impossibility" of the superintendency. These are personal ecology, professional ecology, organizational ecology, and community ecology. Using today's superintendency as an administrative platform, current literature describes a preponderance of…

  19. NAC is associated with additional alleviation of lung injury induced by invasive pulmonary aspergillosis in a neutropenic model

    PubMed Central

    Xu, Peng; Qu, Jie-ming; Xu, Jin-fu; Zhang, Jing; Jiang, Hong-ni; Zhang, Hui-jun

    2009-01-01

    Aim: Neutropenic individuals are at high risk for invasive pulmonary aspergillosis (IPA), a life-threatening infection. To evaluate the therapeutic potential of antioxidants, IPA was induced in neutropenic mice and the effect of N-acetyl-l-cysteine (NAC) on oxidative stress levels and lung injury was analyzed. Methods: Mice were pretreated with three daily intraperitoneal injections of 150 mg/kg cyclophosphamide, followed by intratracheal inoculation with 4.5×106 conidia of Asperǵillus fumiǵatus. The infected mice were then randomly assigned to an amphotericin B (AMB) group, an AMB plus NAC group, or an untreated control (C) group. In each group, the duration of treatment was 24, 48, or 72 h, and activities such as appearance, feeding, and dermal temperature were observed throughout the experiment. Sera and lung tissues were collected and analyzed by quantitative enzyme-linked immunosorbent assay (ELISA) for total protein, superoxide dismutase (SOD), malondialdehyde (MDA), tumor necrosis factor-α (TNF-α), and interleukin-10 (IL-10) levels. The wet/dry weight ratio of the lung was also calculated and lung sections were stained with hematoxylin-eosin for pathological examination and with methenamine silver stain for fungus detection. Results: Compared with the mice untreated with NAC, mice in the AMB plus NAC group had increased SOD and reduced MDA levels both systemically and locally at 24, 48, and 72 h after inoculation with conidia. NAC treatment also decreased the pulmonary protein content at 48 and 72 h and the lung wet/dry weight ratio at 24 and 48 h. Additionally, NAC enhanced pulmonary production of TNF-α and IL-10 at 24 h and 48 h. Conclusion: In combination with antifungal therapy, NAC treatment can alleviate oxidative stress and lung injury associated with IPA in neutropenic mice. PMID:19575001

  20. The inhibition of cocaine-induced locomotor activity by CART 55-102 is lost after repeated cocaine administration.

    PubMed

    Job, Martin O; Shen, Li L; Kuhar, Michael J

    2013-08-29

    CART peptide is known for having an inhibitory effect on cocaine- and dopamine-mediated actions after acute administration of cocaine and dopamine. In this regard, it is postulated to be a homeostatic, regulatory factor on dopaminergic activity in the nucleus accumbens (NAc). However, there is no data on the effect of CART peptide after chronic administration of cocaine, and this study addresses this. It was found that CART peptide blunted cocaine-induced locomotion (LMA) after acute administration of cocaine, as expected, but it did not affect cocaine-mediated LMA after chronic administration of cocaine. The loss of CART peptide's inhibitory effect did not return for up to 9 weeks after stopping the repeated cocaine administration. It may not be surprising that homeostatic regulatory mechanisms in the NAc are lost after repeated cocaine administration, and that this may be a mechanism in the development of addiction.

  1. Expression of sialyl-Tn antigen in breast cancer cells transfected with the human CMP-Neu5Ac: GalNAc alpha2,6-sialyltransferase (ST6GalNac I) cDNA.

    PubMed

    Julien, S; Krzewinski-Recchi, M A; Harduin-Lepers, A; Gouyer, V; Huet, G; Le Bourhis, X; Delannoy, P

    2001-01-01

    Sialyl-Tn antigen (STn) is a cancer associated carbohydrate antigen over-expressed in several cancers including breast cancer, and currently associated with more aggressive diseases and poor prognosis. However, the commonly used breast cancer cell lines (MDA-MB-231, T47-D and MCF7) do not express STn antigen. The key step in the biosynthesis of STn is the transfer of a sialic acid residue in alpha2,6-linkage to GalNAc alpha-O-Ser/Thr. This reaction is mainly catalyzed by a CMP-Neu5Ac GalNAc alpha2,6-sialyltransferase: ST6GalNAc I. In order to generate STn-positive breast cancer cells, we have cloned a cDNA encoding the full-length human ST6GalNAc I from HT-29-MTX cells. The stable transfection of MDA-MB-231 with an expression vector encoding ST6GalNAc I induces the expression of STn antigen at the cell surface. The expression of STn short cuts the initial O-glycosylation pattern of these cell lines, by competing with the Core-1 beta1,3-galactosyltransferase, the first enzyme involved in the elongation of O-glycan chains. Moreover, we show that STn expression is associated with morphological changes, decreased growth and increased migration of MDA-MB-231 cells.

  2. Error-correction coding

    NASA Technical Reports Server (NTRS)

    Hinds, Erold W. (Principal Investigator)

    1996-01-01

    This report describes the progress made towards the completion of a specific task on error-correcting coding. The proposed research consisted of investigating the use of modulation block codes as the inner code of a concatenated coding system in order to improve the overall space link communications performance. The study proposed to identify and analyze candidate codes that will complement the performance of the overall coding system which uses the interleaved RS (255,223) code as the outer code.

  3. Repeated cocaine administration suppresses HVA-Ca2+ potentials and enhances activity of K+ channels in rat nucleus accumbens neurons.

    PubMed

    Hu, Xiu-Ti; Basu, Somnath; White, Francis J

    2004-09-01

    The nucleus accumbens (NAc) is an important forebrain area involved in sensitization, withdrawal effects, and self-administration of cocaine. However, little is known about cocaine-induced alterations in the neuronal excitability and whole cell neuroplasticity in this region that may affect behaviors. Our recent investigations have demonstrated that repeated cocaine administration decreases voltage-sensitive sodium and calcium currents (VSSCs and VSCCs, respectively) in freshly dissociated NAc neurons of rats. In this study, current-clamp recordings were performed in slice preparations to determine the effects of chronic cocaine on evoked Ca(2+) potentials and voltage-sensitive K(+) currents in NAc neurons. Repeated cocaine administration with 3-4 days of withdrawal caused significant alterations in Ca(2+) potentials, including suppression of Ca(2+)-mediated spikes, increase in the intracellular injected current intensity required for generation of Ca(2+) potentials (rheobase), reduced duration of Ca(2+) plateau potentials, and abolishment of secondary Ca(2+) potentials associated with the primary Ca(2+) plateau potential. Application of nickel (Ni(2+)), which blocks low-voltage activated T-type Ca(2+) channels, had no impact on evoked Ca(2+) plateau potentials in NAc neurons, indicating that these Ca(2+) potentials are high-voltage activated (HVA). In addition, repeated cocaine pretreatment also hyperpolarized the resting membrane potential, increased the amplitude of afterhyperpolarization in Ca(2+) spikes, and enhanced the outward rectification observed during membrane depolarization. These findings indicate that repeated cocaine administration not only suppressed HVA-Ca(2+) potentials but also significantly enhanced the activity of various K(+) channels in NAc neurons. They also demonstrate an integrative role of whole cell neuroplasticity during cocaine withdrawal, by which the subthreshold membrane excitability of NAc neurons is significantly decreased.

  4. Methylenedioxypyrovalerone (MDPV) mimics cocaine in its physiological and behavioral effects but induces distinct changes in NAc glucose

    PubMed Central

    Wakabayashi, Ken T.; Ren, Suelynn E.; Kiyatkin, Eugene A.

    2015-01-01

    Methylenedioxypyrovalerone (MDPV) is generally considered to be a more potent cocaine-like psychostimulant, as it shares a similar pharmacological profile with cocaine and induces similar physiological and locomotor responses. Recently, we showed that intravenous cocaine induces rapid rise in nucleus accumbens (NAc) glucose and established its relation to neural activation triggered by the peripheral drug actions. This study was conducted to find out whether MDPV, at a behaviorally equivalent dose, shares a similar pattern of NAc glucose dynamics. Using enzyme-based glucose sensors coupled with amperometery in freely moving rats, we found that MDPV tonically decreases NAc glucose levels, a response that is opposite to what we previously observed with cocaine. By analyzing Skin-Muscle temperature differentials, a valid measure of skin vascular tone, we found that MDPV induces vasoconstriction; a similar effect at the level of cerebral vessels could be responsible for the MDPV-induced decrease in NAc glucose. While cocaine also induced comparable, if not slightly stronger peripheral vasoconstriction, this effect was overpowered by local neural activity-induced vasodilation, resulting in rapid surge in NAc glucose. These results imply that cocaine-users may be more susceptible to addiction than MDPV-users due to the presence of an interoceptive signal (i.e., sensory cue), which may result in earlier and more direct reward detection. Additionally, while health complications arising from acute cocaine use are typically cardiovascular related, MDPV may be more dangerous to the brain due to uncompensated cerebral vasoconstriction. PMID:26441499

  5. GalNAc moieties in O-linked oligosaccharides of the primordial germ cells of Xenopus embryos.

    PubMed

    Alonso, Edurne; Sáez, Francisco José; Madrid, Juan Francisco; Hernández, Francisco

    2002-04-01

    Glycoconjugates could play a role in cell adhesion and migration mechanisms, including the locomotive movements of the primordial germ cells (PGCs) during the development of the embryo. In the present work, we have studied by lectin histochemistry the presence of N-acetylgalactosamine (GalNAc) in the glycans of the Xenopus PGCs, as a first approach to identifying their glycoconjugates which could be involved in the migration mechanism. The PGCs were negative for three of the GalNAc-binding lectins employed (from soybean, SBA; from lima bean, LBA; and from snail, HPA). However, when sialic acid (NeuAc) was previously removed by acid hydrolysis, SBA and HPA, but not LBA, labeled the PGCs, except if the staining was combined with the beta-elimination procedure. This suggests the presence of GalNAc alpha(1,3)-linked to galactose (Gal) in O-linked oligosaccharides, in a subterminal position to NeuAc. As the PGCs were always negative for LBA, the absence of fucose alpha(1,2)-linked to subterminal Gal is suggested. With the lectin from horse gram (DBA), the PGCs were stained, although beta-elimination turned the cells negative and acid hydrolysis increased the labeling, suggesting that GalNAc(alpha)(1,3)GalNAc was in O-linked glycans in terminal and subterminal to NeuAc position.

  6. VND-INTERACTING2, a NAC Domain Transcription Factor, Negatively Regulates Xylem Vessel Formation in Arabidopsis[W][OA

    PubMed Central

    Yamaguchi, Masatoshi; Ohtani, Misato; Mitsuda, Nobutaka; Kubo, Minoru; Ohme-Takagi, Masaru; Fukuda, Hiroo; Demura, Taku

    2010-01-01

    The Arabidopsis thaliana NAC domain transcription factor VASCULAR-RELATED NAC-DOMAIN7 (VND7) acts as a master regulator of xylem vessel differentiation. To understand the mechanism by which VND7 regulates xylem vessel differentiation, we used a yeast two-hybrid system to screen for proteins that interact with VND7 and identified cDNAs encoding two NAC domain proteins, VND-INTERACTING1 (VNI1) and VNI2. Binding assays demonstrated that VNI2 effectively interacts with VND7 and the VND family proteins, VND1-5, as well as with other NAC domain proteins at lower affinity. VNI2 is expressed in both xylem and phloem cells in roots and inflorescence stems. The expression of VNI2 overlaps with that of VND7 in elongating vessel precursors in roots. VNI2 contains a predicted PEST motif and a C-terminally truncated VNI2 protein, which lacks part of the PEST motif, is more stable than full-length VNI2. Transient reporter assays showed that VNI2 is a transcriptional repressor and can repress the expression of vessel-specific genes regulated by VND7. Expression of C-terminally truncated VNI2 under the control of the VND7 promoter inhibited the normal development of xylem vessels in roots and aerial organs. These data suggest that VNI2 regulates xylem cell specification as a transcriptional repressor that interacts with VND proteins and possibly also with other NAC domain proteins. PMID:20388856

  7. Novel UDP-GalNAc Derivative Structures Provide Insight into the Donor Specificity of Human Blood Group Glycosyltransferase.

    PubMed

    Wagner, Gerd K; Pesnot, Thomas; Palcic, Monica M; Jørgensen, Rene

    2015-12-25

    Two closely related glycosyltransferases are responsible for the final step of the biosynthesis of ABO(H) human blood group A and B antigens. The two enzymes differ by only four amino acid residues, which determine whether the enzymes transfer GalNAc from UDP-GalNAc or Gal from UDP-Gal to the H-antigen acceptor. The enzymes belong to the class of GT-A folded enzymes, grouped as GT6 in the CAZy database, and are characterized by a single domain with a metal dependent retaining reaction mechanism. However, the exact role of the four amino acid residues in the specificity of the enzymes is still unresolved. In this study, we report the first structural information of a dual specificity cis-AB blood group glycosyltransferase in complex with a synthetic UDP-GalNAc derivative. Interestingly, the GalNAc moiety adopts an unusual yet catalytically productive conformation in the binding pocket, which is different from the "tucked under" conformation previously observed for the UDP-Gal donor. In addition, we show that this UDP-GalNAc derivative in complex with the H-antigen acceptor provokes the same unusual binding pocket closure as seen for the corresponding UDP-Gal derivative. Despite this, the two derivatives show vastly different kinetic properties. Our results provide a important structural insight into the donor substrate specificity and utilization in blood group biosynthesis, which can very likely be exploited for the development of new glycosyltransferase inhibitors and probes.

  8. A DNA-binding-site landscape and regulatory network analysis for NAC transcription factors in Arabidopsis thaliana

    PubMed Central

    Lindemose, Søren; Jensen, Michael K.; de Velde, Jan Van; O'Shea, Charlotte; Heyndrickx, Ken S.; Workman, Christopher T.; Vandepoele, Klaas; Skriver, Karen; Masi, Federico De

    2014-01-01

    Target gene identification for transcription factors is a prerequisite for the systems wide understanding of organismal behaviour. NAM-ATAF1/2-CUC2 (NAC) transcription factors are amongst the largest transcription factor families in plants, yet limited data exist from unbiased approaches to resolve the DNA-binding preferences of individual members. Here, we present a TF-target gene identification workflow based on the integration of novel protein binding microarray data with gene expression and multi-species promoter sequence conservation to identify the DNA-binding specificities and the gene regulatory networks of 12 NAC transcription factors. Our data offer specific single-base resolution fingerprints for most TFs studied and indicate that NAC DNA-binding specificities might be predicted from their DNA-binding domain's sequence. The developed methodology, including the application of complementary functional genomics filters, makes it possible to translate, for each TF, protein binding microarray data into a set of high-quality target genes. With this approach, we confirm NAC target genes reported from independent in vivo analyses. We emphasize that candidate target gene sets together with the workflow associated with functional modules offer a strong resource to unravel the regulatory potential of NAC genes and that this workflow could be used to study other families of transcription factors. PMID:24914054

  9. An experimental investigation of the thermal/fluid properties of the nitrate to ammonia and ceramic (NAC) product slurry

    SciTech Connect

    Muguercia, I.; Lagos, L.; Yang, G.; Li, W.; Ebadian, M.A.; Mattus, A.J.; Lee, D.D.; Walker, J.W.; Hunt, R.D.

    1994-12-31

    Recently, a new immobilization technique for LLW, the Nitrate to Ammonia and Ceramic (NAC) process, has been developed. Instead of mixing the liquid waste form directly with the cement to make concrete blocks, the NAC process eliminates the nitrate from the LLW by converting it to ammonia gas. Aluminum particles are used as a reductant to complete this conversion. The final product of the NAC process is gibbsite, which can be further sintered to a ceramic waste form. Experimental tests are conducted to measure the apparent viscosity, the pressure drop, and the heat transfer coefficient of the pipe flow of the Nitrate to Ammonia and Ceramic (NAC) process product slurry. The tests indicate that the NAC product slurry exhibits a typical pseudoplastic fluid behavior. The pressure drop in the pipe flow is a function of the Reynolds number and the slurry temperature. The results also indicate that at a low slurry temperature, the slurry is uniformly heated peripherally. At a high slurry temperature, however, the slurry may be thermally stratified. In a straight pipe, the Nusselt number is reduced as the slurry temperature increases.

  10. GlcNAc6ST-1 regulates sulfation of N-glycans and myelination in the peripheral nervous system

    PubMed Central

    Yoshimura, Takeshi; Hayashi, Akiko; Handa-Narumi, Mai; Yagi, Hirokazu; Ohno, Nobuhiko; Koike, Takako; Yamaguchi, Yoshihide; Uchimura, Kenji; Kadomatsu, Kenji; Sedzik, Jan; Kitamura, Kunio; Kato, Koichi; Trapp, Bruce D.; Baba, Hiroko; Ikenaka, Kazuhiro

    2017-01-01

    Highly specialized glial cells wrap axons with a multilayered myelin membrane in vertebrates. Myelin serves essential roles in the functioning of the nervous system. Axonal degeneration is the major cause of permanent neurological disability in primary myelin diseases. Many glycoproteins have been identified in myelin, and a lack of one myelin glycoprotein results in abnormal myelin structures in many cases. However, the roles of glycans on myelin glycoproteins remain poorly understood. Here, we report that sulfated N-glycans are involved in peripheral nervous system (PNS) myelination. PNS myelin glycoproteins contain highly abundant sulfated N-glycans. Major sulfated N-glycans were identified in both porcine and mouse PNS myelin, demonstrating that the 6-O-sulfation of N-acetylglucosamine (GlcNAc-6-O-sulfation) is highly conserved in PNS myelin between these species. P0 protein, the most abundant glycoprotein in PNS myelin and mutations in which at the glycosylation site cause Charcot-Marie-Tooth neuropathy, has abundant GlcNAc-6-O-sulfated N-glycans. Mice deficient in N-acetylglucosamine-6-O-sulfotransferase-1 (GlcNAc6ST-1) failed to synthesize sulfated N-glycans and exhibited abnormal myelination and axonal degeneration in the PNS. Taken together, this study demonstrates that GlcNAc6ST-1 modulates PNS myelination and myelinated axonal survival through the GlcNAc-6-O-sulfation of N-glycans on glycoproteins. These findings may provide novel insights into the pathogenesis of peripheral neuropathy. PMID:28186137

  11. OsNAC5 overexpression enlarges root diameter in rice plants leading to enhanced drought tolerance and increased grain yield in the field.

    PubMed

    Jeong, Jin Seo; Kim, Youn Shic; Redillas, Mark C F R; Jang, Geupil; Jung, Harin; Bang, Seung Woon; Choi, Yang Do; Ha, Sun-Hwa; Reuzeau, Christophe; Kim, Ju-Kon

    2013-01-01

    Drought conditions are among the most serious challenges to crop production worldwide. Here, we report the results of field evaluations of transgenic rice plants overexpressing OsNAC5, under the control of either the root-specific (RCc3) or constitutive (GOS2) promoters. Field evaluations over three growing seasons revealed that the grain yield of the RCc3:OsNAC5 and GOS2:OsNAC5 plants were increased by 9%-23% and 9%-26% under normal conditions, respectively. Under drought conditions, however, RCc3:OsNAC5 plants showed a significantly higher grain yield of 22%-63%, whilst the GOS2:OsNAC5 plants showed a reduced or similar yield to the nontransgenic (NT) controls. Both the RCc3:OsNAC5 and GOS2:OsNAC5 plants were found to have larger roots due to an enlarged stele and aerenchyma at flowering stage. Cell numbers per cortex layer and stele of developing roots were higher in both transgenic plants than NT controls, contributing to the increase in root diameter. The root diameter was enlarged to a greater extent in the RCc3:OsNAC5, suggesting the importance of this phenotype for enhanced drought tolerance. Microarray experiments identified 25 up-regulated genes by more than three-fold (P < 0.01) in the roots of both transgenic lines. Also identified were 19 and 18 up-regulated genes that are specific to the RCc3:OsNAC5 and GOS2:OsNAC5 roots, respectively. Of the genes specifically up-regulated in the RCc3:OsNAC5 roots, GLP, PDX, MERI5 and O-methyltransferase were implicated in root growth and development. Our present findings demonstrate that the root-specific overexpression of OsNAC5 enlarges roots significantly and thereby enhances drought tolerance and grain yield under field conditions.

  12. Differential Expression Analysis of a Subset of Drought-Responsive GmNAC Genes in Two Soybean Cultivars Differing in Drought Tolerance

    PubMed Central

    Thao, Nguyen Phuong; Thu, Nguyen Binh Anh; Hoang, Xuan Lan Thi; Van Ha, Chien; Tran, Lam-Son Phan

    2013-01-01

    The plant-specific NAC transcription factors play important roles in plant response to drought stress. Here, we have compared the expression levels of a subset of GmNAC genes in drought-tolerant DT51 and drought-sensitive MTD720 under both normal and drought stress conditions aimed at identifying correlation between GmNAC expression levels and drought tolerance degree, as well as potential GmNAC candidates for genetic engineering. The expression of 23 selected dehydration-responsive GmNACs was assessed in both stressed and unstressed root tissues of DT51 and MTD720 using real-time quantitative PCR. The results indicated that expression of GmNACs was genotype-dependent. Seven and 13 of 23 tested GmNACs showed higher expression levels in roots of DT51 in comparison with MTD720 under normal and drought stress conditions, respectively, whereas none of them displayed lower transcript levels under any conditions. This finding suggests that the higher drought tolerance of DT51 might be positively correlated with the higher induction of the GmNAC genes during water deficit. The drought-inducible GmNAC011 needs to be mentioned as its transcript accumulation was more than 76-fold higher in drought-stressed DT51 roots relative to MTD720 roots. Additionally, among the GmNAC genes examined, GmNAC085, 092, 095, 101 and 109 were not only drought-inducible but also more highly up-regulated in DT51 roots than in that of MTD720 under both treatment conditions. These data together suggest that GmNAC011, 085, 092, 095, 101 and 109 might be promising candidates for improvement of drought tolerance in soybean by biotechnological approaches. PMID:24322442

  13. Structure of Human O-GlcNAc Transferase and its Complex with a Peptide Substrate

    SciTech Connect

    M Lazarus; Y Nam; J Jiang; P Sliz; S Walker

    2011-12-31

    The essential mammalian enzyme O-linked {beta}-N-acetylglucosamine transferase (O-GlcNAc transferase, here OGT) couples metabolic status to the regulation of a wide variety of cellular signalling pathways by acting as a nutrient sensor. OGT catalyses the transfer of N-acetylglucosamine from UDP-N-acetylglucosamine (UDP-GlcNAc) to serines and threonines of cytoplasmic, nuclear and mitochondrial proteins, including numerous transcription factors, tumour suppressors, kinases, phosphatases and histone-modifying proteins. Aberrant glycosylation by OGT has been linked to insulin resistance, diabetic complications, cancer and neurodegenerative diseases including Alzheimer's. Despite the importance of OGT, the details of how it recognizes and glycosylates its protein substrates are largely unknown. We report here two crystal structures of human OGT, as a binary complex with UDP (2.8 {angstrom} resolution) and as a ternary complex with UDP and a peptide substrate (1.95 {angstrom}). The structures provide clues to the enzyme mechanism, show how OGT recognizes target peptide sequences, and reveal the fold of the unique domain between the two halves of the catalytic region. This information will accelerate the rational design of biological experiments to investigate OGT's functions; it will also help the design of inhibitors for use as cellular probes and help to assess its potential as a therapeutic target.

  14. Apparent NAC effect in chorismate mutase reflects electrostatic transition state stabilization.

    PubMed

    Strajbl, Marek; Shurki, Avital; Kato, Mitsunori; Warshel, Arieh

    2003-08-27

    The catalytic reaction of chorismate mutase (CM) has been the subject of major current attention. Nevertheless, the origin of the catalytic power of CM remains an open question. In particular, it has not been clear whether the enzyme works by providing electrostatic transition state stabilization (TSS), by applying steric strain, or by populating near attack conformation (NAC). The present work explores this issue by a systematic quantitative analysis. The overall catalytic effect is reproduced by the empirical valence bond (EVB) method. In addition, the binding free energy of the ground state and the transition state is evaluated, demonstrating that the enzyme works by TSS. Furthermore, the evaluation of the electrostatic contribution to the reduction of the activation energy establishes that the TSS results from electrostatic effects. It is also found that the apparent NAC effect is not the reason for the catalytic effect but the result of the TSS. It is concluded that in CM as in other enzymes the key catalytic effect is electrostatic TSS. However, since the charge distribution of the transition state and the reactant state is similar, the stabilization of the transition state leads to reduction in the distance between the reacting atoms in the reactant state.

  15. Dual functionality of O-GlcNAc transferase is required for Drosophila development.

    PubMed

    Mariappa, Daniel; Zheng, Xiaowei; Schimpl, Marianne; Raimi, Olawale; Ferenbach, Andrew T; Müller, H-Arno J; van Aalten, Daan M F

    2015-12-01

    Post-translational modification of intracellular proteins with O-linked N-acetylglucosamine (O-GlcNAc) catalysed by O-GlcNAc transferase (OGT) has been linked to regulation of diverse cellular functions. OGT possesses a C-terminal glycosyltransferase catalytic domain and N-terminal tetratricopeptide repeats that are implicated in protein-protein interactions. Drosophila OGT (DmOGT) is encoded by super sex combs (sxc), mutants of which are pupal lethal. However, it is not clear if this phenotype is caused by reduction of O-GlcNAcylation. Here we use a genetic approach to demonstrate that post-pupal Drosophila development can proceed with negligible OGT catalysis, while early embryonic development is OGT activity-dependent. Structural and enzymatic comparison between human OGT (hOGT) and DmOGT informed the rational design of DmOGT point mutants with a range of reduced catalytic activities. Strikingly, a severely hypomorphic OGT mutant complements sxc pupal lethality. However, the hypomorphic OGT mutant-rescued progeny do not produce F2 adults, because a set of Hox genes is de-repressed in F2 embryos, resulting in homeotic phenotypes. Thus, OGT catalytic activity is required up to late pupal stages, while further development proceeds with severely reduced OGT activity.

  16. Synthetic Receptors for the High‐Affinity Recognition of O‐GlcNAc Derivatives

    PubMed Central

    Rios, Pablo; Carter, Tom S.; Crump, Matthew P.; Lisbjerg, Micke; Pittelkow, Michael; Supekar, Nitin T.; Boons, Geert‐Jan

    2016-01-01

    Abstract The combination of a pyrenyl tetraamine with an isophthaloyl spacer has led to two new water‐soluble carbohydrate receptors (“synthetic lectins”). Both systems show outstanding affinities for derivatives of N‐acetylglucosamine (GlcNAc) in aqueous solution. One receptor binds the methyl glycoside GlcNAc‐β‐OMe with K a≈20 000 m −1, whereas the other one binds an O‐GlcNAcylated peptide with K a≈70 000 m −1. These values substantially exceed those usually measured for GlcNAc‐binding lectins. Slow exchange on the NMR timescale enabled structural determinations for several complexes. As expected, the carbohydrate units are sandwiched between the pyrenes, with the alkoxy and NHAc groups emerging at the sides. The high affinity of the GlcNAcyl–peptide complex can be explained by extra‐cavity interactions, raising the possibility of a family of complementary receptors for O‐GlcNAc in different contexts. PMID:26822115

  17. Exploring reaction pathways for O-GlcNAc transferase catalysis. A string method study.

    PubMed

    Kumari, Manju; Kozmon, Stanislav; Kulhánek, Petr; Štepán, Jakub; Tvaroška, Igor; Koča, Jaroslav

    2015-03-26

    The inverting O-GlcNAc glycosyltransferase (OGT) is an important post-translation enzyme, which catalyzes the transfer of N-acetylglucosamine from UDP-N-acetylglucosamine (UDP-GlcNAc) to the hydroxyl group of the Ser/Thr of cytoplasmic, nuclear, and mitochondrial proteins. In the past, three different catalytic bases were proposed for the reaction: His498, α-phosphate, and Asp554. In this study, we used hybrid quantum mechanics/molecular mechanics (QM/MM) Car-Parrinello molecular dynamics to investigate reaction paths using α-phosphate and Asp554 as the catalytic bases. The string method was used to calculate the free-energy reaction profiles of the tested mechanisms. During the investigations, an additional mechanism was observed. In this mechanism, a proton is transferred to α-phosphate via a water molecule. Our calculations show that the mechanism with α-phosphate acting as the base is favorable. This reaction has a rate-limiting free-energy barrier of 23.5 kcal/mol, whereas reactions utilizing Asp554 and water-assisted α-phosphate have barriers of 41.7 and 40.9 kcal/mol, respectively. Our simulations provide a new insight into the catalysis of OGT and may thus guide rational drug design of transition-state analogue inhibitors with potential therapeutic use.

  18. Dual functionality of O-GlcNAc transferase is required for Drosophila development

    PubMed Central

    Mariappa, Daniel; Zheng, Xiaowei; Schimpl, Marianne; Raimi, Olawale; Ferenbach, Andrew T.; Müller, H.-Arno J.; van Aalten, Daan M. F.

    2015-01-01

    Post-translational modification of intracellular proteins with O-linked N-acetylglucosamine (O-GlcNAc) catalysed by O-GlcNAc transferase (OGT) has been linked to regulation of diverse cellular functions. OGT possesses a C-terminal glycosyltransferase catalytic domain and N-terminal tetratricopeptide repeats that are implicated in protein–protein interactions. Drosophila OGT (DmOGT) is encoded by super sex combs (sxc), mutants of which are pupal lethal. However, it is not clear if this phenotype is caused by reduction of O-GlcNAcylation. Here we use a genetic approach to demonstrate that post-pupal Drosophila development can proceed with negligible OGT catalysis, while early embryonic development is OGT activity-dependent. Structural and enzymatic comparison between human OGT (hOGT) and DmOGT informed the rational design of DmOGT point mutants with a range of reduced catalytic activities. Strikingly, a severely hypomorphic OGT mutant complements sxc pupal lethality. However, the hypomorphic OGT mutant-rescued progeny do not produce F2 adults, because a set of Hox genes is de-repressed in F2 embryos, resulting in homeotic phenotypes. Thus, OGT catalytic activity is required up to late pupal stages, while further development proceeds with severely reduced OGT activity. PMID:26674417

  19. The ubiquitin ligase SEVEN IN ABSENTIA (SINA) ubiquitinates a defense-related NAC transcription factor and is involved in defense signaling.

    PubMed

    Miao, Min; Niu, Xiangli; Kud, Joanna; Du, Xinran; Avila, Julian; Devarenne, Timothy P; Kuhl, Joseph C; Liu, Yongsheng; Xiao, Fangming

    2016-07-01

    We recently identified a defense-related tomato (Solanum lycopersicum) NAC (NAM, ATAF1,2, CUC2) transcription factor, NAC1, that is subjected to ubiquitin-proteasome system-dependent degradation in plant cells. In this study, we identified a tomato ubiquitin ligase (termed SEVEN IN ABSENTIA3; SINA3) that ubiquitinates NAC1, promoting its degradation. We conducted coimmunoprecipitation and bimolecular fluorescence complementation to determine that SINA3 specifically interacts with the NAC1 transcription factor in the nucleus. Moreover, we found that SINA3 ubiquitinates NAC1 in vitro and promotes NAC1 degradation via polyubiquitination in vivo, indicating that SINA3 is a ubiquitin ligase that ubiquitinates NAC1, promoting its degradation. Our real-time PCR analysis indicated that, in contrast to our previous finding that NAC1 mRNA abundance increases upon Pseudomonas infection, the SINA3 mRNA abundance decreases in response to Pseudomonas infection. Moreover, using Agrobacterium-mediated transient expression, we found that overexpression of SINA3 interferes with the hypersensitive response cell death triggered by multiple plant resistance proteins. These results suggest that SINA3 ubiquitinates a defense-related NAC transcription factor for degradation and plays a negative role in defense signaling.

  20. Phosphorylation of a NAC Transcription Factor by a Calcium/Calmodulin-Dependent Protein Kinase Regulates Abscisic Acid-Induced Antioxidant Defense in Maize.

    PubMed

    Zhu, Yuan; Yan, Jingwei; Liu, Weijuan; Liu, Lei; Sheng, Yu; Sun, Yue; Li, Yanyun; Scheller, Henrik Vibe; Jiang, Mingyi; Hou, Xilin; Ni, Lan; Zhang, Aying

    2016-07-01

    Calcium/calmodulin-dependent protein kinase (CCaMK) has been shown to play an important role in abscisic acid (ABA)-induced antioxidant defense and enhance the tolerance of plants to drought stress. However, its downstream molecular events are poorly understood. Here, we identify a NAC transcription factor, ZmNAC84, in maize (Zea mays), which physically interacts with ZmCCaMK in vitro and in vivo. ZmNAC84 displays a partially overlapping expression pattern with ZmCCaMK after ABA treatment, and H2O2 is required for ABA-induced ZmNAC84 expression. Functional analysis reveals that ZmNAC84 is essential for ABA-induced antioxidant defense in a ZmCCaMK-dependent manner. Furthermore, ZmCCaMK directly phosphorylates Ser-113 of ZmNAC84 in vitro, and Ser-113 is essential for the ABA-induced stimulation of antioxidant defense by ZmCCaMK. Moreover, overexpression of ZmNAC84 in tobacco (Nicotiana tabacum) can improve drought tolerance and alleviate drought-induced oxidative damage of transgenic plants. These results define a mechanism for ZmCCaMK function in ABA-induced antioxidant defense, where ABA-produced H2O2 first induces expression of ZmCCaMK and ZmNAC84 and activates ZmCCaMK. Subsequently, the activated ZmCCaMK phosphorylates ZmNAC84 at Ser-113, thereby inducing antioxidant defense by activating downstream genes.

  1. Versatile O-GlcNAc transferase assay for high-throughput identification of enzyme variants, substrates, and inhibitors.

    PubMed

    Kim, Eun J; Abramowitz, Lara K; Bond, Michelle R; Love, Dona C; Kang, Dong W; Leucke, Hans F; Kang, Dae W; Ahn, Jong-Seog; Hanover, John A

    2014-06-18

    The dynamic glycosylation of serine/threonine residues on nucleocytoplasmic proteins with a single N-acetylglucosamine (O-GlcNAcylation) is critical for many important cellular processes. Cellular O-GlcNAc levels are highly regulated by two enzymes: O-GlcNAc transferase (OGT) is responsible for GlcNAc addition and O-GlcNAcase (OGA) is responsible for removal of the sugar. The lack of a rapid and simple method for monitoring OGT activity has impeded the efficient discovery of potent OGT inhibitors. In this study we describe a novel, single-well OGT enzyme assay that utilizes 6 × His-tagged substrates, a chemoselective chemical reaction, and unpurified OGT. The high-throughput Ni-NTA Plate OGT Assay will facilitate discovery of potent OGT-specific inhibitors on versatile substrates and the characterization of new enzyme variants.

