Analysis of URI nuclear interaction with RPB5 and components of the R2TP/prefoldin-like complex.

PubMed

Mita, Paolo; Savas, Jeffrey N; Ha, Susan; Djouder, Nabil; Yates, John R; Logan, Susan K

2013-01-01

Unconventional prefoldin RPB5 Interactor (URI) was identified as a transcriptional repressor that binds RNA polymerase II (pol II) through interaction with the RPB5/POLR2E subunit. Despite the fact that many other proteins involved in transcription regulation have been shown to interact with URI, its nuclear function still remains elusive. Previous mass spectrometry analyses reported that URI is part of a novel protein complex called R2TP/prefoldin-like complex responsible for the cytoplasmic assembly of RNA polymerase II. We performed a mass spectrometry (MS)-based proteomic analysis to identify nuclear proteins interacting with URI in prostate cells. We identified all the components of the R2TP/prefoldin-like complex as nuclear URI interactors and we showed that URI binds and regulates RPB5 protein stability and transcription. Moreover, we validated the interaction of URI to the P53 and DNA damage-Regulated Gene 1 (PDRG1) and show that PDRG1 protein is also stabilized by URI binding. We present data demonstrating that URI nuclear/cytoplasmic shuttling is affected by compounds that stall pol II on the DNA (α-amanitin and actinomycin-D) and by leptomycin B, an inhibitor of the CRM1 exportin that mediates the nuclear export of pol II subunits. These data suggest that URI, and probably the entire R2TP/prefoldin-like complex is exported from the nucleus through CRM1. Finally we identified putative URI sites of phosphorylation and acetylation and confirmed URI sites of post-transcriptional modification identified in previous large-scale analyses the importance of which is largely unknown. However URI post-transcriptional modification was shown to be essential for URI function and therefore characterization of novel sites of URI modification will be important to the understanding of URI function.

Analysis of URI Nuclear Interaction with RPB5 and Components of the R2TP/Prefoldin-Like Complex

PubMed Central

Mita, Paolo; Savas, Jeffrey N.; Ha, Susan; Djouder, Nabil; Yates, John R.; Logan, Susan K.

2013-01-01

Unconventional prefoldin RPB5 Interactor (URI) was identified as a transcriptional repressor that binds RNA polymerase II (pol II) through interaction with the RPB5/POLR2E subunit. Despite the fact that many other proteins involved in transcription regulation have been shown to interact with URI, its nuclear function still remains elusive. Previous mass spectrometry analyses reported that URI is part of a novel protein complex called R2TP/prefoldin-like complex responsible for the cytoplasmic assembly of RNA polymerase II. We performed a mass spectrometry (MS)-based proteomic analysis to identify nuclear proteins interacting with URI in prostate cells. We identified all the components of the R2TP/prefoldin-like complex as nuclear URI interactors and we showed that URI binds and regulates RPB5 protein stability and transcription. Moreover, we validated the interaction of URI to the P53 and DNA damage-Regulated Gene 1 (PDRG1) and show that PDRG1 protein is also stabilized by URI binding. We present data demonstrating that URI nuclear/cytoplasmic shuttling is affected by compounds that stall pol II on the DNA (α-amanitin and actinomycin-D) and by leptomycin B, an inhibitor of the CRM1 exportin that mediates the nuclear export of pol II subunits. These data suggest that URI, and probably the entire R2TP/prefoldin-like complex is exported from the nucleus through CRM1. Finally we identified putative URI sites of phosphorylation and acetylation and confirmed URI sites of post-transcriptional modification identified in previous large-scale analyses the importance of which is largely unknown. However URI post-transcriptional modification was shown to be essential for URI function and therefore characterization of novel sites of URI modification will be important to the understanding of URI function. PMID:23667685

Cancer Immunosurveillance by Tissue-resident Innate Lymphoid Cells and Innate-like T Cells

PubMed Central

Dadi, Saïda; Chhangawala, Sagar; Whitlock, Benjamin M.; Franklin, Ruth A.; Luo, Chong T.; Oh, Soyoung A.; Toure, Ahmed; Pritykin, Yuri; Huse, Morgan; Leslie, Christina S.; Li, Ming O.

2016-01-01

Summary Malignancy can be suppressed by the immune system in a process termed immunosurveillance. However, to what extent immunosurveillance occurs in spontaneous cancers and the composition of participating cell types remain obscure. Here we show that cell transformation triggers a tissue-resident lymphocyte response in oncogene-induced murine cancer models. Non-circulating cytotoxic lymphocytes, derived from innate, TCRαβ and TCRγδ lineages, expand in early tumors. Characterized by high expression of NK1.1, CD49a and CD103, these cells share a gene expression signature distinct from those of conventional NK cells, T cells and invariant NKT cells. Generation of these lymphocytes is dependent on the cytokine IL-15, but not the transcription factor Nfil3 that is required for the differentiation of tumor-infiltrating NK cells, and IL-15, but not Nfil3, deficiency results in accelerated tumor growth. These findings reveal a tumor-elicited immunosurveillance mechanism that engages unconventional type 1-like innate lymphoid cells and type 1 innate-like T cells. PMID:26806130

hPDI: a database of experimental human protein-DNA interactions.

PubMed

Xie, Zhi; Hu, Shaohui; Blackshaw, Seth; Zhu, Heng; Qian, Jiang

2010-01-15

The human protein DNA Interactome (hPDI) database holds experimental protein-DNA interaction data for humans identified by protein microarray assays. The unique characteristics of hPDI are that it contains consensus DNA-binding sequences not only for nearly 500 human transcription factors but also for >500 unconventional DNA-binding proteins, which are completely uncharacterized previously. Users can browse, search and download a subset or the entire data via a web interface. This database is freely accessible for any academic purposes. http://bioinfo.wilmer.jhu.edu/PDI/.

Integrating international responses to complex emergencies, unconventional war, and terrorism.

PubMed

Burkle, Frederick M

2005-01-01

The world is experiencing unprecedented violence and threats of violence, taking the form of complex internal nation-state conflicts, unconventional or guerrilla warfare against established governments, and stateless threats of terrorism by potential biologic, chemical, and nuclear weapons. What happens locally has immediate ramifications internationally. Real and potential health consequences of these events have evoked global concerns and realization that capacities and capabilities to respond to such events require unparalleled integration, coordination, and cooperation of the international community. However, politics and the institutions singular governments form are inherently limited in their objectives and capability to effectively respond. Public health, broadly defined, must be recognized as a security and strategic requirement, one that serves to build a foundation for an international integrated response capacity.

Aeroelastic Response of the Adaptive Compliant Trailing Edge Transtition Section

NASA Technical Reports Server (NTRS)

Herrera, Claudia Y.; Spivey, Natalie D.; Lung, Shun-fat

2016-01-01

The Adaptive Compliant Trailing Edge demonstrator was a joint task under the Environmentally Responsible Aviation Project in partnership with the Air Force Research Laboratory and FlexSys, Inc. (Ann Arbor, Michigan), chartered by the National Aeronautics and Space Administration to develop advanced technologies that enable environmentally friendly aircraft, such as continuous mold-line technologies. The Adaptive Compliant Trailing Edge demonstrator encompassed replacing the Fowler flaps on the SubsoniC Aircraft Testbed, a Gulfstream III (Gulfstream Aerospace, Savannah, Georgia) aircraft, with control surfaces developed by FlexSys, Inc., a pair of uniquely-designed, unconventional flaps to be used as lifting surfaces during flight-testing to substantiate their structural effectiveness. The unconventional flaps consisted of a main flap section and two transition sections, inboard and outboard, which demonstrated the continuous mold-line technology. Unique characteristics of the transition sections provided a challenge to the airworthiness assessment for this part of the structure. A series of build-up tests and analyses were conducted to ensure the data required to support the airworthiness assessment were acquired and applied accurately. The transition sections were analyzed both as individual components and as part of the flight-test article assembly. Instrumentation was installed in the transition sections based on the analysis to best capture the in-flight aeroelastic response. Flight-testing was conducted and flight data were acquired to validate the analyses. This paper documents the details of the aeroelastic assessment and in-flight response of the transition sections of the unconventional Adaptive Compliant Trailing Edge flaps.

Heavy fermions, quantum criticality, and unconventional superconductivity in filled skutterudites and related materials

DOE Office of Scientific and Technical Information (OSTI.GOV)

Andraka, Bohdan

2015-05-14

The main goal of this program was to explore the possibility of novel states and behaviors in Pr-based system exhibiting quantum critical behavior, PrOs₄Sb₁₂. Upon small changes of external parameter, such as magnetic field, physical properties of PrOs₄Sb₁₂ are drastically altered from those corresponding to a superconductor, to heavy fermion, to field-induced ordered phase with primary quadrupolar order parameter. All these states are highly unconventional and not understood in terms of current theories thus offer an opportunity to expand our knowledge and understanding of condensed matter. At the same time, these novel states and behaviors are subjects to intense internationalmore » controversies. In particular, two superconducting phases with different transition temperatures were observed in some samples and not observed in others leading to speculations that sample defects might be partially responsible for these exotic behaviors. This work clearly established that crystal disorder is important consideration, but contrary to current consensus this disorder suppresses exotic behavior. Superconducting properties imply unconventional inhomogeneous state that emerges from unconventional homogeneous normal state. Comprehensive structural investigations demonstrated that upper superconducting transition is intrinsic, bulk, and unconventional. The high quality of in-house synthesized single crystals was indirectly confirmed by de Haas-van Alphen quantum oscillation measurements. These measurements, for the first time ever reported, spanned several different phases, offering unprecedented possibility of studying quantum oscillations across phase boundaries.« less

The Theory of Unconventional Warfare: Win, Lose, and Draw

DTIC Science & Technology

2008-12-01

UNCONVENTIONAL WARFARE MODEL ...................................12 1. Planning Phase...Superiority over Time........................................................................11  Figure 3.  Unconventional Warfare Model ...superiority through the six principles of UW illustrated below in the UW model . . B. THE UNCONVENTIONAL WARFARE MODEL Figure 3. Unconventional

Choice of unconventional treatment by patients with cancer.

PubMed

Kimby, Charlotte Kira; Launsø, Laila; Henningsen, Inge; Langgaard, Henrik

2003-08-01

Previous studies conducted on the use of unconventional treatment by patients with cancer have focused on unconventional treatment as a joint group of therapies. The objective of this study is to gather preliminary information about the use of different modes of unconventional cancer treatment by patients with cancer and to describe user profiles of standardized and individualized treatments. Data originate from an ongoing explorative 5-year study of 441 consecutively registered cancer patients who have consulted medical doctors and alternative therapists practicing unconventional treatment in Denmark. This paper is based on data from the first and second of six questionnaires. The unconventional treatments included in this study are categorized into two forms of treatment: standardized and individualized treatment. Four hundred and forty-one (441) Danish patients with cancer who use unconventional cancer treatment. The analysis shows significant correlations between type of treatment and the following variables: gender, education, occupational status, type of cancer, purpose of seeking unconventional treatment, metastatic spread, opinion regarding appropriate unconventional treatment, and simultaneous use of unconventional treatment. The study shows that there are significant differences between patients with cancer choosing standardized and those choosing individualized unconventional treatment. The probability of choosing standardized unconventional treatment is greatest among male participants, patients having shorter school education, and for patients who have recovery as the goal of seeking unconventional treatment. The probability of choosing individualized unconventional treatment is greatest among women, for patients with longer school education, and for patients wanting relief from symptoms, information, and improvement of general condition as the purpose of seeking unconventional cancer treatment. Patients with breast and gynecologic cancer are more inclined to seek individualized treatment than patients with all other cancer diseases. The study points to the fact that it might be essential to differentiate between different forms of unconventional treatment to understand the use by patients with cancer and the outcomes of these treatments.

Regulation of sugar transport and metabolism by the Candida albicans Rgt1 transcriptional repressor.

PubMed

Sexton, Jessica A; Brown, Victoria; Johnston, Mark

2007-10-01

The ability of the fungal pathogen Candida albicans to cause systemic infections depends in part on the function of Hgt4, a cell surface sugar sensor. The orthologues of Hgt4 in Saccharomyces cerevisiae, Snf3 and Rgt2, initiate a signalling cascade that inactivates Rgt1, a transcriptional repressor of genes encoding hexose transporters. To determine whether Hgt4 functions similarly through the C. albicans orthologue of Rgt1, we analysed Cargt1 deletion mutants. We found that Cargt1 mutants are sensitive to the glucose analogue 2-deoxyglucose, a phenotype probably due to uncontrolled expression of genes encoding glucose transporters. Indeed, transcriptional profiling revealed that expression of about two dozen genes, including multiple HGT genes encoding hexose transporters, is increased in the Cargt1 mutant in the absence of sugars, suggesting that CaRgt1 represses expression of several HGT genes under this condition. Some of the HGT genes (probably encoding high-affinity transporters) are also repressed by high levels of glucose, and we show that this repression is mediated by CaMig1, the orthologue of the major glucose-activated repressor in S. cerevisiae, but not by its paralogue CaMig2. Therefore, CaRgt1 and CaMig1 collaborate to control expression of C. albicans hexose transporters in response to different levels of sugars. We were surprised to find that CaRgt1 also regulates expression of GAL1, suggesting that regulation of galactose metabolism in C. albicans is unconventional. Finally, Cargt1 mutations cause cells to hyperfilament, and suppress the hypofilamented phenotype of an hgt4 mutant, indicating that the Hgt4 glucose sensor may affect filamentation by modulating sugar import and metabolism via CaRgt1. Copyright 2007 John Wiley & Sons, Ltd.

Border Security and Responsibility Act 2009

THOMAS, 111th Congress

Rep. Grijalva, Raul M. [D-AZ-7

2009-04-23

House - 05/15/2009 Referred to the Subcommittee on Terrorism, Unconventional Threats and Capabilities. (All Actions) Tracker: This bill has the status IntroducedHere are the steps for Status of Legislation:

Hysteretic magnetoresistance and unconventional anomalous Hall effect in the frustrated magnet TmB 4

DOE PAGES

Sunku, Sai Swaroop; Kong, Tai; Ito, Toshimitsu; ...

2016-05-11

We study TmB 4, a frustrated magnet on the Archimedean Shastry-Sutherland lattice, through magnetization and transport experiments. The lack of anisotropy in resistivity shows that TmB4 is an electronically three-dimensional system. The magnetoresistance (MR) is hysteretic at low temperature even though a corresponding hysteresis in magnetization is absent. The Hall resistivity shows unconventional anomalous Hall effect (AHE) and is linear above saturation despite a large MR. In conclusion, we propose that complex structures at magnetic domain walls may be responsible for the hysteretic MR and may also lead to the AHE.

Purchasing unconventional fuels

DOE Office of Scientific and Technical Information (OSTI.GOV)

Doyal, J.

1995-09-01

The reasons to seek unconventional fuels are to either insure a fuel supply or to reduce existing fuel costs. The keys to successfully utilizing unconventional fuel are: (1) build as much flexibility as possible in the variety, quality, quantity and deliverability of the unconventional fuel sources that you can utilize; (2) provide maximum pricing flexibility; (3) fully commit to work with unconventional fuel suppliers; and to (4) consider unconventional fuel operations as a market opportunity. Unconventional fuels operations are well suited to marginal existing operations and can also supplement new startups with uncertain fuel supplies. Unconventional fuel operations can alsomore » help existing facilities generate above market profits for those willing to accommodate the wide market swings inherent in this fledgling industry.« less

First-Principles Correlated Approach to the Normal State of Strontium Ruthenate

PubMed Central

Acharya, S.; Laad, M. S.; Dey, Dibyendu; Maitra, T.; Taraphder, A.

2017-01-01

The interplay between multiple bands, sizable multi-band electronic correlations and strong spin-orbit coupling may conspire in selecting a rather unusual unconventional pairing symmetry in layered Sr2RuO4. This mandates a detailed revisit of the normal state and, in particular, the T-dependent incoherence-coherence crossover. Using a modern first-principles correlated view, we study this issue in the actual structure of Sr2RuO4 and present a unified and quantitative description of a range of unusual physical responses in the normal state. Armed with these, we propose that a new and important element, that of dominant multi-orbital charge fluctuations in a Hund’s metal, may be a primary pair glue for unconventional superconductivity. Thereby we establish a connection between the normal state responses and superconductivity in this system. PMID:28220879

Unconventional medicine in dermatology outpatients in Turkey.

PubMed

Gönül, Müzeyyen; Gül, Ulker; Cakmak, Seray Külcü; Kiliç, Selim

2009-06-01

Many people use unconventional therapies for health problems, but the extent and pattern of this use in dermatology have not been studied in detail. This article reports the first investigation on the use of unconventional therapies in dermatology in Turkey. To determine the prevalence and characteristics of unconventional therapies used by dermatology outpatients in Turkey. A questionnaire was employed to determine the use of unconventional therapies in patients attending a dermatology clinic in Ankara, Turkey. The patients were questioned about the number of attendances at dermatology clinics, whether they had ever used unconventional therapies and/or drugs without the suggestion of a medical doctor for the current dermatologic disorder, and the forms of unconventional therapies employed. The data were compared statistically with the age, sex, and education status of the patients. The respondents included 443 men and 563 women, with a total of 1006 patients. The mean age of the patients was 36.62 +/- 17.55 years. Of the 1006 patients, 337 (33.5%) had used at least one form of unconventional therapy. The most common diagnoses of the patients using unconventional therapy were acne, psoriasis, contact dermatitis, and fungal infections. The most frequent forms of unconventional therapy used by the patients were humectants, cologne, spiritual healing, and herbs. Unconventional therapy use according to the sex, age, and education status of the patients did not show any significant difference. A significant relationship was found between some forms of unconventional therapy and some skin disorders, including: generalized pruritus and application of cologne; warts and spiritual healing; fungal infections and application of henna; psoriasis and herbal therapy or spiritual healing; alopecia areata and application of garlic; acne and application of lemon juice, clay, or cosmetics. Regardless of patient age, sex, and education status, dermatology outpatients use unconventional therapies for their health. Dermatologists should be aware of the tendency of patients to use unconventional therapies and should guide patients towards the use of harmless treatments.

77 FR 10485 - Unconventional Resources Technology Advisory Committee

Federal Register 2010, 2011, 2012, 2013, 2014

2012-02-22

... DEPARTMENT OF ENERGY Unconventional Resources Technology Advisory Committee AGENCY: Office of... meeting of the Unconventional Resources Technology Advisory Committee. The Federal Advisory Committee Act.... SUPPLEMENTARY INFORMATION: Purpose of the Committee: The purpose of the Unconventional Resources Technology...

78 FR 68430 - Unconventional Resources Technology Advisory Committee

Federal Register 2010, 2011, 2012, 2013, 2014

2013-11-14

... DEPARTMENT OF ENERGY Unconventional Resources Technology Advisory Committee AGENCY: Office of... meeting of the Unconventional Resources Technology Advisory Committee. The Federal Advisory Committee Act... the Unconventional Resources Technology Advisory Committee is to provide advice on development and...

75 FR 57743 - Unconventional Resources Technology Advisory Committee

Federal Register 2010, 2011, 2012, 2013, 2014

2010-09-22

... DEPARTMENT OF ENERGY Unconventional Resources Technology Advisory Committee AGENCY: Department of... of the Unconventional Resources Technology Advisory Committee. The Federal Advisory Committee Act... INFORMATION: Purpose of the Committee: The purpose of the Unconventional Resources Technology Advisory...

78 FR 58294 - Unconventional Resources Technology Advisory Committee

Federal Register 2010, 2011, 2012, 2013, 2014

2013-09-23

... DEPARTMENT OF ENERGY Unconventional Resources Technology Advisory Committee AGENCY: Office of... meeting of the Unconventional Resources Technology Advisory Committee. The Federal Advisory Committee Act... the Unconventional Resources Technology Advisory Committee is to provide advice on development and...

75 FR 48320 - Unconventional Resources Technology Advisory Committee

Federal Register 2010, 2011, 2012, 2013, 2014

2010-08-10

... DEPARTMENT OF ENERGY Unconventional Resources Technology Advisory Committee AGENCY: Department of... of the Unconventional Resources Technology Advisory Committee. The Federal Advisory Committee Act.... SUPPLEMENTARY INFORMATION: Purpose of the Committee: The purpose of the Unconventional Resources Technology...

77 FR 59182 - Unconventional Resources Technology Advisory Committee

Federal Register 2010, 2011, 2012, 2013, 2014

2012-09-26

... DEPARTMENT OF ENERGY Unconventional Resources Technology Advisory Committee AGENCY: Office of... meeting of the Unconventional Resources Technology Advisory Committee. The Federal Advisory Committee Act... INFORMATION: Purpose of the Committee: The purpose of the Unconventional Resources Technology Advisory...

76 FR 77990 - Unconventional Resources Technology Advisory Committee

Federal Register 2010, 2011, 2012, 2013, 2014

2011-12-15

... DEPARTMENT OF ENERGY Unconventional Resources Technology Advisory Committee AGENCY: Office of... meeting of the Unconventional Resources Technology Advisory Committee. The Federal Advisory Committee Act... INFORMATION: Purpose of the Committee: The purpose of the Unconventional Resources Technology Advisory...

76 FR 64923 - Unconventional Resources Technology Advisory Committee

Federal Register 2010, 2011, 2012, 2013, 2014

2011-10-19

... DEPARTMENT OF ENERGY Unconventional Resources Technology Advisory Committee AGENCY: Office of... meeting of the Unconventional Resources Technology Advisory Committee. The Federal Advisory Committee Act.... SUPPLEMENTARY INFORMATION: Purpose of the Committee: The purpose of the Unconventional Resources Technology...

77 FR 53191 - Unconventional Resources Technology Advisory Committee

Federal Register 2010, 2011, 2012, 2013, 2014

2012-08-31

... DEPARTMENT OF ENERGY Unconventional Resources Technology Advisory Committee AGENCY: Department of... of the Unconventional Resources Technology Advisory Committee. The Federal Advisory Committee Act.... SUPPLEMENTARY INFORMATION: Purpose of the Committee: The purpose of the Unconventional Resources Technology...

78 FR 70932 - Unconventional Resources Technology Advisory Committee

Federal Register 2010, 2011, 2012, 2013, 2014

2013-11-27

... DEPARTMENT OF ENERGY Unconventional Resources Technology Advisory Committee AGENCY: Office of... meeting of the Unconventional Resources Technology Advisory Committee. The Federal Advisory Committee Act... of the Unconventional Resources Technology Advisory Committee is to provide advice on development and...

75 FR 57743 - Unconventional Resources Technology Advisory Committee

Federal Register 2010, 2011, 2012, 2013, 2014

2010-09-22

... DEPARTMENT OF ENERGY Unconventional Resources Technology Advisory Committee AGENCY: Department of... of the Unconventional Resources Technology Advisory Committee. The Federal Advisory Committee Act...: Purpose of the Committee: The purpose of the Unconventional Resources Technology Advisory Committee is to...