  2. Coding for effective denial management.

    PubMed

    Miller, Jackie; Lineberry, Joe

    2004-01-01

    Nearly everyone will agree that accurate and consistent coding of diagnoses and procedures is the cornerstone for operating a compliant practice. The CPT or HCPCS procedure code tells the payor what service was performed and also (in most cases) determines the amount of payment. The ICD-9-CM diagnosis code, on the other hand, tells the payor why the service was performed. If the diagnosis code does not meet the payor's criteria for medical necessity, all payment for the service will be denied. Implementation of an effective denial management program can help "stop the bleeding." Denial management is a comprehensive process that works in two ways. First, it evaluates the cause of denials and takes steps to prevent them. Second, denial management creates specific procedures for refiling or appealing claims that are initially denied. Accurate, consistent and compliant coding is key to both of these functions. The process of proactively managing claim denials also reveals a practice's administrative strengths and weaknesses, enabling radiology business managers to streamline processes, eliminate duplicated efforts and shift a larger proportion of the staff's focus from paperwork to servicing patients--all of which are sure to enhance operations and improve practice management and office morale. Accurate coding requires a program of ongoing training and education in both CPT and ICD-9-CM coding. Radiology business managers must make education a top priority for their coding staff. Front office staff, technologists and radiologists should also be familiar with the types of information needed for accurate coding. A good staff training program will also cover the proper use of Advance Beneficiary Notices (ABNs). Registration and coding staff should understand how to determine whether the patient's clinical history meets criteria for Medicare coverage, and how to administer an ABN if the exam is likely to be denied. Staff should also understand the restrictions on use of

  3. pp-GalNAc-T13 induces high metastatic potential of murine Lewis lung cancer by generating trimeric Tn antigen

    SciTech Connect

    Matsumoto, Yasuyuki; Zhang, Qing; Akita, Kaoru; Nakada, Hiroshi; Hamamura, Kazunori; Tokuda, Noriyo; Tsuchida, Akiko; Matsubara, Takeshi; Hori, Tomoko; Okajima, Tetsuya; Furukawa, Keiko; Urano, Takeshi; Furukawa, Koichi

    2012-03-02

    Highlights: Black-Right-Pointing-Pointer ppGalNAc-T13 was up-regulated in high metastatic sublines of Lewis lung cancer. Black-Right-Pointing-Pointer ppGalNAc-T13 expression enhanced cell invasion activity in low metastatic sublines. Black-Right-Pointing-Pointer Trimeric Tn antigen was induced in the transfectant cells of ppGalNAc-T13 cDNA. Black-Right-Pointing-Pointer A major protein carrying trimeric Tn structure was identified as Syndecan-1. Black-Right-Pointing-Pointer Silencing of ppGalNAc-T13 resulted in the reduction of invasion and of metastasis.. -- Abstract: In order to analyze the mechanisms for cancer metastasis, high metastatic sublines (H7-A, H7-Lu, H7-O, C4-sc, and C4-ly) were obtained by repeated injection of mouse Lewis lung cancer sublines H7 and C4 into C57BL/6 mice. These sublines exhibited increased proliferation and invasion activity in vitro. Ganglioside profiles exhibited lower expression of GM1 in high metastatic sublines than the parent lines. Then, we established GM1-Si-1 and GM1-Si-2 by stable silencing of GM1 synthase in H7 cells. These GM1-knockdown clones exhibited increased proliferation and invasion. Then, we explored genes that markedly altered in the expression levels by DNA microarray in the combination of C4 vs. C4-ly or H7 vs. H7 (GM1-Si). Consequently, pp-GalNAc-T13 gene was identified as up-regulated genes in the high metastatic sublines. Stable transfection of pp-GalNAc-T13 cDNA into C4 (T13-TF) resulted in increased invasion and motility. Then, immunoblotting and flow cytometry using various antibodies and lectins were performed. Only anti-trimeric Tn antibody (mAb MLS128), showed increased expression levels of trimeric Tn antigen in T13-TF clones. Moreover, immunoprecipitation/immunoblotting was performed by mAb MLS128, leading to the identification of an 80 kDa band carrying trimeric Tn antigen, i.e. Syndecan-1. Stable silencing of endogenous pp-GalNAc-T13 in C4-sc (T13-KD) revealed that primary tumors generated by

  4. RhNAC2 and RhEXPA4 Are Involved in the Regulation of Dehydration Tolerance during the Expansion of Rose Petals1[C][W][OA

    PubMed Central

    Dai, Fanwei; Zhang, Changqing; Jiang, Xinqiang; Kang, Mei; Yin, Xia; Lü, Peitao; Zhang, Xiao; Zheng, Yi; Gao, Junping

    2012-01-01

    Dehydration inhibits petal expansion resulting in abnormal flower opening and results in quality loss during the marketing of cut flowers. We constructed a suppression subtractive hybridization library from rose (Rosa hybrida) flowers containing 3,513 unique expressed sequence tags and analyzed their expression profiles during cycles of dehydration. We found that 54 genes were up-regulated by the first dehydration, restored or even down-regulated by rehydration, and once again up-regulated by the second dehydration. Among them, we identified a putative NAC family transcription factor (RhNAC2). With transactivation activity of its carboxyl-terminal domain in yeast (Saccharomyces cerevisiae) cell and Arabidopsis (Arabidopsis thaliana) protoplast, RhNAC2 belongs to the NAC transcription factor clade related to plant development in Arabidopsis. A putative expansin gene named RhEXPA4 was also dramatically up-regulated by dehydration. Silencing RhNAC2 or RhEXPA4 in rose petals by virus-induced gene silencing significantly decreased the recovery of intact petals and petal discs during rehydration. Overexpression of RhNAC2 or RhEXPA4 in Arabidopsis conferred strong drought tolerance in the transgenic plants. RhEXPA4 expression was repressed in RhNAC2-silenced rose petals, and the amino-terminal binding domain of RhNAC2 bound to the RhEXPA4 promoter. Twenty cell wall-related genes, including seven expansin family members, were up-regulated in Arabidopsis plants overexpressing RhNAC2. These data indicate that RhNAC2 and RhEXPA4 are involved in the regulation of dehydration tolerance during the expansion of rose petals and that RhEXPA4 expression may be regulated by RhNAC2. PMID:23093360

  5. RhNAC2 and RhEXPA4 are involved in the regulation of dehydration tolerance during the expansion of rose petals.

    PubMed

    Dai, Fanwei; Zhang, Changqing; Jiang, Xinqiang; Kang, Mei; Yin, Xia; Lü, Peitao; Zhang, Xiao; Zheng, Yi; Gao, Junping

    2012-12-01

    Dehydration inhibits petal expansion resulting in abnormal flower opening and results in quality loss during the marketing of cut flowers. We constructed a suppression subtractive hybridization library from rose (Rosa hybrida) flowers containing 3,513 unique expressed sequence tags and analyzed their expression profiles during cycles of dehydration. We found that 54 genes were up-regulated by the first dehydration, restored or even down-regulated by rehydration, and once again up-regulated by the second dehydration. Among them, we identified a putative NAC family transcription factor (RhNAC2). With transactivation activity of its carboxyl-terminal domain in yeast (Saccharomyces cerevisiae) cell and Arabidopsis (Arabidopsis thaliana) protoplast, RhNAC2 belongs to the NAC transcription factor clade related to plant development in Arabidopsis. A putative expansin gene named RhEXPA4 was also dramatically up-regulated by dehydration. Silencing RhNAC2 or RhEXPA4 in rose petals by virus-induced gene silencing significantly decreased the recovery of intact petals and petal discs during rehydration. Overexpression of RhNAC2 or RhEXPA4 in Arabidopsis conferred strong drought tolerance in the transgenic plants. RhEXPA4 expression was repressed in RhNAC2-silenced rose petals, and the amino-terminal binding domain of RhNAC2 bound to the RhEXPA4 promoter. Twenty cell wall-related genes, including seven expansin family members, were up-regulated in Arabidopsis plants overexpressing RhNAC2. These data indicate that RhNAC2 and RhEXPA4 are involved in the regulation of dehydration tolerance during the expansion of rose petals and that RhEXPA4 expression may be regulated by RhNAC2.

  6. Overexpression of TaNAC69 leads to enhanced transcript levels of stress up-regulated genes and dehydration tolerance in bread wheat.

    PubMed

    Xue, Gang-Ping; Way, Heather M; Richardson, Terese; Drenth, Janneke; Joyce, Priya A; McIntyre, C Lynne

    2011-07-01

    NAC proteins are plant-specific transcription factors and enriched with members involved in plant response to drought stress. In this study, we analyzed the expression profiles of TaNAC69 in bread wheat using Affymetrix Wheat Genome Array datasets and quantitative RT-PCR. TaNAC69 expression was positively associated with wheat responses to both abiotic and biotic stresses and was closely correlated with a number of stress up-regulated genes. The functional analyses of TaNAC69 in transgenic wheat showed that TaNAC69 driven by a barley drought-inducible HvDhn4s promoter led to marked drought-inducible overexpression of TaNAC69 in the leaves and roots of transgenic lines. The HvDhn4s:TaNAC69 transgenic lines produced more shoot biomass under combined mild salt stress and water-limitation conditions, had longer root and more root biomass under polyethylene glycol-induced dehydration. Analysis of transgenic lines with constitutive overexpression of TaNAC69 showed the enhanced expression levels of several stress up-regulated genes. DNA-binding assays revealed that TaNAC69 and its rice homolog (ONAC131) were capable of binding to the promoter elements of three rice genes (chitinase, ZIM, and glyoxalase I) and an Arabidopsis glyoxalase I family gene, which are homologs of TaNAC69 up-regulated stress genes. These data suggest that TaNAC69 is involved in regulating stress up-regulated genes and wheat adaptation to drought stress.

  7. Engineering Administration.

    ERIC Educational Resources Information Center

    Naval Personnel Program Support Activity, Washington, DC.

    This book is intended to acquaint naval engineering officers with their duties in the engineering department. Standard shipboard organizations are analyzed in connection with personnel assignments, division operations, and watch systems. Detailed descriptions are included for the administration of directives, ship's bills, damage control, training…

  8. Administrative IT

    ERIC Educational Resources Information Center

    Grayson, Katherine, Ed.

    2006-01-01

    When it comes to Administrative IT solutions and processes, best practices range across the spectrum. Enterprise resource planning (ERP), student information systems (SIS), and tech support are prominent and continuing areas of focus. But widespread change can also be accomplished via the implementation of campuswide document imaging and sharing,…

  9. Database Administrator

    ERIC Educational Resources Information Center

    Moore, Pam

    2010-01-01

    The Internet and electronic commerce (e-commerce) generate lots of data. Data must be stored, organized, and managed. Database administrators, or DBAs, work with database software to find ways to do this. They identify user needs, set up computer databases, and test systems. They ensure that systems perform as they should and add people to the…

  10. Isomer and glycomer complexities of core GlcNAcs in Caenorhabditis elegans.

    PubMed

    Hanneman, Andrew J; Rosa, José César; Ashline, David; Reinhold, Vernon N

    2006-09-01

    Analysis of protein glycosylation within the nematode Caenorhabditis elegans has revealed an abundant and unreported set of core chitobiose modifications (CCMs) to N-linked glycans. With hydrazine release, an array of glycomers and isobars were detected with hexose extensions on the 3- and 3,6-positions of the penultimate and reducing terminus, respectively. A full complement of structures includes a range of glycomers possessing a Galbeta(1-4)Fuc disaccharide at the 3- and 6-positions of the protein-linked GlcNAc. Importantly, enzymatic (PNGase F/A) release failed to liberate many of these extended structures from reduced and alkylated peptides and, as a consequence, such profiles were markedly deficient in a representation of the worm glycome. Moreover, the 3-linked Galbeta(1-4)Fuc moiety was notably resistant to a range of commercial galactosidases. For identification, the fragments were spectrum-matched with synthetic products and library standards using sequential mass spectrometry (MS(n)). A disaccharide observed at the 3-position of penultimate GlcNAc, indicating a Hex-Fuc branch on some structures, was not further characterized because of low ion abundance in MS(n). Additionally, a Hex-Hex-Fuc trisaccharide on the 6-position of proximal GlcNAc was also distinguished on select glycomers. Similar branch extensions on 6-linked core fucosyl residues have recently been reported among other invertebrates. Natural methylation and numerous isobars complement the glycome, which totals well over 100 individual structures. Complex glycans were detected at lower abundance, indicating glucosaminyltransferase-I (GnT-I) and GnT-II activity. A range of phosphorylcholine (PC)-substituted complex glycans were also confirmed following a signature two-stage loss of PC during MS(n) analysis, although the precursor ion was not observed in the mass profiles. In a similar manner, numerous other minor glycans may be present but unobserved in hydrazine-release profiles dominated by

  11. Photometric characterization of the Chang'e-3 landing site using LROC NAC images

    NASA Astrophysics Data System (ADS)

    Clegg-Watkins, R. N.; Jolliff, B. L.; Boyd, A.; Robinson, M. S.; Wagner, R.; Stopar, J. D.; Plescia, J. B.; Speyerer, E. J.

    2016-07-01

    China's robotic Chang'e-3 spacecraft, carrying the Yutu rover, touched down in Mare Imbrium on the lunar surface on 14 December 2013. The Lunar Reconnaissance Orbiter (LRO) Narrow Angle Camera (NAC) imaged the site both before and after landing. Multi-temporal NAC images taken before and after the landing, phase-ratio images made from NAC images taken after the landing, and Hapke photometric techniques were used to evaluate surface changes caused by the disturbance of regolith at the landing site (blast zone) by the descent engines of the Chang'e-3 spacecraft. The reflectance of the landing site increased by 10 ± 1% (from I/F = 0.040 to 0.044 at 30° phase angle) as a result of the landing, a value similar to reflectance increases estimated for the Apollo, Luna, and Surveyor landing sites. The spatial extent of the disturbed area at the Chang'e-3 landing site, 2530 m2, also falls close to what is predicted on the basis of correlations between lander mass, thrust, and blast zone areas for the historic landed missions. A multi-temporal ratio image of the Chang'e-3 landing site reveals a main blast zone (slightly elongate in the N-S direction; ∼75 m across N-S and ∼43 m across in the E-W direction) and an extended diffuse, irregular halo that is less reflective than the main blast zone (extending ∼40-50 m in the N-S direction and ∼10-15 m in the E-W direction beyond the main blast zone). The N-S elongation of the blast zone likely resulted from maneuvering during hazard avoidance just prior to landing. The phase-ratio image reveals that the blast zone is less backscattering than surrounding undisturbed areas. The similarities in magnitude of increased reflectance between the Chang'e-3 landing site and the Surveyor, Apollo, and Luna landing sites suggest that lunar soil reflectance changes caused by interaction with rocket exhaust are not significantly altered over a period of 40-50 years. The reflectance changes are independent of regolith composition

  12. Towards a testbed for malicious code detection

    SciTech Connect

    Lo, R.; Kerchen, P.; Crawford, R.; Ho, W.; Crossley, J.; Fink, G.; Levitt, K.; Olsson, R.; Archer, M. . Div. of Computer Science)

    1991-01-01

    This paper proposes an environment for detecting many types of malicious code, including computer viruses, Trojan horses, and time/logic bombs. This malicious code testbed (MCT) is based upon both static and dynamic analysis tools developed at the University of California, Davis, which have been shown to be effective against certain types of malicious code. The testbed extends the usefulness of these tools by using them in a complementary fashion to detect more general cases of malicious code. Perhaps more importantly, the MCT allows administrators and security analysts to check a program before installation, thereby avoiding any damage a malicious program might inflict. 5 refs., 2 figs., 2 tabs.

  13. 77 FR 125 - Draft Guidance for Industry and Food and Drug Administration Staff; Medical Device Classification...

    Federal Register 2010, 2011, 2012, 2013, 2014

    2012-01-03

    ... Staff; Medical Device Classification Product Codes; Availability AGENCY: Food and Drug Administration... of the draft guidance entitled ``Medical Device Classification Product Codes.'' The purpose of the... classification product codes for medical devices regulated by the Center for Devices and Radiological...

  14. Diagnostic Coding for Epilepsy.

    PubMed

    Williams, Korwyn; Nuwer, Marc R; Buchhalter, Jeffrey R

    2016-02-01

    Accurate coding is an important function of neurologic practice. This contribution to Continuum is part of an ongoing series that presents helpful coding information along with examples related to the issue topic. Tips for diagnosis coding, Evaluation and Management coding, procedure coding, or a combination are presented, depending on which is most applicable to the subject area of the issue.

  15. Model Children's Code.

    ERIC Educational Resources Information Center

    New Mexico Univ., Albuquerque. American Indian Law Center.

    The Model Children's Code was developed to provide a legally correct model code that American Indian tribes can use to enact children's codes that fulfill their legal, cultural and economic needs. Code sections cover the court system, jurisdiction, juvenile offender procedures, minor-in-need-of-care, and termination. Almost every Code section is…

  16. Phylogeny of genetic codes and punctuation codes within genetic codes.

    PubMed

    Seligmann, Hervé

    2015-03-01

    Punctuation codons (starts, stops) delimit genes, reflect translation apparatus properties. Most codon reassignments involve punctuation. Here two complementary approaches classify natural genetic codes: (A) properties of amino acids assigned to codons (classical phylogeny), coding stops as X (A1, antitermination/suppressor tRNAs insert unknown residues), or as gaps (A2, no translation, classical stop); and (B) considering only punctuation status (start, stop and other codons coded as -1, 0 and 1 (B1); 0, -1 and 1 (B2, reflects ribosomal translational dynamics); and 1, -1, and 0 (B3, starts/stops as opposites)). All methods separate most mitochondrial codes from most nuclear codes; Gracilibacteria consistently cluster with metazoan mitochondria; mitochondria co-hosted with chloroplasts cluster with nuclear codes. Method A1 clusters the euplotid nuclear code with metazoan mitochondria; A2 separates euplotids from mitochondria. Firmicute bacteria Mycoplasma/Spiroplasma and Protozoan (and lower metazoan) mitochondria share codon-amino acid assignments. A1 clusters them with mitochondria, they cluster with the standard genetic code under A2: constraints on amino acid ambiguity versus punctuation-signaling produced the mitochondrial versus bacterial versions of this genetic code. Punctuation analysis B2 converges best with classical phylogenetic analyses, stressing the need for a unified theory of genetic code punctuation accounting for ribosomal constraints.

  17. Managing a new medication administration process.

    PubMed

    Englebright, Jane D; Franklin, Michelle

    2005-09-01

    The national focus on medication errors has stimulated rapid adoption of medication administration technologies with bar code verification. The effectiveness of these technologies in preventing errors is directly related to how consistently practitioners use the technology to verify both patient identity and drug identity with each administration. The authors discuss management strategies that have proven effective at increasing staff compliance with using bar code-enabled medication systems.

  18. O-GlcNAc transferase invokes nucleotide sugar pyrophosphate participation in catalysis.

    PubMed

    Schimpl, Marianne; Zheng, Xiaowei; Borodkin, Vladimir S; Blair, David E; Ferenbach, Andrew T; Schüttelkopf, Alexander W; Navratilova, Iva; Aristotelous, Tonia; Albarbarawi, Osama; Robinson, David A; Macnaughtan, Megan A; van Aalten, Daan M F

    2012-12-01

    Protein O-GlcNAcylation is an essential post-translational modification on hundreds of intracellular proteins in metazoa, catalyzed by O-linked β-N-acetylglucosamine (O-GlcNAc) transferase (OGT) using unknown mechanisms of transfer and substrate recognition. Through crystallographic snapshots and mechanism-inspired chemical probes, we define how human OGT recognizes the sugar donor and acceptor peptide and uses a new catalytic mechanism of glycosyl transfer, involving the sugar donor α-phosphate as the catalytic base as well as an essential lysine. This mechanism seems to be a unique evolutionary solution to the spatial constraints imposed by a bulky protein acceptor substrate and explains the unexpected specificity of a recently reported metabolic OGT inhibitor.

  19. Geopositioning Precision Analysis of Multiple Image Triangulation Using Lro Nac Lunar Images

    NASA Astrophysics Data System (ADS)

    Di, K.; Xu, B.; Liu, B.; Jia, M.; Liu, Z.

    2016-06-01

    This paper presents an empirical analysis of the geopositioning precision of multiple image triangulation using Lunar Reconnaissance Orbiter Camera (LROC) Narrow Angle Camera (NAC) images at the Chang'e-3(CE-3) landing site. Nine LROC NAC images are selected for comparative analysis of geopositioning precision. Rigorous sensor models of the images are established based on collinearity equations with interior and exterior orientation elements retrieved from the corresponding SPICE kernels. Rational polynomial coefficients (RPCs) of each image are derived by least squares fitting using vast number of virtual control points generated according to rigorous sensor models. Experiments of different combinations of images are performed for comparisons. The results demonstrate that the plane coordinates can achieve a precision of 0.54 m to 2.54 m, with a height precision of 0.71 m to 8.16 m when only two images are used for three-dimensional triangulation. There is a general trend that the geopositioning precision, especially the height precision, is improved with the convergent angle of the two images increasing from several degrees to about 50°. However, the image matching precision should also be taken into consideration when choosing image pairs for triangulation. The precisions of using all the 9 images are 0.60 m, 0.50 m, 1.23 m in along-track, cross-track, and height directions, which are better than most combinations of two or more images. However, triangulation with selected fewer images could produce better precision than that using all the images.

  20. 24 CFR 200.925c - Model codes.

    Code of Federal Regulations, 2014 CFR

    2014-04-01

    ..., Administration, for the Building, Plumbing and Mechanical Codes and the references to fire retardant treated wood... each standard code and the phrase “or fire retardant treated wood” in reference note (a) of table 600... Part I—Administrative, and the reference to fire retardant treated plywood in section 2504(c)3 and...

  1. 24 CFR 200.925c - Model codes.

    Code of Federal Regulations, 2011 CFR

    2011-04-01

    ..., Administration, for the Building, Plumbing and Mechanical Codes and the references to fire retardant treated wood... each standard code and the phrase “or fire retardant treated wood” in reference note (a) of table 600... Part I—Administrative, and the reference to fire retardant treated plywood in section 2504(c)3 and...

  2. 24 CFR 200.925c - Model codes.

    Code of Federal Regulations, 2013 CFR

    2013-04-01

    ..., Administration, for the Building, Plumbing and Mechanical Codes and the references to fire retardant treated wood... each standard code and the phrase “or fire retardant treated wood” in reference note (a) of table 600... Part I—Administrative, and the reference to fire retardant treated plywood in section 2504(c)3 and...

  3. 20 CFR 435.42 - Codes of conduct.

    Code of Federal Regulations, 2010 CFR

    2010-04-01

    ... 20 Employees' Benefits 2 2010-04-01 2010-04-01 false Codes of conduct. 435.42 Section 435.42 Employees' Benefits SOCIAL SECURITY ADMINISTRATION UNIFORM ADMINISTRATIVE REQUIREMENTS FOR GRANTS AND... ORGANIZATIONS Post-Award Requirements Procurement Standards § 435.42 Codes of conduct. The recipient...

  4. 45 CFR 74.42 - Codes of conduct.

    Code of Federal Regulations, 2010 CFR

    2010-10-01

    ... 45 Public Welfare 1 2010-10-01 2010-10-01 false Codes of conduct. 74.42 Section 74.42 Public Welfare DEPARTMENT OF HEALTH AND HUMAN SERVICES GENERAL ADMINISTRATION UNIFORM ADMINISTRATIVE REQUIREMENTS..., AND COMMERCIAL ORGANIZATIONS Post-Award Requirements Procurement Standards § 74.42 Codes of...

  5. 47 CFR 52.19 - Area code relief.

    Code of Federal Regulations, 2010 CFR

    2010-10-01

    ... 47 Telecommunication 3 2010-10-01 2010-10-01 false Area code relief. 52.19 Section 52.19... Administration § 52.19 Area code relief. (a) State commissions may resolve matters involving the introduction of new area codes within their states. Such matters may include, but are not limited to:...

  6. 7 CFR 28.525 - Symbols and code numbers.

    Code of Federal Regulations, 2010 CFR

    2010-01-01

    ... 7 Agriculture 2 2010-01-01 2010-01-01 false Symbols and code numbers. 28.525 Section 28.525... REGULATIONS COTTON CLASSING, TESTING, AND STANDARDS Standards Symbols and Code Numbers Used in Recording Cotton Classification § 28.525 Symbols and code numbers. For administrative convenience, the symbols...

  7. 30 CFR 56.19094 - Posting signal code.

    Code of Federal Regulations, 2010 CFR

    2010-07-01

    ... 30 Mineral Resources 1 2010-07-01 2010-07-01 false Posting signal code. 56.19094 Section 56.19094 Mineral Resources MINE SAFETY AND HEALTH ADMINISTRATION, DEPARTMENT OF LABOR METAL AND NONMETAL MINE... Signaling § 56.19094 Posting signal code. A legible signal code shall be posted prominently in the...

  8. 30 CFR 57.19094 - Posting signal code.

    Code of Federal Regulations, 2010 CFR

    2010-07-01

    ... 30 Mineral Resources 1 2010-07-01 2010-07-01 false Posting signal code. 57.19094 Section 57.19094 Mineral Resources MINE SAFETY AND HEALTH ADMINISTRATION, DEPARTMENT OF LABOR METAL AND NONMETAL MINE... Signaling § 57.19094 Posting signal code. A legible signal code shall be posted prominently in the...

  9. 48 CFR 204.7202-1 - CAGE codes.

    Code of Federal Regulations, 2010 CFR

    2010-10-01

    ... 48 Federal Acquisition Regulations System 3 2010-10-01 2010-10-01 false CAGE codes. 204.7202-1..., DEPARTMENT OF DEFENSE GENERAL ADMINISTRATIVE MATTERS Contractor Identification 204.7202-1 CAGE codes. (a) DLIS assigns or records and maintains CAGE codes to identify commercial and Government entities....

  10. 30 CFR 56.19093 - Standard signal code.

    Code of Federal Regulations, 2010 CFR

    2010-07-01

    ... 30 Mineral Resources 1 2010-07-01 2010-07-01 false Standard signal code. 56.19093 Section 56.19093 Mineral Resources MINE SAFETY AND HEALTH ADMINISTRATION, DEPARTMENT OF LABOR METAL AND NONMETAL MINE... Signaling § 56.19093 Standard signal code. A standard code of hoisting signals shall be adopted and used...

  11. 50 CFR Table 5 to Part 680 - Crab Size Codes

    Code of Federal Regulations, 2010 CFR

    2010-10-01

    ... 50 Wildlife and Fisheries 9 2010-10-01 2010-10-01 false Crab Size Codes 5 Table 5 to Part 680 Wildlife and Fisheries FISHERY CONSERVATION AND MANAGEMENT, NATIONAL OCEANIC AND ATMOSPHERIC ADMINISTRATION..., Table 5 Table 5 to Part 680—Crab Size Codes Size code Description 1 Standard or large sized crab or...

  12. 30 CFR 57.19093 - Standard signal code.

    Code of Federal Regulations, 2010 CFR

    2010-07-01

    ... 30 Mineral Resources 1 2010-07-01 2010-07-01 false Standard signal code. 57.19093 Section 57.19093 Mineral Resources MINE SAFETY AND HEALTH ADMINISTRATION, DEPARTMENT OF LABOR METAL AND NONMETAL MINE... Signaling § 57.19093 Standard signal code. A standard code of hoisting signals shall be adopted and used...

  13. 50 CFR Table 2 to Part 680 - Crab Species Code

    Code of Federal Regulations, 2010 CFR

    2010-10-01

    ... 50 Wildlife and Fisheries 9 2010-10-01 2010-10-01 false Crab Species Code 2 Table 2 to Part 680 Wildlife and Fisheries FISHERY CONSERVATION AND MANAGEMENT, NATIONAL OCEANIC AND ATMOSPHERIC ADMINISTRATION..., Table 2 Table 2 to Part 680—Crab Species Code Species code Common name Scientific name 900...

  14. 50 CFR Table 4 to Part 680 - Crab Process Codes

    Code of Federal Regulations, 2010 CFR

    2010-10-01

    ... 50 Wildlife and Fisheries 9 2010-10-01 2010-10-01 false Crab Process Codes 4 Table 4 to Part 680 Wildlife and Fisheries FISHERY CONSERVATION AND MANAGEMENT, NATIONAL OCEANIC AND ATMOSPHERIC ADMINISTRATION..., Table 4 Table 4 to Part 680—Crab Process Codes Process code Description 0 Other (specify). 1 Fresh....

  15. 50 CFR Table 6 to Part 680 - Crab Grade Codes

    Code of Federal Regulations, 2010 CFR

    2010-10-01

    ... 50 Wildlife and Fisheries 9 2010-10-01 2010-10-01 false Crab Grade Codes 6 Table 6 to Part 680 Wildlife and Fisheries FISHERY CONSERVATION AND MANAGEMENT, NATIONAL OCEANIC AND ATMOSPHERIC ADMINISTRATION..., Table 6 Table 6 to Part 680—Crab Grade Codes Grade/code Description 1 Standard or premium quality...

  16. 28 CFR 36.607 - Guidance concerning model codes.

    Code of Federal Regulations, 2013 CFR

    2013-07-01

    ... 28 Judicial Administration 1 2013-07-01 2013-07-01 false Guidance concerning model codes. 36.607... BY PUBLIC ACCOMMODATIONS AND IN COMMERCIAL FACILITIES Certification of State Laws or Local Building Codes § 36.607 Guidance concerning model codes. Upon application by an authorized representative of...

  17. Genome-wide analysis, expression dynamics and varietal comparison of NAC gene family at various developmental stages in Morus notabilis.

    PubMed

    Baranwal, Vinay Kumar; Khurana, Paramjit

    2016-06-01

    NAC genes are important transcription factors and forms a large family in plants. They have shown to play an important role in growth and development and have also been shown to involve in regulation of stress-responsive genes. In the present study, a repertoire of NAC genes in recently published mulberry genome has been identified which consists of a total of 79 members. Structural analysis revealed that most of the NAC genes in mulberry contain two introns. The proteins encoded by them show a wide range of isoelectric points suggestive of their varied roles in varying microcellular environment. Phylogenetic and conserved motif analysis elucidate the presence of 15 sub-groups of these genes along with two novel sub-groups having distinct conserved motifs which are not present in Arabidopsis. Gene ontology term enrichment analysis and cis-element identification from their putative 1 K upstream regulatory region indicates their possible role in important biological processes like organ formation, meristem establishment, senescence, and various biotic and abiotic stresses. Expression analysis across various developmental stages led to identification of their preferential expression in diverse tissues. Taken together, this work provides a solid background information related to structure, function, expression and evolution of NAC gene family in mulberry.

  18. Cell cycle-dependent O-GlcNAc modification of tobacco histones and their interaction with the tobacco lectin.

    PubMed

    Delporte, Annelies; De Zaeytijd, Jeroen; De Storme, Nico; Azmi, Abdelkrim; Geelen, Danny; Smagghe, Guy; Guisez, Yves; Van Damme, Els J M

    2014-10-01

    The Nicotiana tabacum agglutinin or Nictaba is a nucleocytoplasmic lectin that is expressed in tobacco after the plants have been exposed to jasmonate treatment or insect herbivory. Nictaba specifically recognizes GlcNAc residues. Recently, it was shown that Nictaba is interacting in vitro with the core histone proteins from calf thymus. Assuming that plant histones - similar to their animal counterparts - undergo O-GlcNAcylation, this interaction presumably occurs through binding of the lectin to the O-GlcNAc modification present on the histones. Hereupon, the question was raised whether this modification also occurs in plants and if it is cell cycle dependent. To this end, histones were purified from tobacco BY-2 suspension cells and the presence of O-GlcNAc modifications was checked. Concomitantly, O-GlcNAcylation of histone proteins was studied. Our data show that similar to animal histones plant histones are modified by O-GlcNAc in a cell cycle-dependent fashion. In addition, the interaction between Nictaba and tobacco histones was confirmed using lectin chromatography and far Western blot analysis. Collectively these findings suggest that Nictaba can act as a modulator of gene transcription through its interaction with core histones.

  19. Mechanism and inhibition of human UDP-GlcNAc 2-epimerase, the key enzyme in sialic acid biosynthesis

    PubMed Central

    Chen, Sheng-Chia; Huang, Chi-Hung; Lai, Shu-Jung; Yang, Chia Shin; Hsiao, Tzu-Hung; Lin, Ching-Heng; Fu, Pin-Kuei; Ko, Tzu-Ping; Chen, Yeh

    2016-01-01

    The bifunctional enzyme UDP-GlcNAc 2-epimerase/ManNAc kinase (GNE) plays a key role in sialic acid production. It is different from the non-hydrolyzing enzymes for bacterial cell wall biosynthesis, and it is feed-back inhibited by the downstream product CMP-Neu5Ac. Here the complex crystal structure of the N-terminal epimerase part of human GNE shows a tetramer in which UDP binds to the active site and CMP-Neu5Ac binds to the dimer-dimer interface. The enzyme is locked in a tightly closed conformation. By comparing the UDP-binding modes of the non-hydrolyzing and hydrolyzing UDP-GlcNAc epimerases, we propose a possible explanation for the mechanistic difference. While the epimerization reactions of both enzymes are similar, Arg113 and Ser302 of GNE are likely involved in product hydrolysis. On the other hand, the CMP-Neu5Ac binding mode clearly elucidates why mutations in Arg263 and Arg266 can cause sialuria. Moreover, full-length modelling suggests a channel for ManNAc trafficking within the bifunctional enzyme. PMID:26980148

  20. Stimulation of IgY responses in gene gun immunized laying hens by combined administration of vector DNA coding for the target antigen Botulinum toxin A1 and for avian cytokine adjuvants.

    PubMed

    Niederstadt, Lars; Hohn, Oliver; Dorner, Brigitte G; Schade, Rüdiger; Bannert, Norbert

    2012-08-31

    DNA immunization is a convenient and effective way of inducing a specific antibody response. In mammals, co-administration of vectors encoding immunostimulatory cytokines can enhance the humoral response resulting in elevated antibody titers. We therefore set out to investigate the effect using avian interleukin 1β (IL-1β) and avian interleukin 6 (IL-6) as genetic adjuvants when immunizing laying hens. A BoNT A1 holotoxoid DNA immunogen carrying two inactivating mutations was evaluated for its ability to induce a specific and sustained IgY antibody response. Both the holotoxoid and the cytokine sequences were codon-optimized. In vitro, the proteins were efficiently expressed in transfected HEK 293T cells and the cytokines were secreted into the culture supernatants. Whereas eggs from hens immunized via gene gun using a prime boost strategy showed no differences in their total IgY content, the specific αBoNT A1 response was slightly elevated up to 1.4× by the IL-1β adjuvant vector and increased by 3.8× by the IL-6 vector. Finally, although hens receiving the IL-1β adjuvant had laying capacities above the average, hens receiving the IL-6 adjuvant experienced laying problems.

  1. GneZ, a UDP-GlcNAc 2-epimerase, is required for S-layer assembly and vegetative growth of Bacillus anthracis.

    PubMed

    Wang, Ya-Ting; Missiakas, Dominique; Schneewind, Olaf

    2014-08-15

    Bacillus anthracis, the causative agent of anthrax, forms an S-layer atop its peptidoglycan envelope and displays S-layer proteins and Bacillus S-layer-associated (BSL) proteins with specific functions to support cell separation of vegetative bacilli and growth in infected mammalian hosts. S-layer and BSL proteins bind via the S-layer homology (SLH) domain to the pyruvylated secondary cell wall polysaccharide (SCWP) with the repeat structure [→4)-β-ManNAc-(1→4)-β-GlcNAc-(1→6)-α-GlcNAc-(1→]n, where α-GlcNAc and β-GlcNAc are substituted with two and one galactosyl residues, respectively. B. anthracis gneY (BAS5048) and gneZ (BAS5117) encode nearly identical UDP-GlcNAc 2-epimerase enzymes that catalyze the reversible conversion of UDP-GlcNAc and UDP-ManNAc. UDP-GlcNAc 2-epimerase enzymes have been shown to be required for the attachment of the phage lysin PlyG with the bacterial envelope and for bacterial growth. Here, we asked whether gneY and gneZ are required for the synthesis of the pyruvylated SCWP and for S-layer assembly. We show that gneZ, but not gneY, is required for B. anthracis vegetative growth, rod cell shape, S-layer assembly, and synthesis of pyruvylated SCWP. Nevertheless, inducible expression of gneY alleviated all the defects associated with the gneZ mutant. In contrast to vegetative growth, neither germination of B. anthracis spores nor the formation of spores in mother cells required UDP-GlcNAc 2-epimerase activity.