77 FR 5246 - Unconventional Resources Technology Advisory Committee

Federal Register 2010, 2011, 2012, 2013, 2014

2012-02-02

... DEPARTMENT OF ENERGY Unconventional Resources Technology Advisory Committee AGENCY: Office of... meeting of the Unconventional Resources Technology Advisory Committee. The Federal Advisory Committee Act... Committee: The purpose of the Unconventional Resources Technology Advisory Committee is to provide advice on...

77 FR 63300 - Unconventional Resources Technology Advisory Committee

Federal Register 2010, 2011, 2012, 2013, 2014

2012-10-16

... DEPARTMENT OF ENERGY Unconventional Resources Technology Advisory Committee AGENCY: Office of... meeting of the Unconventional Resources Technology Advisory Committee. The Federal Advisory Committee Act... Committee: The purpose of the Unconventional Resources Technology Advisory Committee is to provide advice on...

78 FR 53741 - Unconventional Resources Technology Advisory Committee

Federal Register 2010, 2011, 2012, 2013, 2014

2013-08-30

... DEPARTMENT OF ENERGY Unconventional Resources Technology Advisory Committee AGENCY: Office of... meeting of the Unconventional Resources Technology Advisory Committee. The Federal Advisory Committee Act... of the Unconventional Resources Technology Advisory Committee is to provide advice on development and...

Pig Feeding under the Potato-green Forage Base System with or without Addition of Herbs versus a Concentrate Based System: Effect on Post-slaughter Performance and Pork Characteristics

PubMed Central

Turyk, Zofia; Osek, Maria; Olkowski, Bogusław; Janocha, Alina

2014-01-01

This study examined carcass and meat quality parameters in growing/finishing pigs fed unconventionally versus the concentrate-based system. Ninety-six, 12 wk old pigs (34±SD 0.3 kg) were randomly divided into three groups, assigned to one of the three dietary treatments: standard complete concentrate mixture, conventional (C diet); unconventional, steamed potato-green forage-concentrate based diet (U diet), and unconventional basal diet+herbage mix (UH diet). Pigs fed U diet showed lower dressing percentage, meatiness, loin eye area, and weight of pork neck (p≤0.05), but their carcasses were significantly (p≤0.05) longer and had increased backfat depth (p≤0.05). There was no impact of the diet on the meat content of dry matter, crude ash, acidity, and colour parameters of m. longissimus. Unconventional feeding significantly (p≤0.05) elevated water the holding capacity of m. longissimus and slightly improved the sensory attributes analysis of meat. The addition of herbs resulted in increased loin eye area (p≤0.05), decreased fat content (p≤0.05) in m. longissimus, and tended to improve some sensory attributes of meat. There were significant gender differences in response to all diets. There were significant diet×sex interactions for some measured variables, but there were no clearly identifiable trends with regard to any specific carcass or meat parameters. Feeding unconventional diet to pigs may offer better culinary attributes of the meat, and improve some technologically important characteristics of pig carcass, but may negatively affect some carcass or meat parameters. PMID:25050003

The future of oil: unconventional fossil fuels.

PubMed

Chew, Kenneth J

2014-01-13

Unconventional fossil hydrocarbons fall into two categories: resource plays and conversion-sourced hydrocarbons. Resource plays involve the production of accumulations of solid, liquid or gaseous hydro-carbons that have been generated over geological time from organic matter in source rocks. The character of these hydrocarbons may have been modified subsequently, especially in the case of solids and extra-heavy liquids. These unconventional hydrocarbons therefore comprise accumulations of hydrocarbons that are trapped in an unconventional manner and/or whose economic exploitation requires complex and technically advanced production methods. This review focuses primarily on unconventional liquid hydro-carbons. The future potential of unconventional gas, especially shale gas, is also discussed, as it is revolutionizing the energy outlook in North America and elsewhere.

A review of biophysical and socio-economic effects of unconventional oil and gas extraction - Implications for South Africa.

PubMed

Esterhuyse, Surina; Avenant, Marinda; Redelinghuys, Nola; Kijko, Andrzej; Glazewski, Jan; Plit, Lisa; Kemp, Marthie; Smit, Ansie; Vos, A Tascha; Williamson, Richard

2016-12-15

The impacts associated with unconventional oil and gas (UOG) extraction will be cumulative in nature and will most likely occur on a regional scale, highlighting the importance of using strategic decision-making and management tools. Managing possible impacts responsibly is extremely important in a water scarce country such as South Africa, versus countries where more water may be available for UOG extraction activities. This review article explains the possible biophysical and socio-economic impacts associated with UOG extraction within the South African context and how these complex impacts interlink. Relevant policy and governance frameworks to manage these impacts are also highlighted. Copyright © 2016 Elsevier Ltd. All rights reserved.

Topological Magnon Bands and Unconventional Superconductivity in Pyrochlore Iridate Thin Films.

PubMed

Laurell, Pontus; Fiete, Gregory A

2017-04-28

We theoretically study the magnetic properties of pyrochlore iridate bilayer and trilayer thin films grown along the [111] direction using a strong coupling approach. We find the ground state magnetic configurations on a mean field level and carry out a spin-wave analysis about them. In the trilayer case the ground state is found to be the all-in-all-out (AIAO) state, whereas the bilayer has a deformed AIAO state. For all parameters of the spin-orbit coupled Hamiltonian we study, the lowest magnon band in the trilayer case has a nonzero Chern number. In the bilayer case we also find a parameter range with nonzero Chern numbers. We calculate the magnon Hall response for both geometries, finding a striking sign change as a function of temperature. Using a slave-boson mean-field theory we study the doping of the trilayer system and discover an unconventional time-reversal symmetry broken d+id superconducting state. Our study complements prior work in the weak coupling limit and suggests that the [111] grown thin film pyrochlore iridates are a promising candidate for topological properties and unconventional orders.

Unconventional Aqueous Humor Outflow: A Review

PubMed Central

Johnson, Mark; McLaren, Jay W.; Overby, Darryl R.

2016-01-01

Aqueous humor flows out of the eye primarily through the conventional outflow pathway that includes the trabecular meshwork and Schlemm's canal. However, a fraction of aqueous humor passes through an alternative or ‘unconventional’ route that includes the ciliary muscle, supraciliary and suprachoroidal spaces. From there, unconventional outflow may drain through two pathways: a uveoscleral pathway where aqueous drains across the sclera to be resorbed by orbital vessels, and a uveovortex pathway where aqueous humor enters the choroid to drain through the vortex veins. We review the anatomy, physiology and pharmacology of these pathways. We also discuss methods to determine unconventional outflow rate, including direct techniques that use radioactive or fluorescent tracers recovered from tissues in the unconventional pathway and indirect methods that estimate unconventional outflow based on total outflow over a range of pressures. Indirect methods are subject to a number of assumptions and generally give poor agreement with tracer measurements. We review the variety of animal models that have been used to study conventional and unconventional outflow. The mouse appears to be a promising model because it captures several aspects of conventional and unconventional outflow dynamics common to humans, although questions remain regarding the magnitude of unconventional outflow in mice. Finally, we review future directions. There is a clear need to develop improved methods for measuring unconventional outflow in both animals and humans. PMID:26850315

MicroRNA-mediated networks underlie immune response regulation in papillary thyroid carcinoma

NASA Astrophysics Data System (ADS)

Huang, Chen-Tsung; Oyang, Yen-Jen; Huang, Hsuan-Cheng; Juan, Hsueh-Fen

2014-09-01

Papillary thyroid carcinoma (PTC) is a common endocrine malignancy with low death rate but increased incidence and recurrence in recent years. MicroRNAs (miRNAs) are small non-coding RNAs with diverse regulatory capacities in eukaryotes and have been frequently implied in human cancer. Despite current progress, however, a panoramic overview concerning miRNA regulatory networks in PTC is still lacking. Here, we analyzed the expression datasets of PTC from The Cancer Genome Atlas (TCGA) Data Portal and demonstrate for the first time that immune responses are significantly enriched and under specific regulation in the direct miRNA-target network among distinctive PTC variants to different extents. Additionally, considering the unconventional properties of miRNAs, we explore the protein-coding competing endogenous RNA (ceRNA) and the modulatory networks in PTC and unexpectedly disclose concerted regulation of immune responses from these networks. Interestingly, miRNAs from these conventional and unconventional networks share general similarities and differences but tend to be disparate as regulatory activities increase, coordinately tuning the immune responses that in part account for PTC tumor biology. Together, our systematic results uncover the intensive regulation of immune responses underlain by miRNA-mediated networks in PTC, opening up new avenues in the management of thyroid cancer.

A transgenic zebrafish model for monitoring xbp1 splicing and endoplasmic reticulum stress in vivo.

PubMed

Li, Junling; Chen, Zhiliang; Gao, Lian-Yong; Colorni, Angelo; Ucko, Michal; Fang, Shengyun; Du, Shao Jun

2015-08-01

Accumulation of misfolded or unfolded proteins in the endoplasmic reticulum (ER) triggers ER stress that initiates unfolded protein response (UPR). XBP1 is a transcription factor that mediates one of the key signaling pathways of UPR to cope with ER stress through regulating gene expression. Activation of XBP1 involves an unconventional mRNA splicing catalyzed by IRE1 endonuclease that removes an internal 26 nucleotides from xbp1 mRNA transcripts in the cytoplasm. Researchers have taken advantage of this unique activation mechanism to monitor XBP1 activation, thereby UPR, in cell culture and transgenic models. Here we report a Tg(ef1α:xbp1δ-gfp) transgenic zebrafish line to monitor XBP1 activation using GFP as a reporter especially in zebrafish oocytes and developing embryos. The Tg(ef1α:xbp1δ-gfp) transgene was constructed using part of the zebrafish xbp1 cDNA containing the splicing element. ER stress induced splicing results in the cDNA encoding a GFP-tagged partial XBP1 without the transactivation activation domain (XBP1Δ-GFP). The results showed that xbp1 transcripts mainly exist as the spliced active isoform in unfertilized oocytes and zebrafish embryos prior to zygotic gene activation at 3 hours post fertilization. A strong GFP expression was observed in unfertilized oocytes, eyes, brain and skeletal muscle in addition to a weak expression in the hatching gland. Incubation of transgenic zebrafish embryos with (dithiothreitol) DTT significantly induced XBP1Δ-GFP expression. Collectively, these studies unveil the presence of maternal xbp1 splicing in zebrafish oocytes, fertilized eggs and early stage embryos. The Tg(ef1α:xbp1δ-gfp) transgenic zebrafish provides a useful model for in vivo monitoring xbp1 splicing during development and under ER stress conditions. Copyright © 2015 Elsevier Ireland Ltd. All rights reserved.

Unconventional Deterrence Strategy

DTIC Science & Technology

2005-06-01

200 words) This thesis examines a largely unexplored area of deterrence theory – unconventional deterrence. Unconventional deterrence is defined...hypothesis of deterrence theory which says that the balance of the opponents’ military capabilities is the basic determinant of successful deterrence...

Interfacial sciences in unconventional petroleum production: from fundamentals to applications.

PubMed

He, Lin; Lin, Feng; Li, Xingang; Sui, Hong; Xu, Zhenghe

2015-08-07

With the ever increasing demand for energy to meet the needs of growth in population and improvement in the living standards in particular in developing countries, the abundant unconventional oil reserves (about 70% of total world oil), such as heavy oil, oil/tar sands and shale oil, are playing an increasingly important role in securing global energy supply. Compared with the conventional reserves unconventional oil reserves are characterized by extremely high viscosity and density, combined with complex chemistry. As a result, petroleum production from unconventional oil reserves is much more difficult and costly with more serious environmental impacts. As a key underpinning science, understanding the interfacial phenomena involved in unconventional petroleum production, such as oil liberation from host rocks, oil-water emulsions and demulsification, is critical for developing novel processes to improve oil production while reducing GHG emission and other environmental impacts at a lower operating cost. In the past decade, significant efforts and advances have been made in applying the principles of interfacial sciences to better understand complex unconventional oil-systems, while many environmental and production challenges remain. In this critical review, the recent research findings and progress in the interfacial sciences related to unconventional petroleum production are critically reviewed. In particular, the chemistry of unconventional oils, liberation mechanisms of oil from host rocks and mechanisms of emulsion stability and destabilization in unconventional oil production systems are discussed in detail. This review also seeks to summarize the current state-of-the-art characterization techniques and brings forward the challenges and opportunities for future research in this important field of physical chemistry and petroleum.

Study of unconventional aircraft engines designed for low energy consumption

NASA Technical Reports Server (NTRS)

Neitzel, R. E.; Hirschkron, R.; Johnston, R. P.

1976-01-01

A study of unconventional engine cycle concepts, which may offer significantly lower energy consumption than conventional subsonic transport turbofans, is described herein. A number of unconventional engine concepts were identified and parametrically studied to determine their relative fuel-saving potential. Based on results from these studies, regenerative, geared, and variable-boost turbofans, and combinations thereof, were selected along with advanced turboprop cycles for further evaluation and refinement. Preliminary aerodynamic and mechanical designs of these unconventional engine configurations were conducted and mission performance was compared to a conventional, direct-drive turofan reference engine. Consideration is given to the unconventional concepts, and their state of readiness for application. Areas of needed technology advancement are identified.

Unconventional function of an Achaete-Scute homolog as a terminal selector of nociceptive neuron identity

PubMed Central

Masoudi, Neda; Tavazoie, Saeed; Glenwinkel, Lori; Ryu, Leesun; Kim, Kyuhyung

2018-01-01

Proneural genes are among the most early-acting genes in nervous system development, instructing blast cells to commit to a neuronal fate. Drosophila Atonal and Achaete-Scute complex (AS-C) genes, as well as their vertebrate orthologs, are basic helix-loop-helix (bHLH) transcription factors with such proneural activity. We show here that a C. elegans AS-C homolog, hlh-4, functions in a fundamentally different manner. In the embryonic, larval, and adult nervous systems, hlh-4 is expressed exclusively in a single nociceptive neuron class, ADL, and its expression in ADL is maintained via transcriptional autoregulation throughout the life of the animal. However, in hlh-4 null mutants, the ADL neuron is generated and still appears neuronal in overall morphology and expression of panneuronal and pansensory features. Rather than acting as a proneural gene, we find that hlh-4 is required for the ADL neuron to function properly, to adopt its correct morphology, to express its unusually large repertoire of olfactory receptor–encoding genes, and to express other known features of terminal ADL identity, including neurotransmitter phenotype, neuropeptides, ion channels, and electrical synapse proteins. hlh-4 is sufficient to induce ADL identity features upon ectopic expression in other neuron types. The expression of ADL terminal identity features is directly controlled by HLH-4 via a phylogenetically conserved E-box motif, which, through bioinformatic analysis, we find to constitute a predictive feature of ADL-expressed terminal identity markers. The lineage that produces the ADL neuron was previously shown to require the conventional, transient proneural activity of another AS-C homolog, hlh-14, demonstrating sequential activities of distinct AS-C-type bHLH genes in neuronal specification. Taken together, we have defined here an unconventional function of an AS-C-type bHLH gene as a terminal selector of neuronal identity and we speculate that such function could be reflective of an ancestral function of an “ur-” bHLH gene. PMID:29672507

Making sense of "alternative", "complementary", "unconventional" and "integrative" medicine: exploring the terms and meanings through a textual analysis.

PubMed

Ng, Jeremy Y; Boon, Heather S; Thompson, Alison K; Whitehead, Cynthia R

2016-05-20

Medical pluralism has flourished throughout the Western world in spite of efforts to legitimize Western biomedical healthcare as "conventional medicine" and thereby relegate all non-physician-related forms of healthcare to an "other" category. These "other" practitioners have been referred to as "unconventional", "alternative" and "complementary", among other terms throughout the past half century. This study investigates the discourses surrounding the changes in the terms, and their meanings, used to describe unconventional medicine in North America. Terms identified by the literature as synonymous to unconventional medicine were searched using the Scopus database. A textual analysis following the method described by Kripendorff 2013 was subsequently performed on the five most highly-cited unconventional medicine-related peer-reviewed literature published between 1970 and 2013. Five commonly-used, unconventional medicine-related terms were identified. Authors using "complementary and alternative", "complementary", "alternative", or "unconventional" tended to define them by what they are not (e.g., therapies not taught/used in conventional medicine, therapy demands not met by conventional medicine, and therapies that lack research on safety, efficacy and effectiveness). Authors defined "integrated/integrative" medicine by what it is (e.g., a new model of healthcare, the combining of both conventional and unconventional therapies, accounting for the whole person, and preventative maintenance of health). Authors who defined terms by "what is not" stressed that the purpose of conducting research in this area was solely to create knowledge. Comparatively, authors who defined terms by "what is" sought to advocate for the evidence-based combination of unconventional and conventional medicines. Both author groups used scientific rhetoric to define unconventional medical practices. This emergence of two groups of authors who used two different sets of terms to refer to the concept of "unconventional medicine" may explain why some journals, practitioner associations and research/practice centres may choose to use both "what is not" and "what is" terms in their discourse to attract interest from both groups. Since each of the two groups of terms (and authors who use them) has different meanings and goals, the evolution of this discourse will continue to be an interesting phenomenon to explore in the future.

Writing, Reader Response, and the Community College

ERIC Educational Resources Information Center

Shafer, Gregory

2013-01-01

The community college stands as a beacon of democratic, inclusive ideals. Unlike the four year college--where research and advanced degrees are sought--the community college celebrates learning on a personal, heuristic level. And while such unconventional and even seditious practices have been questioned by those who seek to maintain "standards,"…

Colorectal cancer cells display chaperone dependency for the unconventional prefoldin URI1

PubMed Central

Christinat, Yann; Frischknecht, Lukas; Krek, Wilhelm

2016-01-01

Chaperone dependency of cancer cells is an emerging trait that relates to the need of transformed cells to cope with the various stresses associated with the malignant state. URI1 (unconventional prefoldin RPB5 interactor 1) encodes a member of the prefoldin (PFD) family of molecular chaperones that acts as part of a heterohexameric PFD complex, the URI1 complex (URI1C), to promote assembly of multiprotein complexes involved in cell signaling and transcription processes. Here, we report that human colorectal cancer (CRCs) cell lines demonstrate differential dependency on URI1 and on the URI1 partner PFD STAP1 for survival, suggesting that this differential vulnerability of CRC cells is directly linked to URI1C chaperone function. Interestingly, in URI1-dependent CRC cells, URI1 deficiency is associated with non-genotoxic p53 activation and p53-dependent apoptosis. URI1-independent CRC cells do not exhibit such effects even in the context of wildtype p53. Lastly, in tumor xenografts, the conditional depletion of URI1 in URI1-dependent CRC cells was, after tumor establishment, associated with severe inhibition of subsequent tumor growth and activation of p53 target genes. Thus, a subset of CRC cells has acquired a dependency on the URI1 chaperone system for survival, providing an example of ‘non-oncogene addiction’ and vulnerability for therapeutic targeting. PMID:27105489

STAT3 is a critical cell-intrinsic regulator of human unconventional T cell numbers and function

PubMed Central

Wilson, Robert P.; Ives, Megan L.; Rao, Geetha; Lau, Anthony; Payne, Kathryn; Kobayashi, Masao; Arkwright, Peter D.; Peake, Jane; Wong, Melanie; Adelstein, Stephen; Smart, Joanne M.; French, Martyn A.; Fulcher, David A.; Picard, Capucine; Bustamante, Jacinta; Boisson-Dupuis, Stephanie; Gray, Paul; Stepensky, Polina; Warnatz, Klaus; Freeman, Alexandra F.; Rossjohn, Jamie; McCluskey, James; Holland, Steven M.; Casanova, Jean-Laurent; Uzel, Gulbu; Ma, Cindy S.

2015-01-01

Unconventional T cells such as γδ T cells, natural killer T cells (NKT cells) and mucosal-associated invariant T cells (MAIT cells) are a major component of the immune system; however, the cytokine signaling pathways that control their development and function in humans are unknown. Primary immunodeficiencies caused by single gene mutations provide a unique opportunity to investigate the role of specific molecules in regulating human lymphocyte development and function. We found that individuals with loss-of-function mutations in STAT3 had reduced numbers of peripheral blood MAIT and NKT but not γδ T cells. Analysis of STAT3 mosaic individuals revealed that this effect was cell intrinsic. Surprisingly, the residual STAT3-deficient MAIT cells expressed normal levels of the transcription factor RORγt. Despite this, they displayed a deficiency in secretion of IL-17A and IL-17F, but were able to secrete normal levels of cytokines such as IFNγ and TNF. The deficiency in MAIT and NKT cells in STAT3-deficient patients was mirrored by loss-of-function mutations in IL12RB1 and IL21R, respectively. Thus, these results reveal for the first time the essential role of STAT3 signaling downstream of IL-23R and IL-21R in controlling human MAIT and NKT cell numbers. PMID:25941256

Unconventional Word Segmentation in Emerging Bilingual Students' Writing: A Longitudinal Analysis

ERIC Educational Resources Information Center

Sparrow, Wendy

2014-01-01

This study explores cross-language and longitudinal patterns in unconventional word segmentation in 25 emerging bilingual students' (Spanish/English) writing from first through third grade. Spanish and English writing samples were collected annually and analyzed for two basic types of unconventional word segmentation: hyposegmentation, in…

Unconventionality and Originality: Does Self-Assessed Unconventionality Increase Original Achievement?

ERIC Educational Resources Information Center

Andreas, Stuart F. K.; Zech, Stefan; Coyle, Thomas R.; Rindermann, Heiner

2016-01-01

Creativity is negatively associated with certain personality traits (e.g., conformity) and social influences (e.g., group pressure). In this study, creativity was examined in relation to unconventionality, which was expected to correlate positively with creativity, especially originality. This hypothesis was based on the theory that unconventional…

Geology and assessment of unconventional oil and gas resources of northeastern Mexico

USGS Publications Warehouse

,

2015-01-01

The U.S. Geological Survey, in cooperation with the U.S. Department of State, quantitatively assessed the potential for unconventional oil and gas resources within the onshore portions of the Tampico-Misantla Basin, Burgos Basin, and Sabinas Basin provinces of northeastern Mexico. Unconventional resources of the Veracruz Basin were not quantitatively assessed because of a current lack of required geological information. Unconventional resources include shale gas, shale oil, tight gas, tight oil, and coalbed gas. Undiscovered conventional oil and gas resources were assessed in Mexico in 2012.

Assessment of surface water chloride and conductivity trends in areas of unconventional oil and gas development-Why existing national data sets cannot tell us what we would like to know

USGS Publications Warehouse

Bowen, Zachary H.; Oelsner, Gretchen P.; Cade, Brian S.; Gallegos, Tanya J.; Farag, Aïda M.; Mott, David N.; Potter, Christopher J.; Cinotto, Peter J.; Clark, Melanie L.; Kappel, William M.; Kresse, Timothy M.; Melcher, Cynthia P.; Paschke, Suzanne; Susong, David D.; Varela, Brian A.

2015-01-01

Heightened concern regarding the potential effects of unconventional oil and gas development on regional water quality has emerged, but the few studies on this topic are limited in geographic scope. Here we evaluate the potential utility of national and publicly available water-quality data sets for addressing questions regarding unconventional oil and gas development. We used existing U.S. Geological Survey and U.S. Environmental Protection Agency data sets to increase understanding of the spatial distribution of unconventional oil and gas development in the U.S. and broadly assess surface water quality trends in these areas. Based on sample size limitations, we were able to estimate trends in specific conductance (SC) and chloride (Cl-) from 1970 to 2010 in 16% (n=155) of the watersheds with unconventional oil and gas resources. We assessed these trends relative to spatiotemporal distributions of hydraulically fractured wells. Results from this limited analysis suggest no consistent and widespread trends in surface water quality for SC and Cl- in areas with increasing unconventional oil and gas development and highlight limitations of existing national databases for addressing questions regarding unconventional oil and gas development and water quality.

The Design, Pedagogy and Practice of an Integrated Public Affairs Leadership Course

ERIC Educational Resources Information Center

Sandfort, Jodi; Gerdes, Kevin

2017-01-01

Current world events demand public affairs leadership training that generates among professionals a sense of capability, agency, and responsibility to engage in complex public problems. In this paper, we describe a unique course operated in the US focused on achieving these learning outcomes. It uses an unconventional schedule and course design…

Assessment of unconventional oil and gas resources in Northeast Mexico, 2014

USGS Publications Warehouse

Schenk, Christopher J.; Charpentier, Ronald R.; Klett, Timothy R.; Tennyson, Marilyn E.; Gaswirth, Stephanie B.; Brownfield, Michael E.; Pawlewicz, Mark J.; Weaver, Jean Noe

2014-01-01

Using a geology-based assessment methodology, the U.S. Geological Survey estimated means of 0.78 billion barrels of unconventional oil, 23.5 trillion cubic feet of unconventional gas, and 0.88 billion barrels of natural gas liquids in the Sabinas Basin, Burgos Basin, and Tampico-Misantla Basin provinces of northeast Mexico.

Unconventional superconductivity in heavy-fermion compounds

DOE PAGES

White, B. D.; Thompson, J. D.; Maple, M. B.

2015-02-27

Over the past 35 years, research on unconventional superconductivity in heavy-fermion systems has evolved from the surprising observations of unprecedented superconducting properties in compounds that convention dictated should not superconduct at all to performing explorations of rich phase spaces in which the delicate interplay between competing ground states appears to support emergent superconducting states. In this article, we review the current understanding of superconductivity in heavy-fermion com- pounds and identify a set of characteristics that is common to their unconventional superconducting states. These core properties are compared with those of other classes of unconventional superconductors such as the cuprates andmore » iron-based superconductors. Lastly, we conclude by speculating on the prospects for future research in this field and how new advances might contribute towards resolving the long-standing mystery of how unconventional superconductivity works.« less

Data inconsistencies from states with unconventional oil and gas activity.

PubMed

Malone, Samantha; Kelso, Matthew; Auch, Ted; Edelstein, Karen; Ferrar, Kyle; Jalbert, Kirk

2015-01-01

The quality and availability of unconventional oil and gas (O&G) data in the United States have never been compared methodically state-to-state. By conducting such an assessment, this study seeks to better understand private and publicly sourced data variability and to identify data availability gaps. We developed an exploratory data-grading tool - Data Accessibility and Usability Index (DAUI) - to guide the review of O&G data quality. Between July and October 2013, we requested, collected, and assessed 5 categories of unconventional O&G data (wells drilled, violations, production, waste, and Class II disposal wells) from 10 states with active drilling activity. We based our assessment on eight data quality parameters (accessibility, usability, point location, completeness, metadata, agency responsiveness, accuracy, and cost). Using the DAUI, two authors graded the 10 states and then averaged their scores. The average score received across all states, data categories, and parameters was 67.1 out of 100, largely insufficient for proper data transparency. By state, Pennsylvania received the highest average ( = 93.5) and ranked first in all but one data category. The lowest scoring state was Texas ( = 44) largely due to its policy of charging for certain data. This article discusses the various reasons for scores received, as well as methodological limitations of the assessment metrics. We argue that the significant variability of unconventional O&G data-and its availability to the public-is a barrier to regulatory and industry transparency. The lack of transparency also impacts public education and broader participation in industry governance. This study supports the need to develop a set of data best management practices (BMPs) for state regulatory agencies and the O&G industry, and suggests potential BMPs for this purpose.

Superconductivity driven by pairing of the coherent parts of the physical electrons

NASA Astrophysics Data System (ADS)

Su, Yuehua; Zhang, Chao

2018-03-01

How the superconductivity in unconventional superconductors emerges from the diverse mother normal states is still a big puzzle. Whatever the mother normal states are the superconductivity is normal with BCS-like behaviours of the paired quasiparticles in condensation. To reconcile the diverse mother normal states and the normal superconductivity in unconventional superconductors, we revisit a proposal that the emergence of the low-energy coherent parts of the physical electrons, which survive from the interaction correlations, is an essential prerequisite for superconductivity. The superconductivity is driven by the pair condensation of these coherent parts of the physical electrons. Moreover the incoherent parts of the physical electrons can enhance the superconducting transition temperature Tc although they are not in driving role in the emergence of the superconductivity. Some experimental responses of the coherent parts of the physical electrons are predicted.

Bromelain purification through unconventional aqueous two-phase system (PEG/ammonium sulphate).

PubMed

Coelho, D F; Silveira, E; Pessoa Junior, A; Tambourgi, E B

2013-02-01

This paper focuses on the feasibility of unconventional aqueous two-phase systems for bromelain purification from pineapple processing waste. The main difference in comparison with conventional systems is the integration of the liquid-liquid extraction technique with fractional precipitation, which can decrease the protein content with no loss of biological activity by removing of unwanted molecules. The analysis of the results was based on the response surface methodology and revealed that the use of the desirability optimisation methodology (DOM) was necessary to achieve higher purification factor values and greater bromelain recovery. The use of DOM yielded an 11.80-fold purification factor and 66.38 % biological activity recovery using poly(ethylene glycol) (PEG) with a molar mass of 4,000, 10.86 % PEG concentration (m/m) and 36.21 % saturation of ammonium sulphate.

Magnetoresistance in the superconducting state at the (111) LaAlO3/SrTiO3 interface

NASA Astrophysics Data System (ADS)

Davis, S.; Huang, Z.; Han, K.; Ariando, Venkatesan, T.; Chandrasekhar, V.

2017-10-01

Condensed-matter systems that simultaneously exhibit superconductivity and ferromagnetism are rare due the antagonistic relationship between conventional spin-singlet superconductivity and ferromagnetic order. In materials in which superconductivity and magnetic order are known to coexist (such as some heavy-fermion materials), the superconductivity is thought to be of an unconventional nature. Recently, the conducting gas that lives at the interface between the perovskite band insulators LaAlO3 (LAO) and SrTiO3 (STO) has also been shown to host both superconductivity and magnetism. Most previous research has focused on LAO/STO samples in which the interface is on the (001) crystal plane. Relatively little work has focused on the (111) crystal orientation, which has hexagonal symmetry at the interface, and has been predicted to have potentially interesting topological properties, including unconventional superconducting pairing states. Here we report measurements of the magnetoresistance of (111) LAO/STO heterostructures at temperatures at which they are also superconducting. As with the (001) structures, the magnetoresistance is hysteretic, indicating the coexistence of magnetism and superconductivity, but in addition, we find that this magnetoresistance is anisotropic. Such an anisotropic response is completely unexpected in the superconducting state and suggests that (111) LAO/STO heterostructures may support unconventional superconductivity.

Hsp90/Sec22b promotes unconventional secretion of mature-IL-1β through an autophagosomal carrier in porcine alveolar macrophages during Mycoplasma hyopneumoniae infection.

PubMed

Zhang, Zhenzhen; Wei, Yanna; Liu, Beibei; Wu, Yuzi; Wang, Haiyan; Xie, Xing; Feng, Zhixin; Shao, Guoqing; Xiong, Qiyan

2018-06-20

Interleukin-1β (IL-1β) is a critical inflammatory regulator in response to Mycoplasma hyopneumoniae infection. However, the mechanism involved in the secretion of IL-1β during Mycoplasma hyopneumoniae infection is unclear. In this study, we demonstrated that Mycoplasma hyopneumoniae infection increased the secretion of mature-IL-1β (m-IL-1β), but not pro-IL-1β, in porcine alveolar macrophages. Moreover, Mycoplasma hyopneumoniae infection promoted the generation of autophagosomes, which attributed to the unconventional secretion of m-IL-1β. Further results revealed that Hsp90 was required for the entry of m-IL-1β into autophagosomes during Mycoplasma hyopneumoniae infection. The fusion of m-IL-1β-containing autophagosome and plasma membranes was regulated by Sec22b and independent of lysosomal dysfunction. In conclusion, we provide evidence that Hsp90/Sec22b promotes the unconventional secretion of IL-1β through an autophagosomal carrier during Mycoplasma hyopneumoniae infection. The elucidation of the molecular and cellular machinery in Mycoplasma hyopneumoniae infected mammalian cells in this study suggests avenues for further study and applications and paves the way for novel therapeutic strategies to prevent tissue damage in mycoplasma-associated diseases. Copyright © 2018. Published by Elsevier Ltd.

Carbon dioxide storage in unconventional reservoirs workshop: summary of recommendations

USGS Publications Warehouse

Jones, Kevin B.; Blondes, Madalyn S.

2015-01-01

The storage capacity for all unconventional reservoirs may be modeled using a volumetric equation starting with the extent of the rock unit and adjusted using these key factors and reaction terms. The ideas that were developed during this workshop can be used by USGS scientists to develop a methodology to assess the CO2 storage resource in unconventional reservoirs. This methodology could then be released for public comment and peer review. After completing this development process, the USGS could then use the methodology to assess the CO2 storage resource in unconventional reservoirs.

Geology and assessment of unconventional resources of Phitsanulok Basin, Thailand

USGS Publications Warehouse

,

2014-01-01

The U.S. Geological Survey (USGS) quantitatively assessed the potential for unconventional oil and gas resources within the Phitsanulok Basin of Thailand. Unconventional resources for the USGS include shale gas, shale oil, tight gas, tight oil, and coalbed gas. In the Phitsanulok Basin, only potential shale-oil and shale-gas resources were quantitatively assessed.

Marcellus Shale Drilling's Impact on the Dairy Industry in Pennsylvania: A Descriptive Report.

PubMed

Finkel, Madelon L; Selegean, Jane; Hays, Jake; Kondamudi, Nitin

2013-01-01

Unconventional natural gas drilling in Pennsylvania has accelerated over the past five years, and is unlikely to abate soon. Dairy farming is a large component of Pennsylvania's agricultural economy. This study compares milk production, number of cows, and production per cow in counties with significant unconventional drilling activity to that in neighboring counties with less unconventional drilling activity, from 1996 through 2011. Milk production and milk cows decreased in most counties since 1996, with larger decreases occurring from 2007 through 2011 (when unconventional drilling increased substantially) in five counties with the most wells drilled compared to six adjacent counties with fewer than 100 wells drilled. While this descriptive study cannot draw a causal association between well drilling and decline in cows or milk production, given the importance of Pennsylvania's dairy industry and the projected increase in unconventional natural gas drilling, further research to prevent unintended economic and public health consequences is imperative.

The unconventional secretion of IL-1β: Handling a dangerous weapon to optimize inflammatory responses.

PubMed

Sitia, Roberto; Rubartelli, Anna

2018-04-04

Interleukin 1β (IL-1β) is a major mediator of inflammation, with a causative role in many diseases. Unlike most other cytokines, however, it lacks a secretory signal sequence, raising intriguing mechanistic, functional and evolutionary questions. Despite decades of strenuous efforts in many laboratories, how IL-1β is secreted is still a matter of intense debate. Here, we summarize the different mechanisms and pathways that have been proposed for IL-1β secretion. At least two of them, namely the endolysosomal vesicle-based and gasdermin D-dependent pathways (types III and I in the recent Rabouille's classification of unconventional protein secretion), can be triggered in monocytes, the main source of IL-1β in humans, according to the type and strength of the pro-inflammatory stimuli. As during the escalation of human conflicts, monocytes deploy secretory mechanisms of increasing efficiency and dangerousness, shifting from the specific and controlled type III pathway to the much faster release of type I. Thus, the different mechanisms are activated depending on the severity of the conditions, from the self-limiting type III pathways in response of low pathogen load or small trauma, to the uncontrolled responses that underlie autoinflammatory disorders and sepsis. Copyright © 2018 Elsevier Ltd. All rights reserved.

Framework for comparing ecosystem impacts of developing unconventional energy resources on western US rangelands

Treesearch

Urs P. Kreuter; William E. Fox; John A. Tanaka; Kristie A. Maczko; Daniel W. McCollum; John E. Mitchell; Clifford S. Duke; Lori Hidinger

2012-01-01

More diverse sources of energy are needed for countries to progress toward energy independence and to meet future food production needs. The US Task Force on Strategic Unconventional Fuels concluded that to achieve this objective it is essential to develop a domestic unconventional fuels industry. Rangelands, which cover 50% to 70% of the earth's terrestrial...

Interim Report on Interagency National Personnel Recovery Architecture

DTIC Science & Technology

2003-07-01

adversaries are smart , however, and rather than face our forces on open battlefields, they will seek to use any asymmetric advantage open to them. If...Liaison Officer SARNEG Search and Rescue Numeric Encryption Grid SARPO Search and Rescue Planning Officer SARREQ Search and Rescue Request SARSAT...Unconventional Assisted Recovery UARCC Unconventional Assisted Recovery Coordination Center UARM Unconventional Assisted Recovery Mechanism UART

Origins and Evolution of the TPSR Alliance Community of Practice

ERIC Educational Resources Information Center

Balague, Gloria

2016-01-01

Teaching for personal and social responsibility (TPSR) is unconventional in nature, and this article describes the origins of the program and the many hurdles it had to overcome. It is not strictly a form of kinesiology, social work or education. It focuses instead on the whole person: kids' needs, interests and vulnerabilities. But TPSR also…

Seeing Red: Poetry and Metaphor as Responses to Representational Challenges in Critical Narrative Research

ERIC Educational Resources Information Center

Prosser, Brenton J.

2009-01-01

Research with young people who "do not fit the mould" requires innovative and unconventional methods, but what are the implications of such methods for scholarly representation? This paper reports on the development of such a method with students diagnosed Attention Deficit Hyperactivity Disorder and offers one view of the borderland…

Assessing Changes in Medical Student Attitudes toward Non-Traditional Human Sexual Behaviors Using a Confidential Audience Response System

ERIC Educational Resources Information Center

Tucker, Phebe; Candler, Chris; Hamm, Robert M.; Smith, E. Michael; Hudson, Joseph C.

2010-01-01

Medical students encountering patients with unfamiliar, unconventional sexual practices may have attitudes that can affect open communication during sexual history-taking. We measured changes in first-year US medical student attitudes toward 22 non-traditional sexual behaviors before and after exposure to human sexuality instruction. An…

The National Response Plan and the Problems in the Evaluation and Assessment of the Unconventional Modes of Terrorism

DOE Office of Scientific and Technical Information (OSTI.GOV)

LeMone, David V.; Gibbs, Shawn G.; Winston, John W. Jr.

In the wake of the events of 9/11, a presidential mandate ordered the development of a master plan to enable governmental agencies to not only seamlessly cooperate but also rapidly react to disasters. The National Response Plan (NRP) is the document in force (December 2004). It was developed to provide a framework for response to catastrophic events whether those events are natural or man-made. Homeland Security, the coordinating entity, is an integral and critical part of that plan. The NRP is a direct outgrowth of the Initial National Response Plan and operates in tandem with the National Incident Management Systemmore » (NIMS). NIMS was the first real attempt to amalgamate the capabilities and resources of some 22 governmental entities, non-governmental organizations (NGOs), and the private sector. The effectiveness of this system's response to natural disasters has been tested with reference to its performance during the 2005 late summer-early fall series of catastrophic hurricanes (Katrina, Rita, and Wilma). Ongoing evaluation of the response by the system indicates that there are significant lessons to be learned from system errors that occurred from the federal to local levels of government. Nevertheless, the conclusion would seem to be that Homeland Security's organizational structure of NIMS combined with protocols developed in the NRP represents an excellent response to both natural and man-made catastrophes. The lessons learned in these natural occurrences (chain of command failures and missteps from first responders to national level, periodic inaccurate and irresponsible news reporting, evacuation capabilities, quarantine problems, etc.) are directly applicable to potential man-made disaster events. In the yet largely untested areas of man-made disasters, the NRP document forms the basis for responding to terrorism as well as accidental man-made related incidents. There are two major categories of terrorism: conventional and unconventional. Conventional terrorism would include such acts as: assassination, kidnapping, hostage taking, non-nuclear explosive devices, etc. The two NRP categories of catastrophic events and oil and hazardous materials contain sections considered to be in the area of conventional terrorism. Of potentially greater immediate concern are the four major modes of unconventional terrorism that are recognized: cyber-, biological (including agro-), chemical, and nuclear. The problem is to arrive at a mutually agreed upon order of importance of both conventional and unconventional terrorism categories. Consequent ranking of these modes enables the prioritization of those areas in which our limited national human and financial resources are to be expended and allocated (funding of research and development, commitment and selection of personnel, costs distribution, operational time-frame, information distribution level, etc.). Ranking of the terror modes will at best be difficult because of a lack of understanding of the potential impacts of each mode as well as the inherent vested bureaucratic and non-bureaucratic interests and biases. All cases of radiation-related incidents may be considered to be manmade with a potentially significant majority of those incidents assigned to a terrorism origin. Man-made accidental occurrences would be handled with a similar NRP response as would be expected in the case of a terrorist event. Radiation-related devices include the RDDs (Radioactive Dispersal Devices) and nuclear fission and fusion weapons of mass destruction (WMD). Pragmatically, the most likely scenario to develop would involve RDD utilization. This conclusion would seem to be reasonable in view of the current apparent capabilities and sophistication required to construct, transport, and deliver a nuclear WMD. (authors)« less

An emerging case for membrane pore formation as a common mechanism for the unconventional secretion of FGF2 and IL-1β.

PubMed

Brough, David; Pelegrin, Pablo; Nickel, Walter

2017-10-01

Extracellular proteins with important signalling roles in processes, such as inflammation and angiogenesis, are known to employ unconventional routes of protein secretion. Although mechanisms of unconventional protein secretion are beginning to emerge, the precise molecular details have remained elusive for the majority of cargo proteins secreted by unconventional means. Recent findings suggest that for two examples of unconventionally secreted proteins, interleukin 1β (IL-1β) and fibroblast growth factor 2 (FGF2), the common molecular principle of pore formation may be shared. Under specific experimental conditions, secretion of IL-1β and FGF2 is triggered by phosphatidylinositol 4,5-bisphosphate [PI(4,5)P 2 ]-dependent formation of pores across the plasma membrane. However, the underlying mechanisms are different, with FGF2 known to directly interact with PI(4,5)P 2 , whereas in the case of IL-1β secretion, it is proposed that the N-terminal fragment of gasdermin D interacts with PI(4,5)P 2 to form the pore. Thus, although implemented in different ways, these findings suggest that pore formation may be shared by the unconventional secretion mechanisms for FGF2 and IL-1β in at least some cases. In this Opinion article, we discuss the unconventional mechanisms of FGF2 and IL-1β release with a particular emphasis on recent discoveries suggesting the importance of pore formation on the plasma membrane. © 2017. Published by The Company of Biologists Ltd.

Unified conduction mechanism in unconventional VZnCaFeO glasses

NASA Astrophysics Data System (ADS)

Ahmed, E. M.; Abdel-Wahab, F.

2014-09-01

Unconventional glasses with (70-x)%V2O5 - x%ZnO-10%CaO-20%FeO compositions (where x=0, 2.5, 5, 7.5, 10, 12.5 and 15 mol %) were prepared by a normal melt-quench technique. We investigated the DC and AC conductivities of these glasses as functions of temperature and frequency. We have noted that activation energy and pre-exponential factor of the DC conductivity both vary with composition and satisfy Meyer-Neldel rule (MNR). The AC conductivity exhibited a universal dynamic response: σAC=Aωs. The obtained results of the DC, AC and exponent factor S were discussed in terms of the modified correlated barrier hopping model, which assumes that the relaxation time should contain a Meyer-Neldel rule term. An agreement between experimental and theoretical results suggests that the conduction mechanism could be hopping of polarons over barriers.

Status of Advanced Stitched Unitized Composite Aircraft Structures

NASA Technical Reports Server (NTRS)

Jegley, Dawn C.; Velicki, Alex

2013-01-01

NASA has created the Environmentally Responsible Aviation (ERA) Project to explore and document the feasibility, benefits and technical risk of advanced vehicle configurations and enabling technologies that will reduce the impact of aviation on the environment. A critical aspect of this pursuit is the development of a lighter, more robust airframe that will enable the introduction of unconventional aircraft configurations that have higher lift-to-drag ratios, reduced drag, and lower community noise levels. The primary structural concept being developed under the ERA project in the Airframe Technology element is the Pultruded Rod Stitched Efficient Unitized Structure (PRSEUS) concept. This paper describes how researchers at NASA and The Boeing Company are working together to develop fundamental PRSEUS technologies that could someday be implemented on a transport size aircraft with high aspect ratio wings or unconventional shapes such as a hybrid wing body airplane design.

Hybrid nodal loop metal: Unconventional magnetoresponse and material realization

NASA Astrophysics Data System (ADS)

Zhang, Xiaoming; Yu, Zhi-Ming; Lu, Yunhao; Sheng, Xian-Lei; Yang, Hui Ying; Yang, Shengyuan A.

2018-03-01

A nodal loop is formed by a band crossing along a one-dimensional closed manifold, with each point on the loop a linear nodal point in the transverse dimensions, and can be classified as type I or type II depending on the band dispersion. Here, we propose a class of nodal loops composed of both type-I and type-II points, which are hence termed as hybrid nodal loops. Based on first-principles calculations, we predict the realization of such loops in the existing electride material Ca2As . For a hybrid loop, the Fermi surface consists of coexisting electron and hole pockets that touch at isolated points for an extended range of Fermi energies, without the need for fine-tuning. This leads to unconventional magnetic responses, including the zero-field magnetic breakdown and the momentum-space Klein tunneling observable in the magnetic quantum oscillations, as well as the peculiar anisotropy in the cyclotron resonance.

An Unconventional Approach to Reducing Retinal Degeneration After Traumatic Ocular Injury

DTIC Science & Technology

2017-09-01

AWARD NUMBER: W81XWH-15-1-0138 TITLE: An Unconventional Approach to Reducing Retinal Degeneration After Traumatic Ocular Injury PRINCIPAL...2015 - 30 Jun 2017 4. TITLE AND SUBTITLE An Unconventional Approach to Reducing Retinal Degeneration After Traumatic Ocular Injury 5 a . CONTRACT...optic confocal microscope system , test it, and establish protocols for the first successful in vivo retinal microvessel and pericyte advanced

Varieties of healing. 2: a taxonomy of unconventional healing practices.