  2. Comparison of S-Adenosyl-L-methionine (SAMe) and N-Acetylcysteine (NAC) Protective Effects on Hepatic Damage when Administered After Acetaminophen Overdose

    PubMed Central

    Terneus, Marcus V.; Brown, J. Michael; Carpenter, A. Betts; Valentovic, Monica A.

    2008-01-01

    In the clinical setting, antidotes are generally administered after the occurrence of a drug overdose. Therefore, the most pertinent evaluation of any new agent should model human exposure. This study tested whether acetaminophen (APAP) hepatotoxicity was reversed when S-adenosyl-L-methionine (SAMe) was administered after APAP exposure, similar to what occurs in clinical situations. Comparisons were made for potency between SAMe and N-acetylcysteine (NAC), the current treatment for APAP toxicity. Male C57BL/6 mice were fasted overnight and divided into groups: control (VEH), SAMe treated (SAMe), APAP treated (APAP), N-acetylcysteine treated (NAC), SAMe or NAC administered 1 h after APAP (SAMe+APAP) and (NAC+APAP), respectively. Mice were injected Intraperitoneal (ip) with water (VEH) or 250 mg/kg APAP (15 ml/kg). One 1h later, mice were injected (ip) with 1.25 mmol/kg SAMe (SAMe+APAP) or NAC (NAC+APAP). Hepatotoxicity was evaluated 4 h after APAP or VEH treatment. APAP induced centrilobular necrosis, increased liver weight and alanine transaminase (ALT) levels, depressed total hepatic glutathione (GSH), increased protein carbonyls and 4-hydroxynonenal (4-HNE) adducted proteins. Treatment with SAMe 1 hr after APAP overdose (SAMe+APAP) was hepatoprotective and was comparable to NAC+APAP. Treatment with SAMe or NAC 1 h after APAP was sufficient to return total hepatic glutathione (GSH) to levels comparable to the VEH group. Western blot showed reversal of APAP mediated effects in the SAMe+APAP and NAC+APAP groups. In summary, SAMe was protective when given 1 h after APAP and was comparable to NAC. PMID:18068290

  3. Tandem Mass Spectrometry identifies many mouse brain O-GlcNAcylated proteins including EGF domain-specific O-GlcNAc transferase targets

    SciTech Connect

    Alfaro, Joshua F.; Gong, Cheng-Xin; Monroe, Matthew E.; Aldrich, Joshua T.; Clauss, Therese RW; Purvine, Samuel O.; Wang, Zihao; Camp, David G.; Shabanowitz, Jeffrey; Stanley, Pamela; Hart, Gerald W.; Hunt, Donald F.; Yang, Feng; Smith, Richard D.

    2012-05-08

    O-Linked N-Acetylglucosamine (O-GlcNAc) is a reversible post-translational modification of Ser and Thr residues on cytosolic and nuclear proteins found in all higher eukaryotes. Aberrant O-GlcNAc modification of brain proteins has been linked to Alzheimer's disease (AD). However, understanding specific functions of O-GlcNAcylation in AD has been impeded by the difficulty in characterization of O-GlcNAc sites on proteins. In this study, we modified a chemical/enzymatic photochemical cleavage approach for enriching O-GlcNAcylated peptides in samples containing {approx}100 {micro}g of tryptic peptides from mouse cerebrocortical brain tissue. A total of 274 O-GlcNAcylated proteins were identified. Of these 168 were not previously known to be modified by O-GlcNAc. Overall, 458 O-GlcNAc sites on Ser and Thr residues in 195 proteins were identified. Many of the modified residues are either known phosphorylation sites or located in close proximity to known phosphorylation sites. These findings support the proposed regulatory crosstalk between O-GlcNAcylation and phosphorylation. This study produced the most comprehensive O-GlcNAc proteome of mammalian brain tissue with both protein identification and O-GlcNAc site assignment. Interestingly, we observed O-{beta}-GlcNAc on EGF-like repeats in the extracellular domains of five membrane proteins, thus representing the first evidence for extracellular O-GlcNAcylation in mammalian systems by the ER-resident O-GlcNAc transferase (EOGT). We also report a GlcNAc-{beta}-1,3-Fuc-{alpha}-1-O-Thr modification on the EGF-like repeat of the Versican core protein, a novel substrate of Fringe {beta}1,3-N-acetylglucosaminyltransferases.

  4. 77 FR 49818 - Agency Information Collection Activities; Proposed Collection; Comment Request; Bar Code Label...

    Federal Register 2010, 2011, 2012, 2013, 2014

    2012-08-17

    ... HUMAN SERVICES Food and Drug Administration Agency Information Collection Activities; Proposed Collection; Comment Request; Bar Code Label Requirement for Human Drug and Biological Products AGENCY: Food and Drug Administration, HHS. ACTION: Notice. SUMMARY: The Food and Drug Administration (FDA)...

  5. O-linked-N-acetylglucosamine modification of mammalian Notch receptors by an atypical O-GlcNAc transferase Eogt1

    SciTech Connect

    Sakaidani, Yuta; Ichiyanagi, Naoki; Saito, Chika; Nomura, Tomoko; Ito, Makiko; Nishio, Yosuke; Nadano, Daita; Matsuda, Tsukasa; Furukawa, Koichi; Okajima, Tetsuya

    2012-03-02

    Highlights: Black-Right-Pointing-Pointer We characterized A130022J15Rik (Eogt1)-a mouse gene homologous to Drosophila Eogt. Black-Right-Pointing-Pointer Eogt1 encodes EGF domain O-GlcNAc transferase. Black-Right-Pointing-Pointer Expression of Eogt1 in Drosophila rescued the cell-adhesion defect in the Eogt mutant. Black-Right-Pointing-Pointer O-GlcNAcylation reaction in the secretory pathway is conserved through evolution. -- Abstract: O-linked-{beta}-N-acetylglucosamine (O-GlcNAc) modification is a unique cytoplasmic and nuclear protein modification that is common in nearly all eukaryotes, including filamentous fungi, plants, and animals. We had recently reported that epidermal growth factor (EGF) repeats of Notch and Dumpy are O-GlcNAcylated by an atypical O-GlcNAc transferase, EOGT, in Drosophila. However, no study has yet shown whether O-GlcNAcylation of extracellular proteins is limited to insects such as Drosophila or whether it occurs in other organisms, including mammals. Here, we report the characterization of A130022J15Rik, a mouse gene homolog of Drosophila Eogt (Eogt 1). Enzymatic analysis revealed that Eogt1 has a substrate specificity similar to that of Drosophila EOGT, wherein the Thr residue located between the fifth and sixth conserved cysteines of the folded EGF-like domains is modified. This observation is supported by the fact that the expression of Eogt1 in Drosophila rescued the cell-adhesion defect caused by Eogt downregulation. In HEK293T cells, Eogt1 expression promoted modification of Notch1 EGF repeats by O-GlcNAc, which was further modified, at least in part, by galactose to generate a novel O-linked-N-acetyllactosamine structure. These results suggest that Eogt1 encodes EGF domain O-GlcNAc transferase and that O-GlcNAcylation reaction in the secretory pathway is a fundamental biochemical process conserved through evolution.

  6. Functional analysis of recombinant human and Yarrowia lipolytica O-GlcNAc transferases expressed in Saccharomyces cerevisiae.

    PubMed

    Oh, Hye Ji; Moon, Hye Yun; Cheon, Seon Ah; Hahn, Yoonsoo; Kang, Hyun Ah

    2016-10-01

    O-linked β-N-acetylglucosamine (O-GlcNAc) glycosylation is an important post-translational modification in many cellular processes. It is mediated by O-GlcNAc transferases (OGTs), which catalyze the addition of O-GlcNAc to serine or threonine residues of the target proteins. In this study, we expressed a putative Yarrowia lipolytica OGT (YlOGT), the only homolog identified in the subphylum Saccharomycotina through bioinformatics analysis, and the human OGT (hOGT) as recombinant proteins in Saccharomyces cerevisiae, and performed their functional characterization. Immunoblotting assays using antibody against O-GlcNAc revealed that recombinant hOGT (rhOGT), but not the recombinant YlOGT (rYlOGT), undergoes auto-O-GlcNAcylation in the heterologous host S. cerevisiae. Moreover, the rhOGT expressed in S. cerevisiae showed a catalytic activity during in vitro assays using casein kinase II substrates, whereas no such activity was obtained in rYlOGT. However, the chimeric human-Y. lipolytica OGT, carrying the human tetratricopeptide repeat (TPR) domain along with the Y. lipolytica catalytic domain (CTD), mediated the transfer of O-GlcNAc moiety during the in vitro assays. Although the overexpression of full-length OGTs inhibited the growth of S. cerevisiae, no such inhibition was obtained upon overexpression of only the CTD fragment, indicating the role of TPR domain in growth inhibition. This is the first report on the functional analysis of the fungal OGT, indicating that the Y. lipolytica OGT retains its catalytic activity, although the physiological role and substrates of YlOGT remain to be elucidated.

  7. Alterations in left ventricular function during intermittent hypoxia: Possible involvement of O-GlcNAc protein and MAPK signaling.

    PubMed

    Guo, Xueling; Shang, Jin; Deng, Yan; Yuan, Xiao; Zhu, Die; Liu, Huiguo

    2015-07-01

    Obstructive sleep apnea, characterized by recurrent episodes of hypoxia [intermittent hypoxia (IH)], has been identified as a risk factor for cardiovascular diseases. The O-linked β-N-acetylglucosamine (O-GlcNAc) modification (O-GlcNAcylation) of proteins has important regulatory implications on the pathophysiology of cardiovascular disorders. In this study, we examined the role of O-GlcNAcylation in cardiac architecture and left ventricular function following IH. Rats were randomly assigned to a normoxia and IH group (2 min 21% O2; 2 min 6-8% O2). Left ventricular function, myocardial morphology and the levels of signaling molecules were then measured. IH induced a significant increase in blood pressure, associated with a gradually abnormal myocardial architecture. The rats exposed to 2 or 3 weeks of IH presented with augmented left ventricular systolic and diastolic function, which declined at week 4. Consistently, the O-GlcNAc protein and O-GlcNAcase (OGA) levels in the left ventricular tissues steadily increased following IH, reaching peak levels at week 3. The O-GlcNAc transferase (OGT), extracellular signal-regulated kinase 1/2 (ERK1/2) and the p38 mitogen-activated protein kinase (p38 MAPK) phosphorylation levels were affected in an opposite manner. The phosphorylation of calcium/calmodulin-dependent protein kinase II (CaMKII) remained unaltered. In parallel, compared with exposure to normoxia, 4 weeks of IH augmented the O-GlcNAc protein, OGT, phosphorylated ERK1/2 and p38 MAPK levels, accompanied by a decrease in OGA levels and an increase in the levels of myocardial nuclear factor-κB (NF-κB), inflammatory cytokines, caspase-3 and cardiomyocyte apoptosis. Taken together, our suggest a possible involvement of O-GlcNAc protein and MAPK signaling in the alterations of left ventricular function and cardiac injury following IH.

  8. Variation between Hospitals with Regard to Diagnostic Practice, Coding Accuracy, and Case-Mix. A Retrospective Validation Study of Administrative Data versus Medical Records for Estimating 30-Day Mortality after Hip Fracture

    PubMed Central

    Kristoffersen, Doris Tove; Skyrud, Katrine Damgaard; Lindman, Anja Schou

    2016-01-01

    Background The purpose of this study was to assess the validity of patient administrative data (PAS) for calculating 30-day mortality after hip fracture as a quality indicator, by a retrospective study of medical records. Methods We used PAS data from all Norwegian hospitals (2005–2009), merged with vital status from the National Registry, to calculate 30-day case-mix adjusted mortality for each hospital (n = 51). We used stratified sampling to establish a representative sample of both hospitals and cases. The hospitals were stratified according to high, low and medium mortality of which 4, 3, and 5 hospitals were sampled, respectively. Within hospitals, cases were sampled stratified according to year of admission, age, length of stay, and vital 30-day status (alive/dead). The final study sample included 1043 cases from 11 hospitals. Clinical information was abstracted from the medical records. Diagnostic and clinical information from the medical records and PAS were used to define definite and probable hip fracture. We used logistic regression analysis in order to estimate systematic between-hospital variation in unmeasured confounding. Finally, to study the consequences of unmeasured confounding for identifying mortality outlier hospitals, a sensitivity analysis was performed. Results The estimated overall positive predictive value was 95.9% for definite and 99.7% for definite or probable hip fracture, with no statistically significant differences between hospitals. The standard deviation of the additional, systematic hospital bias in mortality estimates was 0.044 on the logistic scale. The effect of unmeasured confounding on outlier detection was small to moderate, noticeable only for large hospital volumes. Conclusions This study showed that PAS data are adequate for identifying cases of hip fracture, and the effect of unmeasured case mix variation was small. In conclusion, PAS data are adequate for calculating 30-day mortality after hip-fracture as a quality

  9. Accumulate repeat accumulate codes

    NASA Technical Reports Server (NTRS)

    Abbasfar, Aliazam; Divsalar, Dariush; Yao, Kung

    2004-01-01

    In this paper we propose an innovative channel coding scheme called 'Accumulate Repeat Accumulate codes' (ARA). This class of codes can be viewed as serial turbo-like codes, or as a subclass of Low Density Parity Check (LDPC) codes, thus belief propagation can be used for iterative decoding of ARA codes on a graph. The structure of encoder for this class can be viewed as precoded Repeat Accumulate (RA) code or as precoded Irregular Repeat Accumulate (IRA) code, where simply an accumulator is chosen as a precoder. Thus ARA codes have simple, and very fast encoder structure when they representing LDPC codes. Based on density evolution for LDPC codes through some examples for ARA codes, we show that for maximum variable node degree 5 a minimum bit SNR as low as 0.08 dB from channel capacity for rate 1/2 can be achieved as the block size goes to infinity. Thus based on fixed low maximum variable node degree, its threshold outperforms not only the RA and IRA codes but also the best known LDPC codes with the dame maximum node degree. Furthermore by puncturing the accumulators any desired high rate codes close to code rate 1 can be obtained with thresholds that stay close to the channel capacity thresholds uniformly. Iterative decoding simulation results are provided. The ARA codes also have projected graph or protograph representation that allows for high speed decoder implementation.

  10. Concatenated Coding Using Trellis-Coded Modulation

    NASA Technical Reports Server (NTRS)

    Thompson, Michael W.

    1997-01-01

    In the late seventies and early eighties a technique known as Trellis Coded Modulation (TCM) was developed for providing spectrally efficient error correction coding. Instead of adding redundant information in the form of parity bits, redundancy is added at the modulation stage thereby increasing bandwidth efficiency. A digital communications system can be designed to use bandwidth-efficient multilevel/phase modulation such as Amplitude Shift Keying (ASK), Phase Shift Keying (PSK), Differential Phase Shift Keying (DPSK) or Quadrature Amplitude Modulation (QAM). Performance gain can be achieved by increasing the number of signals over the corresponding uncoded system to compensate for the redundancy introduced by the code. A considerable amount of research and development has been devoted toward developing good TCM codes for severely bandlimited applications. More recently, the use of TCM for satellite and deep space communications applications has received increased attention. This report describes the general approach of using a concatenated coding scheme that features TCM and RS coding. Results have indicated that substantial (6-10 dB) performance gains can be achieved with this approach with comparatively little bandwidth expansion. Since all of the bandwidth expansion is due to the RS code we see that TCM based concatenated coding results in roughly 10-50% bandwidth expansion compared to 70-150% expansion for similar concatenated scheme which use convolution code. We stress that combined coding and modulation optimization is important for achieving performance gains while maintaining spectral efficiency.

  11. Coset Codes Viewed as Terminated Convolutional Codes

    NASA Technical Reports Server (NTRS)

    Fossorier, Marc P. C.; Lin, Shu

    1996-01-01

    In this paper, coset codes are considered as terminated convolutional codes. Based on this approach, three new general results are presented. First, it is shown that the iterative squaring construction can equivalently be defined from a convolutional code whose trellis terminates. This convolutional code determines a simple encoder for the coset code considered, and the state and branch labelings of the associated trellis diagram become straightforward. Also, from the generator matrix of the code in its convolutional code form, much information about the trade-off between the state connectivity and complexity at each section, and the parallel structure of the trellis, is directly available. Based on this generator matrix, it is shown that the parallel branches in the trellis diagram of the convolutional code represent the same coset code C(sub 1), of smaller dimension and shorter length. Utilizing this fact, a two-stage optimum trellis decoding method is devised. The first stage decodes C(sub 1), while the second stage decodes the associated convolutional code, using the branch metrics delivered by stage 1. Finally, a bidirectional decoding of each received block starting at both ends is presented. If about the same number of computations is required, this approach remains very attractive from a practical point of view as it roughly doubles the decoding speed. This fact is particularly interesting whenever the second half of the trellis is the mirror image of the first half, since the same decoder can be implemented for both parts.

  12. 75 FR 61552 - Federal Railroad Administration

    Federal Register 2010, 2011, 2012, 2013, 2014

    2010-10-05

    ... Federal Railroad Administration Notice of Informational Filing In accordance with Section 236.913 of Title 49 of the Code of Federal Regulations (CFR), notice is hereby given that the Federal Railroad Administration (FRA) has received an informational filing from the Northeast Illinois Regional Commuter...

  13. 75 FR 73935 - Miscellaneous Administrative Changes

    Federal Register 2010, 2011, 2012, 2013, 2014

    2010-11-30

    ... Federal Regulations, which is published #0;under 50 titles pursuant to 44 U.S.C. 1510. #0; #0;The Code of... Administrative Changes AGENCY: Nuclear Regulatory Commission. ACTION: Final rule. SUMMARY: The U.S. Nuclear... Services, Office of Administration, U.S. Nuclear Regulatory Commission, Washington, DC...

  14. Effects of pore sizes and oxygen-containing functional groups on desulfurization activity of Fe/NAC prepared by ultrasonic-assisted impregnation

    NASA Astrophysics Data System (ADS)

    Shu, Song; Guo, Jia-Xiu; Liu, Xiao-Li; Wang, Xue-Jiao; Yin, Hua-Qiang; Luo, De-Ming

    2016-01-01

    A series of Fe-loaded activated carbons treated by HNO3 (Fe/NAC) were prepared by incipient impregnation method with or without ultrasonic assistance and characterized using X-ray diffraction (XRD), Fourier-transform infrared spectroscopy (FTIR), scanning electron microscopy with energy disperse spectroscope (SEM-EDS), transmission electron microscopy (TEM) and N2 adsorption/desorption. The desulfurization activities were evaluated at a fixed bed reactor under a mixed gas simulated from flue gas. The results showed that desulfurization activity from excellent to poor is as follows: Fe/NAC-60 > Fe/NAC-80 > Fe/NAC-30 > Fe/NAC-15 > Fe/NAC-0 > Fe/NAC-100 > NAC. Fe/NAC-60 exhibits the best desulfurization activity and has breakthrough sulfur capacity of 319 mg/g and breakthrough time of 540 min. The introduction of ultrasonic oscillation does not change the form of Fe oxides on activated carbon but can change the dispersion and relative contents of Fe3O4. The types of oxygen-containing functional groups have no obvious change for all samples but the texture properties show some differences when they are oscillated for different times. The fresh Fe/NAC-60 has a surface area of 1045 m2/g and total pore volume of 0.961 cm3/g with micropore volume of 0.437 cm3/g and is larger than Fe/NAC-0 (823 m2/g, 0.733 and 0.342 cm3/g). After desulfurization, surface area and pore volume of all samples decrease significantly, and those of the exhausted Fe/NAC-60 decrease to 233 m2/g and 0.481 cm3/g, indicating that some byproducts deposit on surface to cover pores. Pore size distribution influences SO2 adsorption, and fresh Fe/NAC-60 has more pore widths centralized at about 0.7 nm and 1.0⿿2.0 nm and corresponds to an excellent desulfurization activity, showing that micropore is conducive to the removal of SO2.

  15. Trefoil Factor Family Domains Represent Highly Efficient Conformational Determinants for N-Linked N,N′-di-N-acetyllactosediamine (LacdiNAc) Synthesis*

    PubMed Central

    Bonar, David; Hanisch, Franz-Georg

    2014-01-01

    The disaccharide N,N′-di-N-acetyllactose diamine (LacdiNAc, GalNAcβ1–4GlcNAcβ) is found in a limited number of extracellular matrix glycoproteins and neuropeptide hormones indicating a protein-specific transfer of GalNAc by the glycosyltransferases β4GalNAc-T3/T4. Whereas previous studies have revealed evidence for peptide determinants as controlling elements in LacdiNAc biosynthesis, we report here on an entirely independent conformational control of GalNAc transfer by single TFF (Trefoil factor) domains as high stringency determinants. Human TFF2 was recombinantly expressed in HEK-293 cells as a wild type full-length probe (TFF2-Fl, containing TFF domains P1 and P2), as single P1 or P2 domain probes, as a series of Cys/Gly mutant forms with aberrant domain structures, and as a double point-mutated probe (T68Q/F59Q) lacking aromatic residues within a hydrophobic patch. The N-glycosylation probes were analyzed by mass spectrometry for their glycoprofiles. In agreement with natural gastric TFF2, the recombinant full-length and single domain probes expressed nearly exclusively fucosylated LacdiNAc on bi-antennary complex-type chains indicating that a single TFF domain was sufficient to induce transfer of this modification. Contrasting to this, the Cys/Gly mutants showed strongly reduced LacdiNAc levels and instead preponderant LacNAc expression. The probe with point mutations of two highly conserved aromatic residues in loop 3 (T68Q/F59Q) revealed that these are essential determinant components, as the probe lacked LacdiNAc expression. The structural features of the LacdiNAc-inducing determinant on human TFF2 are discussed on the basis of crystal structures of porcine TFF2, and a series of extracellular matrix-related LacdiNAc-positive glycoproteins detected as novel candidate proteins in the secretome of HEK-293 cells. PMID:25210040

  16. Discussion on LDPC Codes and Uplink Coding

    NASA Technical Reports Server (NTRS)

    Andrews, Ken; Divsalar, Dariush; Dolinar, Sam; Moision, Bruce; Hamkins, Jon; Pollara, Fabrizio

    2007-01-01

    This slide presentation reviews the progress that the workgroup on Low-Density Parity-Check (LDPC) for space link coding. The workgroup is tasked with developing and recommending new error correcting codes for near-Earth, Lunar, and deep space applications. Included in the presentation is a summary of the technical progress of the workgroup. Charts that show the LDPC decoder sensitivity to symbol scaling errors are reviewed, as well as a chart showing the performance of several frame synchronizer algorithms compared to that of some good codes and LDPC decoder tests at ESTL. Also reviewed is a study on Coding, Modulation, and Link Protocol (CMLP), and the recommended codes. A design for the Pseudo-Randomizer with LDPC Decoder and CRC is also reviewed. A chart that summarizes the three proposed coding systems is also presented.

  17. Bar Codes for Libraries.

    ERIC Educational Resources Information Center

    Rahn, Erwin

    1984-01-01

    Discusses the evolution of standards for bar codes (series of printed lines and spaces that represent numbers, symbols, and/or letters of alphabet) and describes the two types most frequently adopted by libraries--Code-A-Bar and CODE 39. Format of the codes is illustrated. Six references and definitions of terminology are appended. (EJS)

  18. Manually operated coded switch

    DOEpatents

    Barnette, Jon H.

    1978-01-01

    The disclosure relates to a manually operated recodable coded switch in which a code may be inserted, tried and used to actuate a lever controlling an external device. After attempting a code, the switch's code wheels must be returned to their zero positions before another try is made.

  19. QR Codes 101

    ERIC Educational Resources Information Center

    Crompton, Helen; LaFrance, Jason; van 't Hooft, Mark

    2012-01-01

    A QR (quick-response) code is a two-dimensional scannable code, similar in function to a traditional bar code that one might find on a product at the supermarket. The main difference between the two is that, while a traditional bar code can hold a maximum of only 20 digits, a QR code can hold up to 7,089 characters, so it can contain much more…

  20. ARA type protograph codes

    NASA Technical Reports Server (NTRS)

    Divsalar, Dariush (Inventor); Abbasfar, Aliazam (Inventor); Jones, Christopher R. (Inventor); Dolinar, Samuel J. (Inventor); Thorpe, Jeremy C. (Inventor); Andrews, Kenneth S. (Inventor); Yao, Kung (Inventor)

    2008-01-01

    An apparatus and method for encoding low-density parity check codes. Together with a repeater, an interleaver and an accumulator, the apparatus comprises a precoder, thus forming accumulate-repeat-accumulate (ARA codes). Protographs representing various types of ARA codes, including AR3A, AR4A and ARJA codes, are described. High performance is obtained when compared to the performance of current repeat-accumulate (RA) or irregular-repeat-accumulate (IRA) codes.

  1. O-GlcNAc protein modification in C2C12 myoblasts exposed to oxidative stress indicates parallels with endogenous antioxidant defense.

    PubMed

    Peternelj, Tina Tinkara; Marsh, Susan A; Morais, Christudas; Small, David M; Dalbo, Vincent J; Tucker, Patrick S; Coombes, Jeff S

    2015-02-01

    A growing body of evidence demonstrates the involvement of protein modification with O-linked β-N-acetylglucosamine (O-GlcNAc) in the stress response and its beneficial effects on cell survival. Here we investigated protein O-GlcNAcylation in skeletal muscle cells exposed to oxidative stress and the crosstalk with endogenous antioxidant system. The study focused on antioxidant enzymes superoxide dismutase 2 (SOD2), catalase (CAT), and glutathione peroxidase 1 (GPX1), and transcriptional regulators proliferator-activated receptor gamma coactivator 1-α (PGC-1α) and forkhead box protein O1 (FOXO1), which play important roles in oxidative stress response and are known to be O-GlcNAc-modified. C2C12 myoblasts were subjected to 24 h incubation with different reagents, including hydrogen peroxide, diethyl maleate, high glucose, and glucosamine, and the inhibitors of O-GlcNAc cycling enzymes. Surprisingly, O-GlcNAc levels were significantly increased only with glucosamine, whilst other treatments showed no effect. Significant changes at the mRNA level were observed with concomitant upregulation of the genes for O-GlcNAc enzymes and stress-related proteins with oxidizing agents and downregulation of these genes with agents promoting O-GlcNAcylation. Our findings suggest a role of O-GlcNAc in the stress response and indicate an inhibitory mechanism controlling O-GlcNAc levels in the muscle cells. This could represent an important homeostatic regulation of the cellular defense system.

  2. Chondroitin sulfate N-acetylgalactosaminyltransferase-1 (CSGalNAcT-1) involved in chondroitin sulfate initiation: Impact of sulfation on activity and specificity.

    PubMed

    Gulberti, Sandrine; Jacquinet, Jean-Claude; Chabel, Matthieu; Ramalanjaona, Nick; Magdalou, Jacques; Netter, Patrick; Coughtrie, Michael W H; Ouzzine, Mohamed; Fournel-Gigleux, Sylvie

    2012-04-01

    Glycosaminoglycan (GAG) assembly initiates through the formation of a linkage tetrasaccharide region serving as a primer for both chondroitin sulfate (CS) and heparan sulfate (HS) chain polymerization. A possible role for sulfation of the linkage structure and of the constitutive disaccharide unit of CS chains in the regulation of CS-GAG chain synthesis has been suggested. To investigate this, we determined whether sulfate substitution of galactose (Gal) residues of the linkage region or of N-acetylgalactosamine (GalNAc) of the disaccharide unit influences activity and specificity of chondroitin sulfate N-acetylgalactosaminyltransferase-1 (CSGalNAcT-1), a key glycosyltransferase of CS biosynthesis. We synthesized a series of sulfated and unsulfated analogs of the linkage oligosaccharide and of the constitutive unit of CS and tested these molecules as potential acceptor substrates for the recombinant human CSGalNAcT-1. We show here that sulfation at C4 or C6 of the Gal residues markedly influences CSGalNAcT-1 initiation activity and catalytic efficiency. Kinetic analysis indicates that CSGalNAcT-1 exhibited 3.6-, 1.6-, and 2.2-fold higher enzymatic efficiency due to lower K(m) values toward monosulfated trisaccharides substituted at C4 or C6 position of Gal1, and at C6 of Gal2, respectively, compared with the unsulfated oligosaccharide. This highlights the critical influence of Gal substitution on both CSGalNAcT-1 activity and specifity. No GalNAcT activity was detected toward sulfated and unsulfated analogs of the CS constitutive disaccharide (GlcA-β1,3-GalNAc), indicating that CSGalNAcT-1 was involved in initiation but not in elongation of CS chains. Our results strongly suggest that sulfation of the linkage region acts as a regulatory signal in CS chain initiation.

  3. Phyllodes tumor of the breast: role of Axl and ST6GalNAcII in the development of mammary phyllodes tumors.

    PubMed

    Ren, Dongliang; Li, Yanyan; Gong, Yanxin; Xu, Jingchao; Miao, Xiaolong; Li, Xiangnan; Liu, Chen; Jia, Li; Zhao, Yongfu

    2014-10-01

    Phyllodes tumor exhibits an aggressive growth. The expression of many biological markers has been explored to discriminate between different grades of phyllodes tumor and to predict their behavior. The purpose of this study was to evaluate the implications of Axl and ST6GalNAcII in phyllodes tumors. Real-time PCR, Western blot, and immunohistochemical were used to analyze differential expression of ST6GalNAcII and Axl in phyllodes tumor (PT) cell lines and tissue specimens. RNAi assay, ECM invasion assay, and tumorigenicity assay were used to analyze the altered expression of ST6GalNAcII gene effects on the expression of Axl and invasive ability of phyllodes tumor cells in vitro and in vivo. Compared to benign tumors, borderline and malignant ones showed a remarkable increase in mRNA levels of Axl and ST6GalNAcII gene, and it was higher in malignant tumor cells than in borderline tumor cells. When ST6GalNAcII was silenced, compared to the control, the expression level of Axl was significantly reduced in malignant tumor cell transfectants and knockdown of ST6GalNAcII gene significantly inhibited invasive activity in malignant tumor cells. The high expression of ST6GalNAcII and Axl was significantly correlated with tumor grade and distance metastasis by immunohistochemical analysis. Axl and ST6GalNAcII expression increases with increasing tumor grade in mammary phyllodes tumors. ST6GalNAc II might be participated in the glycosylation of Axl, and this Axl glycosylation may mediate the tumorigenicity, invasion, and distant metastasis of PT cells.

  4. Members of the barley NAC transcription factor gene family show differential co-regulation with senescence-associated genes during senescence of flag leaves.

    PubMed

    Christiansen, Michael W; Gregersen, Per L

    2014-07-01

    The senescence process of plants is important for the completion of their life cycle, particularly for crop plants, it is essential for efficient nutrient remobilization during seed filling. It is a highly regulated process, and in order to address the regulatory aspect, the role of genes in the NAC transcription factor family during senescence of barley flag leaves was studied. Several members of the NAC transcription factor gene family were up-regulated during senescence in a microarray experiment, together with a large range of senescence-associated genes, reflecting the coordinated activation of degradation processes in senescing barley leaf tissues. This picture was confirmed in a detailed quantitative reverse transcription-PCR (qRT-PCR) experiment, which also showed distinct gene expression patterns for different members of the NAC gene family, suggesting a group of ~15 out of the 47 studied NAC genes to be important for signalling processes and for the execution of degradation processes during leaf senescence in barley. Seven models for DNA-binding motifs for NAC transcription factors were designed based on published motifs, and available promoter sequences of barley genes were screened for the motifs. Genes up-regulated during senescence showed a significant over-representation of the motifs, suggesting regulation by the NAC transcription factors. Furthermore, co-regulation studies showed that genes possessing the motifs in the promoter in general were highly co-expressed with members of the NAC gene family. In conclusion, a list of up to 15 NAC genes from barley that are strong candidates for being regulatory factors of importance for senescence and biotic stress-related traits affecting the productivity of cereal crop plants has been generated. Furthermore, a list of 71 senescence-associated genes that are potential target genes for these NAC transcription factors is presented.

  5. Identification of gangliosides recognized by IgG anti-GalNAc-GD1a antibodies in bovine spinal motor neurons and motor nerves.

    PubMed

    Yoshino, Hiide; Ariga, Toshio; Suzuki, Akemi; Yu, Robert K; Miyatake, Tadashi

    2008-08-28

    The presence of immunoglobulin G (IgG)-type antibodies to the ganglioside, N-acetylgalactosaminyl GD1a (GalNAc-GD1a), is closely associated with the pure motor type of Guillain-Barré syndrome (GBS). In the present study, we isolated disialogangliosides from the motor neurons and motor nerves of bovine spinal cords by DEAE-Sephadex column chromatography. The disialoganglioside fraction contained GD1a, GD2, GD1b, and three gangliosides, designated X1, X2 and X3. Serum from a patient with axonal GBS with IgG anti-GalNAc-GD1a antibody yielded positive immunostaining with X1, X2, and X3. When isolated by preparative thin-layer chromatography (TLC), X1 migrated at the same position as GalNAc-GD1a from Tay-Sachs brain, suggesting that X1 is GalNAc-GD1a containing N-acetylneuraminic acid (NeuAc). TLC of isolated X2 revealed that it migrated between GD1a and GD2. On the other hand, X3 had a migratory rate on TLC between and GD1b and GT1b. Since both X2 and X3 were recognized by IgG anti-GalNAc-GD1a antibody, the results suggest that X2 is a GalNAc-GD1a species containing a mixture containing a NeuAc-and an N-glycolylneuraminic acid (NeuGc) species, and X3 is a GalNAc-GD1a species with two NeuGc. This evidence indicating the specific localization of GalNAc-GD1a and its isomers in spinal motor neurons should be useful in elucidating the pathogenic role of IgG anti-GalNAc-GD1a antibody in pure motor-type GBS.

  6. A common sugar-nucleotide-mediated mechanism of inhibition of (glycosamino)glycan biosynthesis, as evidenced by 6F-GalNAc (Ac3)

    PubMed Central

    van Wijk, Xander M.; Lawrence, Roger; Thijssen, Victor L.; van den Broek, Sebastiaan A.; Troost, Ran; van Scherpenzeel, Monique; Naidu, Natasha; Oosterhof, Arie; Griffioen, Arjan W.; Lefeber, Dirk J.; van Delft, Floris L.; van Kuppevelt, Toin H.

    2015-01-01

    Glycosaminoglycan (GAG) polysaccharides have been implicated in a variety of cellular processes, and alterations in their amount and structure have been associated with diseases such as cancer. In this study, we probed 11 sugar analogs for their capacity to interfere with GAG biosynthesis. One analog, with a modification not directly involved in the glycosidic bond formation, 6F-N-acetyl-d-galactosamine (GalNAc) (Ac3), was selected for further study on its metabolic and biologic effect. Treatment of human ovarian carcinoma cells with 50 μM 6F-GalNAc (Ac3) inhibited biosynthesis of GAGs (chondroitin/dermatan sulfate by ∼50–60%, heparan sulfate by ∼35%), N-acetyl-d-glucosamine (GlcNAc)/GalNAc containing glycans recognized by the lectins Datura stramonium and peanut agglutinin (by ∼74 and ∼43%, respectively), and O-GlcNAc protein modification. With respect to function, 6F-GalNAc (Ac3) treatment inhibited growth factor signaling and reduced in vivo angiogenesis by ∼33%. Although the analog was readily transformed in cells into the uridine 5′-diphosphate (UDP)-activated form, it was not incorporated into GAGs. Rather, it strongly reduced cellular UDP-GalNAc and UDP-GlcNAc pools. Together with data from the literature, these findings indicate that nucleotide sugar depletion without incorporation is a common mechanism of sugar analogs for inhibiting GAG/glycan biosynthesis.—Van Wijk, X. M., Lawrence, R., Thijssen, V. L., van den Broek, S. A., Troost, R., van Scherpenzeel, M., Naidu, N., Oosterhof, A., Griffioen, A. W., Lefeber, D. J., van Delft, F. L., van Kuppevelt, T. H. A common sugar-nucleotide-mediated mechanism of inhibition of (glycosamino)glycan biosynthesis, as evidenced by 6F-GalNAc (Ac3). PMID:25868729

  7. Genome-wide identification and expression analysis of the CaNAC family members in chickpea during development, dehydration and ABA treatments.

    PubMed

    Ha, Chien Van; Esfahani, Maryam Nasr; Watanabe, Yasuko; Tran, Uyen Thi; Sulieman, Saad; Mochida, Keiichi; Nguyen, Dong Van; Tran, Lam-Son Phan

    2014-01-01

    The plant-specific NAC transcription factors (TFs) play important roles in regulation of diverse biological processes, including development, growth, cell division and responses to environmental stimuli. In this study, we identified the members of the NAC TF family of chickpea (Cicer arietinum) and assess their expression profiles during plant development and under dehydration and abscisic acid (ABA) treatments in a systematic manner. Seventy-one CaNAC genes were detected from the chickpea genome, including 8 membrane-bound members of which many might be involved in dehydration responses as judged from published literature. Phylogenetic analysis of the chickpea and well-known stress-related Arabidopsis and rice NACs enabled us to predict several putative stress-related CaNACs. By exploring available transcriptome data, we provided a comprehensive expression atlas of CaNACs in various tissues at different developmental stages. With the highest interest in dehydration responses, we examined the expression of the predicted stress-related and membrane-bound CaNACs in roots and leaves of chickpea seedlings, subjected to well-watered (control), dehydration and ABA treatments, using real-time quantitative PCR (RT-qPCR). Nine-teen of the 23 CaNACs examined were found to be dehydration-responsive in chickpea roots and/or leaves in either ABA-dependent or -independent pathway. Our results have provided a solid foundation for selection of promising tissue-specific and/or dehydration-responsive CaNAC candidates for detailed in planta functional analyses, leading to development of transgenic chickpea varieties with improved productivity under drought.

  8. Antioxidants reverse the changes in energy metabolism of rat brain after chronic administration of L.-tyrosine.

    PubMed

    Teodorak, Brena P; Scaini, Giselli; Carvalho-Silva, Milena; Gomes, Lara M; Teixeira, Letícia J; Rebelo, Joyce; De Prá, Samira D T; Zeni, Neila; Schuck, Patrícia F; Ferreira, Gustavo C; Streck, Emilio L

    2017-04-01

    Tyrosinemia type II is a rare autosomal recessive disease caused by deficiency of hepatic tyrosine aminotransferase and is associated with neurologic and development difficulties in numerous patients. Considering that the mechanisms underlying the neurological dysfunction in hypertyrosinemic patients are poorly known and that high concentrations of tyrosine provoke mitochondrial dysfunction and oxidative stress, in the present study we investigated the in vivo influence of antioxidants (N-acetylcysteine, NAC; and deferoxamine, DFX) administration on the inhibitory effects on parameters of energy metabolism in cerebral cortex, hippocampus and striatum of rats, provoked by chronic administration of L.-tyrosine. Our results showed that chronic administration of L.-tyrosine results in a marked decrease in the activity of citrate synthase in all the analyzed structures and succinate dehydrogenase activities in hippocampus and striatum, and that antioxidants administration can prevent this inhibition in hippocampus and striatum. Moreover, chronic administration of L.-tyrosine inhibited the activity of complex I, II-III and IV in the striatum, which can be prevented by antioxidant treatment. However, the co-administration of NAC plus DFX could not prevent the inhibition of creatine kinase activity in the striatum. In conclusion, the present study demonstrates that the administration of antioxidants NAC and DFX attenuates the L.-tyrosine effects on enzymes of the Krebs cycle and the mitochondrial respiratory chain, suggesting that impairment of energy metabolism can be involved with oxidative stress. These results also indicate a possible neuroprotective role for NAC and DFX as a potential adjuvant therapy to the patients with Tyrosinemia type II.

  9. Analysis of mucolipidosis II/III GNPTAB missense mutations identifies domains of UDP-GlcNAc:lysosomal enzyme GlcNAc-1-phosphotransferase involved in catalytic function and lysosomal enzyme recognition.

    PubMed

    Qian, Yi; van Meel, Eline; Flanagan-Steet, Heather; Yox, Alex; Steet, Richard; Kornfeld, Stuart

    2015-01-30

    UDP-GlcNAc:lysosomal enzyme GlcNAc-1-phosphotransferase tags newly synthesized lysosomal enzymes with mannose 6-phosphate recognition markers, which are required for their targeting to the endolysosomal system. GNPTAB encodes the α and β subunits of GlcNAc-1-phosphotransferase, and mutations in this gene cause the lysosomal storage disorders mucolipidosis II and III αβ. Prior investigation of missense mutations in GNPTAB uncovered amino acids in the N-terminal region and within the DMAP domain involved in Golgi retention of GlcNAc-1-phosphotransferase and its ability to specifically recognize lysosomal hydrolases, respectively. Here, we undertook a comprehensive analysis of the remaining missense mutations in GNPTAB reported in mucolipidosis II and III αβ patients using cell- and zebrafish-based approaches. We show that the Stealth domain harbors the catalytic site, as some mutations in these regions greatly impaired the activity of the enzyme without affecting its Golgi localization and proteolytic processing. We also demonstrate a role for the Notch repeat 1 in lysosomal hydrolase recognition, as missense mutations in conserved cysteine residues in this domain do not affect the catalytic activity but impair mannose phosphorylation of certain lysosomal hydrolases. Rescue experiments using mRNA bearing Notch repeat 1 mutations in GNPTAB-deficient zebrafish revealed selective effects on hydrolase recognition that differ from the DMAP mutation. Finally, the mutant R587P, located in the spacer between Notch 2 and DMAP, was partially rescued by overexpression of the γ subunit, suggesting a role for this region in γ subunit binding. These studies provide new insight into the functions of the different domains of the α and β subunits.

  10. NAC Transcription Factor SPEEDY HYPONASTIC GROWTH Regulates Flooding-Induced Leaf Movement in Arabidopsis[W

    PubMed Central

    Rauf, Mamoona; Arif, Muhammad; Fisahn, Joachim; Xue, Gang-Ping; Balazadeh, Salma; Mueller-Roeber, Bernd

    2013-01-01

    In rosette plants, root flooding (waterlogging) triggers rapid upward (hyponastic) leaf movement representing an important architectural stress response that critically determines plant performance in natural habitats. The directional growth is based on localized longitudinal cell expansion at the lower (abaxial) side of the leaf petiole and involves the volatile phytohormone ethylene (ET). We report the existence of a transcriptional core unit underlying directional petiole growth in Arabidopsis thaliana, governed by the NAC transcription factor SPEEDY HYPONASTIC GROWTH (SHYG). Overexpression of SHYG in transgenic Arabidopsis thaliana enhances waterlogging-triggered hyponastic leaf movement and cell expansion in abaxial cells of the basal petiole region, while both responses are largely diminished in shyg knockout mutants. Expression of several EXPANSIN and XYLOGLUCAN ENDOTRANSGLYCOSYLASE/HYDROLASE genes encoding cell wall–loosening proteins was enhanced in SHYG overexpressors but lowered in shyg. We identified ACC OXIDASE5 (ACO5), encoding a key enzyme of ET biosynthesis, as a direct transcriptional output gene of SHYG and found a significantly reduced leaf movement in response to root flooding in aco5 T-DNA insertion mutants. Expression of SHYG in shoot tissue is triggered by root flooding and treatment with ET, constituting an intrinsic ET-SHYG-ACO5 activator loop for rapid petiole cell expansion upon waterlogging. PMID:24363315

  11. Glucose-induced expression of MIP-1 genes requires O-GlcNAc transferase in monocytes

    SciTech Connect

    Chikanishi, Toshihiro; Fujiki, Ryoji; Hashiba, Waka; Sekine, Hiroki; Yokoyama, Atsushi; Kato, Shigeaki

    2010-04-16

    O-glycosylation has emerged as an important modification of nuclear proteins, and it appears to be involved in gene regulation. Recently, we have shown that one of the histone methyl transferases (MLL5) is activated through O-glycosylation by O-GlcNAc transferase (OGT). Addition of this monosaccharide is essential for forming a functional complex. However, in spite of the abundance of OGT in the nucleus, the impact of nuclear O-glycosylation by OGT remains largely unclear. To address this issue, the present study was undertaken to test the impact of nuclear O-glycosylation in a monocytic cell line, THP-1. Using a cytokine array, MIP-1{alpha} and -1{beta} genes were found to be regulated by nuclear O-glycosylation. Biochemical purification of the OGT interactants from THP-1 revealed that OGT is an associating partner for distinct co-regulatory complexes. OGT recruitment and protein O-glycosylation were observed at the MIP-1{alpha} gene promoter; however, the known OGT partner (HCF-1) was absent when the MIP-1{alpha} gene promoter was not activated. From these findings, we suggest that OGT could be a co-regulatory subunit shared by functionally distinct complexes supporting epigenetic regulation.

  12. Roles of O-GlcNAc in chronic diseases of aging.

    PubMed

    Banerjee, Partha S; Lagerlöf, Olof; Hart, Gerald W

    2016-10-01

    O-GlcNAcylation, a dynamic nutrient and stress sensitive post-translational modification, occurs on myriad proteins in the cell nucleus, cytoplasm and mitochondria. O-GlcNAcylation serves as a nutrient sensor to regulate signaling, transcription, translation, cell division, metabolism, and stress sensitivity in all cells. Aberrant protein O-GlcNAcylation plays a critical role both in the development, as well as in the progression of a variety of age related diseases. O-GlcNAcylation underlies the etiology of diabetes, and changes in specific protein O-GlcNAc levels and sites are responsible for insulin expression and sensitivity and glucose toxicity. Abnormal O-GlcNAcylation contributes directly to diabetes related dysfunction of the heart, kidney and eyes and affects progression of cardiomyopathy, nephropathy and retinopathy. O-GlcNAcylation is a critical modification in the brain and plays a role in both plaque and tangle formation, thus making its study important in neurodegenerative disorders. O-GlcNAcylation also affects cellular growth and metabolism during the development and metastasis of cancer. Finally, alterations in O-GlcNAcylation of transcription factors in macrophages and lymphocytes affect inflammation and cytokine production. Thus, O-GlcNAcylation plays key roles in many of the major diseases associated with aging. Elucidation of its specific functions in both normal and diseased tissues is likely to uncover totally novel avenues for therapeutic intervention.

  13. O-GlcNAc-glycosylation of {beta}-catenin regulates its nuclear localization and transcriptional activity

    SciTech Connect

    Sayat, Ria; Leber, Brian; Grubac, Vanja; Wiltshire, Lesley; Persad, Sujata

    2008-09-10

    {beta}-catenin plays a role in intracellular adhesion and regulating gene expression. The latter role is associated with its oncogenic properties. Phosphorylation of {beta}-catenin controls its intracellular expression but mechanism/s that regulates the nuclear localization of {beta}-catenin is unknown. We demonstrate that O-GlcNAc glycosylation (O-GlcNAcylation) of {beta}-catenin negatively regulates its levels in the nucleus. We show that normal prostate cells (PNT1A) have significantly higher amounts of O-GlcNAcylated {beta}-catenin compared to prostate cancer (CaP) cells. The total nuclear levels of {beta}-catenin are higher in the CaP cells than PNT1A but only a minimal fraction of the nuclear {beta}-catenin in the CaP cells are O-GlcNAcylated. Increasing the levels of O-GlcNAcylated {beta}-catenin in the CaP cells with PUGNAc (O- (2-acetamido-2-deoxy-D-gluco-pyranosylidene) amino-N-phenylcarbamate) treatment is associated with a progressive decrease in the levels of {beta}-catenin in the nucleus. TOPFlash reporter assay and mRNA expressions of {beta}-catenin's target genes indicate that O-GlcNAcylation of {beta}-catenin results in a decrease in its transcriptional activity. We define a novel modification of {beta}-catenin that regulates its nuclear localization and transcriptional function.

  14. Efficient entropy coding for scalable video coding

    NASA Astrophysics Data System (ADS)

    Choi, Woong Il; Yang, Jungyoup; Jeon, Byeungwoo

    2005-10-01

    The standardization for the scalable extension of H.264 has called for additional functionality based on H.264 standard to support the combined spatio-temporal and SNR scalability. For the entropy coding of H.264 scalable extension, Context-based Adaptive Binary Arithmetic Coding (CABAC) scheme is considered so far. In this paper, we present a new context modeling scheme by using inter layer correlation between the syntax elements. As a result, it improves coding efficiency of entropy coding in H.264 scalable extension. In simulation results of applying the proposed scheme to encoding the syntax element mb_type, it is shown that improvement in coding efficiency of the proposed method is up to 16% in terms of bit saving due to estimation of more adequate probability model.

  15. The Putative Eukaryote-Like O-GlcNAc Transferase of the Cyanobacterium Synechococcus elongatus PCC 7942 Hydrolyzes UDP-GlcNAc and Is Involved in Multiple Cellular Processes

    PubMed Central

    Sokol, Kerry A.

    2014-01-01

    The posttranslational addition of a single O-linked β-N-acetylglucosamine (O-GlcNAc) to serine or threonine residues regulates numerous metazoan cellular processes. The enzyme responsible for this modification, O-GlcNAc transferase (OGT), is conserved among a wide variety of organisms and is critical for the viability of many eukaryotes. Although OGTs with domain structures similar to those of eukaryotic OGTs are predicted for many bacterial species, the cellular roles of these OGTs are unknown. We have identified a putative OGT in the cyanobacterium Synechococcus elongatus PCC 7942 that shows active-site homology and similar domain structure to eukaryotic OGTs. An OGT deletion mutant was created and found to exhibit several phenotypes. Without agitation, mutant cells aggregate and settle out of the medium. The mutant cells have higher free inorganic phosphate levels, wider thylakoid lumen, and differential accumulation of electron-dense inclusion bodies. These phenotypes are rescued by reintroduction of the wild-type OGT but are not fully rescued by OGTs with single amino acid substitutions corresponding to mutations that reduce eukaryotic OGT activity. S. elongatus OGT purified from Escherichia coli hydrolyzed the sugar donor, UDP-GlcNAc, while the mutant OGTs that did not fully rescue the deletion mutant phenotypes had reduced or no activity. These results suggest that bacterial eukaryote-like OGTs, like their eukaryotic counterparts, influence multiple processes. PMID:25384478

  16. Identification of the nuclear localisation signal of O-GlcNAc transferase and its nuclear import regulation

    PubMed Central

    Seo, Hyeon Gyu; Kim, Han Byeol; Kang, Min Jueng; Ryum, Joo Hwan; Yi, Eugene C.; Cho, Jin Won

    2016-01-01

    Nucleocytoplasmic O-GlcNAc transferase (OGT) attaches a single GlcNAc to hydroxyl groups of serine and threonine residues. Although the cellular localisation of OGT is important to regulate a variety of cellular processes, the molecular mechanisms regulating the nuclear localisation of OGT is unclear. Here, we characterised three amino acids (DFP; residues 451–453) as the nuclear localisation signal of OGT and demonstrated that this motif mediated the nuclear import of non-diffusible β-galactosidase. OGT bound the importin α5 protein, and this association was abolished when the DFP motif of OGT was mutated or deleted. We also revealed that O-GlcNAcylation of Ser389, which resides in the tetratricopeptide repeats, plays an important role in the nuclear localisation of OGT. Our findings may explain how OGT, which possesses a NLS, exists in the nucleus and cytosol simultaneously. PMID:27713473

  17. Convective heat transfer behavior of the product slurry of the nitrate to ammonia and ceramic (NAC) process

    SciTech Connect

    Muguercia, I.; Yang, G.; Ebadian, M.A.; Lee, D.D.; Mattus, A.J.; Hunt, R.D.

    1995-12-01

    The Nitrate to Ammonia and Ceramic (NAC) process is an innovative technology for immobilizing liquid form low level radioactive waste (LLW). An experimental study has been conducted to measure the heat transfer properties of the NAC product slurry. The results indicate that the heat transfer coefficient for both concentration slurries is much higher than that of pure water, which may be due to the higher conductivity of the gibbsite powder. For the 20% concentration slurry, the heat transfer coefficient increased as the generalized Reynolds number and slurry temperature increased. The heat transfer coefficient of 40% is a function of the Reynolds number only. The test results also indicate that the thermal entrance region can be observed only when the generalized Reynolds number is smaller than 1,000. The correlation equation is also developed based on the experimental data in this paper.

  18. Characterization of OSIRIS NAC filters for the interpretation of multispectral data of comet 67P/Churyumov-Gerasimenko

    NASA Astrophysics Data System (ADS)

    Oklay, N.; Vincent, J.-B.; Sierks, H.; Besse, S.; Pajola, M.; Bertini, I.; Rickman, H.; La Forgia, F.; Barucci, A. M.; Fornasier, S.; Barbieri, C.; Koschny, D.; Lamy, P. L.; Rodrigo, R.; Agarwal, J.; A'Hearn, M. F.; Bertaux, J.-L.; Cremonese, G.; Da Deppo, V.; Davidsson, B.; Debei, S.; De Cecco, M.; Fulle, M.; Groussin, O.; Gutiérrez, P. J.; Güttler, C.; Hviid, S. F.; Ip, W.-H.; Jorda, L.; Keller, H. U.; Knollenberg, J.; Kramm, J.-R.; Kührt, E.; Küppers, M.; Lara, L. M.; Lazzarin, M.; Lopez-Moreno, J. J.; Marzari, F.; Michalik, H.; Naletto, G.; Thomas, N.; Tubiana, C.

    2015-11-01

    Context. We interpret multicolor data from OSIRISNAC for the remote-sensing exploration of comet 67P/Churyumov-Gerasimenko. Aims: We determine the most meaningful definition of color maps for the characterization of surface variegation with filters available on OSIRIS NAC. Methods: We analyzed laboratory spectra of selected minerals and olivine-pyroxene mixtures seen through OSIRIS NAC filters, with spectral methods existing in the literature: reflectance ratios, minimum band wavelength, spectral slopes, band tilt, band curvature, and visible tilt. Results: We emphasize the importance of reflectance ratios and particularly the relation of visible tilt vs. band tilt. This technique provides a reliable diagnostic of the presence of silicates. Color maps constructed by red-green-blue colors defined with the green, orange, red, IR, and Fe2O3 filters let us define regions that may significantly differ in composition. Appendices are available in electronic form at http://www.aanda.org

  19. Administration of the Glial Condition Medium in the Nucleus Accumbens Prolong Maintenance and Intensify Reinstatement of Morphine-Seeking Behavior.

    PubMed

    Arezoomandan, Reza; Khodagholi, Fariba; Haghparast, Abbas

    2016-04-01

    Accumulating evidence suggested that glial cells are involved in synaptic plasticity and behavioral changes induced by drugs abuse. The role of these cells in maintenance and reinstatement of morphine (MRP) conditioned place preference (CPP) remains poorly characterized. The aim of present study was to investigate the direct role of glial cells in nucleus accumbens (NAc) in the maintenance and reinstatement of MRP-seeking behavior. CPP induced with injection of MRP (5 mg/kg, s.c. for 3 days), lasted for 7 days after cessation of MRP treatment and priming dose of MRP (1 mg/kg, s.c.) reinstated the extinguished MRP-induced CPP. The astrocyte-conditioned medium (ACM) and neuroglia conditioned medium (NCM) exposed to MRP (10 and 100 µM) have been microinjected into the NAc. Intra-NAc administration of ACM during extinction period failed to change the maintenance of MRP-CPP, but MRP 100-treated ACM could slightly increase the magnitude of reinstatement. In contrast to ACM, intra-NAc administration of MRP 100-treated NCM caused slower extinction by 3 days and significantly increased the magnitude of reinstatement. Our findings suggest the involvement of glial cells activation in the maintenance and reinstatement of MRP-seeking behaviors, and provides new evidence that these cells might be a potential target for the treatment of MRP addiction.

  20. Combined Antibody/Lectin Enrichment Identifies Extensive Changes in the O-GlcNAc Sub-proteome upon Oxidative Stress.

    PubMed

    Lee, Albert; Miller, Devin; Henry, Roger; Paruchuri, Venkata D P; O'Meally, Robert N; Boronina, Tatiana; Cole, Robert N; Zachara, Natasha E

    2016-12-02

    O-Linked N-acetyl-β-d-glucosamine (O-GlcNAc) is a dynamic post-translational modification that modifies and regulates over 3000 nuclear, cytoplasmic, and mitochondrial proteins. Upon exposure to stress and injury, cells and tissues increase the O-GlcNAc modification, or O-GlcNAcylation, of numerous proteins promoting the cellular stress response and thus survival. The aim of this study was to identify proteins that are differentially O-GlcNAcylated upon acute oxidative stress (H2O2) to provide insight into the mechanisms by which O-GlcNAc promotes survival. We achieved this goal by employing Stable Isotope Labeling of Amino Acids in Cell Culture (SILAC) and a novel "G5-lectibody" immunoprecipitation strategy that combines four O-GlcNAc-specific antibodies (CTD110.6, RL2, HGAC39, and HGAC85) and the lectin WGA. Using the G5-lectibody column in combination with basic reversed phase chromatography and C18 RPLC-MS/MS, 990 proteins were identified and quantified. Hundreds of proteins that were identified demonstrated increased (>250) or decreased (>110) association with the G5-lectibody column upon oxidative stress, of which we validated the O-GlcNAcylation status of 24 proteins. Analysis of proteins with altered glycosylation suggests that stress-induced changes in O-GlcNAcylation cluster into pathways known to regulate the cell's response to injury and include protein folding, transcriptional regulation, epigenetics, and proteins involved in RNA biogenesis. Together, these data suggest that stress-induced O-GlcNAcylation regulates numerous and diverse cellular pathways to promote cell and tissue survival.

  1. The Nutrient-Dependent O-GlcNAc Modification Controls the Expression of Liver Fatty Acid Synthase.

    PubMed

    Baldini, Steffi F; Wavelet, Cindy; Hainault, Isabelle; Guinez, Céline; Lefebvre, Tony

    2016-08-14

    Liver Fatty Acid Synthase (FAS) is pivotal for de novo lipogenesis. Loss of control of this metabolic pathway contributes to the development of liver pathologies ranging from steatosis to nonalcoholic steatohepatitis (NASH) which can lead to cirrhosis and, less frequently, to hepatocellular carcinoma. Therefore, deciphering the molecular mechanisms governing the expression and function of key enzymes such as FAS is crucial. Herein, we link the availability of this lipogenic enzyme to the nutrient-dependent post-translational modification O-GlcNAc that is thought to be deregulated in metabolic diseases (diabetes, obesity, and metabolic syndrome). We demonstrate that expression and activity of liver FAS correlate with O-GlcNAcylation contents in ob/ob mice and in mice fed with a high-carbohydrate diet both in a transcription-dependent and -independent manner. More importantly, inhibiting the removal of O-GlcNAc residues in mice intraperitoneally injected with the selective and potent O-GlcNAcase (OGA) inhibitor Thiamet-G increases FAS expression. FAS and O-GlcNAc transferase (OGT) physically interact, and FAS is O-GlcNAc modified. Treatment of a liver cell line with drugs or nutrients that elevate the O-GlcNAcylation interferes with FAS expression. Inhibition of OGA increases the interaction between FAS and the deubiquitinase Ubiquitin-specific protease-2a (USP2A) in vivo and ex vivo, providing mechanistic insights into the control of FAS expression through O-GlcNAcylation. Together, these results reveal a new type of regulation of FAS, linked to O-GlcNAcylation status, and advance our knowledge on deregulation of lipogenesis in diverse forms of liver diseases.

  2. Strong aphicidal activity of GlcNAc(β1→4)Glc disaccharides: synthesis, physiological effects, and chitinase inhibition.

    PubMed

    Dussouy, Christophe; Bultel, Laurent; Saguez, Julien; Cherqui, Anas; Khelifa, Mounia; Grand, Eric; Giordanengo, Philippe; Kovensky, José

    2012-08-06

    The synthesis of four GlcNAc(β1→4)Glc disaccharides containing 2-O-acetyl and/or 6-sulfate groups was performed in high yields with total 1,2-trans stereoselectivity. These disaccharides were evaluated as candidates for insect chitinase inhibition and aphicidal activity. All the compounds prepared displayed physiological effects on M. persicae aphids; however, the inhibition of chitinases of different sources (bacteria, fungus, and aphid) followed different patterns according to subtle structural characteristics.

  3. An internally consistent dataset of δ13C-DIC in the North Atlantic Ocean - NAC13v1

    NASA Astrophysics Data System (ADS)

    Becker, Meike; Andersen, Nils; Erlenkeuser, Helmut; Humphreys, Matthew P.; Tanhua, Toste; Körtzinger, Arne

    2016-10-01

    The stable carbon isotope composition of dissolved inorganic carbon (δ13C-DIC) can be used to quantify fluxes within the carbon system. For example, knowing the δ13C signature of the inorganic carbon pool can help in describing the amount of anthropogenic carbon in the water column. The measurements can also be used for evaluating modeled carbon fluxes, for making basin-wide estimates of anthropogenic carbon, and for studying seasonal and interannual variability or decadal trends in interior ocean biogeochemistry. For all these purposes, it is not only important to have a sufficient amount of data, but these data must also be internally consistent and of high quality. In this study, we present a δ13C-DIC dataset for the North Atlantic which has undergone secondary quality control. The data originate from oceanographic research cruises between 1981 and 2014. During a primary quality control step based on simple range tests, obviously bad data were flagged. In a second quality control step, biases between measurements from different cruises were quantified through a crossover analysis using nearby data of the respective cruises, and values of biased cruises were adjusted in the data product. The crossover analysis was possible for 24 of the 32 cruises in our dataset, and adjustments were applied to 11 cruises. The internal accuracy of this dataset is 0.017 ‰. The dataset is available via the Carbon Dioxide Information Analysis Center (CDIAC) at NAC13v1.html" target="_blank">http://cdiac.ornl.gov/oceans/ndp_096/NAC13v1.html, NAC13v1" target="_blank">doi:10.3334/CDIAC/OTG.NAC13v1.

  4. Occurrence probability of slopes on the lunar surface: Estimate by the shaded area percentage in the LROC NAC images

    NASA Astrophysics Data System (ADS)

    Abdrakhimov, A. M.; Basilevsky, A. T.; Ivanov, M. A.; Kokhanov, A. A.; Karachevtseva, I. P.; Head, J. W.

    2015-09-01

    The paper describes the method of estimating the distribution of slopes by the portion of shaded areas measured in the images acquired at different Sun elevations. The measurements were performed for the benefit of the Luna-Glob Russian mission. The western ellipse for the spacecraft landing in the crater Bogus-lawsky in the southern polar region of the Moon was investigated. The percentage of the shaded area was measured in the images acquired with the LROC NAC camera with a resolution of ~0.5 m. Due to the close vicinity of the pole, it is difficult to build digital terrain models (DTMs) for this region from the LROC NAC images. Because of this, the method described has been suggested. For the landing ellipse investigated, 52 LROC NAC images obtained at the Sun elevation from 4° to 19° were used. In these images the shaded portions of the area were measured, and the values of these portions were transferred to the values of the occurrence of slopes (in this case, at the 3.5-m baseline) with the calibration by the surface characteristics of the Lunokhod-1 study area. For this area, the digital terrain model of the ~0.5-m resolution and 13 LROC NAC images obtained at different elevations of the Sun are available. From the results of measurements and the corresponding calibration, it was found that, in the studied landing ellipse, the occurrence of slopes gentler than 10° at the baseline of 3.5 m is 90%, while it is 9.6, 5.7, and 3.9% for the slopes steeper than 10°, 15°, and 20°, respectively. Obviously, this method can be recommended for application if there is no DTM of required granularity for the regions of interest, but there are high-resolution images taken at different elevations of the Sun.

  5. Disposition and Pharmacology of a GalNAc3-conjugated ASO Targeting Human Lipoprotein (a) in Mice

    PubMed Central

    Yu, Rosie Z; Graham, Mark J; Post, Noah; Riney, Stan; Zanardi, Thomas; Hall, Shannon; Burkey, Jennifer; Shemesh, Colby S; Prakash, Thazha P; Seth, Punit P; Swayze, Eric E; Geary, Richard S; Wang, Yanfeng; Henry, Scott

    2016-01-01

    Triantennary N-acetyl galactosamine (GalNAc3)-conjugated antisense oligonucleotides (ASOs) have greatly improved potency via receptor-mediated uptake. In the present study, the in vivo pharmacology of a 2′-O-(2-methoxyethyl)-modified ASO conjugated with GalNAc3 (ISIS 681257) together with its unmodified congener (ISIS 494372) targeting human apolipoprotein (a) (apo(a)), were studied in human LPA transgenic mice. Further, the disposition kinetics of ISIS 681257 was studied in CD-1 mice. ISIS 681257 demonstrated over 20-fold improvement in potency over ISIS 494372 as measured by liver apo(a) mRNA and plasma apo(a) protein levels. Following subcutaneous (SC) dosing, ISIS 681257 cleared rapidly from plasma and distributed to tissues. Intact ISIS 681257 was the major full-length oligonucleotide species in plasma. In tissues, however, GalNAc sugar moiety was rapidly metabolized and unconjugated ISIS 681257 accounted > 97% of the total exposure, which was then cleared slowly from tissues with a half-life of 7–8 days, similar to the half-life in plasma. ISIS 681257 is highly bound to plasma proteins (> 94% bound), which limited its urinary excretion. This study confirmed dose-dependent exposure to the parent drug ISIS 681257 in plasma and rapid conversion to unconjugated ASO in tissues. Safety data and the extended half-life support its further development and weekly dosing in phase 1 clinical studies. PMID:27138177

  6. Activity Based High-Throughput Screening for Novel O-GlcNAc Transferase Substrates Using a Dynamic Peptide Microarray

    PubMed Central

    Shi, Jie; Sharif, Suhela; Ruijtenbeek, Rob; Pieters, Roland J.

    2016-01-01

    O-GlcNAcylation is a reversible and dynamic protein post-translational modification in mammalian cells. The O-GlcNAc cycle is catalyzed by O-GlcNAc transferase (OGT) and O-GlcNAcase (OGA). O-GlcNAcylation plays important role in many vital cellular events including transcription, cell cycle regulation, stress response and protein degradation, and altered O-GlcNAcylation has long been implicated in cancer, diabetes and neurodegenerative diseases. Recently, numerous approaches have been developed to identify OGT substrates and study their function, but there is still a strong demand for highly efficient techniques. Here we demonstrated the utility of the peptide microarray approach to discover novel OGT substrates and study its specificity. Interestingly, the protein RBL-2, which is a key regulator of entry into cell division and may function as a tumor suppressor, was identified as a substrate for three isoforms of OGT. Using peptide Ala scanning, we found Ser 420 is one possible O-GlcNAc site in RBL-2. Moreover, substitution of Ser 420, on its own, inhibited OGT activity, raising the possibility of mechanism-based development for selective OGT inhibitors. This approach will prove useful for both discovery of novel OGT substrates and studying OGT specificity. PMID:26960196

  7. O-GlcNAc modification blocks the aggregation and toxicity of the protein α-synuclein associated with Parkinson's disease

    NASA Astrophysics Data System (ADS)

    Marotta, Nicholas P.; Lin, Yu Hsuan; Lewis, Yuka E.; Ambroso, Mark R.; Zaro, Balyn W.; Roth, Maxwell T.; Arnold, Don B.; Langen, Ralf; Pratt, Matthew R.

    2015-11-01

    Several aggregation-prone proteins associated with neurodegenerative diseases can be modified by O-linked N-acetyl-glucosamine (O-GlcNAc) in vivo. One of these proteins, α-synuclein, is a toxic aggregating protein associated with synucleinopathies, including Parkinson's disease. However, the effect of O-GlcNAcylation on α-synuclein is not clear. Here, we use synthetic protein chemistry to generate both unmodified α-synuclein and α-synuclein bearing a site-specific O-GlcNAc modification at the physiologically relevant threonine residue 72. We show that this single modification has a notable and substoichiometric inhibitory effect on α-synuclein aggregation, while not affecting the membrane binding or bending properties of α-synuclein. O-GlcNAcylation is also shown to affect the phosphorylation of α-synuclein in vitro and block the toxicity of α-synuclein that was exogenously added to cells in culture. These results suggest that increasing O-GlcNAcylation may slow the progression of synucleinopathies and further support a general function for O-GlcNAc in preventing protein aggregation.

  8. A functional RNAi screen links O-GlcNAc modification of ribosomal proteins to stress granule and processing body assembly

    PubMed Central

    Ohn, Takbum; Kedersha, Nancy; Hickman, Tyler; Tisdale, Sarah; Anderson, Paul

    2015-01-01

    Stress granules (SGs) and processing bodies (PBs) are microscopically visible ribonucleoprotein granules that cooperatively regulate the translation and decay of messenger RNA1–3. Using an RNA-mediated interference-based screen, we identify 101 human genes required for SG assembly, 39 genes required for PB assembly, and 31 genes required for coordinate SG and PB assembly. Although 51 genes encode proteins involved in mRNA translation, splicing and transcription, most are not obviously associated with RNA metabolism. We find that several components of the hexosamine biosynthetic pathway, which reversibly modifies proteins with O-linked N-acetylglucosamine (O-GlcNAc) in response to stress, are required for SG and PB assembly. O-GlcNAc-modified proteins are prominent components of SGs but not PBs, and include RACK1 (receptor for activated C kinase 1), prohibitin-2, glyceraldehyde-3-phosphate dehydrogenase and numerous ribosomal proteins. Our results suggest that O-GlcNAc modification of the translational machinery is required for aggregation of untranslated messenger ribonucleoproteins into SGs. The lack of enzymes of the hexosamine biosynthetic pathway in budding yeast may contribute to differences between mammalian SGs and related yeast EGP (eIF4E, 4G and Pab1 containing) bodies. PMID:18794846

  9. Honesty and Honor Codes.

    ERIC Educational Resources Information Center

    McCabe, Donald; Trevino, Linda Klebe

    2002-01-01

    Explores the rise in student cheating and evidence that students cheat less often at schools with an honor code. Discusses effective use of such codes and creation of a peer culture that condemns dishonesty. (EV)

  10. Cellulases and coding sequences

    DOEpatents

    Li, Xin-Liang; Ljungdahl, Lars G.; Chen, Huizhong

    2001-02-20

    The present invention provides three fungal cellulases, their coding sequences, recombinant DNA molecules comprising the cellulase coding sequences, recombinant host cells and methods for producing same. The present cellulases are from Orpinomyces PC-2.

  11. Cellulases and coding sequences

    DOEpatents

    Li, Xin-Liang; Ljungdahl, Lars G.; Chen, Huizhong

    2001-01-01

    The present invention provides three fungal cellulases, their coding sequences, recombinant DNA molecules comprising the cellulase coding sequences, recombinant host cells and methods for producing same. The present cellulases are from Orpinomyces PC-2.

  12. QR Code Mania!

    ERIC Educational Resources Information Center

    Shumack, Kellie A.; Reilly, Erin; Chamberlain, Nik

    2013-01-01

    space, has error-correction capacity, and can be read from any direction. These codes are used in manufacturing, shipping, and marketing, as well as in education. QR codes can be created to produce…

  13. DIANE multiparticle transport code

    NASA Astrophysics Data System (ADS)

    Caillaud, M.; Lemaire, S.; Ménard, S.; Rathouit, P.; Ribes, J. C.; Riz, D.

    2014-06-01

    DIANE is the general Monte Carlo code developed at CEA-DAM. DIANE is a 3D multiparticle multigroup code. DIANE includes automated biasing techniques and is optimized for massive parallel calculations.