PubMed

Kaptchuk, T J; Eisenberg, D M

2001-08-07

The first of two essays in this issue demonstrated that the United States has had a rich history of medical pluralism. This essay seeks to present an overview of contemporary unconventional medical practices in the United States. No clear definition of "alternative medicine" is offered because it is a residual category composed of heterogeneous healing methods. A descriptive taxonomy of contemporary unconventional healing could be more helpful. Two broad categories of unconventional medicine are described here: a more prominent, "mainstream" complementary and alternative medicine (CAM) and a more culture-bound, "parochial" unconventional medicine. The CAM component can be divided into professional groups, layperson-initiated popular health reform movements, New Age healing, alternative psychological therapies, and non-normative scientific enterprises. The parochial category can be divided into ethno-medicine, religious healing, and folk medicine. A topologic examination of U.S. health care can provide an important conceptual framework through which health care providers can understand the current situation in U.S. medical pluralism.

Unconventional gas development and its effect on forested ecosystems in the Northern Appalachians, USA

NASA Astrophysics Data System (ADS)

Drohan, Patrick; Brittingham, Margaret; Mortensen, David; Barlow, Kathryn; Langlois, Lillie

2017-04-01

Worldwide unconventional shale-gas development has the potential to cause substantial landscape disturbance. The northeastern U.S.A. Appalachian Mountains across the states of Pennsylvania, West Virginia, Ohio, and Kentucky, are experiencing rapid landscape change as unconventional gas development occurs. We highlight several years of our research from this region in order to demonstrate the unique effect unconventional development has had on forested ecosystems. Infrastructure development has had a wide-reaching and varied effect on forested ecosystems and their services, which has resulted in temporary disturbances and long-lasting ones altering habitats and their viability. Corridor disturbances, such as pipelines, are the most spatially extensive disturbance and have substantially fragmented forest cover. Core forest disturbance, especially, in upper watershed positions, has resulted in disproportionate disturbances to forested ecosystems and their wildlife, and suggests a need for adaptive land management strategies to minimize and mitigate the effects of gas development. Soil and water resources are most affected by surface disturbances; however, soil protection and restoration strategies are evolving as the gas play changes economically. Dynamic soil properties related to soil organic matter and water availability respond uniquely to unconventional gas development and new, flexible restoration strategies are required to support long-term ecosystem stability. While the focus of management and research to date has been on acute disturbances to forested ecosystems, unconventional gas development is clearly a greater chronic, long-term disturbance factor in the Appalachian Mountains. Effectively managing ecosystems where unconventional gas development is occurring is a complicated interplay between public, private and corporate interests.

Unconventional natural gas development and birth outcomes in Pennsylvania, USA

PubMed Central

Casey, Joan A.; Savitz, David A.; Rasmussen, Sara G.; Ogburn, Elizabeth L.; Pollak, Jonathan; Mercer, Dione G.; Schwartz, Brian S.

2015-01-01

Background Unconventional natural gas development has expanded rapidly. In Pennsylvania the number of producing wells increased from zero in 2005 to 3689 in 2013. To our knowledge, no prior publications have focused on unconventional natural gas development and birth outcomes. Methods We performed a retrospective cohort study using electronic health record data on 9384 mothers linked to 10946 neonates in the Geisinger Health System from January 2009-January 2013. We estimated cumulative exposure to unconventional natural gas development activity with an inverse-distance squared model that incorporated distance to the mother’s home; dates and durations of well pad development, drilling, and hydraulic fracturing; and production volume during the pregnancy. We used multilevel linear and logistic regression models to examine associations between activity index quartile and term birth weight, preterm birth, low 5 minute Apgar score and small size for gestational age, while controlling for potential confounding variables. Results In adjusted models, there was an association between unconventional natural gas development activity and preterm birth that increased across quartiles, with a fourth quartile odds ratio of 1.4 (95% CI: 1.0-1.9). There were no associations of activity with Apgar score, small for gestational age, or term birth weight (after adjustment for year). In a post-hoc analysis, there was an association with physician-recorded high-risk pregnancy identified from the problem list (fourth vs. first quartile, 1.3 [95% CI: 1.1-1.7]). Conclusion Prenatal residential exposure to unconventional natural gas development activity was associated with two pregnancy outcomes, adding to evidence that unconventional natural gas development may impact health. PMID:26426945

URI regulates tumorigenicity and chemotherapeutic resistance of multiple myeloma by modulating IL-6 transcription.

PubMed

Fan, J-L; Zhang, J; Dong, L-W; Fu, W-J; Du, J; Shi, H-G; Jiang, H; Ye, F; Xi, H; Zhang, C-Y; Hou, J; Wang, H-Y

2014-03-13

Unconventional prefoldin RPB5 interactor (URI), which acts as an oncoprotein in solid tumors, is associated with RNA polymerase II subunit 5. However, its impact on multiple myeloma (MM) has not been determined. We demonstrate here that URI is overexpressed in MM compared with plasma cells derived from healthy volunteers. Side population (SP) cells sorted from MM cells showed a much higher level of URI than non-SP cells. Using lentivirus-delivered shRNA, we established stable URI knockdown MM cell lines. URI inhibition significantly attenuated the proliferation of MM cells and decreased colony formation compared with the control cells. Tumor growth assays in NOD/SCID mice further confirmed the promotion role of URI during MM development in vivo. Furthermore, URI knockdown markedly reduced the abundance of SP in MM cell lines and enhanced the chemotherapeutic sensitivity of MM towards bortezomib. Mechanically, URI appears to be critically involved in modulating STAT3 activity through regulating interleukin (IL)-6 transcription via interaction with NFκBp65. In conclusion, URI may have an important role in the development of MM and chemotherapeutic resistance through activating the IL-6/STAT3 pathway.

URI regulates tumorigenicity and chemotherapeutic resistance of multiple myeloma by modulating IL-6 transcription

PubMed Central

Fan, J-L; Zhang, J; Dong, L-W; Fu, W-J; Du, J; Shi, H-G; Jiang, H; Ye, F; Xi, H; Zhang, C-Y; Hou, J; Wang, H-Y

2014-01-01

Unconventional prefoldin RPB5 interactor (URI), which acts as an oncoprotein in solid tumors, is associated with RNA polymerase II subunit 5. However, its impact on multiple myeloma (MM) has not been determined. We demonstrate here that URI is overexpressed in MM compared with plasma cells derived from healthy volunteers. Side population (SP) cells sorted from MM cells showed a much higher level of URI than non-SP cells. Using lentivirus-delivered shRNA, we established stable URI knockdown MM cell lines. URI inhibition significantly attenuated the proliferation of MM cells and decreased colony formation compared with the control cells. Tumor growth assays in NOD/SCID mice further confirmed the promotion role of URI during MM development in vivo. Furthermore, URI knockdown markedly reduced the abundance of SP in MM cell lines and enhanced the chemotherapeutic sensitivity of MM towards bortezomib. Mechanically, URI appears to be critically involved in modulating STAT3 activity through regulating interleukin (IL)-6 transcription via interaction with NFκBp65. In conclusion, URI may have an important role in the development of MM and chemotherapeutic resistance through activating the IL-6/STAT3 pathway. PMID:24625985

Deterrence in the Human Domain: A COIN Framework to Deterring Unconventional Warfare in Shaping Operations

DTIC Science & Technology

2017-05-25

Wilkinson US Army School of Advanced Military Studies United States Army Command and General Staff College Fort Leavenworth, Kansas 2017 Approved for...SPONSORING / MONITORING AGENCY NAME(S) AND ADDRESS(ES) Advanced Military Studies Program 10. SPONSOR/MONITOR’S ACRONYM(S) 11. SPONSOR/MONITOR’S...adversary’s unconventional threat. To test this framework, this monograph analyzes a case study of how Russia will likely use unconventional forces and

East-West paths to unconventional computing.

PubMed

Adamatzky, Andrew; Akl, Selim; Burgin, Mark; Calude, Cristian S; Costa, José Félix; Dehshibi, Mohammad Mahdi; Gunji, Yukio-Pegio; Konkoli, Zoran; MacLennan, Bruce; Marchal, Bruno; Margenstern, Maurice; Martínez, Genaro J; Mayne, Richard; Morita, Kenichi; Schumann, Andrew; Sergeyev, Yaroslav D; Sirakoulis, Georgios Ch; Stepney, Susan; Svozil, Karl; Zenil, Hector

2017-12-01

Unconventional computing is about breaking boundaries in thinking, acting and computing. Typical topics of this non-typical field include, but are not limited to physics of computation, non-classical logics, new complexity measures, novel hardware, mechanical, chemical and quantum computing. Unconventional computing encourages a new style of thinking while practical applications are obtained from uncovering and exploiting principles and mechanisms of information processing in and functional properties of, physical, chemical and living systems; in particular, efficient algorithms are developed, (almost) optimal architectures are designed and working prototypes of future computing devices are manufactured. This article includes idiosyncratic accounts of 'unconventional computing' scientists reflecting on their personal experiences, what attracted them to the field, their inspirations and discoveries. Copyright © 2017 Elsevier Ltd. All rights reserved.

Water Use for Unconventional Energy Development: How Much, What Kind, and to What Reaction?

NASA Astrophysics Data System (ADS)

Grubert, E.

2017-12-01

Water resources—access to water, protection of water, and allocation of water in particular—are a major priority for Americans, but water use for the energy sector has not previously been well characterized. Water use and management associated with unconventional energy development is of special interest, in part because it is often new to the locations and contexts where it occurs. This presentation focuses on three major questions about water use for unconventional energy development, drawing on both engineering and anthropological research. First, using results from a recent study of water use for energy in the entire United States, how much water does the US use for unconventional energy resources, and how does that compare with water use for more mature fuel cycles? Second, based on that same study, what kind of water is used for these unconventional energy resource fuel cycles? Specifically, where does the water come from, and what is its quality? Finally, drawing on recent case studies in the US and elsewhere, what has the reaction been to these water uses, and why does that matter? Case studies focused on oil and natural gas resources illustrate societal reactions to issues of both water management, particularly related to induced seismicity associated with produced water injection, and water allocation, particularly related to hydraulic fracturing. Overall, recent work finds that public concern about water used for unconventional energy resources is often better explained by observed or anticipated local impacts and the uncertainty surrounding these impacts than by specifics about quantities, allocation, and management techniques. This work provides both quantitative and qualitative characterization of water management and allocation for unconventional energy development.

Unconventional Natural Gas Development and Birth Outcomes in Pennsylvania, USA.

PubMed

Casey, Joan A; Savitz, David A; Rasmussen, Sara G; Ogburn, Elizabeth L; Pollak, Jonathan; Mercer, Dione G; Schwartz, Brian S

2016-03-01

Unconventional natural gas development has expanded rapidly. In Pennsylvania, the number of producing wells increased from 0 in 2005 to 3,689 in 2013. Few publications have focused on unconventional natural gas development and birth outcomes. We performed a retrospective cohort study using electronic health record data on 9,384 mothers linked to 10,946 neonates in the Geisinger Health System from January 2009 to January 2013. We estimated cumulative exposure to unconventional natural gas development activity with an inverse-distance squared model that incorporated distance to the mother's home; dates and durations of well pad development, drilling, and hydraulic fracturing; and production volume during the pregnancy. We used multilevel linear and logistic regression models to examine associations between activity index quartile and term birth weight, preterm birth, low 5-minute Apgar score and small size for gestational age birth, while controlling for potential confounding variables. In adjusted models, there was an association between unconventional natural gas development activity and preterm birth that increased across quartiles, with a fourth quartile odds ratio of 1.4 (95% confidence interval = 1.0, 1.9). There were no associations of activity with Apgar score, small for gestational age birth, or term birth weight (after adjustment for year). In a posthoc analysis, there was an association with physician-recorded high-risk pregnancy identified from the problem list (fourth vs. first quartile, 1.3 [95% confidence interval = 1.1, 1.7]). Prenatal residential exposure to unconventional natural gas development activity was associated with two pregnancy outcomes, adding to evidence that unconventional natural gas development may impact health.See Video Abstract at http://links.lww.com/EDE/B14.

GaN-based light-emitting diodes on various substrates: a critical review.

PubMed

Li, Guoqiang; Wang, Wenliang; Yang, Weijia; Lin, Yunhao; Wang, Haiyan; Lin, Zhiting; Zhou, Shizhong

2016-05-01

GaN and related III-nitrides have attracted considerable attention as promising materials for application in optoelectronic devices, in particular, light-emitting diodes (LEDs). At present, sapphire is still the most popular commercial substrate for epitaxial growth of GaN-based LEDs. However, due to its relatively large lattice mismatch with GaN and low thermal conductivity, sapphire is not the most ideal substrate for GaN-based LEDs. Therefore, in order to obtain high-performance and high-power LEDs with relatively low cost, unconventional substrates, which are of low lattice mismatch with GaN, high thermal conductivity and low cost, have been tried as substitutes for sapphire. As a matter of fact, it is not easy to obtain high-quality III-nitride films on those substrates for various reasons. However, by developing a variety of techniques, distincts progress has been made during the past decade, with high-performance LEDs being successfully achieved on these unconventional substrates. This review focuses on state-of-the-art high-performance GaN-based LED materials and devices on unconventional substrates. The issues involved in the growth of GaN-based LED structures on each type of unconventional substrate are outlined, and the fundamental physics behind these issues is detailed. The corresponding solutions for III-nitride growth, defect control, and chip processing for each type of unconventional substrate are discussed in depth, together with a brief introduction to some newly developed techniques in order to realize LED structures on unconventional substrates. This is very useful for understanding the progress in this field of physics. In this review, we also speculate on the prospects for LEDs on unconventional substrates.

ON A GENERALIZED SELF-SIMILARITY IN THE p-ADIC FIELD

NASA Astrophysics Data System (ADS)

Mukhamedov, Farrukh; Khakimov, Otabek

2016-08-01

In the present paper, we introduce a new set which defines a generalized self-similar set for contractive functions {fi}i=1N on the unit ball ℤp of p-adic numbers. This set is called unconventional limit set. We prove that the unconventional limit set is compact, perfect and uniformly disconnected. Moreover, we provide an example of two contractions for which the corresponding unconventional limiting set is quasi-symmetrically equivalent to the symbolic Cantor set.

U.S. Joint Special Operations Forces: Two Few, Overworked, Young, Homogenous & Macho to Fulfill the Unconventional Demands of the Long War?

DTIC Science & Technology

2008-05-28

OVERWORKED , YOUNG, HOMOGENOUS, & MACHO TO FULFILL THE UNCONVENTIONAL DEMANDS OF THE LONG WAR? SUBMITTED IN PARTIAL FULFILLMENT OF THE REQUIREMENTS FOR...U.S. Joint Special Operations Forces: Two Few, Overworked , Young, Homogenous & Macho to Fulfill the Unconventional Demands of the Long War? 5a...to be the targets of nearly daily mortar, improvised explosive devices (IEDs), and occasional suicide vehicle-borne IED (SVBIED) attacks. It

Design and life-cycle considerations for unconventional-reservoir wells

DOE Office of Scientific and Technical Information (OSTI.GOV)

Miskimins, J.L.

2009-05-15

This paper provides an overview of design and life-cycle considerations for certain unconventional-reservoir wells. An overview of unconventional-reservoir definitions is provided. Well design and life-cycle considerations are addressed from three aspects: upfront reservoir development, initial well completion, and well-life and long-term considerations. Upfront-reservoir-development issues discussed include well spacing, well orientation, reservoir stress orientations, and tubular metallurgy. Initial-well-completion issues include maximum treatment pressures and rates, treatment diversion, treatment staging, flowback and cleanup, and dewatering needs. Well-life and long-term discussions include liquid loading, corrosion, refracturing and associated fracture reorientation, and the cost of abandonment. These design considerations are evaluated with case studiesmore » for five unconventional-reservoir types: shale gas (Barnett shale), tight gas (Jonah feld), tight oil (Bakken play), coalbed methane (CBM) (San Juan basin), and tight heavy oil (Lost Hills field). In evaluating the life cycle and design of unconventional-reservoir wells, 'one size' does not fit all and valuable knowledge and a shortening of the learning curve can be achieved for new developments by studying similar, more-mature fields.« less

The health implications of unconventional natural gas development in Pennsylvania.

PubMed

Peng, Lizhong; Meyerhoefer, Chad; Chou, Shin-Yi

2018-06-01

We investigate the health impacts of unconventional natural gas development of Marcellus shale in Pennsylvania between 2001 and 2013 by merging well permit data from the Pennsylvania Department of Environmental Protection with a database of all inpatient hospital admissions. After comparing changes in hospitalization rates over time for air pollution-sensitive diseases in counties with unconventional gas wells to changes in hospitalization rates in nonwell counties, we find a significant association between shale gas development and hospitalizations for pneumonia among the elderly, which is consistent with higher levels of air pollution resulting from unconventional natural gas development. We note that the lack of any detectable impact of shale gas development on younger populations may be due to unobserved factors contemporaneous with drilling, such as migration. Copyright © 2018 John Wiley & Sons, Ltd.

Theory of disordered unconventional superconductors

DOE Office of Scientific and Technical Information (OSTI.GOV)

Keles, A.; Andreev, A. V.; Spivak, B. Z., E-mail: spivak@uw.edu

In contrast to conventional s-wave superconductivity, unconventional (e.g., p- or d-wave) superconductivity is strongly suppressed even by relatively weak disorder. Upon approaching the superconductormetal transition, the order parameter amplitude becomes increasingly inhomogeneous, leading to effective granularity and a phase ordering transition described by the Mattis model of spin glasses. One consequence of this is that at sufficiently low temperatures, between the clean unconventional superconducting and the diffusive metallic phases, there is necessarily an intermediate superconducting phase that exhibits s-wave symmetry on macroscopic scales.

PerSEUS: Ultra-Low-Power High Performance Computing for Plasma Simulations

NASA Astrophysics Data System (ADS)

Doxas, I.; Andreou, A.; Lyon, J.; Angelopoulos, V.; Lu, S.; Pritchett, P. L.

2017-12-01

Peta-op SupErcomputing Unconventional System (PerSEUS) aims to explore the use for High Performance Scientific Computing (HPC) of ultra-low-power mixed signal unconventional computational elements developed by Johns Hopkins University (JHU), and demonstrate that capability on both fluid and particle Plasma codes. We will describe the JHU Mixed-signal Unconventional Supercomputing Elements (MUSE), and report initial results for the Lyon-Fedder-Mobarry (LFM) global magnetospheric MHD code, and a UCLA general purpose relativistic Particle-In-Cell (PIC) code.

Investigating operation at geometrically unconventional intersections.

DOT National Transportation Integrated Search

2014-08-01

This report documents the development of decision assistance curves (DAC) for unconventional intersections, particularly : median U-turns (MUT), continuous flow intersections (CFI), and jughandles. The operational measure of effectiveness : such as d...

Unconventional Oil and Gas Extraction Effluent Guidelines

EPA Pesticide Factsheets

Overview and documents for the Unconventional Oil and Gas Extraction Pretreatment Standards final rule (6/28/2016), direct final rule (Sept. 2016) and proposed rule (Sept. 2016). 40 CFR Part 435, Subpart C.

Quantity of flowback and produced waters from unconventional oil and gas exploration.

PubMed

Kondash, Andrew J; Albright, Elizabeth; Vengosh, Avner

2017-01-01

The management and disposal of flowback and produced waters (FP water) is one of the greatest challenges associated with unconventional oil and gas development. The development and production of unconventional natural gas and oil is projected to increase in the coming years, and a better understanding of the volume and quality of FP water is crucial for the safe management of the associated wastewater. We analyzed production data using multiple statistical methods to estimate the total FP water generated per well from six of the major unconventional oil and gas formations in the United States. The estimated median volume ranges from 1.7 to 14.3millionL (0.5 to 3.8milliongal) of FP per well over the first 5-10years of production. Using temporal volume production and water quality data, we show a rapid increase of the salinity associated with a decrease of FP production rates during the first months of unconventional oil and gas production. Based on mass-balance calculations, we estimate that only 4-8% of FP water is composed of returned hydraulic fracturing fluids, while the remaining 92-96% of FP water is derived from naturally occurring formation brines that is extracted together with oil and gas. The salinity and chemical composition of the formation brines are therefore the main limiting factors for beneficial reuse of unconventional oil and gas wastewater. Copyright © 2016 Elsevier B.V. All rights reserved.

A Comparison of the Impacts of Wind Energy and Unconventional Gas Development on Land-use and Ecosystem Services: An Example from the Anadarko Basin of Oklahoma, USA.

PubMed

Davis, Kendall M; Nguyen, Michael N; McClung, Maureen R; Moran, Matthew D

2018-05-01

The United States energy industry is transforming with the rapid development of alternative energy sources and technological advancements in fossil fuels. Two major changes include the growth of wind turbines and unconventional oil and gas. We measured land-use impacts and associated ecosystem services costs of unconventional gas and wind energy development within the Anadarko Basin of the Oklahoma Woodford Shale, an area that has experienced large increases in both energy sectors. Unconventional gas wells developed three times as much land compared to wind turbines (on a per unit basis), resulting in higher ecosystem services costs for gas. Gas wells had higher impacts on intensive agricultural lands (i.e., row crops) compared to wind turbines that had higher impacts on natural grasslands/pastures. Because wind turbines produced on average less energy compared to gas wells, the average land-use-related ecosystem cost per gigajoule of energy produced was almost the same. Our results demonstrate that both unconventional gas and wind energy have substantial impacts on land use, which likely affect wildlife populations and land-use-related ecosystem services. Although wind energy does not have the associated greenhouse gas emissions, we suggest that the direct impacts on ecosystems in terms of land use are similar to unconventional fossil fuels. Considering the expected rapid global expansion of these two forms of energy production, many ecosystems are likely to be at risk.

Hidden magnetism and quantum criticality in the heavy fermion superconductor CeRhIn5.

PubMed

Park, Tuson; Ronning, F; Yuan, H Q; Salamon, M B; Movshovich, R; Sarrao, J L; Thompson, J D

2006-03-02

With only a few exceptions that are well understood, conventional superconductivity does not coexist with long-range magnetic order (for example, ref. 1). Unconventional superconductivity, on the other hand, develops near a phase boundary separating magnetically ordered and magnetically disordered phases. A maximum in the superconducting transition temperature T(c) develops where this boundary extrapolates to zero Kelvin, suggesting that fluctuations associated with this magnetic quantum-critical point are essential for unconventional superconductivity. Invariably, though, unconventional superconductivity masks the magnetic phase boundary when T < T(c), preventing proof of a magnetic quantum-critical point. Here we report specific-heat measurements of the pressure-tuned unconventional superconductor CeRhIn5 in which we find a line of quantum-phase transitions induced inside the superconducting state by an applied magnetic field. This quantum-critical line separates a phase of coexisting antiferromagnetism and superconductivity from a purely unconventional superconducting phase, and terminates at a quantum tetracritical point where the magnetic field completely suppresses superconductivity. The T --> 0 K magnetic field-pressure phase diagram of CeRhIn5 is well described with a theoretical model developed to explain field-induced magnetism in the high-T(c) copper oxides, but in which a clear delineation of quantum-phase boundaries has not been possible. These experiments establish a common relationship among hidden magnetism, quantum criticality and unconventional superconductivity in copper oxides and heavy-electron systems such as CeRhIn5.