  14. N-Acetylcysteine Administration Prevents Nonthyroidal Illness Syndrome in Patients With Acute Myocardial Infarction: A Randomized Clinical Trial

    PubMed Central

    Vidart, Josi; Wajner, Simone Magagnin; Leite, Rogério Sarmento; Manica, André; Schaan, Beatriz D.; Larsen, P. Reed

    2014-01-01

    Context: The acute phase of the nonthyroidal illness syndrome (NTIS) is characterized by low T3 and high rT3 levels, affecting up to 75% of critically ill patients. Oxidative stress has been implicated as a causative factor of the disturbed peripheral thyroid hormone metabolism. Objective: The objective of the study was to investigate whether N-acetylcysteine (NAC), a potent intracellular antioxidant, can prevent NTIS in patients with acute myocardial infarction. Design: This was a randomized, multicenter clinical trial. Settings: Consecutive patients admitted to the emergency and intensive care units of two tertiary hospitals in southern Brazil were recruited. Patients and intervention included 67 patients were randomized to receive NAC or placebo during 48 hours. Baseline characteristics and blood samples for thyroid hormones and oxidative parameters were collected. Main Outcome: Variation of serum T3 and rT3 levels was measured. Results: Baseline characteristics were similar between groups (all P > .05). T3 levels decreased in the placebo group at 12 hours of follow-up (P = .002) but not in NAC-treated patients (P = .10). Baseline rT3 levels were elevated in both groups and decreased over the initial 48 hours in the NAC-treated patients (P = .003) but not in the control group (P = .75). The free T4 and TSH levels were virtually identical between the groups throughout the study period (P > .05). Measurement of total antioxidant status and total carbonyl content demonstrated that oxidative balance was deranged in acute myocardial infarction patients, whereas NAC corrected these alterations (P < .001). Conclusions: NAC administration prevents the derangement in thyroid hormone concentrations commonly occurring in the acute phase of acute myocardial infarction, indicating that oxidative stress is involved in the NTIS pathophysiology. PMID:25148231

  15. Resolution of norfloxacin-induced acute liver failure after N-acetylcysteine therapy: further support for the use of NAC in drug-induced ALF?

    PubMed

    Elliott, Timothy Ross; Symes, Tiffany; Kannourakis, George; Angus, Peter

    2016-01-06

    Liver injury due to idiosyncratic drug reactions can be difficult to diagnose and may lead to acute liver failure (ALF), which has a high mortality rate. N-acetylcysteine (NAC) is effective treatment for paracetamol toxicity, but its role in non-paracetamol drug-induced ALF is controversial. We report on the use of a validated bedside tool to establish causality for drug-induced liver injury (DILI) and describe the first case of resolution of norfloxacin-induced ALF after NAC therapy. NAC is easy to administer and generally has a good safety profile. We discuss the evidence to support the use of NAC in ALF secondary to DILI and possibilities for further clinical research in this field.

  16. EMF wire code research

    SciTech Connect

    Jones, T.

    1993-11-01

    This paper examines the results of previous wire code research to determines the relationship with childhood cancer, wire codes and electromagnetic fields. The paper suggests that, in the original Savitz study, biases toward producing a false positive association between high wire codes and childhood cancer were created by the selection procedure.

  17. Universal Noiseless Coding Subroutines

    NASA Technical Reports Server (NTRS)

    Schlutsmeyer, A. P.; Rice, R. F.

    1986-01-01

    Software package consists of FORTRAN subroutines that perform universal noiseless coding and decoding of integer and binary data strings. Purpose of this type of coding to achieve data compression in sense that coded data represents original data perfectly (noiselessly) while taking fewer bits to do so. Routines universal because they apply to virtually any "real-world" data source.

  18. Identification of O-GlcNAc modification targets in mouse retinal pericytes: implication of p53 in pathogenesis of diabetic retinopathy.

    PubMed

    Gurel, Zafer; Zaro, Balyn W; Pratt, Matthew R; Sheibani, Nader

    2014-01-01

    Hyperglycemia is the primary cause of the majority of diabetes complications, including diabetic retinopathy (DR). Hyperglycemic conditions have a detrimental effect on many tissues and cell types, especially the retinal vascular cells including early loss of pericytes (PC). However, the mechanisms behind this selective sensitivity of retinal PC to hyperglycemia are undefined. The O-linked β-N-acetylglucosamine (O-GlcNAc) modification is elevated under hyperglycemic condition, and thus, may present an important molecular modification impacting the hyperglycemia-driven complications of diabetes. We have recently demonstrated that the level of O-GlcNAc modification in response to high glucose is variable in various retinal vascular cells. Retinal PC responded with the highest increase in O-GlcNAc modification compared to retinal endothelial cells and astrocytes. Here we show that these differences translated into functional changes, with an increase in apoptosis of retinal PC, not just under high glucose but also under treatment with O-GlcNAc modification inducers, PUGNAc and Thiamet-G. To gain insight into the molecular mechanisms involved, we have used click-It chemistry and LC-MS analysis and identified 431 target proteins of O-GlcNAc modification in retinal PC using an alkynyl-modified GlcNAc analog (GlcNAlk). Among the O-GlcNAc target proteins identified here 115 of them were not previously reported to be target of O-GlcNAc modification. We have identified at least 34 of these proteins with important roles in various aspects of cell death processes. Our results indicated that increased O-GlcNAc modification of p53 was associated with an increase in its protein levels in retinal PC. Together our results suggest that post-translational O-GlcNAc modification of p53 and its increased levels may contribute to selective early loss of PC during diabetes. Thus, modulation of O-GlcNAc modification may provide a novel treatment strategy to prevent the initiation and

  19. Mapping Local Codes to Read Codes.

    PubMed

    Bonney, Wilfred; Galloway, James; Hall, Christopher; Ghattas, Mikhail; Tramma, Leandro; Nind, Thomas; Donnelly, Louise; Jefferson, Emily; Doney, Alexander

    2017-01-01

    Background & Objectives: Legacy laboratory test codes make it difficult to use clinical datasets for meaningful translational research, where populations are followed for disease risk and outcomes over many years. The Health Informatics Centre (HIC) at the University of Dundee hosts continuous biochemistry data from the clinical laboratories in Tayside and Fife dating back as far as 1987. However, the HIC-managed biochemistry dataset is coupled with incoherent sample types and unstandardised legacy local test codes, which increases the complexity of using the dataset for reasonable population health outcomes. The objective of this study was to map the legacy local test codes to the Scottish 5-byte Version 2 Read Codes using biochemistry data extracted from the repository of the Scottish Care Information (SCI) Store.

  20. Aluminum Enhances Growth and Sugar Concentration, Alters Macronutrient Status and Regulates the Expression of NAC Transcription Factors in Rice.

    PubMed

    Moreno-Alvarado, Marcos; García-Morales, Soledad; Trejo-Téllez, Libia Iris; Hidalgo-Contreras, Juan Valente; Gómez-Merino, Fernando Carlos

    2017-01-01

    Aluminum (Al) is a beneficial element for some plant species, especially when used at low concentrations. Though some transcription factors are induced by exposure to this element, no data indicate that Al regulates the expression of NAC genes in rice. In this study we tested the effect of applying 200 μM Al on growth, chlorophyll, amino acids, sugars, macronutrient concentration and regulation of NAC transcription factors gene expression in 24-day-old plants of four rice (Oryza sativa ssp. indica) cultivars: Cotaxtla, Tres Ríos, Huimanguillo and Temporalero, grown hydroponically under greenhouse conditions. Twenty days after treatment, we observed that Al enhanced growth in the four cultivars studied. On average, plants grown in the presence of Al produced 140% more root dry biomass and were 30% taller than control plants. Cotaxtla and Temporalero showed double the root length, while Huimanguillo and Cotaxtla had three times more root fresh biomass and 2.5 times more root dry biomass. Huimanguillo plants showed 1.5 times more shoot height, while Cotaxtla had almost double the root dry biomass. With the exception of Tres Ríos, the rest of the cultivars had almost double the chlorophyll concentration when treated with Al, whereas amino acid and proline concentrations were not affected by Al. Sugar concentration was also increased in plants treated with Al, almost 11-fold in comparison to the control. Furthermore, we observed a synergic response of Al application on P and K concentration in roots, and on Mg concentration in shoots. Twenty-four hours after Al treatment, NAC transcription factors gene expression was measured in roots by quantitative RT-PCR. Of the 57 NAC transcription factors genes primer-pairs tested, we could distinguish that 44% (25 genes) showed different expression patterns among rice cultivars, with most of the genes induced in Cotaxtla and Temporalero plants. Of the 25 transcription factors up-regulated, those showing differential expression

  1. Aluminum Enhances Growth and Sugar Concentration, Alters Macronutrient Status and Regulates the Expression of NAC Transcription Factors in Rice

    PubMed Central

    Moreno-Alvarado, Marcos; García-Morales, Soledad; Trejo-Téllez, Libia Iris; Hidalgo-Contreras, Juan Valente; Gómez-Merino, Fernando Carlos

    2017-01-01

    Aluminum (Al) is a beneficial element for some plant species, especially when used at low concentrations. Though some transcription factors are induced by exposure to this element, no data indicate that Al regulates the expression of NAC genes in rice. In this study we tested the effect of applying 200 μM Al on growth, chlorophyll, amino acids, sugars, macronutrient concentration and regulation of NAC transcription factors gene expression in 24-day-old plants of four rice (Oryza sativa ssp. indica) cultivars: Cotaxtla, Tres Ríos, Huimanguillo and Temporalero, grown hydroponically under greenhouse conditions. Twenty days after treatment, we observed that Al enhanced growth in the four cultivars studied. On average, plants grown in the presence of Al produced 140% more root dry biomass and were 30% taller than control plants. Cotaxtla and Temporalero showed double the root length, while Huimanguillo and Cotaxtla had three times more root fresh biomass and 2.5 times more root dry biomass. Huimanguillo plants showed 1.5 times more shoot height, while Cotaxtla had almost double the root dry biomass. With the exception of Tres Ríos, the rest of the cultivars had almost double the chlorophyll concentration when treated with Al, whereas amino acid and proline concentrations were not affected by Al. Sugar concentration was also increased in plants treated with Al, almost 11-fold in comparison to the control. Furthermore, we observed a synergic response of Al application on P and K concentration in roots, and on Mg concentration in shoots. Twenty-four hours after Al treatment, NAC transcription factors gene expression was measured in roots by quantitative RT-PCR. Of the 57 NAC transcription factors genes primer-pairs tested, we could distinguish that 44% (25 genes) showed different expression patterns among rice cultivars, with most of the genes induced in Cotaxtla and Temporalero plants. Of the 25 transcription factors up-regulated, those showing differential expression

  2. Making Home Sweet and Sturdy: Toxoplasma gondii ppGalNAc-Ts Glycosylate in Hierarchical Order and Confer Cyst Wall Rigidity

    PubMed Central

    Tomita, Tadakimi; Sugi, Tatsuki; Yakubu, Rama; Tu, Vincent; Ma, Yanfen

    2017-01-01

    ABSTRACT The protozoan intracellular parasite Toxoplasma gondii forms latent cysts in the central nervous system (CNS) and persists for the lifetime of the host. This cyst is cloaked with a glycosylated structure called the cyst wall. Previously, we demonstrated that a mucin-like glycoprotein, CST1, localizes to the cyst wall and confers structural rigidity on brain cysts in a mucin-like domain-dependent manner. The mucin-like domain of CST1 is composed of 20 units of threonine-rich tandem repeats that are O-GalNAc glycosylated. A family of enzymes termed polypeptide N-acetylgalactosaminyltransferases (ppGalNAc-Ts) initiates O-GalNAc glycosylation. To identify which isoforms of ppGalNAc-Ts are responsible for the glycosylation of the CST1 mucin-like domain and to evaluate the function of each ppGalNAc-T in the overall glycosylation of the cyst wall, all five ppGalNAc-T isoforms were deleted individually from the T. gondii genome. The ppGalNAc-T2 and -T3 deletion mutants produced various glycosylation defects on the cyst wall, implying that many cyst wall glycoproteins are glycosylated by T2 and T3. Both T2 and T3 glycosylate the CST1 mucin-like domain, and this glycosylation is necessary for CST1 to confer structural rigidity on the cyst wall. We established that T2 is required for the initial glycosylation of the mucin-like domain and that T3 is responsible for the sequential glycosylation on neighboring acceptor sites, demonstrating hierarchical glycosylation by two distinct initiating and filling-in ppGalNAc-Ts in an intact organism. PMID:28074022

  3. Altered expression of O-GlcNAc-modified proteins in a mouse model whose glycemic status is controlled by a low carbohydrate ketogenic diet.

    PubMed

    Okuda, Tetsuya; Fukui, Asami; Morita, Naoki

    2013-11-01

    Abnormal modification of proteins by O-linked N-acetylglucosamine (O-GlcNAc) is known to be associated with the pathology induced by hyperglycemia. However, the dynamic mechanism of O-GlcNAc modification under hyperglycemic conditions in vivo has not been fully characterized. To understand the mechanism, we established an animal model in which the glycemic status is controlled by the diet. A mutant mouse (ob/ob) which exhibits diet-induced hyperglycemia when fed a regular chow (chow) was used to establish this model; the mice were fed a very low carbohydrate ketogenic diet (KD) to improve hyperglycemia. Using this model, we evaluated the levels of O-GlcNAc-modified proteins in tissues under a hyperglycemic or its improved condition. ELISA and Western blot analyses revealed that altered expression of certain proteins modified by O-GlcNAc were found in the mice tissues, although global O-GlcNAc levels in the tissues remained unaltered by improvement of hyperglycemia. We also found the Akt protein kinase was modified by O-GlcNAc in the liver of ob/ob mice, and the modification levels were decreased by improvement of hyperglycemia. Furthermore, aberrant phosphorylation of Akt was found in the liver of ob/ob mice under hyperglycemic condition. In conclusion, our established mouse model is useful for evaluating the dynamics of O-GlcNAc-modified proteins in tissues associated with glycemic status. This study revealed that the expression level of certain proteins modified by O-GlcNAc is altered when KD improves the hyperglycemia. These proteins could be prospective indexes for nutritional therapy for hyperglycemia-associated diseases, such as diabetes mellitus.

  4. IgG anti-GalNAc-GD1a antibody inhibits the voltage-dependent calcium channel currents in PC12 pheochromocytoma cells.

    PubMed

    Nakatani, Yoshihiko; Nagaoka, Takumi; Hotta, Sayako; Utsunomiya, Iku; Yoshino, Hiide; Miyatake, Tadashi; Hoshi, Keiko; Taguchi, Kyoji

    2007-03-01

    We investigated the effects of IgG anti-GalNAc-GD1a antibodies, produced by immunizing rabbits with GalNAc-GD1a, on the voltage-dependent calcium channel (VDCCs) currents in nerve growth factor (NGF)-differentiated PC12 pheochromocytoma cells. VDCCs currents in NGF-differentiated PC12 cells were recorded using the whole-cell patch-clamp technique. Immunized rabbit serum that had a high titer of anti-GalNAc-GD1a antibodies inhibited the VDCCs currents in the NGF-differentiated PC12 cells (36.0+/-9.6% reduction). The inhibitory effect of this serum was reversed to some degree within 3-4 min by washing with bath solution. Similarly, application of purified IgG from rabbit serum immunized with GalNAc-GD1a significantly inhibited the VDCCs currents in PC12 cells (30.6+/-2.5% reduction), and this inhibition was recovered by washing with bath solution. Furthermore, the inhibitory effect was also observed in the GalNAc-GD1a affinity column binding fraction (reduction of 31.1+/-9.85%), while the GalNAc-GD1a affinity column pass-through fraction attenuated the inhibitory effect on VDCCs currents. Normal rabbit serum and normal rabbit IgG did not affect the VDCCs currents in the PC12 cells. In an immunocytochemical study using fluorescence staining, the PC12 cells were stained using GalNAc-GD1a binding fraction. These results indicate that anti-GalNAc-GD1a antibodies inhibit the VDCCs currents in NGF-differentiated PC12 cells.

  5. Enhanced nicotine self-administration and suppressed dopaminergic systems in a rat model of diabetes.

    PubMed

    O'Dell, Laura E; Natividad, Luis A; Pipkin, Joseph A; Roman, Francisco; Torres, Ivan; Jurado, Jesus; Torres, Oscar V; Friedman, Theodore C; Tenayuca, John M; Nazarian, Arbi

    2014-11-01

    Patients with diabetes display a heightened propensity to use tobacco; however, it is unclear whether they experience enhanced rewarding effects of nicotine. Thus, this study examined the reinforcing effects of nicotine in a rodent model of diabetes involving administration of streptozotocin (STZ), a drug that is toxic to pancreatic insulin-producing cells. The first study compared STZ- and vehicle-treated rats that had 23-hour access to intravenous self-administration (IVSA) of nicotine or saline and concomitant access to food and water. In order to examine the contribution of dopamine to our behavioral effects, dopamine transporter (DAT), D1 and D2 receptor levels were compared in the nucleus accumbens (NAc) following 10 days of nicotine or saline IVSA. Dopamine levels in the NAc were also compared following nicotine administration. Lastly, nicotine metabolism and dose-dependent effects of nicotine IVSA were assessed. The results revealed that STZ-treated rats displayed enhanced nicotine intake and a robust increase in food and water intake relative to controls. Protein analysis revealed an increase in DAT and a decrease in D1 receptor levels in the NAc of STZ- versus vehicle-treated rats regardless of IVSA condition. STZ-treated rats also displayed suppressed NAc dopamine levels during baseline and in response to nicotine. STZ treatment did not alter our assessment of nicotine metabolism. Furthermore, STZ treatment increased nicotine IVSA in a dose-dependent manner. Our findings suggest that STZ-treatment increased the rewarding effects of nicotine. This suggests that strong reinforcing effects of nicotine may contribute to greater tobacco use in patients with diabetes.

  6. Enhanced nicotine self-administration and suppressed dopaminergic systems in a rat model of diabetes

    PubMed Central

    O'Dell, Laura E.; Natividad, Luis A.; Pipkin, Joseph A.; Roman, Francisco; Torres, Ivan; Jurado, Jesus; Torres, Oscar V.; Friedman, Theodore C.; Tenayuca, John M.; Nazarian, Arbi

    2013-01-01

    Patients with diabetes display a heightened propensity to use tobacco; however, it is unclear whether they experience enhanced rewarding effects of nicotine. Thus, this study examined the reinforcing effects of nicotine in a rodent model of diabetes involving administration of streptozotocin (STZ), a drug that is toxic to pancreatic insulin-producing cells. The first study compared STZ- and vehicle-treated rats that had 23-hour access to intravenous self-administration (IVSA) of nicotine or saline and concomitant access to food and water. In order to examine the contribution of dopamine to our behavioral effects, dopamine transporter (DAT), D1 and D2 receptor levels were compared in the nucleus accumbens (NAc) following 10 days of nicotine or saline IVSA. Dopamine levels in the NAc were also compared following nicotine administration. Lastly, nicotine metabolism and dose-dependent effects of nicotine IVSA were assessed. The results revealed that STZ-treated rats displayed enhanced nicotine intake and a robust increase in food and water intake relative to controls. Protein analysis revealed an increase in DAT and a decrease in D1 receptor levels in the NAc of STZ- versus vehicle-treated rats regardless of IVSA condition. STZ-treated rats also displayed suppressed NAc dopamine levels during baseline and in response to nicotine. STZ treatment did not alter our assessment of nicotine metabolism. Furthermore, STZ treatment increased nicotine IVSA in a dose-dependent manner. Our findings suggest that STZ-treatment increased the rewarding effects of nicotine. This suggests that strong reinforcing effects of nicotine may contribute to greater tobacco use in patients with diabetes. PMID:23834715

  7. Changes in dopamine transporter binding in nucleus accumbens following chronic self-administration cocaine: heroin combinations.

    PubMed

    Pattison, Lindsey P; McIntosh, Scot; Sexton, Tammy; Childers, Steven R; Hemby, Scott E

    2014-10-01

    Concurrent use of cocaine and heroin (speedball) has been shown to exert synergistic effects on dopamine neurotransmission in the nucleus accumbens (NAc), as observed by significant increases in extracellular dopamine levels and compensatory elevations in the maximal reuptake rate of dopamine. The present studies were undertaken to determine whether chronic self-administration of cocaine, heroin or a combination of cocaine:heroin led to compensatory changes in the abundance and/or affinity of high- and low-affinity DAT binding sites. Saturation binding of the cocaine analog [(125) I] 3β-(4-iodophenyl)tropan-2β-carboxylic acid methyl ester ([(125) I]RTI-55) in rat NAc membranes resulted in binding curves that were best fit to two-site binding models, allowing calculation of dissociation constant (Kd ) and binding density (Bmax ) values corresponding to high- and low-affinity DAT binding sites. Scatchard analysis of the saturation binding curves clearly demonstrate the presence of high- and low- affinity binding sites in the NAc, with low-affinity sites comprising 85 to 94% of the binding sites. DAT binding analyses revealed that self-administration of cocaine and a cocaine:heroin combination increased the affinity of the low-affinity site for the cocaine congener RTI-55 compared to saline. These results indicate that the alterations observed following chronic speedball self-administration are likely due to the cocaine component alone; thus further studies are necessary to elaborate upon the synergistic effect of cocaine:heroin combinations on the dopamine system in the NAc.

  8. Functional Characterization of Poplar Wood-Associated NAC Domain Transcription Factors1[C][OA

    PubMed Central

    Zhong, Ruiqin; Lee, Chanhui; Ye, Zheng-Hua

    2010-01-01

    Wood is the most abundant biomass produced by land plants. Dissection of the molecular mechanisms underlying the transcriptional regulation of wood formation is a fundamental issue in plant biology and has important implications in tree biotechnology. Although a number of transcription factors in tree species have been shown to be associated with wood formation and some of them are implicated in lignin biosynthesis, none of them have been demonstrated to be key regulators of the biosynthesis of all three major components of wood. In this report, we have identified a group of NAC domain transcription factors, PtrWNDs, that are preferentially expressed in developing wood of poplar (Populus trichocarpa). Expression of PtrWNDs in the Arabidopsis (Arabidopsis thaliana) snd1 nst1 double mutant effectively complemented the secondary wall defects in fibers, indicating that PtrWNDs are capable of activating the entire secondary wall biosynthetic program. Overexpression of PtrWND2B and PtrWND6B in Arabidopsis induced the expression of secondary wall-associated transcription factors and secondary wall biosynthetic genes and, concomitantly, the ectopic deposition of cellulose, xylan, and lignin. Furthermore, PtrWND2B and PtrWND6B were able to activate the promoter activities of a number of poplar wood-associated transcription factors and wood biosynthetic genes. Together, these results demonstrate that PtrWNDs are functional orthologs of SND1 and suggest that PtrWNDs together with their downstream transcription factors form a transcriptional network involved in the regulation of wood formation in poplar. PMID:19965968

  9. Gene and protein expression of O-GlcNAc-cycling enzymes in human laryngeal cancer.

    PubMed

    Starska, Katarzyna; Forma, Ewa; Brzezińska-Błaszczyk, Ewa; Lewy-Trenda, Iwona; Bryś, Magdalena; Jóźwiak, Paweł; Krześlak, Anna

    2015-11-01

    Aberrant protein O-GlcNAcylation may contribute to the development and malignant behavior of many cancers. This modification is controlled by O-linked β-N-acetylglucosamine transferase (OGT) and O-GlcNAcase (OGA). The aim of this study was to determine the expression of O-GlcNAc cycling enzymes mRNA/protein and to investigate their relationship with clinicopathological parameters in laryngeal cancer. The mRNA levels of OGT and MGEA5 genes were determined in 106 squamous cell laryngeal cancer (SCLC) cases and 73 non-cancerous adjacent laryngeal mucosa (NCLM) controls using quantitative real-time PCR. The level of OGT and OGA proteins was analyzed by Western blot. A positive expression of OGT and MGEA5 transcripts and OGT and OGA proteins was confirmed in 75.5 and 68.9 % and in 43.7 and 59.4 % samples of SCLC, respectively. Higher levels of mRNA/protein for both OGT and OGA as well as significant increases of 60 % in total protein O-GlcNAcylation levels were noted in SCLC compared with NCLM (p < 0.05). As a result, an increased level of OGT and MGEA5 mRNA was related to larger tumor size, nodal metastases, higher grade and tumor behavior according to TFG scale, as well as incidence of disease recurrence (p < 0.05). An inverse association between OGT and MGEA5 transcripts was determined with regard to prognosis (p < 0.05). In addition, the highest OGT and OGA protein levels were observed in poorly differentiated tumors (p < 0.05). No correlations with other parameters were noted, but the results showed a trend of more advanced tumors to be more frequently OGT and OGA positive. The results suggest that increased O-GlcNAcylation may have an effect on tumor aggressiveness and prognosis in laryngeal cancer.

  10. 76 FR 4113 - Federal Procurement Data System Product Service Code Manual Update

    Federal Register 2010, 2011, 2012, 2013, 2014

    2011-01-24

    ... ADMINISTRATION Federal Procurement Data System Product Service Code Manual Update AGENCY: Office of... the Products and Services Code (PSC) Manual, which provides codes to describe products, services, and... pat.brooks@gsa.gov . SUPPLEMENTARY INFORMATION: The Products and Services Code (PSC) Manual...

  11. 76 FR 49772 - Guidance for Industry: Bar Code Label Requirements-Questions and Answers; Availability

    Federal Register 2010, 2011, 2012, 2013, 2014

    2011-08-11

    ... HUMAN SERVICES Food and Drug Administration Guidance for Industry: Bar Code Label Requirements... Industry: Bar Code Label Requirements--Questions and Answers'' dated August 2011. The guidance announced in... alternative coding technologies to the linear bar code requirement. The guidance announced in this...

  12. Software Certification - Coding, Code, and Coders

    NASA Technical Reports Server (NTRS)

    Havelund, Klaus; Holzmann, Gerard J.

    2011-01-01

    We describe a certification approach for software development that has been adopted at our organization. JPL develops robotic spacecraft for the exploration of the solar system. The flight software that controls these spacecraft is considered to be mission critical. We argue that the goal of a software certification process cannot be the development of "perfect" software, i.e., software that can be formally proven to be correct under all imaginable and unimaginable circumstances. More realistically, the goal is to guarantee a software development process that is conducted by knowledgeable engineers, who follow generally accepted procedures to control known risks, while meeting agreed upon standards of workmanship. We target three specific issues that must be addressed in such a certification procedure: the coding process, the code that is developed, and the skills of the coders. The coding process is driven by standards (e.g., a coding standard) and tools. The code is mechanically checked against the standard with the help of state-of-the-art static source code analyzers. The coders, finally, are certified in on-site training courses that include formal exams.

  13. Modification of STIM1 by O-linked N-Acetylglucosamine (O-GlcNAc) Attenuates Store-operated Calcium Entry in Neonatal Cardiomyocytes*

    PubMed Central

    Zhu-Mauldin, Xiaoyuan; Marsh, Susan A.; Zou, Luyun; Marchase, Richard B.; Chatham, John C.

    2012-01-01

    Store-operated calcium entry (SOCE) is a major Ca2+ signaling pathway responsible for regulating numerous transcriptional events. In cardiomyocytes SOCE has been shown to play an important role in regulating hypertrophic signaling pathways, including nuclear translocation of NFAT. Acute activation of pathways leading to O-GlcNAc synthesis have been shown to impair SOCE-mediated transcription and in diabetes, where O-GlcNAc levels are chronically elevated, cardiac hypertrophic signaling is also impaired. Therefore the goal of this study was to determine whether changes in cardiomyocyte O-GlcNAc levels impaired the function of STIM1, a widely recognized mediator of SOCE. We demonstrated that acute activation of SOCE in neonatal cardiomyocytes resulted in STIM1 puncta formation, which was inhibited in a dose-dependent manner by increasing O-GlcNAc synthesis with glucosamine or inhibiting O-GlcNAcase with thiamet-G. Glucosamine and thiamet-G also inhibited SOCE and were associated with increased O-GlcNAc modification of STIM1. These results suggest that activation of cardiomyocyte O-GlcNAcylation attenuates SOCE via STIM1 O-GlcNAcylation and that this may represent a new mechanism by which increased O-GlcNAc levels regulate Ca2+-mediated events in cardiomyocytes. Further, since SOCE is a fundamental mechanism underlying Ca2+ signaling in most cells and tissues, it is possible that STIM1 represents a nexus linking protein O-GlcNAcylation with Ca2+-mediated transcription. PMID:22992728

  14. Vaccination-induced IgG response to Galα1-3GalNAc glycan epitopes in lambs protected against Haemonchus contortus challenge infection

    PubMed Central

    van Stijn, Caroline M.W.; van den Broek, Marloes; Vervelde, Lonneke; Alvarez, Richard A.; Cummings, Richard D.; Tefsen, Boris; van Die, Irma

    2009-01-01

    Lambs vaccinated with Haemonchus contortus excretory/secretory (ES) glycoproteins in combination with the adjuvant Alhydrogel are protected against H. contortus challenge infection. Using glycan microarray analysis we showed that serum from such vaccinated lambs contains IgG antibodies that recognize the glycan antigen Galα1-3GalNAc-R and GalNAcβ1-4(Fucα1-3)GlcNAc-R. Our studies revealed that H. contortus glycoproteins contain Galα1-3Gal-R as well as significant levels of Galα1-3GalNAc-R, which has not been previously reported. Extracts from H. contortus adult worms contain a galactosyltransferase acting on glycan substrates with a terminal GalNAc, indicating that the worms possess the enzymatic potential to synthesize terminal Gal-GalNAc moieties. These data illustrate that glycan microarrays constitute a promising technology for fast and specific analysis of serum anti-glycan antibodies in vaccination studies. In addition, this approach facilitates the discovery of novel, antigenic parasite glycan antigens that may have potential for developing glycoconjugate vaccines or utilization in diagnostics. PMID:19695255

  15. 21 CFR 106.90 - Coding.

    Code of Federal Regulations, 2013 CFR

    2013-04-01

    ... 21 Food and Drugs 2 2013-04-01 2013-04-01 false Coding. 106.90 Section 106.90 Food and Drugs FOOD AND DRUG ADMINISTRATION, DEPARTMENT OF HEALTH AND HUMAN SERVICES (CONTINUED) FOOD FOR HUMAN CONSUMPTION INFANT FORMULA QUALITY CONTROL PROCEDURES Quality Control Procedures for Assuring Nutrient...

  16. 21 CFR 106.90 - Coding.

    Code of Federal Regulations, 2011 CFR

    2011-04-01

    ... 21 Food and Drugs 2 2011-04-01 2011-04-01 false Coding. 106.90 Section 106.90 Food and Drugs FOOD AND DRUG ADMINISTRATION, DEPARTMENT OF HEALTH AND HUMAN SERVICES (CONTINUED) FOOD FOR HUMAN CONSUMPTION INFANT FORMULA QUALITY CONTROL PROCEDURES Quality Control Procedures for Assuring Nutrient...

  17. 21 CFR 106.90 - Coding.

    Code of Federal Regulations, 2012 CFR

    2012-04-01

    ... 21 Food and Drugs 2 2012-04-01 2012-04-01 false Coding. 106.90 Section 106.90 Food and Drugs FOOD AND DRUG ADMINISTRATION, DEPARTMENT OF HEALTH AND HUMAN SERVICES (CONTINUED) FOOD FOR HUMAN CONSUMPTION INFANT FORMULA QUALITY CONTROL PROCEDURES Quality Control Procedures for Assuring Nutrient...

  18. 21 CFR 106.90 - Coding.

    Code of Federal Regulations, 2010 CFR

    2010-04-01

    ... 21 Food and Drugs 2 2010-04-01 2010-04-01 false Coding. 106.90 Section 106.90 Food and Drugs FOOD AND DRUG ADMINISTRATION, DEPARTMENT OF HEALTH AND HUMAN SERVICES (CONTINUED) FOOD FOR HUMAN CONSUMPTION INFANT FORMULA QUALITY CONTROL PROCEDURES Quality Control Procedures for Assuring Nutrient...

  19. A Code of Ethics for Democratic Leadership

    ERIC Educational Resources Information Center

    Molina, Ricardo; Klinker, JoAnn Franklin

    2012-01-01

    Democratic leadership rests on sacred values, awareness, judgement, motivation and courage. Four turning points in a 38-year school administrator's career revealed decision-making in problematic moments stemmed from values in a personal and professional code of ethics. Reflection on practice and theory added vocabulary and understanding to make…

  20. XSOR codes users manual

    SciTech Connect

    Jow, Hong-Nian; Murfin, W.B.; Johnson, J.D.

    1993-11-01

    This report describes the source term estimation codes, XSORs. The codes are written for three pressurized water reactors (Surry, Sequoyah, and Zion) and two boiling water reactors (Peach Bottom and Grand Gulf). The ensemble of codes has been named ``XSOR``. The purpose of XSOR codes is to estimate the source terms which would be released to the atmosphere in severe accidents. A source term includes the release fractions of several radionuclide groups, the timing and duration of releases, the rates of energy release, and the elevation of releases. The codes have been developed by Sandia National Laboratories for the US Nuclear Regulatory Commission (NRC) in support of the NUREG-1150 program. The XSOR codes are fast running parametric codes and are used as surrogates for detailed mechanistic codes. The XSOR codes also provide the capability to explore the phenomena and their uncertainty which are not currently modeled by the mechanistic codes. The uncertainty distributions of input parameters may be used by an. XSOR code to estimate the uncertainty of source terms.

  1. DLLExternalCode

    SciTech Connect

    Greg Flach, Frank Smith

    2014-05-14

    DLLExternalCode is the a general dynamic-link library (DLL) interface for linking GoldSim (www.goldsim.com) with external codes. The overall concept is to use GoldSim as top level modeling software with interfaces to external codes for specific calculations. The DLLExternalCode DLL that performs the linking function is designed to take a list of code inputs from GoldSim, create an input file for the external application, run the external code, and return a list of outputs, read from files created by the external application, back to GoldSim. Instructions for creating the input file, running the external code, and reading the output are contained in an instructions file that is read and interpreted by the DLL.

  2. Defeating the coding monsters.

    PubMed

    Colt, Ross

    2007-02-01

    Accuracy in coding is rapidly becoming a required skill for military health care providers. Clinic staffing, equipment purchase decisions, and even reimbursement will soon be based on the coding data that we provide. Learning the complicated myriad of rules to code accurately can seem overwhelming. However, the majority of clinic visits in a typical outpatient clinic generally fall into two major evaluation and management codes, 99213 and 99214. If health care providers can learn the rules required to code a 99214 visit, then this will provide a 90% solution that can enable them to accurately code the majority of their clinic visits. This article demonstrates a step-by-step method to code a 99214 visit, by viewing each of the three requirements as a monster to be defeated.

  3. Biochemical characterization of the Campylobacter jejuni Cj1294, a novel UDP-4-keto-6-deoxy-GlcNAc aminotransferase that generates UDP-4-amino-4,6-dideoxy-GalNAc.

    PubMed

    Obhi, Ravinder Kaur; Creuzenet, Carole

    2005-05-27

    Campylobacter jejuni produces multiple glycoproteins whose glycans contain 4-amino 6-deoxy sugars or their derivatives, such as diacetamidobacillosamine or pseudaminic acid. Because the proteoglycans contribute to bacterial virulence and their constitutive sugars are not commonly found in humans, inhibitors developed against the enzymes that are responsible for their biosynthesis could be novel therapeutic targets to fight this important food-borne pathogen. The biosynthesis of diacetamidobacillosamine is anticipated to involve a sugar nucleotide C6 dehydratase, a C4 aminotransferase and an acetyltransferase. We have identified a set of genes (cj1293, cj1294, and cj1298) potentially encoding one of each enzymatic activity, and demonstrated earlier that Cj1293 was a UDP-GlcNAc-specific C6 dehydratase. Others have shown that Cj1293 was involved in protein glycosylation. Here, we report on our investigation of the potential activity of Cj1294 as a sugar nucleotide C4 aminotransferase. Our biochemical characterization of overexpressed and purified protein shows that Cj1294 is a pyridoxal phosphate-dependent aminotransferase specific for UDP-4-keto-6-deoxy-GlcNAc that uses preferentially glutamic acid as an amino donor. A detailed physicokinetic study of Cj1294 was performed to determine the K(m) of 1.28 +/- 0.2 mm and k(cat) of 11.5 +/- 1.3 min(-1). Also, two residues essential for protein stability and activity, Arg(228) and Lys(181), respectively, were identified by site-directed mutagenesis. Finally, we demonstrated by NMR analysis of purified reaction product that Cj1294 produces UDP-4-amino-4,6-dideoxy-GalNAc. These results indicate that Cj1294 is involved in the biosynthesis of diacetamidofucosamine, a C4 epimer of diacetamidobacillosamine not yet described in C. jejuni proteoglycans, suggesting that the composition of C. jejuni proteoglycans is more variable than anticipated.

  4. Evaluation of the effect of N-acetyl-glucosamine administration on biomarkers for cartilage metabolism in healthy individuals without symptoms of arthritis: A randomized double-blind placebo-controlled clinical study

    PubMed Central

    Tomonaga, Akihito; Watanabe, Keita; Fukagawa, Mitsuhiko; Suzuki, Asahi; Kurokawa, Mihoko; Nagaoka, Isao

    2016-01-01

    The present study aimed to evaluate the effect of N-acetyl-glucosamine (GlcNAc) on the joint health of healthy individuals without arthritic symptoms. A randomized double-blind placebo-controlled clinical trial was performed to investigate the effect of oral administration of a GlcNAc-containing test supplement (low dose, 500 mg/day and high dose, 1,000 mg/day) on cartilage metabolism in healthy individuals with a mean age of 48.6±1.3 years (range, 23–64 years) by analyzing the ratio of type II collagen degradation to type II collagen synthesis using type II collagen degradation (C2C) and synthesis (PIICP) markers. The results indicated that the changes in C2C/PIICP ratios from the baseline were suppressed in the treated with low and high doses of GlcNAc, compared with the placebo group at week 16 during intervention. To further elucidate the effect of GlcNAc, subjects with impaired cartilage metabolism were evaluated. Notably, the changes in the C2C/PIICP ratios were markedly suppressed in the groups treated with low and high doses of GlcNAc at week 16. Finally, to exclude the effect of heavy body weight on joint loading, subjects weighing <70 kg with impaired cartilage metabolism were analyzed. Notably, the changes in the C2C/PIICP ratios were suppressed in the groups treated with low and high doses of GlcNAc at weeks 12 and 16. No test supplement-related adverse events were observed during or following the intervention. Together, these observations suggest that oral administration of GlcNAc at doses of 500 mg and 1,000 mg/day exhibits a chondroprotective effect on healthy individuals by reducing the C2C/PIICP ratio (relatively decreasing type II collagen degradation and increasing type II collagen synthesis) without any apparent adverse effects. PMID:27588069

  5. Mechanical code comparator

    DOEpatents

    Peter, Frank J.; Dalton, Larry J.; Plummer, David W.

    2002-01-01

    A new class of mechanical code comparators is described which have broad potential for application in safety, surety, and security applications. These devices can be implemented as micro-scale electromechanical systems that isolate a secure or otherwise controlled device until an access code is entered. This access code is converted into a series of mechanical inputs to the mechanical code comparator, which compares the access code to a pre-input combination, entered previously into the mechanical code comparator by an operator at the system security control point. These devices provide extremely high levels of robust security. Being totally mechanical in operation, an access control system properly based on such devices cannot be circumvented by software attack alone.

  6. More box codes

    NASA Technical Reports Server (NTRS)

    Solomon, G.

    1992-01-01

    A new investigation shows that, starting from the BCH (21,15;3) code represented as a 7 x 3 matrix and adding a row and column to add even parity, one obtains an 8 x 4 matrix (32,15;8) code. An additional dimension is obtained by specifying odd parity on the rows and even parity on the columns, i.e., adjoining to the 8 x 4 matrix, the matrix, which is zero except for the fourth column (of all ones). Furthermore, any seven rows and three columns will form the BCH (21,15;3) code. This box code has the same weight structure as the quadratic residue and BCH codes of the same dimensions. Whether there exists an algebraic isomorphism to either code is as yet unknown.

  7. Generating code adapted for interlinking legacy scalar code and extended vector code

    DOEpatents

    Gschwind, Michael K

    2013-06-04

    Mechanisms for intermixing code are provided. Source code is received for compilation using an extended Application Binary Interface (ABI) that extends a legacy ABI and uses a different register configuration than the legacy ABI. First compiled code is generated based on the source code, the first compiled code comprising code for accommodating the difference in register configurations used by the extended ABI and the legacy ABI. The first compiled code and second compiled code are intermixed to generate intermixed code, the second compiled code being compiled code that uses the legacy ABI. The intermixed code comprises at least one call instruction that is one of a call from the first compiled code to the second compiled code or a call from the second compiled code to the first compiled code. The code for accommodating the difference in register configurations is associated with the at least one call instruction.

  8. Industrial Computer Codes

    NASA Technical Reports Server (NTRS)

    Shapiro, Wilbur

    1996-01-01

    This is an overview of new and updated industrial codes for seal design and testing. GCYLT (gas cylindrical seals -- turbulent), SPIRALI (spiral-groove seals -- incompressible), KTK (knife to knife) Labyrinth Seal Code, and DYSEAL (dynamic seal analysis) are covered. CGYLT uses G-factors for Poiseuille and Couette turbulence coefficients. SPIRALI is updated to include turbulence and inertia, but maintains the narrow groove theory. KTK labyrinth seal code handles straight or stepped seals. And DYSEAL provides dynamics for the seal geometry.

  9. Phonological coding during reading

    PubMed Central

    Leinenger, Mallorie

    2014-01-01

    The exact role that phonological coding (the recoding of written, orthographic information into a sound based code) plays during silent reading has been extensively studied for more than a century. Despite the large body of research surrounding the topic, varying theories as to the time course and function of this recoding still exist. The present review synthesizes this body of research, addressing the topics of time course and function in tandem. The varying theories surrounding the function of phonological coding (e.g., that phonological codes aid lexical access, that phonological codes aid comprehension and bolster short-term memory, or that phonological codes are largely epiphenomenal in skilled readers) are first outlined, and the time courses that each maps onto (e.g., that phonological codes come online early (pre-lexical) or that phonological codes come online late (post-lexical)) are discussed. Next the research relevant to each of these proposed functions is reviewed, discussing the varying methodologies that have been used to investigate phonological coding (e.g., response time methods, reading while eyetracking or recording EEG and MEG, concurrent articulation) and highlighting the advantages and limitations of each with respect to the study of phonological coding. In response to the view that phonological coding is largely epiphenomenal in skilled readers, research on the use of phonological codes in prelingually, profoundly deaf readers is reviewed. Finally, implications for current models of word identification (activation-verification model (Van Order, 1987), dual-route model (e.g., Coltheart, Rastle, Perry, Langdon, & Ziegler, 2001), parallel distributed processing model (Seidenberg & McClelland, 1989)) are discussed. PMID:25150679

  10. 21 CFR 610.67 - Bar code label requirements.

    Code of Federal Regulations, 2013 CFR

    2013-04-01

    ... 21 Food and Drugs 7 2013-04-01 2013-04-01 false Bar code label requirements. 610.67 Section 610.67 Food and Drugs FOOD AND DRUG ADMINISTRATION, DEPARTMENT OF HEALTH AND HUMAN SERVICES (CONTINUED) BIOLOGICS GENERAL BIOLOGICAL PRODUCTS STANDARDS Labeling Standards § 610.67 Bar code label...

  11. 21 CFR 610.67 - Bar code label requirements.

    Code of Federal Regulations, 2014 CFR

    2014-04-01

    ... 21 Food and Drugs 7 2014-04-01 2014-04-01 false Bar code label requirements. 610.67 Section 610.67 Food and Drugs FOOD AND DRUG ADMINISTRATION, DEPARTMENT OF HEALTH AND HUMAN SERVICES (CONTINUED) BIOLOGICS GENERAL BIOLOGICAL PRODUCTS STANDARDS Labeling Standards § 610.67 Bar code label...

  12. 21 CFR 610.67 - Bar code label requirements.

    Code of Federal Regulations, 2012 CFR

    2012-04-01

    ... 21 Food and Drugs 7 2012-04-01 2012-04-01 false Bar code label requirements. 610.67 Section 610.67 Food and Drugs FOOD AND DRUG ADMINISTRATION, DEPARTMENT OF HEALTH AND HUMAN SERVICES (CONTINUED) BIOLOGICS GENERAL BIOLOGICAL PRODUCTS STANDARDS Labeling Standards § 610.67 Bar code label...

  13. 1 CFR 11.3 - Code of Federal Regulations.

    Code of Federal Regulations, 2011 CFR

    2011-01-01

    ... 1 General Provisions 1 2011-01-01 2011-01-01 false Code of Federal Regulations. 11.3 Section 11.3 General Provisions ADMINISTRATIVE COMMITTEE OF THE FEDERAL REGISTER AVAILABILITY OF OFFICE OF THE FEDERAL... complete set of the Code of Federal Regulations is $1,019 per year for the bound, paper edition, or...

  14. 34 CFR 74.42 - Codes of conduct.

    Code of Federal Regulations, 2010 CFR

    2010-07-01

    ... 34 Education 1 2010-07-01 2010-07-01 false Codes of conduct. 74.42 Section 74.42 Education Office of the Secretary, Department of Education ADMINISTRATION OF GRANTS AND AGREEMENTS WITH INSTITUTIONS... Procurement Standards § 74.42 Codes of conduct. The recipient shall maintain written standards of...

  15. 22 CFR 226.42 - Codes of conduct.

    Code of Federal Regulations, 2010 CFR

    2010-04-01

    ... 22 Foreign Relations 1 2010-04-01 2010-04-01 false Codes of conduct. 226.42 Section 226.42 Foreign Relations AGENCY FOR INTERNATIONAL DEVELOPMENT ADMINISTRATION OF ASSISTANCE AWARDS TO U.S. NON-GOVERNMENTAL ORGANIZATIONS Post-award Requirements Procurement Standards § 226.42 Codes of conduct. The recipient...

  16. 14 CFR 1274.503 - Codes of conduct.

    Code of Federal Regulations, 2010 CFR

    2010-01-01

    ... 14 Aeronautics and Space 5 2010-01-01 2010-01-01 false Codes of conduct. 1274.503 Section 1274.503 Aeronautics and Space NATIONAL AERONAUTICS AND SPACE ADMINISTRATION COOPERATIVE AGREEMENTS WITH COMMERCIAL FIRMS Procurement Standards § 1274.503 Codes of conduct. The recipient shall maintain written...

  17. 43 CFR 12.942 - Codes of conduct.

    Code of Federal Regulations, 2010 CFR

    2010-10-01

    ... 43 Public Lands: Interior 1 2010-10-01 2010-10-01 false Codes of conduct. 12.942 Section 12.942 Public Lands: Interior Office of the Secretary of the Interior ADMINISTRATIVE AND AUDIT REQUIREMENTS AND... Requirements § 12.942 Codes of conduct. The recipient shall maintain written standards of conduct governing...

  18. 15 CFR 14.42 - Codes of conduct.

    Code of Federal Regulations, 2010 CFR

    2010-01-01

    ... 15 Commerce and Foreign Trade 1 2010-01-01 2010-01-01 false Codes of conduct. 14.42 Section 14.42 Commerce and Foreign Trade Office of the Secretary of Commerce UNIFORM ADMINISTRATIVE REQUIREMENTS FOR... ORGANIZATIONS Post-Award Requirements Procurement Standards § 14.42 Codes of conduct. The recipient...

  19. 14 CFR 1260.142 - Codes of conduct.

    Code of Federal Regulations, 2010 CFR

    2010-01-01

    ... 14 Aeronautics and Space 5 2010-01-01 2010-01-01 false Codes of conduct. 1260.142 Section 1260.142 Aeronautics and Space NATIONAL AERONAUTICS AND SPACE ADMINISTRATION GRANTS AND COOPERATIVE AGREEMENTS Uniform..., Hospitals, and Other Non-Profit Organizations Procurement Standards § 1260.142 Codes of conduct....

  20. 22 CFR 518.42 - Codes of conduct.

    Code of Federal Regulations, 2010 CFR

    2010-04-01

    ... 22 Foreign Relations 2 2010-04-01 2010-04-01 true Codes of conduct. 518.42 Section 518.42 Foreign Relations BROADCASTING BOARD OF GOVERNORS UNIFORM ADMINISTRATIVE REQUIREMENTS FOR GRANTS AND AGREEMENTS WITH... Procurement Standards § 518.42 Codes of conduct. The recipient shall maintain written standards of...

  1. 10 CFR 600.142 - Codes of conduct.

    Code of Federal Regulations, 2010 CFR

    2010-01-01

    ... 10 Energy 4 2010-01-01 2010-01-01 false Codes of conduct. 600.142 Section 600.142 Energy DEPARTMENT OF ENERGY (CONTINUED) ASSISTANCE REGULATIONS FINANCIAL ASSISTANCE RULES Uniform Administrative... Nonprofit Organizations Post-Award Requirements § 600.142 Codes of conduct. The recipient shall...

  2. 49 CFR 19.42 - Codes of conduct.

    Code of Federal Regulations, 2010 CFR

    2010-10-01

    ... 49 Transportation 1 2010-10-01 2010-10-01 false Codes of conduct. 19.42 Section 19.42 Transportation Office of the Secretary of Transportation UNIFORM ADMINISTRATIVE REQUIREMENTS FOR GRANTS AND... Requirements Procurement Standards § 19.42 Codes of conduct. The recipient shall maintain written standards...

  3. 49 CFR 236.727 - Circuit, track; coded.

    Code of Federal Regulations, 2010 CFR

    2010-10-01

    ... 49 Transportation 4 2010-10-01 2010-10-01 false Circuit, track; coded. 236.727 Section 236.727 Transportation Other Regulations Relating to Transportation (Continued) FEDERAL RAILROAD ADMINISTRATION... Circuit, track; coded. A track circuit in which the energy is varied or interrupted periodically....

  4. 21 CFR 610.67 - Bar code label requirements.

    Code of Federal Regulations, 2011 CFR

    2011-04-01

    ... 21 Food and Drugs 7 2011-04-01 2010-04-01 true Bar code label requirements. 610.67 Section 610.67 Food and Drugs FOOD AND DRUG ADMINISTRATION, DEPARTMENT OF HEALTH AND HUMAN SERVICES (CONTINUED) BIOLOGICS GENERAL BIOLOGICAL PRODUCTS STANDARDS Labeling Standards § 610.67 Bar code label...

  5. Eating 'Junk-Food' Produces Rapid and Long-Lasting Increases in NAc CP-AMPA Receptors: Implications for Enhanced Cue-Induced Motivation and Food Addiction.

    PubMed

    Oginsky, Max F; Goforth, Paulette B; Nobile, Cameron W; Lopez-Santiago, Luis F; Ferrario, Carrie R

    2016-12-01

    Urges to eat are influenced by stimuli in the environment that are associated with food (food cues). Obese people are more sensitive to food cues, reporting stronger craving and consuming larger portions after food cue exposure. The nucleus accumbens (NAc) mediates cue-triggered motivational responses, and activations in the NAc triggered by food cues are stronger in people who are susceptible to obesity. This has led to the idea that alterations in NAc function similar to those underlying drug addiction may contribute to obesity, particularly in obesity-susceptible individuals. Motivational responses are mediated in part by NAc AMPA receptor (AMPAR) transmission, and recent work shows that cue-triggered motivation is enhanced in obesity-susceptible rats after 'junk-food' diet consumption. Therefore, here we determined whether NAc AMPAR expression and function is increased by 'junk-food' diet consumption in obesity-susceptible vs -resistant populations using both outbred and selectively bred models of susceptibility. In addition, cocaine-induced locomotor activity was used as a general 'read out' of mesolimbic function after 'junk-food' consumption. We found a sensitized locomotor response to cocaine in rats that gained weight on a 'junk-food' diet, consistent with greater responsivity of mesolimbic circuits in obesity-susceptible groups. In addition, eating 'junk-food' increased NAc calcium-permeable-AMPAR (CP-AMPAR) function only in obesity-susceptible rats. This increase occurred rapidly, persisted for weeks after 'junk-food' consumption ceased, and preceded the development of obesity. These data are considered in light of enhanced cue-triggered motivation and striatal function in obesity-susceptible rats and the role of NAc CP-AMPARs in enhanced motivation and addiction.

  6. D1 and D2 antagonists reverse the effects of appetite suppressants on weight loss, food intake, locomotion, and rebalance spiking inhibition in the rat NAc shell.

    PubMed

    Kalyanasundar, B; Perez, Claudia I; Luna, Alvaro; Solorio, Jessica; Moreno, Mario G; Elias, David; Simon, Sidney A; Gutierrez, Ranier

    2015-07-01

    Obesity is a worldwide health problem that has reached epidemic proportions. To ameliorate this problem, one approach is the use of appetite suppressants. These compounds are frequently amphetamine congeners such as diethylpropion (DEP), phentermine (PHEN), and bupropion (BUP), whose effects are mediated through serotonin, norepinephrine, and dopaminergic pathways. The nucleus accumbens (NAc) shell receives dopaminergic inputs and is involved in feeding and motor activity. However, little is known about how appetite suppressants modulate its activity. Therefore, we characterized behavioral and neuronal NAc shell responses to short-term treatments of DEP, PHEN, and BUP. These compounds caused a transient decrease in weight and food intake while increasing locomotion, stereotypy, and insomnia. They evoked a large inhibitory imbalance in NAc shell spiking activity that correlated with the onset of locomotion and stereotypy. Analysis of the local field potentials (LFPs) showed that all three drugs modulated beta, theta, and delta oscillations. These oscillations do not reflect an aversive-malaise brain state, as ascertained from taste aversion experiments, but tracked both the initial decrease in weight and food intake and the subsequent tolerance to these drugs. Importantly, the appetite suppressant-induced weight loss and locomotion were markedly reduced by intragastric (and intra-NAc shell) infusions of dopamine antagonists SCH-23390 (D1 receptor) or raclopride (D2 receptor). Furthermore, both antagonists attenuated appetite suppressant-induced LFP oscillations and partially restored the imbalance in NAc shell activity. These data reveal that appetite suppressant-induced behavioral and neuronal activity recorded in the NAc shell depend, to various extents, on dopaminergic activation and thus point to an important role for D1/D2-like receptors (in the NAc shell) in the mechanism of action for these anorexic compounds.

  7. Caenorhabditis elegans ortholog of a diabetes susceptibility locus: oga-1 (O-GlcNAcase) knockout impacts O-GlcNAc cycling, metabolism, and dauer.

    PubMed

    Forsythe, Michele E; Love, Dona C; Lazarus, Brooke D; Kim, Eun Ju; Prinz, William A; Ashwell, Gilbert; Krause, Michael W; Hanover, John A

    2006-08-08

    A dynamic cycle of O-linked N-acetylglucosamine (O-GlcNAc) addition and removal acts on nuclear pore proteins, transcription factors, and kinases to modulate cellular signaling cascades. Two highly conserved enzymes (O-GlcNAc transferase and O-GlcNAcase) catalyze the final steps in this nutrient-driven "hexosamine-signaling pathway." A single nucleotide polymorphism in the human O-GlcNAcase gene is linked to type 2 diabetes. Here, we show that Caenorhabditis elegans oga-1 encodes an active O-GlcNAcase. We also describe a knockout allele, oga-1(ok1207), that is viable and fertile yet accumulates O-GlcNAc on nuclear pores and other cellular proteins. Interfering with O-GlcNAc cycling with either oga-1(ok1207) or the O-GlcNAc transferase-null ogt-1(ok430) altered Ser- and Thr-phosphoprotein profiles and increased glycogen synthase kinase 3beta (GSK-3beta) levels. Both the oga-1(ok1207) and ogt-1(ok430) strains showed elevated stores of glycogen and trehalose, and decreased lipid storage. These striking metabolic changes prompted us to examine the insulin-like signaling pathway controlling nutrient storage, longevity, and dauer formation in the C. elegans O-GlcNAc cycling mutants. Indeed, we found that the oga-1(ok1207) knockout augmented dauer formation induced by a temperature sensitive insulin-like receptor (daf-2) mutant under conditions in which the ogt-1(ok430)-null diminished dauer formation. Our findings suggest that the enzymes of O-GlcNAc cycling "fine-tune" insulin-like signaling in response to nutrient flux. The knockout of O-GlcNAcase (oga-1) in C. elegans mimics many of the metabolic and signaling changes associated with human insulin resistance and provides a genetically amenable model of non-insulin-dependent diabetes.

  8. D1 and D2 antagonists reverse the effects of appetite suppressants on weight loss, food intake, locomotion, and rebalance spiking inhibition in the rat NAc shell

    PubMed Central

    Kalyanasundar, B.; Perez, Claudia I.; Luna, Alvaro; Solorio, Jessica; Moreno, Mario G.; Elias, David; Simon, Sidney A.

    2015-01-01

    Obesity is a worldwide health problem that has reached epidemic proportions. To ameliorate this problem, one approach is the use of appetite suppressants. These compounds are frequently amphetamine congeners such as diethylpropion (DEP), phentermine (PHEN), and bupropion (BUP), whose effects are mediated through serotonin, norepinephrine, and dopaminergic pathways. The nucleus accumbens (NAc) shell receives dopaminergic inputs and is involved in feeding and motor activity. However, little is known about how appetite suppressants modulate its activity. Therefore, we characterized behavioral and neuronal NAc shell responses to short-term treatments of DEP, PHEN, and BUP. These compounds caused a transient decrease in weight and food intake while increasing locomotion, stereotypy, and insomnia. They evoked a large inhibitory imbalance in NAc shell spiking activity that correlated with the onset of locomotion and stereotypy. Analysis of the local field potentials (LFPs) showed that all three drugs modulated beta, theta, and delta oscillations. These oscillations do not reflect an aversive-malaise brain state, as ascertained from taste aversion experiments, but tracked both the initial decrease in weight and food intake and the subsequent tolerance to these drugs. Importantly, the appetite suppressant-induced weight loss and locomotion were markedly reduced by intragastric (and intra-NAc shell) infusions of dopamine antagonists SCH-23390 (D1 receptor) or raclopride (D2 receptor). Furthermore, both antagonists attenuated appetite suppressant-induced LFP oscillations and partially restored the imbalance in NAc shell activity. These data reveal that appetite suppressant-induced behavioral and neuronal activity recorded in the NAc shell depend, to various extents, on dopaminergic activation and thus point to an important role for D1/D2-like receptors (in the NAc shell) in the mechanism of action for these anorexic compounds. PMID:25972577

  9. Eating ‘Junk-Food' Produces Rapid and Long-Lasting Increases in NAc CP-AMPA Receptors: Implications for Enhanced Cue-Induced Motivation and Food Addiction

    PubMed Central

    Oginsky, Max F; Goforth, Paulette B; Nobile, Cameron W; Lopez-Santiago, Luis F; Ferrario, Carrie R

    2016-01-01

    Urges to eat are influenced by stimuli in the environment that are associated with food (food cues). Obese people are more sensitive to food cues, reporting stronger craving and consuming larger portions after food cue exposure. The nucleus accumbens (NAc) mediates cue-triggered motivational responses, and activations in the NAc triggered by food cues are stronger in people who are susceptible to obesity. This has led to the idea that alterations in NAc function similar to those underlying drug addiction may contribute to obesity, particularly in obesity-susceptible individuals. Motivational responses are mediated in part by NAc AMPA receptor (AMPAR) transmission, and recent work shows that cue-triggered motivation is enhanced in obesity-susceptible rats after ‘junk-food' diet consumption. Therefore, here we determined whether NAc AMPAR expression and function is increased by ‘junk-food' diet consumption in obesity-susceptible vs -resistant populations using both outbred and selectively bred models of susceptibility. In addition, cocaine-induced locomotor activity was used as a general ‘read out' of mesolimbic function after ‘junk-food' consumption. We found a sensitized locomotor response to cocaine in rats that gained weight on a ‘junk-food' diet, consistent with greater responsivity of mesolimbic circuits in obesity-susceptible groups. In addition, eating ‘junk-food' increased NAc calcium-permeable-AMPAR (CP-AMPAR) function only in obesity-susceptible rats. This increase occurred rapidly, persisted for weeks after ‘junk-food' consumption ceased, and preceded the development of obesity. These data are considered in light of enhanced cue-triggered motivation and striatal function in obesity-susceptible rats and the role of NAc CP-AMPARs in enhanced motivation and addiction. PMID:27383008

  10. The role of O-linked GlcNAc modification on the glucose response of ChREBP

    SciTech Connect

    Sakiyama, Haruhiko; Fujiwara, Noriko; Noguchi, Takahiro; Eguchi, Hironobu; Yoshihara, Daisaku; Uyeda, Kosaku; Suzuki, Keiichiro

    2010-11-26

    Research highlights: {yields} The O-linked GlcNAc modification is crucial for the glucose response. {yields} Mlx is required for nuclear localization and transcription activity of ChREBP. {yields} The presence of Mlx stabilizes ChREBP protein. -- Abstract: The carbohydrate response element-binding protein (ChREBP) functions as a transcription factor in mediating the glucose-activated gene expression of multiple liver enzymes, which are responsible for converting excess carbohydrate to storage fat. ChREBP is translocated into the nucleus in response to high glucose levels, and then up-regulates transcriptional activity. Although this glucose activation of ChREBP is generally observed only in liver cells, overexpression of wild type max-like protein X (Mlx), but not an inactive mutant Mlx, resulted in the exhibition of the ChREBP functions also in a human kidney cell line. Because high glucose conditions induce the glycosylation of cellular proteins, the effect of O-linked GlcNAc modification on ChREBP functions was examined. Treatment with an O-GlcNAcase inhibitor (PUGNAc), which increases the O-linked GlcNAc modification of cellular proteins, caused an increase in the glucose response of ChREBP. In contrast, treatment with a glutamine fructose amidotransferase inhibitor (DON), which decreases O-GlcNAcylation by inhibiting the hexosamine biosynthetic pathway, completely blocked the glucose response of ChREBP. These results suggest that the O-linked glycosylation of ChREBP itself or other proteins that regulate ChREBP is essential for the production of functional ChREBP.

  11. Arabidopsis NAC Domain Proteins, VND1 to VND5, Are Transcriptional Regulators of Secondary Wall Biosynthesis in Vessels

    PubMed Central

    Zhou, Jianli; Zhong, Ruiqin; Ye, Zheng-Hua

    2014-01-01

    One of the most prominent features of xylem conducting cells is the deposition of secondary walls. In Arabidopsis, secondary wall biosynthesis in the xylem conducting cells, vessels, has been shown to be regulated by two VASCULAR-RELATED NAC-DOMAIN (VND) genes, VND6 and VND7. In this report, we have investigated the roles of five additional Arabidopsis VND genes, VND1 to VND5, in regulating secondary wall biosynthesis in vessels. The VND1 to VND5 genes were shown to be specifically expressed in vessels but not in interfascicular fibers in stems. The expression of VND4 and VND5 was also seen specifically in vessels in the secondary xylem of the root-hypocotyl region. When overexpressed, VND1 to VND5 were able to activate the expression of secondary wall-associated transcription factors and genes involved in secondary wall biosynthesis and programmed cell death. As a result, many normally parenchymatous cells in leaves and stems acquired thickened secondary walls in the VND1 to VND5 overexpressors. In contrast, dominant repression of VND3 function resulted in reduced secondary wall thickening in vessels and a collapsed vessel phenotype. In addition, VND1 to VND5 were shown to be capable of rescuing the secondary wall defects in the fibers of the snd1 nst1 double mutant when expressed under the SND1 promoter. Furthermore, transactivation analysis revealed that VND1 to VND5 could activate expression of the GUS reporter gene driven by the secondary wall NAC binding element (SNBE). Together, these results demonstrate that VND1 to VND5 possess functions similar to that of the SND1 secondary wall NAC and are transcriptional regulators of secondary wall biosynthesis in vessels. PMID:25148240

  12. Tokamak Systems Code

    SciTech Connect

    Reid, R.L.; Barrett, R.J.; Brown, T.G.; Gorker, G.E.; Hooper, R.J.; Kalsi, S.S.; Metzler, D.H.; Peng, Y.K.M.; Roth, K.E.; Spampinato, P.T.

    1985-03-01

    The FEDC Tokamak Systems Code calculates tokamak performance, cost, and configuration as a function of plasma engineering parameters. This version of the code models experimental tokamaks. It does not currently consider tokamak configurations that generate electrical power or incorporate breeding blankets. The code has a modular (or subroutine) structure to allow independent modeling for each major tokamak component or system. A primary benefit of modularization is that a component module may be updated without disturbing the remainder of the systems code as long as the imput to or output from the module remains unchanged.

  13. Topological subsystem codes

    SciTech Connect

    Bombin, H.

    2010-03-15

    We introduce a family of two-dimensional (2D) topological subsystem quantum error-correcting codes. The gauge group is generated by two-local Pauli operators, so that two-local measurements are enough to recover the error syndrome. We study the computational power of code deformation in these codes and show that boundaries cannot be introduced in the usual way. In addition, we give a general mapping connecting suitable classical statistical mechanical models to optimal error correction in subsystem stabilizer codes that suffer from depolarizing noise.

  14. FAA Smoke Transport Code

    SciTech Connect

    Domino, Stefan; Luketa-Hanlin, Anay; Gallegos, Carlos

    2006-10-27

    FAA Smoke Transport Code, a physics-based Computational Fluid Dynamics tool, which couples heat, mass, and momentum transfer, has been developed to provide information on smoke transport in cargo compartments with various geometries and flight conditions. The software package contains a graphical user interface for specification of geometry and boundary conditions, analysis module for solving the governing equations, and a post-processing tool. The current code was produced by making substantial improvements and additions to a code obtained from a university. The original code was able to compute steady, uniform, isothermal turbulent pressurization. In addition, a preprocessor and postprocessor were added to arrive at the current software package.

  15. Transonic airfoil codes

    NASA Technical Reports Server (NTRS)

    Garabedian, P. R.

    1979-01-01

    Computer codes for the design and analysis of transonic airfoils are considered. The design code relies on the method of complex characteristics in the hodograph plane to construct shockless airfoil. The analysis code uses artificial viscosity to calculate flows with weak shock waves at off-design conditions. Comparisons with experiments show that an excellent simulation of two dimensional wind tunnel tests is obtained. The codes have been widely adopted by the aircraft industry as a tool for the development of supercritical wing technology.

  16. Senior Administrators Should Have Administrative Contracts.

    ERIC Educational Resources Information Center

    Posner, Gary J.

    1987-01-01

    Recognizing that termination is viewed by the employee as the equivalent to capital punishment of a career, an administrative contract can reduce the emotional and financial entanglements that often result. Administrative contracts are described. (MLW)

  17. Expression Cloning of a Pseudomonas Gene Encoding a Hydroxydecanoyl-Acyl Carrier Protein-Dependent UDP-GlcNAc Acyltransferase

    PubMed Central

    Dotson, Garry D.; Kaltashov, Igor A.; Cotter, Robert J.; Raetz, Christian R. H.

    1998-01-01

    UDP-N-acetylglucosamine-3-O-acyltransferase (UDP-GlcNAc acyltransferase) catalyzes the first step of lipid A biosynthesis (M. S. Anderson and C. R. H. Raetz, J. Biol. Chem. 262:5159–5169, 1987). We here report the isolation of the lpxA gene of Pseudomonas aeruginosa from a library of Pseudomonas strain PAO1 expressed in Escherichia coli LE392 (J. Lightfoot and J. S. Lam, J. Bacteriol. 173:5624–5630, 1991). Pseudomonas lpxA encodes a 10-carbon-specific UDP-GlcNAc acyltransferase, whereas the E. coli transferase is selective for a 14-carbon acyl chain. Recombinant cosmid 1137 enabled production of a 3-hydroxydecanoyl-specific UDP-GlcNAc acyltransferase in E. coli. It was identified by assaying lysozyme-EDTA lysates of individual members of the library with 3-hydroxydecanoyl-acyl carrier protein (ACP) as the substrate. Cosmid 1137 contained a 20-kb insert of P. aeruginosa DNA. The lpxA gene region was localized to a 1.3-kb SalI-PstI fragment. Sequencing revealed that it contains one complete open reading frame (777 bp) encoding a new lpxA homolog. The predicted Pseudomonas LpxA is 258 amino acids long and contains 21 complete hexapeptide repeating units, spaced in approximately the same manner as the 24 repeats of E. coli LpxA. The P. aeruginosa UDP-GlcNAc acyltransferase is 54% identical and 67% similar to the E. coli enzyme. A plasmid (pGD3) containing the 1.3-kb SalI-PstI fragment complemented E. coli RO138, a temperature-sensitive mutant harboring lpxA2. LpxA assays of extracts of this construct indicated that it is >1,000-fold more selective for 3-hydroxydecanoyl-ACP than for 3-hydroxymyristoyl-ACP. Mass spectrometry of lipid A isolated from this strain by hydrolysis at pH 4.5 revealed [M-H]− 1,684.5 (versus 1,796.5 for wild-type lipid A), consistent with 3-hydroxydecanoate rather than 3-hydroxymyristate at positions 3 and 3′. PMID:9440522

  18. Exposure to siRNA-GalNAc Conjugates in Systems of the Standard Test Battery for Genotoxicity.

    PubMed

    Janas, Maja M; Jiang, Yongfeng; Duncan, Richard G; Hayes, Antoinette N; Liu, Ju; Kasperkovitz, Pia V; Placke, Michael E; Barros, Scott A

    2016-12-01

    Registration of pharmaceuticals requires an assessment of their genotoxic potential using in vitro and in vivo tests outlined in the International Conference on Harmonisation (ICH) guidance S2(R1). We have evaluated numerous siRNA-N-acetylgalactosamine (GalNAc) conjugates containing phosphorothioate linkages and various combinations of 2'-fluoro and 2'-O-methyl ribose modifications of multiple nucleotides in the ICH battery of assays, all of which have uniformly yielded negative results. To verify these negative genotoxicity results, in this study we confirm test article exposure using toolkit small interfering RNAs (siRNAs) representative of those in the clinic. In the Ames test, the highest uptake of the siRNA-GalNAc conjugates occurred at 1 h postdose in all bacterial strains independent of siRNA sequence or chemistry (up to ∼14,000 siRNA molecules per cell), followed by metabolic degradation of the parent siRNA at 6, 24, and 48 h postdose. siRNA-GalNAc conjugates were internalized by bacteria as assessed by protection from the addition of nucleases to the culture media following uptake and by the requirement of cell lysis for detection of the siRNA. In the in vitro chromosome aberration assay, uptake was observed in Chinese hamster ovary cells (up to ∼5,500 siRNA molecules per cell at 21 h postdose) and in CD3(+) human peripheral blood lymphocytes (up to ∼500 siRNA molecules per cell at 21 h postdose). In the in vivo micronucleus assay in rat bone marrow, exposure to parent siRNA was 100-350 μg of antisense strand per gram of protein at 24 and 48 h postlimit dose of 2 g/kg. Loss of terminal nucleotides was detected in bone marrow by mass spectrometry, indicating exposure to monomer metabolites as well. Negative genotoxicity results were also confirmed in an in vitro double-strand DNA break assay in HeLa and HepG2 cells where exposure was maximized using transfection reagents. Thus negative genotoxicity assay results for siRNA-GalNAc

  19. NAC transcription factors play an important role in ethylene biosynthesis, reception and signaling of tomato fruit ripening.