Deep geothermal: The ‘Moon Landing’ mission in the unconventional energy and minerals space

DOE PAGES

Regenauer-Lieb, Klaus; Bunger, Andrew; Chua, Hui Tong; ...

2015-01-30

Deep geothermal from the hot crystalline basement has remained an unsolved frontier for the geothermal industry for the past 30 years. This poses the challenge for developing a new unconventional geomechanics approach to stimulate such reservoirs. While a number of new unconventional brittle techniques are still available to improve stimulation on short time scales, the astonishing richness of failure modes of longer time scales in hot rocks has so far been overlooked. These failure modes represent a series of microscopic processes: brittle microfracturing prevails at low temperatures and fairly high deviatoric stresses, while upon increasing temperature and decreasing applied stressmore » or longer time scales, the failure modes switch to transgranular and intergranular creep fractures. Accordingly, fluids play an active role and create their own pathways through facilitating shear localization by a process of time-dependent dissolution and precipitation creep, rather than being a passive constituent by simply following brittle fractures that are generated inside a shear zone caused by other localization mechanisms. We lay out a new paradigm for reservoir stimulation by reactivating pre-existing faults at reservoir scale in a reservoir scale aseismic, ductile manner. A side effect of the new “soft” stimulation method is that owing to the design specification of a macroscopic ductile response, the proposed method offers the potential of a safer control over the stimulation process compared to conventional stimulation protocols such as currently employed in shale gas reservoirs.« less

Unconventional molecule-resolved current rectification in diamondoid–fullerene hybrids

PubMed Central

Randel, Jason C.; Niestemski, Francis C.; Botello-Mendez, Andrés R.; Mar, Warren; Ndabashimiye, Georges; Melinte, Sorin; Dahl, Jeremy E. P.; Carlson, Robert M. K.; Butova, Ekaterina D.; Fokin, Andrey A.; Schreiner, Peter R.; Charlier, Jean-Christophe; Manoharan, Hari C.

2014-01-01

The unimolecular rectifier is a fundamental building block of molecular electronics. Rectification in single molecules can arise from electron transfer between molecular orbitals displaying asymmetric spatial charge distributions, akin to p–n junction diodes in semiconductors. Here we report a novel all-hydrocarbon molecular rectifier consisting of a diamantane–C60 conjugate. By linking both sp3 (diamondoid) and sp2 (fullerene) carbon allotropes, this hybrid molecule opposingly pairs negative and positive electron affinities. The single-molecule conductances of self-assembled domains on Au(111), probed by low-temperature scanning tunnelling microscopy and spectroscopy, reveal a large rectifying response of the molecular constructs. This specific electronic behaviour is postulated to originate from the electrostatic repulsion of diamantane–C60 molecules due to positively charged terminal hydrogen atoms on the diamondoid interacting with the top electrode (scanning tip) at various bias voltages. Density functional theory computations scrutinize the electronic and vibrational spectroscopic fingerprints of this unique molecular structure and corroborate the unconventional rectification mechanism. PMID:25202942

Natural Gas and the Transformation of the U.S. Energy Sector: Electricity

DOE Office of Scientific and Technical Information (OSTI.GOV)

Logan, Jeffrey; Heath, Garvin; Macknick, Jordan

2012-11-01

Domestic natural gas production was largely stagnant from the mid-1970s until about 2005. However, beginning in the late 1990s, advances linking horizontal drilling techniques with hydraulic fracturing allowed drilling to proceed in shale and other formations at much lower cost. The result was a slow, steady increase in unconventional gas production. The Joint Institute for Strategic Energy Analysis (JISEA) designed this study to address four related key questions, which are a subset from the wider dialogue on natural gas; regarding the life cycle greenhouse gas (GHG) emissions associated with shale gas compared to conventional natural gas and other fuels usedmore » to generate electricity; existing legal and regulatory frameworks governing unconventional gas development at federal, state, and local levels, and changes in response to the rapid industry growth and public concerns; natural gas production companies changing their water-related practices; and demand for natural gas in the electric sector.« less

Health Concerns of Northeastern Pennsylvania Residents Living in an Unconventional Oil and Gas Development County.

PubMed

McDermott-Levy, Ruth; Garcia, Victoria

2016-11-01

This study was conducted to describe the health concerns of residents of an unconventional oil and natural gas development (UOGD) community and identify methods to best disseminate health information to the residents. A qualitative descriptive study of 27 residents of Wyoming County, Pennsylvania, was conducted. Residents described their health concerns in terms of their changing community as a result of UOGD, their feelings of stress and powerlessness related to these changes, and the limited response of their local policymakers and protective agencies. There were indications of misinformation related to routine environmental health and UOGD environmental risks. Web-based educational programs with downloadable printed materials to bridge the knowledge gaps of residents and health professionals are recommended. Recommendations include public health nurses providing education to communities and other health professionals regarding environmental health risks, working with communities to advocate for health-protective regulations, and adopting a community-based participatory approach to meet the needs of community members. © 2016 Wiley Periodicals, Inc.

Unconventional Secretion of Heat Shock Proteins in Cancer

PubMed Central

Santos, Tiago Góss; Martins, Vilma Regina; Hajj, Glaucia Noeli Maroso

2017-01-01

Heat shock proteins (HSPs) are abundant cellular proteins involved with protein homeostasis. They have both constitutive and inducible isoforms, whose expression levels are further increased by stress conditions, such as temperature elevation, reduced oxygen levels, infection, inflammation and exposure to toxic substances. In these situations, HSPs exert a pivotal role in offering protection, preventing cell death and promoting cell recovery. Although the majority of HSPs functions are exerted in the cytoplasm and organelles, several lines of evidence reveal that HSPs are able to induce cell responses in the extracellular milieu. HSPs do not possess secretion signal peptides, and their secretion was subject to widespread skepticism until the demonstration of the role of unconventional secretion forms such as exosomes. Secretion of HSPs may confer immune system modulation and be a cell-to-cell mediated form of increasing stress resistance. Thus, there is a wide potential for secreted HSPs in resistance of cancer therapy and in the development new therapeutic strategies. PMID:28468249

Rotational Symmetry Breaking in a Trigonal Superconductor Nb-doped Bi 2 Se 3

DOE Office of Scientific and Technical Information (OSTI.GOV)

Asaba, Tomoya; Lawson, B. J.; Tinsman, Colin

2017-01-27

The search for unconventional superconductivity has been focused on materials with strong spin-orbit coupling and unique crystal lattices. Doped bismuth selenide (Bi 2Se 3) is a strong candidate, given the topological insulator nature of the parent compound and its triangular lattice. The coupling between the physical properties in the superconducting state and its underlying crystal symmetry is a crucial test for unconventional superconductivity. In this paper, we report direct evidence that the superconducting magnetic response couples strongly to the underlying trigonal crystal symmetry in the recently discovered superconductor with trigonal crystal structure, niobium (Nb)-doped Bi 2Se 3. As a result,more » the in-plane magnetic torque signal vanishes every 60°. More importantly, the superconducting hysteresis loop amplitude is enhanced along one preferred direction, spontaneously breaking the rotational symmetry. This observation indicates the presence of nematic order in the superconducting ground state of Nb-doped Bi 2Se 3.« less

Associations between Unconventional Natural Gas Development and Nasal and Sinus, Migraine Headache, and Fatigue Symptoms in Pennsylvania

PubMed Central

Tustin, Aaron W.; Hirsch, Annemarie G.; Rasmussen, Sara G.; Casey, Joan A.; Bandeen-Roche, Karen; Schwartz, Brian S.

2016-01-01

Background: Unconventional natural gas development (UNGD) produces environmental contaminants and psychosocial stressors. Despite these concerns, few studies have evaluated the health effects of UNGD. Objectives: We investigated associations between UNGD activity and symptoms in a cross-sectional study in Pennsylvania. Methods: We mailed a self-administered questionnaire to 23,700 adult patients of the Geisinger Clinic. Using standardized and validated questionnaire items, we identified respondents with chronic rhinosinusitis (CRS), migraine headache, and fatigue symptoms. We created a summary UNGD activity metric that incorporated well phase, location, total depth, daily gas production and inverse distance–squared to patient residences. We used logistic regression, weighted for sampling and response rates, to assess associations between quartiles of UNGD activity and outcomes, both alone and in combination. Results: The response rate was 33%. Of 7,785 study participants, 1,850 (24%) had current CRS symptoms, 1,765 (23%) had migraine headache, and 1,930 (25%) had higher levels of fatigue. Among individuals who met criteria for two or more outcomes, adjusted odds ratios for the highest quartile of UNGD activity compared with the lowest were [OR (95% CI)] 1.49 (0.78, 2.85) for CRS plus migraine, 1.88 (1.08, 3.25) for CRS plus fatigue, 1.95 (1.18, 3.21) for migraine plus fatigue, and 1.84 (1.08, 3.14) for all three outcomes together. Significant associations were also present in some models of single outcomes. Conclusions: This study provides evidence that UNGD is associated with nasal and sinus, migraine headache, and fatigue symptoms in a general population representative sample. Citation: Tustin AW, Hirsch AG, Rasmussen SG, Casey JA, Bandeen-Roche K, Schwartz BS. 2017. Associations between unconventional natural gas development and nasal and sinus, migraine headache, and fatigue symptoms in Pennsylvania. Environ Health Perspect 125:189–197; http://dx.doi.org/10.1289/EHP281 PMID:27561132

Associations between Unconventional Natural Gas Development and Nasal and Sinus, Migraine Headache, and Fatigue Symptoms in Pennsylvania.

PubMed

Tustin, Aaron W; Hirsch, Annemarie G; Rasmussen, Sara G; Casey, Joan A; Bandeen-Roche, Karen; Schwartz, Brian S

2017-02-01

Unconventional natural gas development (UNGD) produces environmental contaminants and psychosocial stressors. Despite these concerns, few studies have evaluated the health effects of UNGD. We investigated associations between UNGD activity and symptoms in a cross-sectional study in Pennsylvania. We mailed a self-administered questionnaire to 23,700 adult patients of the Geisinger Clinic. Using standardized and validated questionnaire items, we identified respondents with chronic rhinosinusitis (CRS), migraine headache, and fatigue symptoms. We created a summary UNGD activity metric that incorporated well phase, location, total depth, daily gas production and inverse distance-squared to patient residences. We used logistic regression, weighted for sampling and response rates, to assess associations between quartiles of UNGD activity and outcomes, both alone and in combination. The response rate was 33%. Of 7,785 study participants, 1,850 (24%) had current CRS symptoms, 1,765 (23%) had migraine headache, and 1,930 (25%) had higher levels of fatigue. Among individuals who met criteria for two or more outcomes, adjusted odds ratios for the highest quartile of UNGD activity compared with the lowest were [OR (95% CI)] 1.49 (0.78, 2.85) for CRS plus migraine, 1.88 (1.08, 3.25) for CRS plus fatigue, 1.95 (1.18, 3.21) for migraine plus fatigue, and 1.84 (1.08, 3.14) for all three outcomes together. Significant associations were also present in some models of single outcomes. This study provides evidence that UNGD is associated with nasal and sinus, migraine headache, and fatigue symptoms in a general population representative sample. Citation: Tustin AW, Hirsch AG, Rasmussen SG, Casey JA, Bandeen-Roche K, Schwartz BS. 2017. Associations between unconventional natural gas development and nasal and sinus, migraine headache, and fatigue symptoms in Pennsylvania. Environ Health Perspect 125:189-197; http://dx.doi.org/10.1289/EHP281.

Unconventional Transport Routes of Soluble and Membrane Proteins and Their Role in Developmental Biology

PubMed Central

Pompa, Andrea; De Marchis, Francesca; Pallotta, Maria Teresa; Benitez-Alfonso, Yoselin; Jones, Alexandra; Schipper, Kerstin; Moreau, Kevin; Žárský, Viktor; Di Sansebastiano, Gian Pietro; Bellucci, Michele

2017-01-01

Many proteins and cargoes in eukaryotic cells are secreted through the conventional secretory pathway that brings proteins and membranes from the endoplasmic reticulum to the plasma membrane, passing through various cell compartments, and then the extracellular space. The recent identification of an increasing number of leaderless secreted proteins bypassing the Golgi apparatus unveiled the existence of alternative protein secretion pathways. Moreover, other unconventional routes for secretion of soluble or transmembrane proteins with initial endoplasmic reticulum localization were identified. Furthermore, other proteins normally functioning in conventional membrane traffic or in the biogenesis of unique plant/fungi organelles or in plasmodesmata transport seem to be involved in unconventional secretory pathways. These alternative pathways are functionally related to biotic stress and development, and are becoming more and more important in cell biology studies in yeast, mammalian cells and in plants. The city of Lecce hosted specialists working on mammals, plants and microorganisms for the inaugural meeting on “Unconventional Protein and Membrane Traffic” (UPMT) during 4–7 October 2016. The main aim of the meeting was to include the highest number of topics, summarized in this report, related to the unconventional transport routes of protein and membranes. PMID:28346345

Impact of Unconventional Gas Technology in the Annual Energy Outlook 2000

EIA Publications

2000-01-01

This paper describes the methodology used in the National Energy Modeling System (NEMS) to represent unconventional gas technologies and their impacts on projections in the Annual Energy Outlook 2000 (AEO2000).

Silicon solar cell process development, fabrication and analysis

NASA Technical Reports Server (NTRS)

Minahan, J. A.

1981-01-01

The fabrication of solar cells from several unconventional silicon materials is described, and cell performance measured and analyzed. Unconventional materials evaluated are edge defined film fed grown (EFG), heat exchanger method (HEM), dendritic web grown, and continuous CZ silicons. Resistivity, current voltage, and spectral sensitivity of the cells were measured. Current voltage was measured under AM0 and AM1 conditions. Maximum conversion efficiencies of cells fabricated from these and other unconventional silicons were compared and test results analyzed. The HEM and continuous CZ silicon were found to be superior to silicon materials considered previously.

REVIEW ARTICLE: Unconventional isotope effects in the high-temperature cuprate superconductors

NASA Astrophysics Data System (ADS)

Zhao, Guo-meng; Keller, H.; Conder, K.

2001-07-01

We review various isotope effects in the high-Tc cuprate superconductors to assess the role of the electron-phonon interaction in the basic physics of these materials. Of particular interest are the unconventional isotope effects on the supercarrier mass, on the charge-stripe formation temperature, on the pseudogap formation temperature, on the electron paramagnetic resonance (EPR) linewidth, on the spin-glass freezing temperature and on the antiferromagnetic ordering temperature. The observed unconventional isotope effects strongly suggest that lattice vibrations play an important role in the microscopic pairing mechanism of high-temperature superconductivity.

Radon in unconventional natural gas from gulf coast geopressured-geothermal reservoirs

USGS Publications Warehouse

Kraemer, T.F.

1986-01-01

Radon-222 has been measured in natural gas produced from experimental geopressured-geothermal test wells. Comparison with published data suggests that while radon activity of this unconventional natural gas resource is higher than conventional gas produced in the gulf coast, it is within the range found for conventional gas produced throughout the U.S. A method of predicting the likely radon activity of this unconventional gas is described on the basis of the data presented, methane solubility, and known or assumed reservoir conditions of temperature, fluid pressure, and formation water salinity.

Genome scale transcriptional response diversity among ten ecotypes of Arabidopsis thaliana during heat stress

PubMed Central

Barah, Pankaj; Jayavelu, Naresh D.; Mundy, John; Bones, Atle M.

2013-01-01

In the scenario of global warming and climate change, heat stress is a serious threat to crop production worldwide. Being sessile, plants cannot escape from heat. Plants have developed various adaptive mechanisms to survive heat stress. Several studies have focused on diversity of heat tolerance levels in divergent Arabidopsis thaliana (A. thaliana) ecotypes, but comprehensive genome scale understanding of heat stress response in plants is still lacking. Here we report the genome scale transcript responses to heat stress of 10 A. thaliana ecotypes (Col, Ler, C24, Cvi, Kas1, An1, Sha, Kyo2, Eri, and Kond) originated from different geographical locations. During the experiment, A. thaliana plants were subjected to heat stress (38°C) and transcript responses were monitored using Arabidopsis NimbleGen ATH6 microarrays. The responses of A. thaliana ecotypes exhibited considerable variation in the transcript abundance levels. In total, 3644 transcripts were significantly heat regulated (p < 0.01) in the 10 ecotypes, including 244 transcription factors and 203 transposable elements. By employing a systems genetics approach- Network Component Analysis (NCA), we have constructed an in silico transcript regulatory network model for 35 heat responsive transcription factors during cellular responses to heat stress in A. thaliana. The computed activities of the 35 transcription factors showed ecotype specific responses to the heat treatment. PMID:24409190

There Are Better Ways. Building Smaller, Safer, Effective and Efficient Public Schools. New Ideas for School Construction in North Carolina and a Model for Implementation. New Ideas, Number 1.

ERIC Educational Resources Information Center

Haynes, Doug; Hood, John

This paper offers unconventional and innovative ideas for school planning and construction in North Carolina for creating smaller and safer community schools in response to rising enrollment, tight budgets, and dwindling school space. Often using examples from across the country, the paper discusses school construction costs and economy of scale…

Terrorism in Bulgaria.

PubMed

Shanduorkov, George

2003-01-01

The Republic of Bulgaria is one of the smallest countries in southeastern Europe and has little experience with terrorist acts. During the past 20 years, only nine terrorism-related events have been recorded in Bulgaria, and no unconventional weapons have been used. Factors contributing to terrorism in Bulgaria have been: (1) Communist Party domination of the government and political process from 1944 to 1989; (2) ethnic and religious conflicts between the Bulgarian Orthodox Christian majority and the Turkish Muslim minority from 1983 to 1987; and (3) the relatively high level of organized crime after the Communist regime ended in 1990. The structure and function of the Disaster Relief System in Bulgaria not only are focused on the prevention of terrorism, but also on preparedness for the emergency response to terrorism-related events. Institutional components of the Disaster Relief System structure responsible for the emergency response to terrorism-related events include: (1) the Government of Bulgaria; (2) the State Agency for Civil Protection with 28 regional directorates; (3) the Ministry of Health with five national hospitals, 28 regional hospitals, and 28 EMS systems; (4) the Ministry of Defense with special military units for response to unconventional terrorist events, including nuclear, biological, and chemical weapons; (5) the Ministry of Internal Affairs with 28 police departments, 28 fire departments, and specialized anti-terrorist units; and (6) the Bulgarian Red Cross. A major future challenge in Bulgaria is the prevention of terrorism through political stability, economic prosperity, ethnic and religious tolerance, and more effective measures against organized criminal activities. A related challenge will be to improve the level of preparedness of all components of Disaster Relief.

Novel highly dispersible, thermally stable core/shell proppants for geothermal applications

DOE Office of Scientific and Technical Information (OSTI.GOV)

Childers, Ian M.; Endres, Mackenzie; Burns, Carolyne

The use of proppants during reservoir stimulation in tight oil and gas plays requires the introduction of highly viscous fluids to transport the proppants (µm–mm) with the fracturing fluid. The highly viscous fluids required result in increased pump loads and energy costs. Furthermore, although proppant deployment with fracturing fluids is a standard practice for unconventional oil and gas stimulation operations, there are only a few examples in the US of the applying proppant technology to geothermal energy production. This is due to proppant dissolution, proppant flowback and loss of permeability associated with the extreme temperatures found in enhanced geothermal systemsmore » (EGS). This work demonstrates proof-of-concept of a novel, CO2-responsive, lightweight sintered-bauxite/polymer core/shell proppant. The polymer shell has two main roles; 1) increase the stability of the proppant dispersion in water without the addition of rheology modifiers, and 2) once at the fracture network react with CO2 to promote particle aggregation and prop fractures open. In this work, both of these roles are demonstrated together with the thermal and chemical stability of the materials showing the potential of these CO2-responsive proppants as an alternative proppant technology for geothermal and unconventional oil/gas applications.« less

Application of solidifiers for oil spill containment: A review.

PubMed

Motta, Fernanda L; Stoyanov, Stanislav R; Soares, João B P

2018-03-01

The need for new and/or improvement of existing oil spill remediation measures has increased substantially amidst growing public concern with the increased transportation of unconventional crudes, such as diluted bitumen products. Solidifiers may be a very good spill response measure to contain and mitigate the effects of oil discharge incidents, as these interact with the oil to limit hydrocarbon release into air and water, prevent it from adhering onto sediment and debris, and could allow for oil recovery and reuse. Solidifiers change the physical state of the spilled oil from liquid to a coherent mass by chemical interactions between the spilled oil and the solidifier. Currently, the use of solidifiers is limited to small spills near shorelines. To extend their use to large-scale spill containment operations, it is necessary to understand the mechanism of solidifier action and to establish consistent criteria for evaluation of their effectiveness. The research effort to date has been focused mainly on gelators and cross-linking agents, with particularly impressive advancements in the areas of phase-selective polymeric and small-molecule gelators. Substantial research efforts are needed to improve solidifier performance and integrate solidifiers as part of spill response procedures, particularly for acute oil spills involving unconventional petroleum products. Crown Copyright © 2017. Published by Elsevier Ltd. All rights reserved.

The MluI cell cycle box (MCB) motifs, but not damage-responsive elements (DREs), are responsible for the transcriptional induction of the rhp51+ gene in response to DNA replication stress.

PubMed

Sartagul, Wugangerile; Zhou, Xin; Yamada, Yuki; Ma, Ning; Tanaka, Katsunori; Furuyashiki, Tomoyuki; Ma, Yan

2014-01-01

DNA replication stress induces the transcriptional activation of rhp51+, a fission yeast recA homolog required for repair of DNA double strand breaks. However, the mechanism by which DNA replication stress activates rhp51+ transcription is not understood. The promoter region of rhp51+ contains two damage-responsive elements (DREs) and two MluI cell cycle box (MCB) motifs. Using luciferase reporter assays, we examined the role of these elements in rhp51+ transcription. The full-length rhp51+ promoter and a promoter fragment containing MCB motifs only, but not a fragment containing DREs, mediated transcriptional activation upon DNA replication stress. Removal of the MCB motifs from the rhp51+ promoter abolished the induction of rhp51+ transcription by DNA replication stress. Consistent with a role for MCB motifs in rhp51+ transcription activation, deletion of the MBF (MCB-binding factor) co-repressors Nrm1 and Yox1 precluded rhp51+ transcriptional induction in response to DNA replication stress. Using cells deficient in checkpoint signaling molecules, we found that the Rad3-Cds1/Chk1 pathway partially mediated rhp51+ transcription in response to DNA replication stress, suggesting the involvement of unidentified checkpoint signaling pathways. Because MBF is critical for G1/S transcription, we examined how the cell cycle affected rhp51+ transcription. The transcription of rhp51+ and cdc18+, an MBF-dependent G1/S gene, peaked simultaneously in synchronized cdc25-22 cells. Furthermore, DNA replication stress maintained transcription of rhp51+ similarly to cdc18+. Collectively, these results suggest that MBF and its regulators mediate rhp51+ transcription in response to DNA replication stress, and underlie rhp51+ transcription at the G1/S transition.

Just fracking: a distributive environmental justice analysis of unconventional gas development in Pennsylvania, USA

NASA Astrophysics Data System (ADS)

Clough, Emily; Bell, Derek

2016-02-01

This letter presents a distributive environmental justice analysis of unconventional gas development in the area of Pennsylvania lying over the Marcellus Shale, the largest shale gas formation in play in the United States. The extraction of shale gas using unconventional wells, which are hydraulically fractured (fracking), has increased dramatically since 2005. As the number of wells has grown, so have concerns about the potential public health effects on nearby communities. These concerns make shale gas development an environmental justice issue. This letter examines whether the hazards associated with proximity to wells and the economic benefits of shale gas production are fairly distributed. We distinguish two types of distributive environmental justice: traditional and benefit sharing. We ask the traditional question: are there a disproportionate number of minority or low-income residents in areas near to unconventional wells in Pennsylvania? However, we extend this analysis in two ways: we examine income distribution and level of education; and we compare before and after shale gas development. This contributes to discussions of benefit sharing by showing how the income distribution of the population has changed. We use a binary dasymetric technique to remap the data from the 2000 US Census and the 2009-2013 American Communities Survey and combine that data with a buffer containment analysis of unconventional wells to compare the characteristics of the population living nearer to unconventional wells with those further away before and after shale gas development. Our analysis indicates that there is no evidence of traditional distributive environmental injustice: there is not a disproportionate number of minority or low-income residents in areas near to unconventional wells. However, our analysis is consistent with the claim that there is benefit sharing distributive environmental injustice: the income distribution of the population nearer to shale gas wells has not been transformed since shale gas development.

Fatty acid profile of unconventional oilseeds.

PubMed

Sabikhi, Latha; Sathish Kumar, M H

2012-01-01

The continued increase in human population has resulted in the rise in the demand as well as the price of edible oils, leading to the search for alternative unconventional sources of oils, particularly in the developing countries. There are hundreds of un- or underexplored plant seeds rich in oil suitable for edible or industrial purposes. Many of them are rich in polyunsaturated essential fatty acids, which establish their utility as "healthy oils." Some agrowaste products such as rice bran have gained importance as a potential source of edible oil. Genetic modification has paved the way for increasing the oil yields and improving the fatty acid profiles of traditional as well as unconventional oilseeds. Single cell oils are also novel sources of edible oil. Some of these unconventional oils may have excellent potential for medicinal and therapeutic uses, even if their low oil contents do not promote commercial production as edible oils. Copyright © 2012 Elsevier Inc. All rights reserved.

Insights into the nuclear export of murine leukemia virus intron-containing RNA.

PubMed

Pessel-Vivares, Lucie; Houzet, Laurent; Lainé, Sébastien; Mougel, Marylène

2015-01-01

The retroviral genome consists of an intron-containing transcript that has essential cytoplasmic functions in the infected cell. This viral transcript can escape splicing, circumvent the nuclear checkpoint mechanisms and be transported to the cytoplasm by hijacking the host machinery. Once in the cytoplasm, viral unspliced RNA acts as mRNA to be translated and as genomic RNA to be packaged into nascent viruses. The murine leukemia virus (MLV) is among the first retroviruses discovered and is classified as simple Retroviridae due to its minimal encoding capacity. The oncogenic and transduction abilities of MLV are extensively studied, whereas surprisingly the crucial step of its nuclear export has remained unsolved until 2014. Recent work has revealed the recruitment by MLV of the cellular NXF1/Tap-dependent pathway for export. Unconventionally, MLV uses of Tap to export both spliced and unspliced viral RNAs. Unlike other retroviruses, MLV does not harbor a unique RNA signal for export. Indeed, multiple sequences throughout the MLV genome appear to promote export of the unspliced MLV RNA. We review here the current understanding of the export mechanism and highlight the determinants that influence MLV export. As the molecular mechanism of MLV export is elucidated, we will gain insight into the contribution of the export pathway to the cytoplasmic fate of the viral RNA.

Phenotype comparison confirms ZMYND11 as a critical gene for 10p15.3 microdeletion syndrome.

PubMed

Tumiene, Birute; Čiuladaitė, Ž; Preikšaitienė, E; Mameniškienė, R; Utkus, A; Kučinskas, V

2017-11-01

Proper epigenetic regulation processes are crucial in the normal development of the human brain. An ever-increasing group of neurodevelopmental disorders due to derangements of epigenetic regulation involve both microdeletion and monogenic syndromes. Some of these syndromes have overlapping clinical phenotypes due to haploinsufficiency-sensitive genes involved in microdeletions. It was shown recently that the ZMYND11 gene has important functions in epigenetic regulation as an unconventional transcription co-repressor of highly expressed genes, possibly acting in the repression of cryptic transcription from gene bodies. The aim of our study was to compare the clinical phenotypes of patients with 10p15.3 deletions with the phenotypes of patients with loss-of-function ZMYND11 mutations. The results of our study further confirm that the ZMYND11 gene is the critical gene for the clinical phenotype of 10p15.3 microdeletion involving the terminal ~4 Mb of chromosome 10p. In addition, accumulating clinical data allow for further characterisation of this syndrome, including neurodevelopmental disorder, characteristic dysmorphic features and some other more frequent symptoms, such as behavioural disturbances, hypotonia, seizures, low birth weight, short stature in those older than 10 years of age, genitourinary malformations and recurrent infections.

Detectable Changes in The Blood Transcriptome Are Present after Two Weeks of Antituberculosis Therapy

PubMed Central

Bloom, Chloe I.; Graham, Christine M.; Berry, Matthew P. R.; Wilkinson, Katalin A.; Oni, Tolu; Rozakeas, Fotini; Xu, Zhaohui; Rossello-Urgell, Jose; Chaussabel, Damien; Banchereau, Jacques; Pascual, Virginia; Lipman, Marc; Wilkinson, Robert J.; O’Garra, Anne

2012-01-01

Rationale Globally there are approximately 9 million new active tuberculosis cases and 1.4 million deaths annually. Effective antituberculosis treatment monitoring is difficult as there are no existing biomarkers of poor adherence or inadequate treatment earlier than 2 months after treatment initiation. Inadequate treatment leads to worsening disease, disease transmission and drug resistance. Objectives To determine if blood transcriptional signatures change in response to antituberculosis treatment and could act as early biomarkers of a successful response. Methods Blood transcriptional profiles of untreated active tuberculosis patients in South Africa were analysed before, during (2 weeks and 2 months), at the end of (6 months) and after (12 months) antituberculosis treatment, and compared to individuals with latent tuberculosis. An active-tuberculosis transcriptional signature and a specific treatment-response transcriptional signature were derived. The specific treatment response transcriptional signature was tested in two independent cohorts. Two quantitative scoring algorithms were applied to measure the changes in the transcriptional response. The most significantly represented pathways were determined using Ingenuity Pathway Analysis. Results An active tuberculosis 664-transcript signature and a treatment specific 320-transcript signature significantly diminished after 2 weeks of treatment in all cohorts, and continued to diminish until 6 months. The transcriptional response to treatment could be individually measured in each patient. Conclusions Significant changes in the transcriptional signatures measured by blood tests were readily detectable just 2 weeks after treatment initiation. These findings suggest that blood transcriptional signatures could be used as early surrogate biomarkers of successful treatment response. PMID:23056259

Unconventional Treatments for Vitiligo: Are They (Un) Satisfactory?

PubMed

Gianfaldoni, Serena; Tchernev, Georgi; Lotti, Jacopo; Wollina, Uwe; Satolli, Francesca; Rovesti, Miriam; França, Katlein; Lotti, Torello

2018-01-25

The authors show a brief overview of the vitiligo's unconventional therapies. A part for well-documented effectiveness of L-phenylalanine, PGE2 and antioxidant agents in the treatment of vitiligo, for the other therapeutical approaches more investigations are needed.

The nature of immune responses to urinary tract infections

PubMed Central

Abraham, Soman N.; Miao, Yuxuan

2016-01-01

The urinary tract is constantly exposed to microorganisms that inhabit the gastrointestinal tract, but generally the urinary tract resists infection by gut microorganisms. This resistance to infection is mainly ascribed to the versatility of the innate immune defences in the urinary tract as the adaptive immune responses are limited, particularly when only the lower urinary tract is infected. In recent years, as the strengths and weaknesses of the immune system of the urinary tract have emerged and as the virulence attributes of uropathogens are recognized, several potentially effective and unconventional strategies to contain or prevent urinary tract infections have emerged. PMID:26388331

An integrated computer system for analysis, selection, and evaluation of unconventional intersections.

DOT National Transportation Integrated Search

2011-03-01

The emergence of unconventional intersections in the traffic community has been motivated by the notion : of improving service quality with innovative control strategies, such as rerouting the turning movements : or flipping the paths of two traffic ...

Unconventional microfluidics: expanding the discipline.

PubMed

Nawaz, Ahmad Ahsan; Mao, Xiaole; Stratton, Zackary S; Huang, Tony Jun

2013-04-21

Since its inception, the discipline of microfluidics has been harnessed for innovations in the biomedicine/chemistry fields-and to great effect. This success has had the natural side-effect of stereotyping microfluidics as a platform for medical diagnostics and miniaturized lab processes. But microfluidics has more to offer. And very recently, some researchers have successfully applied microfluidics to fields outside its traditional domains. In this Focus article, we highlight notable examples of such "unconventional" microfluidics applications (e.g., robotics, electronics). It is our hope that these early successes in unconventional microfluidics prompt further creativity, and inspire readers to expand the microfluidics discipline.

Water Issues Related to Transitioning from Conventional to Unconventional Oil Production in the Permian Basin.

PubMed

Scanlon, Bridget R; Reedy, Robert C; Male, Frank; Walsh, Mark

2017-09-19

The Permian Basin is being transformed by the "shale revolution" from a major conventional play to the world's largest unconventional play, but water management is critical in this semiarid region. Here we explore evolving issues associated with produced water (PW) management and hydraulic fracturing water demands based on detailed well-by-well analyses. Our results show that although conventional wells produce ∼13 times more water than oil (PW to oil ratio, PWOR = 13), this produced water has been mostly injected back into pressure-depleted oil-producing reservoirs for enhanced oil recovery. Unconventional horizontal wells use large volumes of water for hydraulic fracturing that increased by a factor of ∼10-16 per well and ∼7-10 if normalized by lateral well length (2008-2015). Although unconventional wells have a much lower PWOR of 3 versus 13 from conventional wells, this PW cannot be reinjected into the shale reservoirs but is disposed into nonproducing geologic intervals that could result in overpressuring and induced seismicity. The potential for PW reuse from unconventional wells is high because PW volumes can support hydraulic fracturing water demand based on 2014 data. Reuse of PW with minimal treatment (clean brine) can partially mitigate PW injection concerns while reducing water demand for hydraulic fracturing.

Global Transcriptional Responses to Osmotic, Oxidative, and Imipenem Stress Conditions in Pseudomonas putida

PubMed Central

Bojanovič, Klara; D'Arrigo, Isotta

2017-01-01

ABSTRACT Bacteria cope with and adapt to stress by modulating gene expression in response to specific environmental cues. In this study, the transcriptional response of Pseudomonas putida KT2440 to osmotic, oxidative, and imipenem stress conditions at two time points was investigated via identification of differentially expressed mRNAs and small RNAs (sRNAs). A total of 440 sRNA transcripts were detected, of which 10% correspond to previously annotated sRNAs, 40% to novel intergenic transcripts, and 50% to novel transcripts antisense to annotated genes. Each stress elicits a unique response as far as the extent and dynamics of the transcriptional changes. Nearly 200 protein-encoding genes exhibited significant changes in all stress types, implicating their participation in a general stress response. Almost half of the sRNA transcripts were differentially expressed under at least one condition, suggesting possible functional roles in the cellular response to stress conditions. The data show a larger fraction of differentially expressed sRNAs than of mRNAs with >5-fold expression changes. The work provides detailed insights into the mechanisms through which P. putida responds to different stress conditions and increases understanding of bacterial adaptation in natural and industrial settings. IMPORTANCE This study maps the complete transcriptional response of P. putida KT2440 to osmotic, oxidative, and imipenem stress conditions at short and long exposure times. Over 400 sRNA transcripts, consisting of both intergenic and antisense transcripts, were detected, increasing the number of identified sRNA transcripts in the strain by a factor of 10. Unique responses to each type of stress are documented, including both the extent and dynamics of the gene expression changes. The work adds rich detail to previous knowledge of stress response mechanisms due to the depth of the RNA sequencing data. Almost half of the sRNAs exhibit significant expression changes under at least one condition, suggesting their involvement in adaptation to stress conditions and identifying interesting candidates for further functional characterization. PMID:28130298

Def1 interacts with TFIIH and modulates RNA polymerase II transcription.

PubMed

Damodaren, Nivedita; Van Eeuwen, Trevor; Zamel, Joanna; Lin-Shiao, Enrique; Kalisman, Nir; Murakami, Kenji

2017-12-12

The DNA damage response is an essential process for the survival of living cells. In a subset of stress-responsive genes in humans, Elongin controls transcription in response to multiple stimuli, such as DNA damage, oxidative stress, and heat shock. Yeast Elongin (Ela1-Elc1), along with Def1, is known to facilitate ubiquitylation and degradation of RNA polymerase II (pol II) in response to multiple stimuli, yet transcription activity has not been examined. We have found that Def1 copurifies from yeast whole-cell extract with TFIIH, the largest general transcription factor required for transcription initiation and nucleotide excision repair. The addition of recombinant Def1 and Ela1-Elc1 enhanced transcription initiation in an in vitro reconstituted system including pol II, the general transcription factors, and TFIIS. Def1 also enhanced transcription restart from TFIIS-induced cleavage in a pol II transcribing complex. In the Δdef1 strain, heat shock genes were misregulated, indicating that Def1 is required for induction of some stress-responsive genes in yeast. Taken together, our results extend the understanding of the molecular mechanism of transcription regulation on cellular stress and reveal functional similarities to the mammalian system.

Turkey’s Response to Threats of Weapons of Mass Destruction

DTIC Science & Technology

2001-12-01

categories of unconventional weapons and was prepared to invest enormous financial and human resources to achieve this goal. 5 Iraqi attempts to seek...Ministry of Defense White Paper of 2001 defines “Religious Fundementalism ” among the internal threats directed against Turkey’s security in the post...Therefore, Syria will likely continue to develop an extensive chemical and biological weapons arsenal and will also invest in upgrading the accuracy of

Assessment of unconventional tight-gas resources of the Magallanes Basin Province, Chile, 2015

USGS Publications Warehouse

Schenk, Christopher J.; Charpentier, Ronald R.; Pitman, Janet K.; Tennyson, Marilyn E.; Brownfield, Michael E.; Gaswirth, Stephanie B.; Le, Phuong A.; Leathers-Miller, Heidi M.; Marra, Kristen R.

2016-01-20

Using a geology-based assessment methodology, the U.S. Geological Survey assessed a technically recoverable mean resource of 8.3 trillion cubic feet of unconventional tight gas in the Zona Glauconitica of the Magallanes Basin Province, Chile.

Unconventional eating practices and their health implications.

PubMed

Hanning, R M; Zlotkin, S H

1985-04-01

The authors discuss a number of unconventional or faddist foods and eating practices and their health implications. Among the topics included are vegetarianism, Zen macrobiotic diets, fast foods, junk foods, megavitamins and their toxicity, health foods, fad diets in infancy, and elimination diets.

Effective Control of Chronic γ-Herpesvirus Infection by Unconventional MHC Class Ia–Independent CD8 T Cells

PubMed Central

Tibbetts, Scott A; McClellan, Kelly B

2006-01-01

Control of virus infection is mediated in part by major histocompatibility complex (MHC) Class Ia presentation of viral peptides to conventional CD8 T cells. Although important, the absolute requirement for MHC Class Ia–dependent CD8 T cells for control of chronic virus infection has not been formally demonstrated. We show here that mice lacking MHC Class Ia molecules (Kb−/−xDb−/− mice) effectively control chronic γ-herpesvirus 68 (γHV68) infection via a robust expansion of β2-microglobulin (β2-m)-dependent, but CD1d-independent, unconventional CD8 T cells. These unconventional CD8 T cells expressed: (1) CD8αβ and CD3, (2) cell surface molecules associated with conventional effector/memory CD8 T cells, (3) TCRαβ with a significant Vβ4, Vβ3, and Vβ10 bias, and (4) the key effector cytokine interferon-γ (IFNγ). Unconventional CD8 T cells utilized a diverse TCR repertoire, and CDR3 analysis suggests that some of that repertoire may be utilized even in the presence of conventional CD8 T cells. This is the first demonstration to our knowledge that β2-m–dependent, but Class Ia–independent, unconventional CD8 T cells can efficiently control chronic virus infection, implicating a role for β2-n–dependent non-classical MHC molecules in control of chronic viral infection. We speculate that similar unconventional CD8 T cells may be able to control of other chronic viral infections, especially when viruses evade immunity by inhibiting generation of Class Ia–restricted T cells. PMID:16733540

Assessment of Methane Emissions – Impact of Using Natural Gas Engines in Unconventional Resource Development

DOE Office of Scientific and Technical Information (OSTI.GOV)

Nix, Andrew; Johnson, Derek; Heltzel, Robert

Researchers at the Center for Alternative Fuels, Engines, and Emissions (CAFEE) completed a multi-year program under DE-FE0013689 entitled, “Assessing Fugitive Methane Emissions Impact Using Natural Gas Engines in Unconventional Resource Development.” When drilling activity was high and industry sought to lower operating costs and reduce emissions they began investing in dual fuel and dedicated natural gas engines to power unconventional well equipment. From a review of literature we determined that the prime-movers (or major fuel consumers) of unconventional well development were the service trucks (trucking), horizontal drilling rig (drilling) engines, and hydraulic stimulation pump (fracturing) engines. Based on early findingsmore » from on-road studies we assessed that conversion of prime movers to operate on natural gas could contribute to methane emissions associated with unconventional wells. As such, we collected significant in-use activity data from service trucks and in-use activity, fuel consumption, and gaseous emissions data from drilling and fracturing engines. Our findings confirmed that conversion of the prime movers to operate as dual fuel or dedicated natural gas – created an additional source of methane emissions. While some gaseous emissions were decreased from implementation of these technologies – methane and CO 2 equivalent emissions tended to increase, especially for non-road engines. The increases were highest for dual fuel engines due to methane slip from the exhaust and engine crankcase. Dedicated natural gas engines tended to have lower exhaust methane emissions but higher CO 2 emissions due to lower efficiency. Therefore, investing in currently available natural gas technologies for prime movers will increase the greenhouse gas footprint of the unconventional well development industry.« less

MYC2 Orchestrates a Hierarchical Transcriptional Cascade That Regulates Jasmonate-Mediated Plant Immunity in Tomato.

PubMed

Du, Minmin; Zhao, Jiuhai; Tzeng, David T W; Liu, Yuanyuan; Deng, Lei; Yang, Tianxia; Zhai, Qingzhe; Wu, Fangming; Huang, Zhuo; Zhou, Ming; Wang, Qiaomei; Chen, Qian; Zhong, Silin; Li, Chang-Bao; Li, Chuanyou

2017-08-01

The hormone jasmonate (JA), which functions in plant immunity, regulates resistance to pathogen infection and insect attack through triggering genome-wide transcriptional reprogramming in plants. We show that the basic helix-loop-helix transcription factor (TF) MYC2 in tomato ( Solanum lycopersicum ) acts downstream of the JA receptor to orchestrate JA-mediated activation of both the wounding and pathogen responses. Using chromatin immunoprecipitation sequencing (ChIP-seq) coupled with RNA sequencing (RNA-seq) assays, we identified 655 MYC2-targeted JA-responsive genes. These genes are highly enriched in Gene Ontology categories related to TFs and the early response to JA, indicating that MYC2 functions at a high hierarchical level to regulate JA-mediated gene transcription. We also identified a group of MYC2-targeted TFs (MTFs) that may directly regulate the JA-induced transcription of late defense genes. Our findings suggest that MYC2 and its downstream MTFs form a hierarchical transcriptional cascade during JA-mediated plant immunity that initiates and amplifies transcriptional output. As proof of concept, we showed that during plant resistance to the necrotrophic pathogen Botrytis cinerea , MYC2 and the MTF JA2-Like form a transcription module that preferentially regulates wounding-responsive genes, whereas MYC2 and the MTF ETHYLENE RESPONSE FACTOR.C3 form a transcription module that preferentially regulates pathogen-responsive genes. © 2017 American Society of Plant Biologists. All rights reserved.

MYC2 Orchestrates a Hierarchical Transcriptional Cascade That Regulates Jasmonate-Mediated Plant Immunity in Tomato[OPEN

PubMed Central

Liu, Yuanyuan; Deng, Lei; Wu, Fangming; Huang, Zhuo; Zhou, Ming; Chen, Qian; Zhong, Silin

2017-01-01

The hormone jasmonate (JA), which functions in plant immunity, regulates resistance to pathogen infection and insect attack through triggering genome-wide transcriptional reprogramming in plants. We show that the basic helix-loop-helix transcription factor (TF) MYC2 in tomato (Solanum lycopersicum) acts downstream of the JA receptor to orchestrate JA-mediated activation of both the wounding and pathogen responses. Using chromatin immunoprecipitation sequencing (ChIP-seq) coupled with RNA sequencing (RNA-seq) assays, we identified 655 MYC2-targeted JA-responsive genes. These genes are highly enriched in Gene Ontology categories related to TFs and the early response to JA, indicating that MYC2 functions at a high hierarchical level to regulate JA-mediated gene transcription. We also identified a group of MYC2-targeted TFs (MTFs) that may directly regulate the JA-induced transcription of late defense genes. Our findings suggest that MYC2 and its downstream MTFs form a hierarchical transcriptional cascade during JA-mediated plant immunity that initiates and amplifies transcriptional output. As proof of concept, we showed that during plant resistance to the necrotrophic pathogen Botrytis cinerea, MYC2 and the MTF JA2-Like form a transcription module that preferentially regulates wounding-responsive genes, whereas MYC2 and the MTF ETHYLENE RESPONSE FACTOR.C3 form a transcription module that preferentially regulates pathogen-responsive genes. PMID:28733419

Temporal transcriptional response to ethylene gas drives growth hormone cross-regulation in Arabidopsis

DOE PAGES

Chang, Katherine Noelani; Zhong, Shan; Weirauch, Matthew T.; ...