    PubMed

    Kou, Xiaohong; Liu, Chen; Han, Lihua; Wang, Shuang; Xue, Zhaohui

    2016-06-01

    NAC proteins comprise a large family of transcription factors that play important roles in diverse physiological processes during development. To explore the role of NAC transcription factors in the ripening of fruits, we predicted the secondary and tertiary structure as well as regulative function of the SNAC4 (SlNAC48, Accession number: NM 001279348.2) and SNAC9 (SlNAC19, Accession number: XM 004236996.2) transcription factors in tomato. We found that the tertiary structure of SNAC9 was similar to that of ATNAP, which played an important role in the fruit senescence and was required for ethylene stimulation. Likewise, the bio-function prediction results indicated that SNAC4 and SNAC9 participated in various plant hormone signaling and senescence processes. More information about SNACs was obtained by the application of VIGS (virus-induced gene silencing). The silencing of SNAC4 and SNAC9 dramatically repressed the LeACS2, LeACS4 and LeACO1 expression, which consequently led to the inhibition of the ripening process. The silencing of SNACs down-regulated the mRNA levels of the ethylene perception genes and, at the same time, suppressed the expression of ethylene signaling-related genes except for LeERF2 which was induced by the silencing of SNAC4. The expressions of LeRIN were different in two silenced fruits. In addition, the silencing of SNAC4 reduced its mRNA level, while the silencing of SNAC9 induced its expression. Furthermore, the silencing of LeACS4, LeACO1 and LeERF2 reduced the expression of SNAC4 and SNAC9, while the silencing of NR induced the expression of all of them. In particular, these results indicate that SNAC transcription factors bind to the promoter of the ethylene synthesis genes in vitro. This experimental evidence demonstrates that SNAC4 and SNAC9 could positively regulate the tomato fruit ripening process by functioning upstream of ethylene synthesis genes. These outcomes will be helpful to provide a theoretical foundation for further

  20. 77 FR 17460 - Multistakeholder Process To Develop Consumer Data Privacy Codes of Conduct

    Federal Register 2010, 2011, 2012, 2013, 2014

    2012-03-26

    ... National Telecommunications and Information Administration RIN 0660-XA27 Multistakeholder Process To Develop Consumer Data Privacy Codes of Conduct AGENCY: National Telecommunications and Information... Telecommunications and Information Administration (NTIA) announces that the closing deadline for submitting...

  1. Fast Coding Unit Encoding Mechanism for Low Complexity Video Coding

    PubMed Central

    Wu, Yueying; Jia, Kebin; Gao, Guandong

    2016-01-01

    In high efficiency video coding (HEVC), coding tree contributes to excellent compression performance. However, coding tree brings extremely high computational complexity. Innovative works for improving coding tree to further reduce encoding time are stated in this paper. A novel low complexity coding tree mechanism is proposed for HEVC fast coding unit (CU) encoding. Firstly, this paper makes an in-depth study of the relationship among CU distribution, quantization parameter (QP) and content change (CC). Secondly, a CU coding tree probability model is proposed for modeling and predicting CU distribution. Eventually, a CU coding tree probability update is proposed, aiming to address probabilistic model distortion problems caused by CC. Experimental results show that the proposed low complexity CU coding tree mechanism significantly reduces encoding time by 27% for lossy coding and 42% for visually lossless coding and lossless coding. The proposed low complexity CU coding tree mechanism devotes to improving coding performance under various application conditions. PMID:26999741

  2. Fast Coding Unit Encoding Mechanism for Low Complexity Video Coding.

    PubMed

    Gao, Yuan; Liu, Pengyu; Wu, Yueying; Jia, Kebin; Gao, Guandong

    2016-01-01

    In high efficiency video coding (HEVC), coding tree contributes to excellent compression performance. However, coding tree brings extremely high computational complexity. Innovative works for improving coding tree to further reduce encoding time are stated in this paper. A novel low complexity coding tree mechanism is proposed for HEVC fast coding unit (CU) encoding. Firstly, this paper makes an in-depth study of the relationship among CU distribution, quantization parameter (QP) and content change (CC). Secondly, a CU coding tree probability model is proposed for modeling and predicting CU distribution. Eventually, a CU coding tree probability update is proposed, aiming to address probabilistic model distortion problems caused by CC. Experimental results show that the proposed low complexity CU coding tree mechanism significantly reduces encoding time by 27% for lossy coding and 42% for visually lossless coding and lossless coding. The proposed low complexity CU coding tree mechanism devotes to improving coding performance under various application conditions.

  3. Natural variation in monoterpene synthesis in kiwifruit: transcriptional regulation of terpene synthases by NAC and ETHYLENE-INSENSITIVE3-like transcription factors.

    PubMed

    Nieuwenhuizen, Niels J; Chen, Xiuyin; Wang, Mindy Y; Matich, Adam J; Perez, Ramon Lopez; Allan, Andrew C; Green, Sol A; Atkinson, Ross G

    2015-04-01

    Two kiwifruit (Actinidia) species with contrasting terpene profiles were compared to understand the regulation of fruit monoterpene production. High rates of terpinolene production in ripe Actinidia arguta fruit were correlated with increasing gene and protein expression of A. arguta terpene synthase1 (AaTPS1) and correlated with an increase in transcript levels of the 2-C-methyl-D-erythritol 4-phosphate pathway enzyme 1-deoxy-D-xylulose-5-phosphate synthase (DXS). Actinidia chinensis terpene synthase1 (AcTPS1) was identified as part of an array of eight tandemly duplicated genes, and AcTPS1 expression and terpene production were observed only at low levels in developing fruit. Transient overexpression of DXS in Nicotiana benthamiana leaves elevated monoterpene synthesis by AaTPS1 more than 100-fold, indicating that DXS is likely to be the key step in regulating 2-C-methyl-D-erythritol 4-phosphate substrate flux in kiwifruit. Comparative promoter analysis identified potential NAC (for no apical meristem [NAM], Arabidopsis transcription activation factor [ATAF], and cup-shaped cotyledon [CUC])-domain transcription factor) and ETHYLENE-INSENSITIVE3-like transcription factor (TF) binding sites in the AaTPS1 promoter, and cloned members of both TF classes were able to activate the AaTPS1 promoter in transient assays. Electrophoretic mobility shift assays showed that AaNAC2, AaNAC3, and AaNAC4 bind a 28-bp fragment of the proximal NAC binding site in the AaTPS1 promoter but not the A. chinensis AcTPS1 promoter, where the NAC binding site was mutated. Activation could be restored by reintroducing multiple repeats of the 12-bp NAC core-binding motif. The absence of NAC transcriptional activation in ripe A. chinensis fruit can account for the low accumulation of AcTPS1 transcript, protein, and monoterpene volatiles in this species. These results indicate the importance of NAC TFs in controlling monoterpene production and other traits in ripening fruits.

  4. Natural Variation in Monoterpene Synthesis in Kiwifruit: Transcriptional Regulation of Terpene Synthases by NAC and ETHYLENE-INSENSITIVE3-Like Transcription Factors1

    PubMed Central

    Nieuwenhuizen, Niels J.; Chen, Xiuyin; Wang, Mindy Y.; Matich, Adam J.; Perez, Ramon Lopez; Allan, Andrew C.; Green, Sol A.; Atkinson, Ross G.

    2015-01-01

    Two kiwifruit (Actinidia) species with contrasting terpene profiles were compared to understand the regulation of fruit monoterpene production. High rates of terpinolene production in ripe Actinidia arguta fruit were correlated with increasing gene and protein expression of A. arguta terpene synthase1 (AaTPS1) and correlated with an increase in transcript levels of the 2-C-methyl-d-erythritol 4-phosphate pathway enzyme 1-deoxy-d-xylulose-5-phosphate synthase (DXS). Actinidia chinensis terpene synthase1 (AcTPS1) was identified as part of an array of eight tandemly duplicated genes, and AcTPS1 expression and terpene production were observed only at low levels in developing fruit. Transient overexpression of DXS in Nicotiana benthamiana leaves elevated monoterpene synthesis by AaTPS1 more than 100-fold, indicating that DXS is likely to be the key step in regulating 2-C-methyl-d-erythritol 4-phosphate substrate flux in kiwifruit. Comparative promoter analysis identified potential NAC (for no apical meristem [NAM], Arabidopsis transcription activation factor [ATAF], and cup-shaped cotyledon [CUC])-domain transcription factor) and ETHYLENE-INSENSITIVE3-like transcription factor (TF) binding sites in the AaTPS1 promoter, and cloned members of both TF classes were able to activate the AaTPS1 promoter in transient assays. Electrophoretic mobility shift assays showed that AaNAC2, AaNAC3, and AaNAC4 bind a 28-bp fragment of the proximal NAC binding site in the AaTPS1 promoter but not the A. chinensis AcTPS1 promoter, where the NAC binding site was mutated. Activation could be restored by reintroducing multiple repeats of the 12-bp NAC core-binding motif. The absence of NAC transcriptional activation in ripe A. chinensis fruit can account for the low accumulation of AcTPS1 transcript, protein, and monoterpene volatiles in this species. These results indicate the importance of NAC TFs in controlling monoterpene production and other traits in ripening fruits. PMID:25649633

  5. Dress Codes for Teachers?

    ERIC Educational Resources Information Center

    Million, June

    2004-01-01

    In this article, the author discusses an e-mail survey of principals from across the country regarding whether or not their school had a formal staff dress code. The results indicate that most did not have a formal dress code, but agreed that professional dress for teachers was not only necessary, but showed respect for the school and had a…

  6. Lichenase and coding sequences

    DOEpatents

    Li, Xin-Liang; Ljungdahl, Lars G.; Chen, Huizhong

    2000-08-15

    The present invention provides a fungal lichenase, i.e., an endo-1,3-1,4-.beta.-D-glucanohydrolase, its coding sequence, recombinant DNA molecules comprising the lichenase coding sequences, recombinant host cells and methods for producing same. The present lichenase is from Orpinomyces PC-2.

  7. Legacy Code Modernization

    NASA Technical Reports Server (NTRS)

    Hribar, Michelle R.; Frumkin, Michael; Jin, Haoqiang; Waheed, Abdul; Yan, Jerry; Saini, Subhash (Technical Monitor)

    1998-01-01

    Over the past decade, high performance computing has evolved rapidly; systems based on commodity microprocessors have been introduced in quick succession from at least seven vendors/families. Porting codes to every new architecture is a difficult problem; in particular, here at NASA, there are many large CFD applications that are very costly to port to new machines by hand. The LCM ("Legacy Code Modernization") Project is the development of an integrated parallelization environment (IPE) which performs the automated mapping of legacy CFD (Fortran) applications to state-of-the-art high performance computers. While most projects to port codes focus on the parallelization of the code, we consider porting to be an iterative process consisting of several steps: 1) code cleanup, 2) serial optimization,3) parallelization, 4) performance monitoring and visualization, 5) intelligent tools for automated tuning using performance prediction and 6) machine specific optimization. The approach for building this parallelization environment is to build the components for each of the steps simultaneously and then integrate them together. The demonstration will exhibit our latest research in building this environment: 1. Parallelizing tools and compiler evaluation. 2. Code cleanup and serial optimization using automated scripts 3. Development of a code generator for performance prediction 4. Automated partitioning 5. Automated insertion of directives. These demonstrations will exhibit the effectiveness of an automated approach for all the steps involved with porting and tuning a legacy code application for a new architecture.

  8. Synthesizing Certified Code

    NASA Technical Reports Server (NTRS)

    Whalen, Michael; Schumann, Johann; Fischer, Bernd

    2002-01-01

    Code certification is a lightweight approach to demonstrate software quality on a formal level. Its basic idea is to require producers to provide formal proofs that their code satisfies certain quality properties. These proofs serve as certificates which can be checked independently. Since code certification uses the same underlying technology as program verification, it also requires many detailed annotations (e.g., loop invariants) to make the proofs possible. However, manually adding theses annotations to the code is time-consuming and error-prone. We address this problem by combining code certification with automatic program synthesis. We propose an approach to generate simultaneously, from a high-level specification, code and all annotations required to certify generated code. Here, we describe a certification extension of AUTOBAYES, a synthesis tool which automatically generates complex data analysis programs from compact specifications. AUTOBAYES contains sufficient high-level domain knowledge to generate detailed annotations. This allows us to use a general-purpose verification condition generator to produce a set of proof obligations in first-order logic. The obligations are then discharged using the automated theorem E-SETHEO. We demonstrate our approach by certifying operator safety for a generated iterative data classification program without manual annotation of the code.

  9. Coding Acoustic Metasurfaces.

    PubMed

    Xie, Boyang; Tang, Kun; Cheng, Hua; Liu, Zhengyou; Chen, Shuqi; Tian, Jianguo

    2017-02-01

    Coding acoustic metasurfaces can combine simple logical bits to acquire sophisticated functions in wave control. The acoustic logical bits can achieve a phase difference of exactly π and a perfect match of the amplitudes for the transmitted waves. By programming the coding sequences, acoustic metasurfaces with various functions, including creating peculiar antenna patterns and waves focusing, have been demonstrated.

  10. Computerized mega code recording.

    PubMed

    Burt, T W; Bock, H C

    1988-04-01

    A system has been developed to facilitate recording of advanced cardiac life support mega code testing scenarios. By scanning a paper "keyboard" using a bar code wand attached to a portable microcomputer, the person assigned to record the scenario can easily generate an accurate, complete, timed, and typewritten record of the given situations and the obtained responses.

  11. Pseudonoise code tracking loop

    NASA Technical Reports Server (NTRS)

    Laflame, D. T. (Inventor)

    1980-01-01

    A delay-locked loop is presented for tracking a pseudonoise (PN) reference code in an incoming communication signal. The loop is less sensitive to gain imbalances, which can otherwise introduce timing errors in the PN reference code formed by the loop.

  12. Study of global transcriptional changes of N-GlcNAc2 proteins-producing T24 bladder carcinoma cells under glucose deprivation.

    PubMed

    Isono, Takahiro; Chano, Tokuhiro; Okabe, Hidetoshi; Suzaki, Masafumi

    2013-01-01

    Increased levels of N-linked (β-N- acetylglucosamine)2 [N-GlcNAc2]-modified proteins have been recognized to be an effective response to glucose deprivation. In the first step of this study, using a next generation sequencer, we investigated the global transcriptional changes induced by glucose deprivation in a T24 bladder carcinoma cell line, producing N-GlcNAc2-modified proteins under glucose deprivation. Our transcriptome analysis revealed significant up-regulation of the UDP-GlcNAc biosynthesis pathway and unfolded protein response genes, and down-regulation of G2/M transition-related genes containing mitotic kinases. Our biological analysis confirmed that N-GlcNAc2-modified proteins were localized with BiP proteins in the ER. G2/M arrest was caused by glucose deprivation in T24 cells. Moreover, the knockdown of unfolded protein response genes induced the expressional recovery of mitotic kinases under glucose deprivation. Taken together, our results suggest N-GlcNAc2-modified proteins produced under glucose deprivation caused unfolded protein response in the ER, and that this response induced G2/M arrest.

  13. The rice OsNAC6 transcription factor orchestrates multiple molecular mechanisms involving root structural adaptions and nicotianamine biosynthesis for drought tolerance.

    PubMed

    Lee, Dong-Keun; Chung, Pil Joong; Jeong, Jin Seo; Jang, Geupil; Bang, Seung Woon; Jung, Harin; Kim, Youn Shic; Ha, Sun-Hwa; Choi, Yang Do; Kim, Ju-Kon

    2016-11-28

    Drought has a serious impact on agriculture worldwide. A plant's ability to adapt to rhizosphere drought stress requires reprogramming of root growth and development. Although physiological studies have documented the root adaption for tolerance to the drought stress, underlying molecular mechanisms is still incomplete, which is essential for crop engineering. Here, we identified OsNAC6-mediated root structural adaptations, including increased root number and root diameter, which enhanced drought tolerance. Multiyear drought field tests demonstrated that the grain yield of OsNAC6 root-specific overexpressing transgenic rice lines was less affected by drought stress than were nontransgenic controls. Genome-wide analyses of loss- and gain-of-function mutants revealed that OsNAC6 up-regulates the expression of direct target genes involved in membrane modification, nicotianamine (NA) biosynthesis, glutathione relocation, 3'-phophoadenosine 5'-phosphosulphate accumulation and glycosylation, which represent multiple drought tolerance pathways. Moreover, overexpression of NICOTIANAMINE SYNTHASE genes, direct targets of OsNAC6, promoted the accumulation of the metal chelator NA and, consequently, drought tolerance. Collectively, OsNAC6 orchestrates novel molecular drought tolerance mechanisms and has potential for the biotechnological development of high-yielding crops under water-limiting conditions.

  14. Disruption of O-GlcNAc cycling by deletion of O-GlcNAcase (Oga/Mgea5) changed gene expression pattern in mouse embryonic fibroblast (MEF) cells.

    PubMed

    Keembiyehetty, Chithra

    2015-09-01

    Adding a single O-GlcNAc moiety to a Ser/Thr molecule of a protein by O-GlcNAc transferase and transiently removing it by O-GlcNAcase is referred to as O-GlcNAc cycling (or O-GlcNAcylation). This O-GlcNAc modification is sensitive to nutrient availability and also shows cross talk with phosphorylation signaling, affecting downstream targets. A mouse model system was developed and evaluated to show genome wide transcriptional changes associated with disruption of O-GlcNAc cycling. Mouse embryonic fibroblast cells derived from O-GlcNAcase (Oga) knock out (KO), heterozygous (Het) and wild type (WT) embryos were used for an Affymetrix based microarray. Results are deposited in GEO dataset GSE52721. Data reveals that Oga KO MEFs had 2534 transcripts differentially expressed at 1.5 fold level while Oga heterozygous MEFs had 959 transcripts changed compared to WT MEFs. There were 1835 transcripts differentially expressed at 1.5 fold Het versus WT comparison group. Gene ontology analysis indicated differentially expressed genes enriched in metabolic, growth, and cell proliferation categories.

  15. Evolving genetic code

    PubMed Central

    OHAMA, Takeshi; INAGAKI, Yuji; BESSHO, Yoshitaka; OSAWA, Syozo

    2008-01-01

    In 1985, we reported that a bacterium, Mycoplasma capricolum, used a deviant genetic code, namely UGA, a “universal” stop codon, was read as tryptophan. This finding, together with the deviant nuclear genetic codes in not a few organisms and a number of mitochondria, shows that the genetic code is not universal, and is in a state of evolution. To account for the changes in codon meanings, we proposed the codon capture theory stating that all the code changes are non-disruptive without accompanied changes of amino acid sequences of proteins. Supporting evidence for the theory is presented in this review. A possible evolutionary process from the ancient to the present-day genetic code is also discussed. PMID:18941287

  16. Combustion chamber analysis code

    NASA Technical Reports Server (NTRS)

    Przekwas, A. J.; Lai, Y. G.; Krishnan, A.; Avva, R. K.; Giridharan, M. G.

    1993-01-01

    A three-dimensional, time dependent, Favre averaged, finite volume Navier-Stokes code has been developed to model compressible and incompressible flows (with and without chemical reactions) in liquid rocket engines. The code has a non-staggered formulation with generalized body-fitted-coordinates (BFC) capability. Higher order differencing methodologies such as MUSCL and Osher-Chakravarthy schemes are available. Turbulent flows can be modeled using any of the five turbulent models present in the code. A two-phase, two-liquid, Lagrangian spray model has been incorporated into the code. Chemical equilibrium and finite rate reaction models are available to model chemically reacting flows. The discrete ordinate method is used to model effects of thermal radiation. The code has been validated extensively against benchmark experimental data and has been applied to model flows in several propulsion system components of the SSME and the STME.

  17. User's manual for HDR3 computer code

    SciTech Connect

    Arundale, C.J.

    1982-10-01

    A description of the HDR3 computer code and instructions for its use are provided. HDR3 calculates space heating costs for a hot dry rock (HDR) geothermal space heating system. The code also compares these costs to those of a specific oil heating system in use at the National Aeronautics and Space Administration Flight Center at Wallops Island, Virginia. HDR3 allows many HDR system parameters to be varied so that the user may examine various reservoir management schemes and may optimize reservoir design to suit a particular set of geophysical and economic parameters.

  18. Inhibition of actin polymerization in the NAc shell inhibits morphine-induced CPP by disrupting its reconsolidation

    PubMed Central

    Li, Gongying; Wang, Yanmei; Yan, Min; Xu, Yunshuai; Song, Xiuli; Li, Qingqing; Zhang, Jinxiang; Ma, Hongxia; Wu, Yili

    2015-01-01

    Drug-associated contextual cues contribute to drug craving and relapse after abstinence, which is a major challenge to drug addiction treatment. Previous studies showed that disrupting memory reconsolidation impairs drug reward memory. However, the underlying mechanisms remain elusive. Although actin polymerization is involved in memory formation, its role in the reconsolidation of drug reward memory is unknown. In addition, the specific brain areas responsible for drug memory have not been fully identified. In the present study, we found that inhibiting actin polymerization in the nucleus accumbens (NAc) shell, but not the NAc core, abolishes morphine-induced conditioned place preference (CPP) by disrupting its reconsolidation in rats. Moreover, this effect persists for more than 2 weeks by a single injection of the actin polymerization inhibitor, which is not reversed by a morphine-priming injection. Furthermore, the application of actin polymerization inhibitor outside the reconsolidation window has no effect on morphine-associated contextual memory. Taken together, our findings first demonstrate that inhibiting actin polymerization erases morphine-induced CPP by disrupting its reconsolidation. Our study suggests that inhibition of actin polymerization during drug memory reconsolidation may be a potential approach to prevent drug relapse. PMID:26538334

  19. Inhibition of actin polymerization in the NAc shell inhibits morphine-induced CPP by disrupting its reconsolidation.

    PubMed

    Li, Gongying; Wang, Yanmei; Yan, Min; Xu, Yunshuai; Song, Xiuli; Li, Qingqing; Zhang, Jinxiang; Ma, Hongxia; Wu, Yili

    2015-11-05

    Drug-associated contextual cues contribute to drug craving and relapse after abstinence, which is a major challenge to drug addiction treatment. Previous studies showed that disrupting memory reconsolidation impairs drug reward memory. However, the underlying mechanisms remain elusive. Although actin polymerization is involved in memory formation, its role in the reconsolidation of drug reward memory is unknown. In addition, the specific brain areas responsible for drug memory have not been fully identified. In the present study, we found that inhibiting actin polymerization in the nucleus accumbens (NAc) shell, but not the NAc core, abolishes morphine-induced conditioned place preference (CPP) by disrupting its reconsolidation in rats. Moreover, this effect persists for more than 2 weeks by a single injection of the actin polymerization inhibitor, which is not reversed by a morphine-priming injection. Furthermore, the application of actin polymerization inhibitor outside the reconsolidation window has no effect on morphine-associated contextual memory. Taken together, our findings first demonstrate that inhibiting actin polymerization erases morphine-induced CPP by disrupting its reconsolidation. Our study suggests that inhibition of actin polymerization during drug memory reconsolidation may be a potential approach to prevent drug relapse.

  20. A local regulatory network around three NAC transcription factors in stress responses and senescence in Arabidopsis leaves

    PubMed Central

    Hickman, Richard; Hill, Claire; Penfold, Christopher A; Breeze, Emily; Bowden, Laura; Moore, Jonathan D; Zhang, Peijun; Jackson, Alison; Cooke, Emma; Bewicke-Copley, Findlay; Mead, Andrew; Beynon, Jim; Wild, David L; Denby, Katherine J; Ott, Sascha; Buchanan-Wollaston, Vicky

    2013-01-01

    Summary A model is presented describing the gene regulatory network surrounding three similar NAC transcription factors that have roles in Arabidopsis leaf senescence and stress responses. ANAC019, ANAC055 and ANAC072 belong to the same clade of NAC domain genes and have overlapping expression patterns. A combination of promoter DNA/protein interactions identified using yeast 1-hybrid analysis and modelling using gene expression time course data has been applied to predict the regulatory network upstream of these genes. Similarities and divergence in regulation during a variety of stress responses are predicted by different combinations of upstream transcription factors binding and also by the modelling. Mutant analysis with potential upstream genes was used to test and confirm some of the predicted interactions. Gene expression analysis in mutants of ANAC019 and ANAC055 at different times during leaf senescence has revealed a distinctly different role for each of these genes. Yeast 1-hybrid analysis is shown to be a valuable tool that can distinguish clades of binding proteins and be used to test and quantify protein binding to predicted promoter motifs. PMID:23578292

  1. Fasciola hepatica Immune Regulates CD11c+ Cells by Interacting with the Macrophage Gal/GalNAc Lectin

    PubMed Central

    Rodríguez, Ernesto; Carasi, Paula; Frigerio, Sofía; da Costa, Valeria; van Vliet, Sandra; Noya, Verónica; Brossard, Natalie; van Kooyk, Yvette; García-Vallejo, Juan J.; Freire, Teresa

    2017-01-01

    Fasciolosis, caused by Fasciola hepatica and Fasciola gigantica, is a trematode zoonosis of interest in public health and livestock production. Like other helminths, F. hepatica modulates the host immune response by inducing potent polarized Th2 and regulatory T cell immune responses and by downregulating the production of Th1 cytokines. In this work, we show that F. hepatica glycans increase Th2 immune responses by immunomodulating TLR-induced maturation and function of dendritic cells (DCs). This process was mediated by the macrophage Gal/GalNAc lectin (MGL) expressed on DCs, which recognizes the Tn antigen (GalNAc-Ser/Thr) on parasite components. More interestingly, we identified MGL-expressing CD11c+ cells in infected animals and showed that these cells are recruited both to the peritoneum and the liver upon F. hepatica infection. These cells express the regulatory cytokines IL-10, TNFα and TGFβ and a variety of regulatory markers. Furthermore, MGL+ CD11c+ cells expand parasite-specific Th2/regulatory cells and suppress Th1 polarization. The results presented here suggest a potential role of MGL in the immunomodulation of DCs induced by F. hepatica and contribute to a better understanding of the molecular and immunoregulatory mechanisms induced by this parasite. PMID:28360908

  2. A cotton (Gossypium hirsutum) gene encoding a NAC transcription factor is involved in negative regulation of plant xylem development.

    PubMed

    Li, Wen; Huang, Geng-Qing; Zhou, Wei; Xia, Xiao-Cong; Li, Deng-Di; Li, Xue-Bao

    2014-10-01

    NAC proteins that compose of one large family of plant specific transcription factors (TF) play the important roles in many biological processes (such as morphogenesis, development, senescence and stress signal transduction). In this study, a gene (designated as GhXND1) encoding a NAC transcription factor was identified in cotton. Sequence analysis indicated that GhXND1 gene contains two introns inserted in its open reading frame (ORF). GhXND1 protein is localized in the cell nucleus, and displays the transactivation activity. GhXND1 transcripts were mainly detected in cotyledons, petals, roots, hypocotyls and stems, but little or no signals of GhXND1 expression were found in the other tissues. Ectopic expression of GhXND1 in Arabidopsis resulted in a reduction in number of xylem vessel cells and cell wall thickness of interfascicular fibers in the transgenic plants, compared with those of wild type. And expression of some cell wall biosynthesis-related genes was down-regulated in the GhXND1 transgenic plants. Collectively, the data presented in this study suggested that GhXND1 may be involved in regulation of plant xylem development.

  3. SND1, a NAC domain transcription factor, is a key regulator of secondary wall synthesis in fibers of Arabidopsis.

    PubMed

    Zhong, Ruiqin; Demura, Taku; Ye, Zheng-Hua

    2006-11-01

    Secondary walls in fibers and tracheary elements constitute the most abundant biomass produced by plants. Although a number of genes involved in the biosynthesis of secondary wall components have been characterized, little is known about the molecular mechanisms underlying the coordinated expression of these genes. Here, we demonstrate that the Arabidopsis thaliana NAC (for NAM, ATAF1/2, and CUC2) domain transcription factor, SND1 (for secondary wall-associated NAC domain protein), is a key transcriptional switch regulating secondary wall synthesis in fibers. We show that SND1 is expressed specifically in interfascicular fibers and xylary fibers in stems and that dominant repression of SND1 causes a drastic reduction in the secondary wall thickening of fibers. Ectopic overexpression of SND1 results in activation of the expression of secondary wall biosynthetic genes, leading to massive deposition of secondary walls in cells that are normally nonsclerenchymatous. In addition, we have found that SND1 upregulates the expression of several transcription factors that are highly expressed in fibers during secondary wall synthesis. Together, our results reveal that SND1 is a key transcriptional activator involved in secondary wall biosynthesis in fibers.

  4. Fasciola hepatica Immune Regulates CD11c(+) Cells by Interacting with the Macrophage Gal/GalNAc Lectin.

    PubMed

    Rodríguez, Ernesto; Carasi, Paula; Frigerio, Sofía; da Costa, Valeria; van Vliet, Sandra; Noya, Verónica; Brossard, Natalie; van Kooyk, Yvette; García-Vallejo, Juan J; Freire, Teresa

    2017-01-01

    Fasciolosis, caused by Fasciola hepatica and Fasciola gigantica, is a trematode zoonosis of interest in public health and livestock production. Like other helminths, F. hepatica modulates the host immune response by inducing potent polarized Th2 and regulatory T cell immune responses and by downregulating the production of Th1 cytokines. In this work, we show that F. hepatica glycans increase Th2 immune responses by immunomodulating TLR-induced maturation and function of dendritic cells (DCs). This process was mediated by the macrophage Gal/GalNAc lectin (MGL) expressed on DCs, which recognizes the Tn antigen (GalNAc-Ser/Thr) on parasite components. More interestingly, we identified MGL-expressing CD11c(+) cells in infected animals and showed that these cells are recruited both to the peritoneum and the liver upon F. hepatica infection. These cells express the regulatory cytokines IL-10, TNFα and TGFβ and a variety of regulatory markers. Furthermore, MGL(+) CD11c(+) cells expand parasite-specific Th2/regulatory cells and suppress Th1 polarization. The results presented here suggest a potential role of MGL in the immunomodulation of DCs induced by F. hepatica and contribute to a better understanding of the molecular and immunoregulatory mechanisms induced by this parasite.

  5. The GalNAc-type O-Glycoproteome of CHO cells characterized by the SimpleCell strategy.

    PubMed

    Yang, Zhang; Halim, Adnan; Narimatsu, Yoshiki; Jitendra Joshi, Hiren; Steentoft, Catharina; Schjoldager, Katrine Ter-Borch Gram; Alder Schulz, Morten; Sealover, Natalie R; Kayser, Kevin J; Paul Bennett, Eric; Levery, Steven B; Vakhrushev, Sergey Y; Clausen, Henrik

    2014-12-01

    The Chinese hamster ovary cell (CHO) is the major host cell factory for recombinant production of biological therapeutics primarily because of its "human-like" glycosylation features. CHO is used for production of several O-glycoprotein therapeutics including erythropoietin, coagulation factors, and chimeric receptor IgG1-Fc-fusion proteins, however, some O-glycoproteins are not produced efficiently in CHO. We have previously shown that the capacity for O-glycosylation of proteins can be one limiting parameter for production of active proteins in CHO. Although the capacity of CHO for biosynthesis of glycan structures (glycostructures) on glycoproteins are well established, our knowledge of the capacity of CHO cells for attaching GalNAc-type O-glycans to proteins (glycosites) is minimal. This type of O-glycosylation is one of the most abundant forms of glycosylation, and it is differentially regulated in cells by expression of a subset of homologous polypeptide GalNAc-transferases. Here, we have genetically engineered CHO cells to produce homogeneous truncated O-glycans, so-called SimpleCells, which enabled lectin enrichment of O-glycoproteins and characterization of the O-glycoproteome. We identified 738 O-glycoproteins (1548 O-glycosites) in cell lysates and secretomes providing the first comprehensive insight into the O-glycosylation capacity of CHO (http://glycomics.ku.dk/o-glycoproteome_db/).

  6. O-GlcNAc glycosylation stoichiometry of the FET protein family: only EWS is glycosylated with a high stoichiometry.

    PubMed

    Kamemura, Kazuo

    2017-03-01

    Of the FET (fused in sarcoma [FUS]/Ewing sarcoma protein [EWS]/TATA binding protein-associated factor 15 [TAF15]) family of heterogeneous nuclear ribonucleoprotein particle proteins, FUS and TAF15 are consistently and EWS variably found in inclusion bodies in neurodegenerative diseases such as frontotemporal lobar degeneration associated with FUS. It is speculated that dysregulation of FET proteins at the post-translational level is involved in their cytoplasmic deposition. Here, the O-linked β-N-acetylglucosamine (O-GlcNAc) glycosylation stoichiometry of the FET proteins was chemoenzymatically analyzed, and it was found that only EWS is dynamically glycosylated with a high stoichiometry in the neural cell lines tested and in mouse brain. It was also confirmed that EWS, but not FUS and TAF15, is glycosylated with a high stoichiometry not only in the neural cells but also in the non-neural cell lines tested. These results indicate that O-GlcNAc glycosylation imparts a physicochemical property on EWS that is distinct from that of the other FET proteins in most of cell lineages or tissues.

  7. Regulation of secondary wall synthesis and cell death by NAC transcription factors in the monocot Brachypodium distachyon.

    PubMed

    Valdivia, Elene R; Herrera, María Teresa; Gianzo, Cristina; Fidalgo, Javier; Revilla, Gloria; Zarra, Ignacio; Sampedro, Javier

    2013-03-01

    In several dicotyledonous species, NAC transcription factors act as master switches capable of turning on programmes of secondary cell-wall synthesis and cell death. This work used an oestradiol-inducible system to overexpress the NAC transcription factor BdSWN5 in the monocot model Brachypodium distachyon. This resulted in ectopic secondary cell-wall formation in both roots and shoots. Some of the genes upregulated in the process were a secondary cell-wall cellulose synthase (BdCESA4), a xylem-specific protease (BdXCP1) and an orthologue of AtMYB46 (BdMYB1). While activation of BdMYB1 may not be direct, this study showed that BdSWN5 is capable of transactivating the BdXCP1 promoter through two conserved binding sites. In the course of Brachypodium development, the BdXCP1 promoter was observed to be active in all types of differentiating tracheary elements. Together, these results suggest that Brachypodium SWNs can act as switches that turn on secondary cell-wall synthesis and programmed cell death.

  8. 78 FR 66852 - State Fiscal Administration

    Federal Register 2010, 2011, 2012, 2013, 2014

    2013-11-07

    ... From the Federal Register Online via the Government Publishing Office ] DEPARTMENT OF HEALTH AND HUMAN SERVICES Centers for Medicare & Medicaid Services 42 CFR Part 433 State Fiscal Administration CFR Correction 0 In Title 42 of the Code of Federal Regulations, Parts 430 to 481, revised as of October 1,...

  9. 14 CFR 1274.503 - Codes of conduct.

    Code of Federal Regulations, 2012 CFR

    2012-01-01

    ... 14 Aeronautics and Space 5 2012-01-01 2012-01-01 false Codes of conduct. 1274.503 Section 1274.503 Aeronautics and Space NATIONAL AERONAUTICS AND SPACE ADMINISTRATION COOPERATIVE AGREEMENTS WITH COMMERCIAL... of conduct governing the performance of its employees engaged in the award and administration...