2013-06-11

The gaseous plant hormone ethylene regulates a multitude of growth and developmental processes. How the numerous growth control pathways are coordinated by the ethylene transcriptional response remains elusive. We characterized the dynamic ethylene transcriptional response by identifying targets of the master regulator of the ethylene signaling pathway, ETHYLENE INSENSITIVE3 (EIN3), using chromatin immunoprecipitation sequencing and transcript sequencing during a timecourse of ethylene treatment. Ethylene-induced transcription occurs in temporal waves regulated by EIN3, suggesting distinct layers of transcriptional control. EIN3 binding was found to modulate a multitude of downstream transcriptional cascades, including a major feedback regulatory circuitry of the ethylene signalingmore » pathway, as well as integrating numerous connections between most of the hormone mediated growth response pathways. These findings provide direct evidence linking each of the major plant growth and development networks in novel ways.« less

Temporal transcriptional response to ethylene gas drives growth hormone cross-regulation in Arabidopsis

PubMed Central

Chang, Katherine Noelani; Zhong, Shan; Weirauch, Matthew T; Hon, Gary; Pelizzola, Mattia; Li, Hai; Huang, Shao-shan Carol; Schmitz, Robert J; Urich, Mark A; Kuo, Dwight; Nery, Joseph R; Qiao, Hong; Yang, Ally; Jamali, Abdullah; Chen, Huaming; Ideker, Trey; Ren, Bing; Bar-Joseph, Ziv; Hughes, Timothy R; Ecker, Joseph R

2013-01-01

The gaseous plant hormone ethylene regulates a multitude of growth and developmental processes. How the numerous growth control pathways are coordinated by the ethylene transcriptional response remains elusive. We characterized the dynamic ethylene transcriptional response by identifying targets of the master regulator of the ethylene signaling pathway, ETHYLENE INSENSITIVE3 (EIN3), using chromatin immunoprecipitation sequencing and transcript sequencing during a timecourse of ethylene treatment. Ethylene-induced transcription occurs in temporal waves regulated by EIN3, suggesting distinct layers of transcriptional control. EIN3 binding was found to modulate a multitude of downstream transcriptional cascades, including a major feedback regulatory circuitry of the ethylene signaling pathway, as well as integrating numerous connections between most of the hormone mediated growth response pathways. These findings provide direct evidence linking each of the major plant growth and development networks in novel ways. DOI: http://dx.doi.org/10.7554/eLife.00675.001 PMID:23795294

Unconventional oil and gas: The role of politics and proximity

NASA Astrophysics Data System (ADS)

Schelly, Chelsea

2016-10-01

Political divisions are important in understanding public perceptions of unconventional oil and natural gas development, but so is proximity to drilling activities. New research highlights that, as geographical distance from development areas increases, political ideology becomes more influential in explaining diverging perceptions.

Energy-Water Modeling and Analysis | Energy Analysis | NREL

Science.gov Websites

future electricity scenarios under cases of limited water availability and electricity sector impacts of Manufacturing Water Use The Water Intensity and Resource Impacts of Unconventional Hydrocarbon Development Impacts of Unconventional Hydrocarbon Development Life Cycle Harmonization Project (Water) Sample

Induced unconventional superconductivity on the surface states of Bi2Te3 topological insulator.

PubMed

Charpentier, Sophie; Galletti, Luca; Kunakova, Gunta; Arpaia, Riccardo; Song, Yuxin; Baghdadi, Reza; Wang, Shu Min; Kalaboukhov, Alexei; Olsson, Eva; Tafuri, Francesco; Golubev, Dmitry; Linder, Jacob; Bauch, Thilo; Lombardi, Floriana

2017-12-08

Topological superconductivity is central to a variety of novel phenomena involving the interplay between topologically ordered phases and broken-symmetry states. The key ingredient is an unconventional order parameter, with an orbital component containing a chiral p x  + ip y wave term. Here we present phase-sensitive measurements, based on the quantum interference in nanoscale Josephson junctions, realized by using Bi 2 Te 3 topological insulator. We demonstrate that the induced superconductivity is unconventional and consistent with a sign-changing order parameter, such as a chiral p x  + ip y component. The magnetic field pattern of the junctions shows a dip at zero externally applied magnetic field, which is an incontrovertible signature of the simultaneous existence of 0 and π coupling within the junction, inherent to a non trivial order parameter phase. The nano-textured morphology of the Bi 2 Te 3 flakes, and the dramatic role played by thermal strain are the surprising key factors for the display of an unconventional induced order parameter.

Material requirements for the adoption of unconventional silicon crystal and wafer growth techniques for high-efficiency solar cells

DOE PAGES

Hofstetter, Jasmin; del Cañizo, Carlos; Wagner, Hannes; ...

2015-10-15

Silicon wafers comprise approximately 40% of crystalline silicon module cost and represent an area of great technological innovation potential. Paradoxically, unconventional wafer-growth techniques have thus far failed to displace multicrystalline and Czochralski silicon, despite four decades of innovation. One of the shortcomings of most unconventional materials has been a persistent carrier lifetime deficit in comparison to established wafer technologies, which limits the device efficiency potential. In this perspective article, we review a defect-management framework that has proven successful in enabling millisecond lifetimes in kerfless and cast materials. Control of dislocations and slowly diffusing metal point defects during growth, coupled tomore » effective control of fast-diffusing species during cell processing, is critical to enable high cell efficiencies. As a result, to accelerate the pace of novel wafer development, we discuss approaches to rapidly evaluate the device efficiency potential of unconventional wafers from injection-dependent lifetime measurements.« less

Unconventional Consumption Methods and Enjoying Things Consumed: Recapturing the "First-Time" Experience.

PubMed

O'Brien, Ed; Smith, Robert W

2018-06-01

People commonly lament the inability to re-experience familiar things as they were first experienced. Four experiments suggest that consuming familiar things in new ways can disrupt adaptation and revitalize enjoyment. Participants better enjoyed the same familiar food (Experiment 1), drink (Experiment 2), and video (Experiments 3a-3b) simply when re-experiencing the entity via unusual means (e.g., eating popcorn using chopsticks vs. hands). This occurs because unconventional methods invite an immersive "first-time" perspective on the consumption object: boosts in enjoyment were mediated by revitalized immersion into the consumption experience and were moderated by time such that they were strongest when using unconventional methods for the first time (Experiments 1-2); likewise, unconventional methods that actively disrupted immersion did not elicit the boost, despite being novel (Experiments 3a-3b). Before abandoning once-enjoyable entities, knowing to consume old things in new ways (vs. attaining new things altogether) might temporarily restore enjoyment and postpone wasteful replacement.

Enhanced recovery of unconventional gas. Volume II. The program. [Tight gas basins; Devonian shale; coal seams; geopressured aquifers

DOE Office of Scientific and Technical Information (OSTI.GOV)

Kuuskraa, V.A.; Brashear, J.P.; Doscher, T.M.

1978-10-01

This study was conducted to assist public decision-makers in selecting among many choices to obtain new gas supplies by addressing 2 questions: 1) how severe is the need for additional future supplies of natural gas, and what is the economic potential of providing part of future supply through enhanced recovery from unconventional natural gas resources. The study also serves to assist the DOE in designing a cost-effective R and D program to stimulate industry to recover this unconventional gas and to produce it sooner. Tight gas basins, Devonian shale, methane from coal seams, and methane from geopressured aquifers are considered.more » It is concluded that unconventional sources, already providing about 1 Tcf per year, could provide from 3 to 4 Tcf in 1985 and from 6 to 8 Tcf in 1990 (at $1.75 and $3.00 per Mcf, respectively). However, even with these additions to supply, gas supply is projected to remain below 1977 usage levels. (DLC)« less

Material requirements for the adoption of unconventional silicon crystal and wafer growth techniques for high-efficiency solar cells

DOE Office of Scientific and Technical Information (OSTI.GOV)

Hofstetter, Jasmin; del Cañizo, Carlos; Wagner, Hannes

Silicon wafers comprise approximately 40% of crystalline silicon module cost and represent an area of great technological innovation potential. Paradoxically, unconventional wafer-growth techniques have thus far failed to displace multicrystalline and Czochralski silicon, despite four decades of innovation. One of the shortcomings of most unconventional materials has been a persistent carrier lifetime deficit in comparison to established wafer technologies, which limits the device efficiency potential. In this perspective article, we review a defect-management framework that has proven successful in enabling millisecond lifetimes in kerfless and cast materials. Control of dislocations and slowly diffusing metal point defects during growth, coupled tomore » effective control of fast-diffusing species during cell processing, is critical to enable high cell efficiencies. As a result, to accelerate the pace of novel wafer development, we discuss approaches to rapidly evaluate the device efficiency potential of unconventional wafers from injection-dependent lifetime measurements.« less

Transcriptional blood signatures distinguish pulmonary tuberculosis, pulmonary sarcoidosis, pneumonias and lung cancers.

PubMed

Bloom, Chloe I; Graham, Christine M; Berry, Matthew P R; Rozakeas, Fotini; Redford, Paul S; Wang, Yuanyuan; Xu, Zhaohui; Wilkinson, Katalin A; Wilkinson, Robert J; Kendrick, Yvonne; Devouassoux, Gilles; Ferry, Tristan; Miyara, Makoto; Bouvry, Diane; Valeyre, Dominique; Dominique, Valeyre; Gorochov, Guy; Blankenship, Derek; Saadatian, Mitra; Vanhems, Phillip; Beynon, Huw; Vancheeswaran, Rama; Wickremasinghe, Melissa; Chaussabel, Damien; Banchereau, Jacques; Pascual, Virginia; Ho, Ling-Pei; Lipman, Marc; O'Garra, Anne

2013-01-01

New approaches to define factors underlying the immunopathogenesis of pulmonary diseases including sarcoidosis and tuberculosis are needed to develop new treatments and biomarkers. Comparing the blood transcriptional response of tuberculosis to other similar pulmonary diseases will advance knowledge of disease pathways and help distinguish diseases with similar clinical presentations. To determine the factors underlying the immunopathogenesis of the granulomatous diseases, sarcoidosis and tuberculosis, by comparing the blood transcriptional responses in these and other pulmonary diseases. We compared whole blood genome-wide transcriptional profiles in pulmonary sarcoidosis, pulmonary tuberculosis, to community acquired pneumonia and primary lung cancer and healthy controls, before and after treatment, and in purified leucocyte populations. An Interferon-inducible neutrophil-driven blood transcriptional signature was present in both sarcoidosis and tuberculosis, with a higher abundance and expression in tuberculosis. Heterogeneity of the sarcoidosis signature correlated significantly with disease activity. Transcriptional profiles in pneumonia and lung cancer revealed an over-abundance of inflammatory transcripts. After successful treatment the transcriptional activity in tuberculosis and pneumonia patients was significantly reduced. However the glucocorticoid-responsive sarcoidosis patients showed a significant increase in transcriptional activity. 144-blood transcripts were able to distinguish tuberculosis from other lung diseases and controls. Tuberculosis and sarcoidosis revealed similar blood transcriptional profiles, dominated by interferon-inducible transcripts, while pneumonia and lung cancer showed distinct signatures, dominated by inflammatory genes. There were also significant differences between tuberculosis and sarcoidosis in the degree of their transcriptional activity, the heterogeneity of their profiles and their transcriptional response to treatment.

Creating unconventional geometric beams with large depth of field using double freeform-surface optics.

PubMed

Feng, Zexin; Froese, Brittany D; Huang, Chih-Yu; Ma, Donglin; Liang, Rongguang

2015-07-10

We consider here creation of an unconventional flattop beam with a large depth of field by employing double freeform optical surfaces. The output beam is designed with continuous variations from the flattop to almost zero near the edges to resist the influence of diffraction on its propagation. We solve this challenging problem by naturally incorporating an optimal transport map computation scheme for unconventional boundary conditions with a simultaneous point-by-point double surface construction procedure. We demonstrate experimentally the generation of a long-range propagated triangular beam through a plano-freeform lens pair fabricated by a diamond-tuning machine.

Unconventional cancer remedies.

PubMed Central

Danielson, K J; Stewart, D E; Lippert, G P

1988-01-01

Unproven and disproven remedies continue to abound for illnesses for which conventional treatment is only partially effective. This is particularly true with cancer, for which up to 50% of patients may be receiving unorthodox therapy. This article examines unconventional cancer remedies, their adverse effects, their common factors and the basis for their appeal, as well as what motivates and characterizes patients who choose these treatments. Also discussed is an approach that may be used by the conventional physician for patients who are likely to seek unorthodox treatment. This approach will help patients make the best decision about their treatment and protect them from the hazards of unconventional remedies. PMID:3285984

Complex regulatory network encompassing the Csr, c-di-GMP and motility systems of Salmonella Typhimurium.

PubMed

Jonas, Kristina; Edwards, Adrianne N; Ahmad, Irfan; Romeo, Tony; Römling, Ute; Melefors, Ojar

2010-02-01

Bacterial survival depends on the ability to switch between sessile and motile lifestyles in response to changing environmental conditions. In many species, this switch is governed by (3'-5')-cyclic-diguanosine monophosphate (c-di-GMP), a signalling molecule, which is metabolized by proteins containing GGDEF and/or EAL domains. Salmonella Typhimurium contains 20 such proteins. Here, we show that the RNA-binding protein CsrA regulates the expression of eight genes encoding GGDEF, GGDEF-EAL and EAL domain proteins. CsrA bound directly to the mRNA leaders of five of these genes, suggesting that it may regulate these genes post-transcriptionally. The c-di-GMP-specific phosphodiesterase STM3611, which reciprocally controls flagella function and production of biofilm matrix components, was regulated by CsrA binding to the mRNA, but was also indirectly regulated by CsrA through the FlhDC/FliA flagella cascade and STM1344. STM1344 is an unconventional (c-di-GMP-inactive) EAL domain protein, recently identified as a negative regulator of flagella gene expression. Here, we demonstrate that CsrA directly downregulates expression of STM1344, which in turn regulates STM3611 through fliA and thus reciprocally controls motility and biofilm factors. Altogether, our data reveal that the concerted and complex regulation of several genes encoding GGDEF/EAL domain proteins allows CsrA to control the motility-sessility switch in S. Typhimurium at multiple levels.

Downregulation of dTps1 in Drosophila melanogaster larvae confirms involvement of trehalose in redox regulation following desiccation.

PubMed

Thorat, Leena; Mani, Krishna-Priya; Thangaraj, Pradeep; Chatterjee, Suvro; Nath, Bimalendu B

2016-03-01

As a survival strategy to environmental water deficits, desiccation-tolerant organisms are commonly known for their ability to recruit stress-protective biomolecules such as trehalose. We have previously reported the pivotal role of trehalose in larval desiccation tolerance in Drosophila melanogaster. Trehalose has emerged as a versatile molecule, serving mainly as energy source in insects and also being a stress protectant. While several recent reports have revealed the unconventional role of trehalose in scavenging reactive oxygen species in yeast and plants, this aspect has not received much attention in animals. We examined the status of desiccation-induced generation of reactive oxygen species in D. melanogaster larvae and the possible involvement of trehalose in ameliorating the harmful consequences thereof. Insect trehalose synthesis is governed by the enzyme trehalose 6-phosphate synthase 1 (TPS1). Using the ubiquitous da-GAL4-driven expression of the dTps1-RNAi transgene, we generated dTps1-downregulated Drosophila larvae possessing depleted levels of dTps1 transcripts. This resulted in the inability of the larvae for trehalose synthesis, thereby allowing us to elucidate the significance of trehalose in the regulation of desiccation-responsive redox homeostasis. Furthermore, the results from molecular genetics studies, biochemical assays, electron spin resonance analyses and a simple, non-invasive method of whole larval live imaging suggested that trehalose in collaboration with superoxide dismutase (SOD) is involved in the maintenance of redox state in D. melanogaster.

Non-coding RNAs: Therapeutic Strategies and Delivery Systems.

PubMed

Ling, Hui

The vast majority of the human genome is transcribed into RNA molecules that do not code for proteins, which could be small ones approximately 20 nucleotide in length, known as microRNAs, or transcripts longer than 200 bp, defined as long noncoding RNAs. The prevalent deregulation of microRNAs in human cancers prompted immediate interest on the therapeutic value of microRNAs as drugs and drug targets. Many features of microRNAs such as well-defined mechanisms, and straightforward oligonucleotide design further make them attractive candidates for therapeutic development. The intensive efforts of exploring microRNA therapeutics are reflected by the large body of preclinical studies using oligonucleotide-based mimicking and blocking, culminated by the recent entry of microRNA therapeutics in clinical trial for several human diseases including cancer. Meanwhile, microRNA therapeutics faces the challenge of effective and safe delivery of nucleic acid therapeutics into the target site. Various chemical modifications of nucleic acids and delivery systems have been developed to increase targeting specificity and efficacy, and reduce the associated side effects including activation of immune response. Recently, long noncoding RNAs become attractive targets for therapeutic intervention because of their association with complex and delicate phenotypes, and their unconventional pharmaceutical activities such as capacity of increasing output of proteins. Here I discuss the general therapeutic strategies targeting noncoding RNAs, review delivery systems developed to maximize noncoding RNA therapeutic efficacy, and offer perspectives on the future development of noncoding RNA targeting agents for colorectal cancer.

Unconventional Synthesis of γ-Fe2O3: Excellent Low-Concentration Ethanol Sensing Performance

NASA Astrophysics Data System (ADS)

Naskar, Atanu; Narjinary, Mousumi; Kundu, Susmita

2017-01-01

This study reports on a simple unconventional procedure for synthesis of γ-Fe2O3 nanopowder and its fabrication as a resistive ethanol sensor. γ-Fe2O3 powder having an average particle size of ˜15 nm was prepared by thermal decomposition of iron(III) acetylacetonate. Platinum incorporation (0.5-1.5 wt.%) was also carried out for enhancing sensing performance. The powders were characterized using an x-ray diffractometer, x-ray photoelectron spectroscopy, Brunauer-Emmett-Teller surface area, field area scanning electron microscopy, transmission electron microscopy along with energy dispersion x-ray analyses. Sensor fabricated from pure γ-Fe2O3 exhibited excellent ethanol sensing performance at concentrations down to 1 ppm, having a great demand in medical diagnosis and food-processing industries. The response observed for pure γ-Fe2O3 (˜75% for 1 ppm ethanol) was enhanced ˜10% after 1 wt.% Pt impregnation. Sensors were quite stable and selective towards ethanol vapour detection. A possible mechanism for high sensing performance has been discussed.

Emergence of superconductivity in heavy-electron materials

PubMed Central

Yang, Yi-feng; Pines, David

2014-01-01

Although the pairing glue for the attractive quasiparticle interaction responsible for unconventional superconductivity in heavy-electron materials has been identified as the spin fluctuations that arise from their proximity to a magnetic quantum critical point, there has been no model to describe their superconducting transition at temperature Tc that is comparable to that found by Bardeen, Cooper, and Schrieffer (BCS) for conventional superconductors, where phonons provide the pairing glue. Here we propose such a model: a phenomenological BCS-like expression for Tc in heavy-electron materials that is based on a simple model for the effective range and strength of the spin-fluctuation-induced quasiparticle interaction and reflects the unusual properties of the heavy-electron normal state from which superconductivity emerges. We show that it provides a quantitative understanding of the pressure-induced variation of Tc in the “hydrogen atoms” of unconventional superconductivity, CeCoIn5 and CeRhIn5, predicts scaling behavior and a dome-like structure for Tc in all heavy-electron quantum critical superconductors, provides unexpected connections between members of this family, and quantifies their variations in Tc with a single parameter. PMID:25489102

Roles of an Unconventional Protein Kinase and Myosin II in Amoeba Osmotic Shock Responses

PubMed Central

Betapudi, Venkaiah; Egelhoff, Thomas T.

2009-01-01

The contractile vacuole (CV) is a dynamic organelle that enables Dictyostelium amoeba and other protist to maintain osmotic homeostasis by expelling excess water. In the present study, we have uncovered a mechanism that coordinates the mechanics of the CV with myosin II, regulated by VwkA, an unconventional protein kinase that is conserved in an array of protozoa. GFP-VwkA fusion proteins localize persistently to the CV during both filling and expulsion phases of water. In vwkA null cells, the established CV marker dajumin still localizes to the CV, but these structures are large, spherical, and severely impaired for discharge. Furthermore, myosin II cortical localization and assembly are abnormal in vwkA null cells. Parallel analysis of wild type cells treated with myosin II inhibitors or of myosin II null cells also results in enlarged CVs with impaired dynamics. We suggest that the myosin II cortical cytoskeleton, regulated by VwkA, serves a critical conserved role in the periodic contractions of the CV, as part of the osmotic protective mechanism of protozoa. PMID:19843280

Widespread antisense transcription of Populus genome under drought.

PubMed

Yuan, Yinan; Chen, Su

2018-06-06

Antisense transcription is widespread in many genomes and plays important regulatory roles in gene expression. The objective of our study was to investigate the extent and functional relevance of antisense transcription in forest trees. We employed Populus, a model tree species, to probe the antisense transcriptional response of tree genome under drought, through stranded RNA-seq analysis. We detected nearly 48% of annotated Populus gene loci with antisense transcripts and 44% of them with co-transcription from both DNA strands. Global distribution of reads pattern across annotated gene regions uncovered that antisense transcription was enriched in untranslated regions while sense reads were predominantly mapped in coding exons. We further detected 1185 drought-responsive sense and antisense gene loci and identified a strong positive correlation between the expression of antisense and sense transcripts. Additionally, we assessed the antisense expression in introns and found a strong correlation between intronic expression and exonic expression, confirming antisense transcription of introns contributes to transcriptional activity of Populus genome under drought. Finally, we functionally characterized drought-responsive sense-antisense transcript pairs through gene ontology analysis and discovered that functional groups including transcription factors and histones were concordantly regulated at both sense and antisense transcriptional level. Overall, our study demonstrated the extensive occurrence of antisense transcripts of Populus genes under drought and provided insights into genome structure, regulation pattern and functional significance of drought-responsive antisense genes in forest trees. Datasets generated in this study serve as a foundation for future genetic analysis to improve our understanding of gene regulation by antisense transcription.

Global Transcriptional Responses to Osmotic, Oxidative, and Imipenem Stress Conditions in Pseudomonas putida.

PubMed

Bojanovič, Klara; D'Arrigo, Isotta; Long, Katherine S

2017-04-01

Bacteria cope with and adapt to stress by modulating gene expression in response to specific environmental cues. In this study, the transcriptional response of Pseudomonas putida KT2440 to osmotic, oxidative, and imipenem stress conditions at two time points was investigated via identification of differentially expressed mRNAs and small RNAs (sRNAs). A total of 440 sRNA transcripts were detected, of which 10% correspond to previously annotated sRNAs, 40% to novel intergenic transcripts, and 50% to novel transcripts antisense to annotated genes. Each stress elicits a unique response as far as the extent and dynamics of the transcriptional changes. Nearly 200 protein-encoding genes exhibited significant changes in all stress types, implicating their participation in a general stress response. Almost half of the sRNA transcripts were differentially expressed under at least one condition, suggesting possible functional roles in the cellular response to stress conditions. The data show a larger fraction of differentially expressed sRNAs than of mRNAs with >5-fold expression changes. The work provides detailed insights into the mechanisms through which P. putida responds to different stress conditions and increases understanding of bacterial adaptation in natural and industrial settings. IMPORTANCE This study maps the complete transcriptional response of P. putida KT2440 to osmotic, oxidative, and imipenem stress conditions at short and long exposure times. Over 400 sRNA transcripts, consisting of both intergenic and antisense transcripts, were detected, increasing the number of identified sRNA transcripts in the strain by a factor of 10. Unique responses to each type of stress are documented, including both the extent and dynamics of the gene expression changes. The work adds rich detail to previous knowledge of stress response mechanisms due to the depth of the RNA sequencing data. Almost half of the sRNAs exhibit significant expression changes under at least one condition, suggesting their involvement in adaptation to stress conditions and identifying interesting candidates for further functional characterization. Copyright © 2017 American Society for Microbiology.