  10. RH-TRU Waste Content Codes

    SciTech Connect

    Washington TRU Solutions

    2007-07-01

    The Remote-Handled Transuranic (RH-TRU) Content Codes (RH-TRUCON) document describes the inventory of RH-TRU waste within the transportation parameters specified by the Remote-Handled Transuranic Waste Authorized Methods for Payload Control (RH-TRAMPAC).1 The RH-TRAMPAC defines the allowable payload for the RH-TRU 72-B. This document is a catalog of RH-TRU 72-B authorized contents by site. A content code is defined by the following components: • A two-letter site abbreviation that designates the physical location of the generated/stored waste (e.g., ID for Idaho National Laboratory [INL]). The site-specific letter designations for each of the sites are provided in Table 1. • A three-digit code that designates the physical and chemical form of the waste (e.g., content code 317 denotes TRU Metal Waste). For RH-TRU waste to be transported in the RH-TRU 72-B, the first number of this three-digit code is “3.” The second and third numbers of the three-digit code describe the physical and chemical form of the waste. Table 2 provides a brief description of each generic code. Content codes are further defined as subcodes by an alpha trailer after the three-digit code to allow segregation of wastes that differ in one or more parameter(s). For example, the alpha trailers of the subcodes ID 322A and ID 322B may be used to differentiate between waste packaging configurations. As detailed in the RH-TRAMPAC, compliance with flammable gas limits may be demonstrated through the evaluation of compliance with either a decay heat limit or flammable gas generation rate (FGGR) limit per container specified in approved content codes. As applicable, if a container meets the watt*year criteria specified by the RH-TRAMPAC, the decay heat limits based on the dose-dependent G value may be used as specified in an approved content code. If a site implements the administrative controls outlined in the RH-TRAMPAC and Appendix 2.4 of the RH-TRU Payload Appendices, the decay heat or FGGR

  11. Pyramid image codes

    NASA Technical Reports Server (NTRS)

    Watson, Andrew B.

    1990-01-01

    All vision systems, both human and machine, transform the spatial image into a coded representation. Particular codes may be optimized for efficiency or to extract useful image features. Researchers explored image codes based on primary visual cortex in man and other primates. Understanding these codes will advance the art in image coding, autonomous vision, and computational human factors. In cortex, imagery is coded by features that vary in size, orientation, and position. Researchers have devised a mathematical model of this transformation, called the Hexagonal oriented Orthogonal quadrature Pyramid (HOP). In a pyramid code, features are segregated by size into layers, with fewer features in the layers devoted to large features. Pyramid schemes provide scale invariance, and are useful for coarse-to-fine searching and for progressive transmission of images. The HOP Pyramid is novel in three respects: (1) it uses a hexagonal pixel lattice, (2) it uses oriented features, and (3) it accurately models most of the prominent aspects of primary visual cortex. The transform uses seven basic features (kernels), which may be regarded as three oriented edges, three oriented bars, and one non-oriented blob. Application of these kernels to non-overlapping seven-pixel neighborhoods yields six oriented, high-pass pyramid layers, and one low-pass (blob) layer.

  12. Report number codes

    SciTech Connect

    Nelson, R.N.

    1985-05-01

    This publication lists all report number codes processed by the Office of Scientific and Technical Information. The report codes are substantially based on the American National Standards Institute, Standard Technical Report Number (STRN)-Format and Creation Z39.23-1983. The Standard Technical Report Number (STRN) provides one of the primary methods of identifying a specific technical report. The STRN consists of two parts: The report code and the sequential number. The report code identifies the issuing organization, a specific program, or a type of document. The sequential number, which is assigned in sequence by each report issuing entity, is not included in this publication. Part I of this compilation is alphabetized by report codes followed by issuing installations. Part II lists the issuing organization followed by the assigned report code(s). In both Parts I and II, the names of issuing organizations appear for the most part in the form used at the time the reports were issued. However, for some of the more prolific installations which have had name changes, all entries have been merged under the current name.

  13. Embedded foveation image coding.

    PubMed

    Wang, Z; Bovik, A C

    2001-01-01

    The human visual system (HVS) is highly space-variant in sampling, coding, processing, and understanding. The spatial resolution of the HVS is highest around the point of fixation (foveation point) and decreases rapidly with increasing eccentricity. By taking advantage of this fact, it is possible to remove considerable high-frequency information redundancy from the peripheral regions and still reconstruct a perceptually good quality image. Great success has been obtained previously by a class of embedded wavelet image coding algorithms, such as the embedded zerotree wavelet (EZW) and the set partitioning in hierarchical trees (SPIHT) algorithms. Embedded wavelet coding not only provides very good compression performance, but also has the property that the bitstream can be truncated at any point and still be decoded to recreate a reasonably good quality image. In this paper, we propose an embedded foveation image coding (EFIC) algorithm, which orders the encoded bitstream to optimize foveated visual quality at arbitrary bit-rates. A foveation-based image quality metric, namely, foveated wavelet image quality index (FWQI), plays an important role in the EFIC system. We also developed a modified SPIHT algorithm to improve the coding efficiency. Experiments show that EFIC integrates foveation filtering with foveated image coding and demonstrates very good coding performance and scalability in terms of foveated image quality measurement.

  14. High-sensitivity immunoassay with surface plasmon field-enhanced fluorescence spectroscopy using a plastic sensor chip: application to quantitative analysis of total prostate-specific antigen and GalNAcβ1-4GlcNAc-linked prostate-specific antigen for prostate cancer diagnosis.

    PubMed

    Kaya, Takatoshi; Kaneko, Tomonori; Kojima, Shun; Nakamura, Yukito; Ide, Youichi; Ishida, Kenji; Suda, Yoshihiko; Yamashita, Katsuko

    2015-02-03

    A high-sensitivity immunoassay system with surface plasmon field-enhanced fluorescence spectrometry (SPFS) was constructed using a plastic sensor chip and then applied to the detection of total prostate-specific antigen (total PSA) and GalNAcβ1-4GlcNAc-linked prostate-specific antigen (LacdiNAc-PSA) in serum, to discriminate between prostate cancer (PC) and benign prostate hyperplasia (BPH). By using this automated SPFS immunoassay, the detection limit for total PSA in serum was as low as 0.04 pg/mL, and the dynamic range was estimated to be at least five digits. A two-step sandwich SPFS immunoassay for LacdiNAc-PSA was constructed using both the anti-PSA IgG antibody to capture PSA and Wisteria floribunda agglutinin (WFA) for the detection of LacdiNAc. The results of the LacdiNAc-PSA immunoassay with SPFS showed that the assay had a sensitivity of 20.0 pg/mL and permitted the specific distinction between PC and BPH within the PSA gray zone. These results suggested that high-sensitivity automated SPFS immunoassay systems might become a powerful tool for the diagnosis of PC and other diseases.

  15. Control of oxidative reactions of hemoglobin in the design of blood substitutes: role of the Vc, NAC, TEMPO and their reductant system.

    PubMed

    Su, Xiulan; Guo, Song; Huang, Xiaoxia; Wang, Xiang; Qi, Donglai; Yang, Chengmin

    2014-08-01

    Oxidative reactions of hemoglobin (Hb) are still a serious problem for Hb-based blood substitute development. Although varieties of antioxidant strategies have been suggested, this in vitro study examined the ability of the ascorbate, N-Acetyl-L-Cysteine (NAC), 4-hydroxy-2, 2, 6, 6-tetramethylpiperidine-1-oxygen free radicals (TEMPO) and their reductant system in preventing Hb oxidation. The content of ferric Hb is monitored in the process of vitamin C (Vc), NAC, TEMPO and their reductant system. The results suggest that ascorbate is effective in reducing ferryl Hb, and TEMPO with Vc/NAC could obviously shorten the reaction time, but it does not play the role of Met-Hb reductases. It demonstrates that TEMPO did little to recover Hb under oxidative stress.

  16. Convergent Synthesis of Homogeneous Glc1Man9GlcNAc2-Protein and Derivatives as Ligands of Molecular Chaperones in Protein Quality Control

    PubMed Central

    Amin, Mohammed N.; Huang, Wei; Mizanur, Rahman M.

    2011-01-01

    A detailed understanding of the molecular mechanism of chaperone-assisted protein quality control is often hampered by the lack of well-defined homogeneous glycoprotein probes. We describe here a highly convergent chemoenzymatic synthesis of the monoglucosylated glycoforms of bovine ribonuclease (RNase) as specific ligands of lectin-like chaperones calnexin (CNX) and calreticulin (CRT) that are known to recognize the monoglucosylated high-mannose oligosaccharide component of glycoproteins in protein folding. The synthesis of a selectively modified glycoform Gal1Glc1Man9GlcNAc2-RNase was accomplished by chemical synthesis of a large N-glycan oxazoline and its subsequent enzymatic ligation to GlcNAc-RNase under the catalysis of a glycosynthase. Selective removal of the terminal galactose by a β-galactosidase gave the Glc1Man9GlcNAc2-RNase glycoform in excellent yield. CD spectroscopic analysis and RNA-hydrolyzing assay indicated that the synthetic RNase glycoforms maintained essentially the same global conformations and were fully active as the natural bovine ribonuclease B. SPR binding studies revealed that the Glc1Man9GlcNAc2-RNase had high affinity to lectin CRT, while the synthetic Man9GlcNAc2-RNase glycoform and natural RNase B did not show CRT-binding activity. These results confirmed the essential role of the glucose moiety in the chaperone molecular recognition. Interestingly, the galactose-masked glycoform Gal1Glc1Man9GlcNAc2-RNase also showed significant affinity to lectin CRT, suggesting that a galactose β-1,4-linked to the key glucose moiety does not significantly block the lectin binding. These synthetic homogeneous glycoprotein probes should be valuable for a detailed mechanistic study on how molecular chaperones work in concert to distinguish between mis-folded and folded glycoproteins in the protein quality control cycle. PMID:21819116

  17. Glucose deprivation induces G2/M transition-arrest and cell death in N-GlcNAc2-modified protein-producing renal carcinoma cells.

    PubMed

    Isono, Takahiro; Chano, Tokuhiro; Kitamura, Asuka; Yuasa, Takeshi

    2014-01-01

    Some cancer cells can survive under glucose deprivation within the microenvironment of a tumor. Recently, we reported that N-linked (β-N-acetylglucosamine)2 [N-GlcNAc2]-modified proteins induce G2/M arrest and cell death under glucose deprivation. Here, we investigated whether such a response to glucose deprivation contributes to the survival of renal cell carcinomas, which are sensitive to nutritional stress. Specifically, we analyzed seven renal carcinoma cell lines. Four of these cell lines produced N-GlcNAc2-modified proteins and led G2/M-phase arrest under glucose deprivation, leading to cell death. The remaining three cell lines did not produce N-GlcNAc2-modified proteins and undergo G1/S-phase arrest under glucose deprivation, leading to survival. The four dead cell lines displayed significant up-regulation in the UDP-GlcNAc biosynthesis pathway as well as increased phosphorylation of p53, which was not observed in the surviving three cell lines. In addition, the four dead cell lines showed prolonged up-regulated expression of ATF3, which is related to unfolded protein response (UPR), while the surviving three cell lines showed only transient up-regulation of ATF3. In this study, we demonstrated that the renal carcinoma cells which accumulate N-GlcNAc2-modified proteins under glucose deprivation do not survive with abnormaly prolonged UPR pathway. By contrast, renal carcinoma cells that do not accumulate N-GlcNAc2-modified proteins under these conditions survive. Morover, we demonstrated that buformin, a UPR inhibitor, efficiently reduced cell survival under conditions of glucose deprivation for both sensitive and resistant phenotypes. Further studies to clarify these findings will lead to the development of novel chemotherapeutic treatments for renal cancer.

  18. Glucose Deprivation Induces G2/M Transition-Arrest and Cell Death in N-GlcNAc2-Modified Protein-Producing Renal Carcinoma Cells

    PubMed Central

    Isono, Takahiro; Chano, Tokuhiro; Kitamura, Asuka; Yuasa, Takeshi

    2014-01-01

    Some cancer cells can survive under glucose deprivation within the microenvironment of a tumor. Recently, we reported that N-linked (β-N-acetylglucosamine)2 [N-GlcNAc2]-modified proteins induce G2/M arrest and cell death under glucose deprivation. Here, we investigated whether such a response to glucose deprivation contributes to the survival of renal cell carcinomas, which are sensitive to nutritional stress. Specifically, we analyzed seven renal carcinoma cell lines. Four of these cell lines produced N-GlcNAc2-modified proteins and led G2/M-phase arrest under glucose deprivation, leading to cell death. The remaining three cell lines did not produce N-GlcNAc2-modified proteins and undergo G1/S-phase arrest under glucose deprivation, leading to survival. The four dead cell lines displayed significant up-regulation in the UDP-GlcNAc biosynthesis pathway as well as increased phosphorylation of p53, which was not observed in the surviving three cell lines. In addition, the four dead cell lines showed prolonged up-regulated expression of ATF3, which is related to unfolded protein response (UPR), while the surviving three cell lines showed only transient up-regulation of ATF3. In this study, we demonstrated that the renal carcinoma cells which accumulate N-GlcNAc2-modified proteins under glucose deprivation do not survive with abnormaly prolonged UPR pathway. By contrast, renal carcinoma cells that do not accumulate N-GlcNAc2-modified proteins under these conditions survive. Morover, we demonstrated that buformin, a UPR inhibitor, efficiently reduced cell survival under conditions of glucose deprivation for both sensitive and resistant phenotypes. Further studies to clarify these findings will lead to the development of novel chemotherapeutic treatments for renal cancer. PMID:24796485

  19. Glutamine-induced protection of isolated rat heart from ischemia/reperfusion injury is mediated via the hexosamine biosynthesis pathway and increased protein O-GlcNAc levels

    PubMed Central

    Liu, Jia; Marchase, Richard B.; Chatham, John C.

    2007-01-01

    It has been shown that glutamine protects the heart from ischemia/reperfusion (I/R) injury; however, the mechanisms underlying this protection have not been identfied. Glutamine: fructose-6-phosphate amidotransferase (GFAT) regulates the entry of glucose into the hexosamine biosynthesis pathway (HBP) and activation of this pathway has been shown to be cardioprotective. Glutamine is required for metabolism of glucose via GFAT; therefore, the goal of this study was to determine whether glutamine cardioprotection could be attributed to increased flux through the HBP and elevated levels of O-linked N-acetyl-glucosamine (O-GlcNAc) on proteins. Hearts from male rats were isolated and perfused with Krebs-Henseliet buffer containing 5mM glucose, and global, no-flow ischemia was induced for 20 minutes followed by 60 minutes of reperfusion. 30 minute pre-treatment with 2.5 mM glutamine significantly improved functional recovery (RPP: 15.6±5.7% Vs. 59.4±6.1%; p<0.05) and decreased cardiac Troponin I release (25.4±3.0 Vs. 4.7±1.9; p<0.05) during reperfusion. This protection was associated with a significant increase in the levels of protein O-GlcNAc and ATP. Pre-treatment with 80 μM azaserine, an inhibitor of GFAT, completely reversed the protection seen with glutamine and prevented the increase in protein O-GlcNAc. O-GlcNAc transferase (OGT) catalyzes the formation of O-GlcNAc, and inhibition of OGT with 5mM alloxan also reversed the protection associated with glutamine. These data support the hypothesis that in the ex vivo perfused heart glutamine cardioprotection is due, at least in part, to enhanced flux through the HBP and increased protein O-GlcNAc levels. PMID:17069847

  20. Code Disentanglement: Initial Plan

    SciTech Connect

    Wohlbier, John Greaton; Kelley, Timothy M.; Rockefeller, Gabriel M.; Calef, Matthew Thomas

    2015-01-27

    The first step to making more ambitious changes in the EAP code base is to disentangle the code into a set of independent, levelized packages. We define a package as a collection of code, most often across a set of files, that provides a defined set of functionality; a package a) can be built and tested as an entity and b) fits within an overall levelization design. Each package contributes one or more libraries, or an application that uses the other libraries. A package set is levelized if the relationships between packages form a directed, acyclic graph and each package uses only packages at lower levels of the diagram (in Fortran this relationship is often describable by the use relationship between modules). Independent packages permit independent- and therefore parallel|development. The packages form separable units for the purposes of development and testing. This is a proven path for enabling finer-grained changes to a complex code.

  1. Compressible Astrophysics Simulation Code

    SciTech Connect

    Howell, L.; Singer, M.

    2007-07-18

    This is an astrophysics simulation code involving a radiation diffusion module developed at LLNL coupled to compressible hydrodynamics and adaptive mesh infrastructure developed at LBNL. One intended application is to neutrino diffusion in core collapse supernovae.

  2. NMDA and dopamine D1 receptors within NAc-shell regulate IEG proteins expression in reward circuit during cocaine memory reconsolidation.

    PubMed

    Li, Y; Ge, S; Li, N; Chen, L; Zhang, S; Wang, J; Wu, H; Wang, X; Wang, X

    2016-02-19

    Reactivation of consolidated memory initiates a memory reconsolidation process, during which the reactivated memory is susceptible to strengthening, weakening or updating. Therefore, effective interference with the memory reconsolidation process is expected to be an important treatment for drug addiction. The nucleus accumbens (NAc) has been well recognized as a pathway component that can prevent drug relapse, although the mechanism underlying this function is poorly understood. We aimed to clarify the regulatory role of the NAc in the cocaine memory reconsolidation process, by examining the effect of applying different pharmacological interventions to the NAc on Zif 268 and Fos B expression in the entire reward circuit after cocaine memory reactivation. Through the cocaine-induced conditioned place preference (CPP) model, immunohistochemical and immunofluorescence staining for Zif 268 and Fos B were used to explore the functional activated brain nuclei after cocaine memory reactivation. Our results showed that the expression of Zif 268 and Fos B was commonly increased in the medial prefrontal cortex (mPFC), the infralimbic cortex (IL), the NAc-core, the NAc-shell, the hippocampus (CA1, CA2, and CA3 subregions), the amygdala, the ventral tegmental area (VTA), and the supramammillary nucleus (SuM) following memory reconsolidation, and Zif 268/Fos B co-expression was commonly observed (for Zif 268: 51-68%; for Fos B: 52-66%). Further, bilateral NAc-shell infusion of MK 801 and SCH 23390, but not raclopride or propranolol, prior to addictive memory reconsolidation, decreased Zif 268 and Fos B expression in the entire reward circuit, except for the amygdala, and effectively disturbed subsequent CPP-related behavior. In summary, N-methyl-d-aspartate (NMDA) and dopamine D1 receptors, but not dopamine D2 or β adrenergic receptors, within the NAc-shell, may regulate Zif 268 and Fos B expression in most brain nuclei of the reward circuit after cocaine memory reactivation

  3. Augmented O-GlcNAc signaling via glucosamine attenuates oxidative stress and apoptosis following contrast-induced acute kidney injury in rats.

    PubMed

    Hu, Jiachang; Chen, Rongyi; Jia, Ping; Fang, Yi; Liu, Tongqiang; Song, Nana; Xu, Xialian; Ji, Jun; Ding, Xiaoqiang

    2017-02-01

    Contrast-induced acute kidney injury (CI-AKI) is an iatrogenic renal injury and associated with substantial morbidity and mortality in susceptible individuals. Despite extensive study of a variety of agents for renal protection, limited strategies have been shown to be effective in the reduction of CI-AKI. O-linked β-N-acetylglucosamine (O-GlcNAc) is a post-translational regulatory modification of intracellular proteins and governs the function of numerous proteins, both cytosolic and nuclear. Increasing evidence suggests that O-GlcNAc levels are increased in response to stress and that acute augmentation of this reaction is cytoprotective. However, the underlying mechanisms by which augmented OGlcNAc signaling provides renoprotection against contrast media insults is still unknown. Here, we investigated the effect of augmented O-GlcNAc signaling via glucosamine on CI-AKI and explored the underlying molecular mechanisms, particularly its relationship with PI3-kinase (PI3K)/Akt signaling. We used a novel and reliable CI-AKI model consisting of 5/6 nephrectomized (NE) rats, and a low-osmolar contrast media (iohexol, 10mL/kg, 3.5gI) injected via the tail vein after dehydration for 48h. The results showed that augmented O-GlcNAc signaling by glucosamine prevented the kidneys against iohexol-induced injury characterized by the attenuation of renal dysfunction, tubular damage, apoptosis and oxidative stress. Furthermore, this renoprotection was blocked by treatment with alloxan, an O-GlcNAc transferase inhibitor. Augmented O-GlcNAc signaling also increased the protein expression levels of phospho-Akt (Ser473, but not Thr308 and Thr450), phospho-GSK-3β, Nrf2, and Bcl-2, and decreased the levels of Bax and cleaved caspase-3. Both alloxan and specific inhibitors of PI3K (Wortmannin and LY294002) blocked the protection of glucosamine via inhibiting Akt signaling pathway. We further identified O-GlcNAcylated Akt through immunoprecipitation and western blot. We confirmed

  4. Remote-Handled Transuranic Content Codes

    SciTech Connect

    Washington TRU Solutions

    2006-12-01

    The Remote-Handled Transuranic (RH-TRU) Content Codes (RH-TRUCON) document describes the inventory of RH-TRU waste within the transportation parameters specified by the Remote-Handled Transuranic Waste Authorized Methods for Payload Control (RH-TRAMPAC).1 The RH-TRAMPAC defines the allowable payload for the RH-TRU 72-B. This document is a catalog of RH-TRU 72-B authorized contents by site. A content code is defined by the following components: • A two-letter site abbreviation that designates the physical location of the generated/stored waste (e.g., ID for Idaho National Laboratory [INL]). The site-specific letter designations for each of the sites are provided in Table 1. • A three-digit code that designates the physical and chemical form of the waste (e.g., content code 317 denotes TRU Metal Waste). For RH-TRU waste to be transported in the RH-TRU 72-B, the first number of this three-digit code is “3.” The second and third numbers of the three-digit code describe the physical and chemical form of the waste. Table 2 provides a brief description of each generic code. Content codes are further defined as subcodes by an alpha trailer after the three-digit code to allow segregation of wastes that differ in one or more parameter(s). For example, the alpha trailers of the subcodes ID 322A and ID 322B may be used to differentiate between waste packaging configurations. As detailed in the RH-TRAMPAC, compliance with flammable gas limits may be demonstrated through the evaluation of compliance with either a decay heat limit or flammable gas generation rate (FGGR) limit per container specified in approved content codes. As applicable, if a container meets the watt*year criteria specified by the RH-TRAMPAC, the decay heat limits based on the dose-dependent G value may be used as specified in an approved content code. If a site implements the administrative controls outlined in the RH-TRAMPAC and Appendix 2.4 of the RH-TRU Payload Appendices, the decay heat or FGGR

  5. Seals Flow Code Development

    NASA Technical Reports Server (NTRS)

    1991-01-01

    In recognition of a deficiency in the current modeling capability for seals, an effort was established by NASA to develop verified computational fluid dynamic concepts, codes, and analyses for seals. The objectives were to develop advanced concepts for the design and analysis of seals, to effectively disseminate the information to potential users by way of annual workshops, and to provide experimental verification for the models and codes under a wide range of operating conditions.

  6. Conformational studies of the glycopeptide Ac-Tyr-[Man5GlcNAc-beta-(1-->4)GlcNAc-beta-(1-->Ndelta)]-Asn-Leu-Thr-Se r-OBz and the constituent peptide and oligosaccharide.

    PubMed

    Bailey, D; Renouf, D V; Large, D G; Warren, C D; Hounsell, E F

    2000-03-10

    Glycopeptides of desired structure can be conveniently prepared by the coupling of reducing oligosaccharides to aspartic acid of peptides via their glycosylamines formed in the presence of saturated aqueous ammonium hydrogen carbonate. The resulting oligosaccharide chains are N-linked to asparagine as in natural glycoproteins, allowing different peptide oligosaccharide combinations to be analysed for conformational effects. In the present paper, a pentapeptide of ovalbumin was coupled to Man5GlcNAc2 oligosaccharide and the glycopeptide and the two parent compounds compared by NMR ROESY experiments and molecular dynamics simulations. Despite the small size of the peptide, conformational effects were observed suggestive of the oligosaccharide stabilising the peptide in solution and of the peptide influencing oligosaccharide conformation. These effects are relevant to the function of glycosylation and the enzymic processing of oligosaccharide chains.

  7. Correlation between differential drought tolerability of two contrasting drought-responsive chickpea cultivars and differential expression of a subset of CaNAC genes under normal and dehydration conditions.

    PubMed

    Nguyen, Kien Huu; Ha, Chien Van; Watanabe, Yasuko; Tran, Uyen Thi; Nasr Esfahani, Maryam; Nguyen, Dong Van; Tran, Lam-Son Phan

    2015-01-01

    Drought causes detrimental effect to growth and productivity of many plants, including crops. NAC transcription factors have been reported to play important role in drought tolerance. In this study, we assessed the expression profiles of 19 dehydration-responsive CaNAC genes in roots and leaves of two contrasting drought-responsive chickpea varieties treated with water (control) and dehydration to examine the correlation between the differential expression levels of the CaNAC genes and the differential drought tolerability of these two cultivars. Results of real-time quantitative PCR indicated a positive relationship between the number of dehydration-inducible and -repressible CaNAC genes and drought tolerability. The higher drought-tolerant capacity of ILC482 cultivar vs. Hashem cultivar might be, at least partly, attributed to the higher number of dehydration-inducible and lower number of dehydration-repressible CaNAC genes identified in both root and leaf tissues of ILC482 than in those of Hashem. In addition, our comparative expression analysis of the selected CaNAC genes in roots and leaves of ILC482 and Hashem cultivars revealed different dehydration-responsive expression patterns, indicating that CaNAC gene expression is tissue- and genotype-specific. Furthermore, the analysis suggested that the enhanced drought tolerance of ILC482 vs. Hashem might be associated with five genes, namely CaNAC02, 04, 05, 16, and 24. CaNAC16 could be a potential candidate gene, contributing to the better drought tolerance of ILC482 vs. Hashem as a positive regulator. Conversely, CaNAC02 could be a potential negative regulator, contributing to the differential drought tolerability of these two cultivars. Thus, our results have also provided a solid foundation for selection of promising tissue-specific and/or dehydration-responsive CaNAC candidates for detailed in planta functional analyses, leading to development of transgenic chickpea varieties with improved productivity under

  8. Robust Nonlinear Neural Codes

    NASA Astrophysics Data System (ADS)

    Yang, Qianli; Pitkow, Xaq

    2015-03-01

    Most interesting natural sensory stimuli are encoded in the brain in a form that can only be decoded nonlinearly. But despite being a core function of the brain, nonlinear population codes are rarely studied and poorly understood. Interestingly, the few existing models of nonlinear codes are inconsistent with known architectural features of the brain. In particular, these codes have information content that scales with the size of the cortical population, even if that violates the data processing inequality by exceeding the amount of information entering the sensory system. Here we provide a valid theory of nonlinear population codes by generalizing recent work on information-limiting correlations in linear population codes. Although these generalized, nonlinear information-limiting correlations bound the performance of any decoder, they also make decoding more robust to suboptimal computation, allowing many suboptimal decoders to achieve nearly the same efficiency as an optimal decoder. Although these correlations are extremely difficult to measure directly, particularly for nonlinear codes, we provide a simple, practical test by which one can use choice-related activity in small populations of neurons to determine whether decoding is suboptimal or optimal and limited by correlated noise. We conclude by describing an example computation in the vestibular system where this theory applies. QY and XP was supported by a grant from the McNair foundation.

  9. Paine Appointed Administrator

    NASA Technical Reports Server (NTRS)

    1969-01-01

    President Richard M. Nixon announcing the appointment of Dr. Thomas O. Paine as Administrator for the National Aeronautics and Space Administration. The ceremony was held at the White House. Paine had been serving as acting administrator. From left to right: President Richard M. Nixon NASA Administrator Dr. Thomas O. Paine Vice President Spiro T. Agnew

  10. Purification and characterization of UDP-GalNAc:polypeptide N-acetylgalactosaminyl transferase from swine trachea epithelium.

    PubMed

    Mendicino, J; Sangadala, S

    1998-08-01

    UDP-GalNac: polypeptide N-acetylgalactosaminyltransferase from swine trachea epithelium was purified to homogeneity by procedures which included affinity chromatography on Sepharose 4B columns containing bound deglycosylated Cowper's gland mucin. The enzyme, purified 12,000-fold from microsomes with a yield of 40%, showed only a single band on dodecyl sulfate polyacrylamide gel electrophoresis. The homogenous enzyme has an apparent molecular mass of 70,000 Da, as determined by gel electrophoresis or gel filtration. The transferase has a broad pH optimum between 6.7-7.8 with maximal activity at pH 7.2, and required Mn2+ for activity with maximal activity at 5-7.5 mM. Higher concentrations of Mn2+, inhibited the enzyme. The purified transferase was specific for UDPGalNAc and glycosylated both threonine and serine residues in tryptic peptides prepared from deglycosylated Cowper's gland and swine and human trachea mucins. The apparent Km of the transferase for UDPGalNAc was 6.3 microM, and the Km values for deglycosylated Cowper's gland and human and swine trachea mucins were 0.83, 1.12 and 0.94 mg/ml, respectively. The Vmax of the purified enzyme was 2.1 micromol/min/mg with deglycosylated Cowper's gland mucin, as the glycosyl acceptor. However, the activities with peptides prepared from deglycosylated mucins by limited acid hydrolysis were 20-fold greater than the intact glycoprotein under identical conditions. The deglycosylated mucins and larger peptides aggregated with time of storage and precipitated from solution. Aggregation was accompanied by a corresponding loss of enzymatic activity even after dispersion of the aggregate by sonication. The deglycosylated mucins which were prepared by chemical treatment and periodate oxidation still contained about 20% of the N-acetylgalactosamine present in the intact mucin. When this residual amino sugar was removed by periodate oxidation the completely deglycosylated mucins became very poor substrates for the purified

  11. ICD9 Code Assistant: A prototype.

    PubMed

    Erdal, Selnur; Ding, Jing; Osborn, Carol; Mekhjian, Hagop; Kamal, Jyoti

    2007-10-11

    At The Ohio State University Medical Center (OSUMC) patient reports are available in real time along with other clinical and financial data in the OSUMC Information Warehouse (IW). Using the UMLS Meta Thesaurus we have leveraged the IW to develop a tool that can assist the medical record coders as well as administrators, physicians and researchers to quickly identify clinical concepts and their associated ICD-9 codes.

  12. HCPCS Coding: An Integral Part of Your Reimbursement Strategy

    PubMed Central

    Nusgart, Marcia

    2013-01-01

    The first step to a successful reimbursement strategy is to ensure that your wound care product has the most appropriate Healthcare Common Procedure Coding System (HCPCS) code (or billing) for your product. The correct HCPCS code plays an essential role in patient access to new and existing technologies. When devising a strategy to obtain a HCPCS code for its product, companies must consider a number of factors as follows: (1) Has the product gone through the Food and Drug Administration (FDA) regulatory process or does it need to do so? Will the FDA code designation impact which HCPCS code will be assigned to your product? (2) In what “site of service” do you intend to market your product? Where will your customers use the product? Which coding system (CPT® or HCPCS) applies to your product? (3) Does a HCPCS code for a similar product already exist? Does your product fit under the existing HCPCS code? (4) Does your product need a new HCPCS code? What is the linkage, if any, between coding, payment, and coverage for the product? Researchers and companies need to start early and place the same emphasis on a reimbursement strategy as it does on a regulatory strategy. Your reimbursement strategy staff should be involved early in the process, preferably during product research and development and clinical trial discussions. PMID:24761331

  13. HCPCS Coding: An Integral Part of Your Reimbursement Strategy.

    PubMed

    Nusgart, Marcia

    2013-12-01

    The first step to a successful reimbursement strategy is to ensure that your wound care product has the most appropriate Healthcare Common Procedure Coding System (HCPCS) code (or billing) for your product. The correct HCPCS code plays an essential role in patient access to new and existing technologies. When devising a strategy to obtain a HCPCS code for its product, companies must consider a number of factors as follows: (1) Has the product gone through the Food and Drug Administration (FDA) regulatory process or does it need to do so? Will the FDA code designation impact which HCPCS code will be assigned to your product? (2) In what "site of service" do you intend to market your product? Where will your customers use the product? Which coding system (CPT(®) or HCPCS) applies to your product? (3) Does a HCPCS code for a similar product already exist? Does your product fit under the existing HCPCS code? (4) Does your product need a new HCPCS code? What is the linkage, if any, between coding, payment, and coverage for the product? Researchers and companies need to start early and place the same emphasis on a reimbursement strategy as it does on a regulatory strategy. Your reimbursement strategy staff should be involved early in the process, preferably during product research and development and clinical trial discussions.

  14. 1 CFR 21.23 - Parallel citations of Code and Federal Register.

    Code of Federal Regulations, 2012 CFR

    2012-01-01

    ... 1 General Provisions 1 2012-01-01 2012-01-01 false Parallel citations of Code and Federal Register. 21.23 Section 21.23 General Provisions ADMINISTRATIVE COMMITTEE OF THE FEDERAL REGISTER PREPARATION... § 21.23 Parallel citations of Code and Federal Register. For parallel reference, the Code of...

  15. 1 CFR 21.23 - Parallel citations of Code and Federal Register.

    Code of Federal Regulations, 2010 CFR

    2010-01-01

    ... 1 General Provisions 1 2010-01-01 2010-01-01 false Parallel citations of Code and Federal Register. 21.23 Section 21.23 General Provisions ADMINISTRATIVE COMMITTEE OF THE FEDERAL REGISTER PREPARATION... § 21.23 Parallel citations of Code and Federal Register. For parallel reference, the Code of...

  16. 1 CFR 21.23 - Parallel citations of Code and Federal Register.

    Code of Federal Regulations, 2014 CFR

    2014-01-01

    ... 1 General Provisions 1 2014-01-01 2012-01-01 true Parallel citations of Code and Federal Register. 21.23 Section 21.23 General Provisions ADMINISTRATIVE COMMITTEE OF THE FEDERAL REGISTER PREPARATION... § 21.23 Parallel citations of Code and Federal Register. For parallel reference, the Code of...

  17. 1 CFR 21.23 - Parallel citations of Code and Federal Register.

    Code of Federal Regulations, 2011 CFR

    2011-01-01

    ... 1 General Provisions 1 2011-01-01 2011-01-01 false Parallel citations of Code and Federal Register. 21.23 Section 21.23 General Provisions ADMINISTRATIVE COMMITTEE OF THE FEDERAL REGISTER PREPARATION... § 21.23 Parallel citations of Code and Federal Register. For parallel reference, the Code of...

  18. 1 CFR 21.23 - Parallel citations of Code and Federal Register.

    Code of Federal Regulations, 2013 CFR

    2013-01-01

    ... 1 General Provisions 1 2013-01-01 2012-01-01 true Parallel citations of Code and Federal Register. 21.23 Section 21.23 General Provisions ADMINISTRATIVE COMMITTEE OF THE FEDERAL REGISTER PREPARATION... § 21.23 Parallel citations of Code and Federal Register. For parallel reference, the Code of...

  19. 77 FR 69897 - Comment Request for Information Collection for Occupational Code Assignment, Extension Without...

    Federal Register 2010, 2011, 2012, 2013, 2014

    2012-11-21

    ... Employment and Training Administration Comment Request for Information Collection for Occupational Code... about the Occupational Code Assignment Form (ETA 741), which expires on March 31, 2013. A copy of the... Code Assignment form (ETA 741) was developed as a public service to the users of the...

  20. 50 CFR Table 1c to Part 679 - Product Tyoe Codes

    Code of Federal Regulations, 2010 CFR

    2010-10-01

    ... 50 Wildlife and Fisheries 9 2010-10-01 2010-10-01 false Product Tyoe Codes 1c Table 1c to Part 679 Wildlife and Fisheries FISHERY CONSERVATION AND MANAGEMENT, NATIONAL OCEANIC AND ATMOSPHERIC ADMINISTRATION... Table 1c to Part 679—Product Tyoe Codes Description Code Ancillary product.A product, such as...