Unconventional Operational Concepts and the Homeland

DTIC Science & Technology

2009-03-01

Lessons Learned . Learning and Teaching There are many theories on organizational learning behaviors, and most agree on four essential phases, such as...those described by Kolb in Figure 9. 54 I C H A P T E R 4 Figure 9. The Learning Cycle The scope of Kolb’s model applies to individuals and...of play and experiential learning that will be long lasting. Lack of realism both with respect to scenarios and what can be expected of the response

Growth response, nutrient and mineral retention, bone mineralisation and walking ability of broiler chickens fed with dietary inclusion of various unconventional mineral sources.

PubMed

Oso, A O; Idowu, A A; Niameh, O T

2011-08-01

Growth response, nutrient and mineral retention, bone mineral content and walking ability of broiler chicken fed dietary inclusion of various unconventional calcium sources were studied using 160-day-old broilers. Four isonitrogenous, isocaloric diets balanced for Ca and P were formulated such that oyster shell, snail shell, wood ash and limestone were used as main non-phytate (Ca from other sources apart from plant) calcium sources. Each dietary treatment consisted of 40 birds replicated four times with 10 birds per replicate. A single diet was fed to the broilers throughout the duration of the study which lasted for 8 weeks. Broilers fed diet containing oyster shell as calcium sources recorded the highest (p < 0.05) feed intake of 5863.30 g, while those fed diet containing limestone consumed the least intake (p < 0.05) of 5432.56 g. Occurrence of lameness and evidences of gaits were highest (p < 0.05) for broilers fed diet containing wood ash. Lowest (p < 0.05) Ca and ash retention were recorded for broiler fed diet containing wood ash as Ca sources. Similar tibia ash values were recorded for broilers fed oyster shell, snail shell and limestone. Wood ash inclusion resulted in a low Ca availability hence its inclusion in feeds for broilers should be discouraged. © 2011 Blackwell Verlag GmbH.

Endoplasmic reticulum stress-responsive transcription factor ATF6α directs recruitment of the Mediator of RNA polymerase II transcription and multiple histone acetyltransferase complexes.

PubMed

Sela, Dotan; Chen, Lu; Martin-Brown, Skylar; Washburn, Michael P; Florens, Laurence; Conaway, Joan Weliky; Conaway, Ronald C

2012-06-29

The basic leucine zipper transcription factor ATF6α functions as a master regulator of endoplasmic reticulum (ER) stress response genes. Previous studies have established that, in response to ER stress, ATF6α translocates to the nucleus and activates transcription of ER stress response genes upon binding sequence specifically to ER stress response enhancer elements in their promoters. In this study, we investigate the biochemical mechanism by which ATF6α activates transcription. By exploiting a combination of biochemical and multidimensional protein identification technology-based mass spectrometry approaches, we have obtained evidence that ATF6α functions at least in part by recruiting to the ER stress response enhancer elements of ER stress response genes a collection of RNA polymerase II coregulatory complexes, including the Mediator and multiple histone acetyltransferase complexes, among which are the Spt-Ada-Gcn5 acetyltransferase (SAGA) and Ada-Two-A-containing (ATAC) complexes. Our findings shed new light on the mechanism of action of ATF6α, and they outline a straightforward strategy for applying multidimensional protein identification technology mass spectrometry to determine which RNA polymerase II transcription factors and coregulators are recruited to promoters and other regulatory elements to control transcription.

Adapting Unconventional Warfare Doctrine to Cyberspace Operations: An Examination of Hacktivist Based Insurgencies

DTIC Science & Technology

2015-06-12

Unconventional Warfare, Cyberspace Operations, Cyber Warfare , Hacktivism, China, Russia, Georgia, Estonia, Umbrella Revolution, UW, Cyber, Guerilla, Hacktivist...6 Cyber Warfare ............................................................................................................. 7...Internet, and cyber warfare , the nature of the human element in cyberspace exhibits only a scientific advancement in the evolution of warfare, not a

Assessment of potential unconventional Carboniferous-Permian gas resources of the Liaohe Basin eastern uplift, Liaoning Province, China, 2011

USGS Publications Warehouse

Pollastro, Richard M.; Potter, Christopher J.; Schenk, Christopher J.; Charpentier, Ronald R.; Cook, Troy A.; Klett, Timothy R.; Kirschbaum, Mark A.

2012-01-01

The U.S. Geological Survey estimated a mean of 448 billion cubic feet of potential technically recoverable unconventional natural gas in Carboniferous and Permian coal-bearing strata in the eastern uplift of the Liaohe Basin, Liaoning Province, China.

Conquest from Within: A Comparative Analysis between Soviet Active Measures and United States Unconventional Warfare Doctrine

DTIC Science & Technology

2015-05-27

irregular threats. Unconventional Warfare (UW), traditionally a Special Operations Forces core activity, has served U.S. strategic interests in a variety...Special Operations Forces core activity, has served U.S. strategic interests in a variety of operational environments. Throughout the Cold War, the

Retrospective Case Study in Wise County, Texas, Study of the Potential Impacts of Hydraulic Fracturing on Drinking Water Resources

EPA Science Inventory

This report describes the retrospective case study in north central Texas, conducted at three locations in Wise County where both conventional and unconventional gas production occurred in the past. Currently unconventional gas production occurs from the Mississippian-aged Barne...

Myonuclear transcription is responsive to mechanical load and DNA content but uncoupled from cell size during hypertrophy

PubMed Central

Kirby, Tyler J.; Patel, Rooshil M.; McClintock, Timothy S.; Dupont-Versteegden, Esther E.; Peterson, Charlotte A.; McCarthy, John J.

2016-01-01

Myofibers increase size and DNA content in response to a hypertrophic stimulus, thus providing a physiological model with which to study how these factors affect global transcription. Using 5-ethynyl uridine (EU) to metabolically label nascent RNA, we measured a sevenfold increase in myofiber transcription during early hypertrophy before a change in cell size and DNA content. The typical increase in myofiber DNA content observed at the later stage of hypertrophy was associated with a significant decrease in the percentage of EU-positive myonuclei; however, when DNA content was held constant by preventing myonuclear accretion via satellite cell depletion, both the number of transcriptionally active myonuclei and the amount of RNA generated by each myonucleus increased. During late hypertrophy, transcription did not scale with cell size, as smaller myofibers (<1000 μm2) demonstrated the highest transcriptional activity. Finally, transcription was primarily responsible for changes in the expression of genes known to regulate myofiber size. These findings show that resident myonuclei possess a significant reserve capacity to up-regulate transcription during hypertrophy and that myofiber transcription is responsive to DNA content but uncoupled from cell size during hypertrophy. PMID:26764089

Transcriptional Blood Signatures Distinguish Pulmonary Tuberculosis, Pulmonary Sarcoidosis, Pneumonias and Lung Cancers

PubMed Central

Bloom, Chloe I.; Graham, Christine M.; Berry, Matthew P. R.; Rozakeas, Fotini; Redford, Paul S.; Wang, Yuanyuan; Xu, Zhaohui; Wilkinson, Katalin A.; Wilkinson, Robert J.; Kendrick, Yvonne; Devouassoux, Gilles; Ferry, Tristan; Miyara, Makoto; Bouvry, Diane; Dominique, Valeyre; Gorochov, Guy; Blankenship, Derek; Saadatian, Mitra; Vanhems, Phillip; Beynon, Huw; Vancheeswaran, Rama; Wickremasinghe, Melissa; Chaussabel, Damien; Banchereau, Jacques; Pascual, Virginia; Ho, Ling-pei; Lipman, Marc; O’Garra, Anne

2013-01-01

Rationale New approaches to define factors underlying the immunopathogenesis of pulmonary diseases including sarcoidosis and tuberculosis are needed to develop new treatments and biomarkers. Comparing the blood transcriptional response of tuberculosis to other similar pulmonary diseases will advance knowledge of disease pathways and help distinguish diseases with similar clinical presentations. Objectives To determine the factors underlying the immunopathogenesis of the granulomatous diseases, sarcoidosis and tuberculosis, by comparing the blood transcriptional responses in these and other pulmonary diseases. Methods We compared whole blood genome-wide transcriptional profiles in pulmonary sarcoidosis, pulmonary tuberculosis, to community acquired pneumonia and primary lung cancer and healthy controls, before and after treatment, and in purified leucocyte populations. Measurements and Main Results An Interferon-inducible neutrophil-driven blood transcriptional signature was present in both sarcoidosis and tuberculosis, with a higher abundance and expression in tuberculosis. Heterogeneity of the sarcoidosis signature correlated significantly with disease activity. Transcriptional profiles in pneumonia and lung cancer revealed an over-abundance of inflammatory transcripts. After successful treatment the transcriptional activity in tuberculosis and pneumonia patients was significantly reduced. However the glucocorticoid-responsive sarcoidosis patients showed a significant increase in transcriptional activity. 144-blood transcripts were able to distinguish tuberculosis from other lung diseases and controls. Conclusions Tuberculosis and sarcoidosis revealed similar blood transcriptional profiles, dominated by interferon-inducible transcripts, while pneumonia and lung cancer showed distinct signatures, dominated by inflammatory genes. There were also significant differences between tuberculosis and sarcoidosis in the degree of their transcriptional activity, the heterogeneity of their profiles and their transcriptional response to treatment. PMID:23940611

Innate T cell responses in human gut.

PubMed

Meresse, Bertrand; Cerf-Bensussan, Nadine

2009-06-01

One arm of the gut-associated immune system is represented by a vast collection of T lymphocytes which participate in the subtle interplay between innate and adaptive immune mechanisms and maintain homeostasis at the main body external surface. Mounting data are providing exciting new insight into the innate-like mechanisms which enable intestinal T cells to rapidly sense local conditions and which broaden the spectrum of their functions and regulation at this strategic location. Herein we discuss how innate-like T cell recognition by unconventional T cell subsets and expression of innate NK receptors might modulate immune T cell responses in the human normal or diseased intestine.

Bombyx mori Transcription Factors: Genome-Wide Identification, Expression Profiles and Response to Pathogens by Microarray Analysis

PubMed Central

Huang, Lulin; Cheng, Tingcai; Xu, Pingzhen; Fang, Ting; Xia, Qingyou

2012-01-01

Transcription factors are present in all living organisms, and play vital roles in a wide range of biological processes. Studies of transcription factors will help reveal the complex regulation mechanism of organisms. So far, hundreds of domains have been identified that show transcription factor activity. Here, 281 reported transcription factor domains were used as seeds to search the transcription factors in genomes of Bombyx mori L. (Lepidoptera: Bombycidae) and four other model insects. Overall, 666 transcription factors including 36 basal factors and 630 other factors were identified in B. mori genome, which accounted for 4.56% of its genome. The silkworm transcription factors' expression profiles were investigated in relation to multiple tissues, developmental stages, sexual dimorphism, and responses to oral infection by pathogens and direct bacterial injection. These all provided rich clues for revealing the transcriptional regulation mechanism of silkworm organ differentiation, growth and development, sexual dimorphism, and response to pathogen infection. PMID:22943524

Mechanics and Activation of Unconventional Myosins.

PubMed

Batters, Christopher; Veigel, Claudia

2016-08-01

Many types of cellular motility are based on the myosin family of motor proteins ranging from muscle contraction to exo- and endocytosis, cytokinesis, cell locomotion or signal transduction in hearing. At the center of this wide range of motile processes lies the adaptation of the myosins for each specific mechanical task and the ability to coordinate the timing of motor protein mobilization and targeting. In recent years, great progress has been made in developing single molecule technology to characterize the diverse mechanical properties of the unconventional myosins. Here, we discuss the basic mechanisms and mechanical adaptations of unconventional myosins, and emerging principles regulating motor mobilization and targeting. © 2016 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.

Transcriptomic and proteomic analyses of the Aspergillus fumigatus hypoxia response using an oxygen-controlled fermenter

PubMed Central

2012-01-01

Background Aspergillus fumigatus is a mold responsible for the majority of cases of aspergillosis in humans. To survive in the human body, A. fumigatus must adapt to microenvironments that are often characterized by low nutrient and oxygen availability. Recent research suggests that the ability of A. fumigatus and other pathogenic fungi to adapt to hypoxia contributes to their virulence. However, molecular mechanisms of A. fumigatus hypoxia adaptation are poorly understood. Thus, to better understand how A. fumigatus adapts to hypoxic microenvironments found in vivo during human fungal pathogenesis, the dynamic changes of the fungal transcriptome and proteome in hypoxia were investigated over a period of 24 hours utilizing an oxygen-controlled fermenter system. Results Significant increases in transcripts associated with iron and sterol metabolism, the cell wall, the GABA shunt, and transcriptional regulators were observed in response to hypoxia. A concomitant reduction in transcripts was observed with ribosome and terpenoid backbone biosynthesis, TCA cycle, amino acid metabolism and RNA degradation. Analysis of changes in transcription factor mRNA abundance shows that hypoxia induces significant positive and negative changes that may be important for regulating the hypoxia response in this pathogenic mold. Growth in hypoxia resulted in changes in the protein levels of several glycolytic enzymes, but these changes were not always reflected by the corresponding transcriptional profiling data. However, a good correlation overall (R2 = 0.2, p < 0.05) existed between the transcriptomic and proteomics datasets for all time points. The lack of correlation between some transcript levels and their subsequent protein levels suggests another regulatory layer of the hypoxia response in A. fumigatus. Conclusions Taken together, our data suggest a robust cellular response that is likely regulated both at the transcriptional and post-transcriptional level in response to hypoxia by the human pathogenic mold A. fumigatus. As with other pathogenic fungi, the induction of glycolysis and transcriptional down-regulation of the TCA cycle and oxidative phosphorylation appear to major components of the hypoxia response in this pathogenic mold. In addition, a significant induction of the transcripts involved in ergosterol biosynthesis is consistent with previous observations in the pathogenic yeasts Candida albicans and Cryptococcus neoformans indicating conservation of this response to hypoxia in pathogenic fungi. Because ergosterol biosynthesis enzymes also require iron as a co-factor, the increase in iron uptake transcripts is consistent with an increased need for iron under hypoxia. However, unlike C. albicans and C. neoformans, the GABA shunt appears to play an important role in reducing NADH levels in response to hypoxia in A. fumigatus and it will be intriguing to determine whether this is critical for fungal virulence. Overall, regulatory mechanisms of the A. fumigatus hypoxia response appear to involve both transcriptional and post-transcriptional control of transcript and protein levels and thus provide candidate genes for future analysis of their role in hypoxia adaptation and fungal virulence. PMID:22309491

Heat Shock Response in Yeast Involves Changes in Both Transcription Rates and mRNA Stabilities

PubMed Central

Castells-Roca, Laia; García-Martínez, José; Moreno, Joaquín; Herrero, Enrique; Bellí, Gemma; Pérez-Ortín, José E.

2011-01-01

We have analyzed the heat stress response in the yeast Saccharomyces cerevisiae by determining mRNA levels and transcription rates for the whole transcriptome after a shift from 25°C to 37°C. Using an established mathematical algorithm, theoretical mRNA decay rates have also been calculated from the experimental data. We have verified the mathematical predictions for selected genes by determining their mRNA decay rates at different times during heat stress response using the regulatable tetO promoter. This study indicates that the yeast response to heat shock is not only due to changes in transcription rates, but also to changes in the mRNA stabilities. mRNA stability is affected in 62% of the yeast genes and it is particularly important in shaping the mRNA profile of the genes belonging to the environmental stress response. In most cases, changes in transcription rates and mRNA stabilities are homodirectional for both parameters, although some interesting cases of antagonist behavior are found. The statistical analysis of gene targets and sequence motifs within the clusters of genes with similar behaviors shows that both transcriptional and post-transcriptional regulons apparently contribute to the general heat stress response by means of transcriptional factors and RNA binding proteins. PMID:21364882

78 FR 15377 - Agency Information Collection Activities; Submission for OMB Review; Comment Request; Requests To...

Federal Register 2010, 2011, 2012, 2013, 2014

2013-03-11

... for OMB Review; Comment Request; Requests To Approve Conformed Wage Classifications and Unconventional... Classifications and Unconventional Fringe Benefit Plans Under the Davis-Bacon and Related Acts and Contract Work... collection consist of: (A) Reports of conformed classifications and wage rates and (B) requests for approval...

Assessment of undiscovered oil and gas resources of the Paris Basin, France, 2015

USGS Publications Warehouse

Schenk, Christopher J.; Charpentier, Ronald R.; Klett, Timothy R.; Tennyson, Marilyn E.; Mercier, Tracey J.; Le, Phoung A.; Brownfield, Michael E.; Pitman, Janet K.; Gaswirth, Stephanie B.; Marra, Kristen R.; Leathers, Heidi M.

2015-01-01

Using a geology-based assessment methodology, the U.S. Geological Survey estimated means of 222 million barrels of unconventional oil; 2,092 billion cubic feet of unconventional gas; 18 million barrels of conventional oil; and 47 billion cubic feet of conventional gas resources in the Paris Basin of France.

Aspects of a Neoteric Approach to Advance Students' Ability to Conjecture, Prove, or Disprove

ERIC Educational Resources Information Center

McLoughlin, M. Padraig M. M.

2010-01-01

The author of this paper suggests several neoteric, unconventional, idiosyncratic, or unique approaches to beginning Set Theory that he found seems to work well in building students' introductory understanding of the Foundations of Mathematics. This paper offers some ideas on how the author uses certain "unconventional" definitions and…

Unconventional topological Hall effect in skyrmion crystals caused by the topology of the lattice

NASA Astrophysics Data System (ADS)

Göbel, Börge; Mook, Alexander; Henk, Jürgen; Mertig, Ingrid

2017-03-01

The hallmark of a skyrmion crystal (SkX) is the topological Hall effect (THE). In this article we predict and explain an unconventional behavior of the topological Hall conductivity in SkXs. In simple terms, the spin texture of the skyrmions causes an inhomogeneous emergent magnetic field whose associated Lorentz force acts on the electrons. By making the emergent field homogeneous, the THE is mapped onto the quantum Hall effect (QHE). Consequently, each electronic band of the SkX is assigned to a Landau level. This correspondence of THE and QHE allows us to explain the unconventional behavior of the THE of electrons in SkXs. For example, a skyrmion crystal on a triangular lattice exhibits a quantized topological Hall conductivity with steps of 2 .e2/h below and with steps of 1 .e2/h above the van Hove singularity. On top of this, the conductivity shows a prominent sign change at the van Hove singularity. These unconventional features are deeply connected to the topology of the structural lattice.

Associations Between Positive Body Image, Sexual Liberalism, and Unconventional Sexual Practices in U.S. Adults.

PubMed

Swami, Viren; Weis, Laura; Barron, David; Furnham, Adrian

2017-11-01

While studies have documented robust relationships between body image and sexual health outcomes, few studies have looked beyond sexual functioning in women. Here, we hypothesized that more positive body image would be associated with greater sexual liberalism and more positive attitudes toward unconventional sexual practices. An online sample of 151 women and 164 men from the U.S. completed measures of sexual liberalism, attitudes toward unconventional sexual practices, and indices of positive body image (i.e., body appreciation, body acceptance by others, body image flexibility, and body pride), and provided their demographic details. Regression analyses indicated that, once the effects of sexual orientation, relationship status, age, and body mass index had been accounted for, higher body appreciation was significantly associated with greater sexual liberalism in women and men. Furthermore, higher body appreciation and body image flexibility were significantly associated with more positive attitudes toward unconventional sexual practices in women and men. These results may have implications for scholars working from a sex-positive perspective, particularly in terms of understanding the role body image plays in sexual attitudes and behaviors.

Aeroelastic Airworthiness Assesment of the Adaptive Compliant Trailing Edge Flaps

NASA Technical Reports Server (NTRS)

Herrera, Claudia Y.; Spivey, Natalie D.; Lung, Shun-fat; Ervin, Gregory; Flick, Peter

2015-01-01

The Adaptive Compliant Trailing Edge (ACTE) demonstrator is a joint task under the National Aeronautics and Space Administration Environmentally Responsible Aviation Project in partnership with the Air Force Research Laboratory and FlexSys, Inc. (Ann Arbor, Michigan). The project goal is to develop advanced technologies that enable environmentally friendly aircraft, such as adaptive compliant technologies. The ACTE demonstrator flight-test program encompassed replacing the Fowler flaps on the SubsoniC Aircraft Testbed, a modified Gulfstream III (Gulfstream Aerospace, Savannah, Georgia) aircraft, with control surfaces developed by FlexSys. The control surfaces developed by FlexSys are a pair of uniquely-designed unconventional flaps to be used as lifting surfaces during flight-testing to validate their structural effectiveness. The unconventional flaps required a multidisciplinary airworthiness assessment to prove they could withstand the prescribed flight envelope. Several challenges were posed due to the large deflections experienced by the structure, requiring non-linear analysis methods. The aeroelastic assessment necessitated both conventional and extensive testing and analysis methods. A series of ground vibration tests (GVTs) were conducted to provide modal characteristics to validate and update finite element models (FEMs) used for the flutter analyses for a subset of the various flight configurations. Numerous FEMs were developed using data from FlexSys and the ground tests. The flap FEMs were then attached to the aircraft model to generate a combined FEM that could be analyzed for aeroelastic instabilities. The aeroelastic analysis results showed the combined system of aircraft and flaps were predicted to have the required flutter margin to successfully demonstrate the adaptive compliant technology. This paper documents the details of the aeroelastic airworthiness assessment described, including the ground testing and analyses, and subsequent flight-testing performed on the unconventional ACTE flaps.

The Effect of Geographic Proximity to Unconventional Oil and Gas Development on Public Support for Hydraulic Fracturing.

PubMed

Boudet, Hilary S; Zanocco, Chad M; Howe, Peter D; Clarke, Christopher E

2018-04-10

With the rapid growth of unconventional oil and natural gas development transforming the U.S. economic and physical landscape, social scientists have increasingly explored the spatial dynamics of public support for this issue-that is, whether people closer to unconventional oil and gas development are more supportive or more opposed. While theoretical frameworks like construal-level theory and the "Not in My Backyard" (or NIMBY) moniker provide insight into these spatial dynamics, case studies in specific locations experiencing energy development reveal substantial variation in community responses. Larger-scale studies exploring the link between proximity and support have been hampered by data quality and availability. We draw on a unique data set that includes geo-coded data from national surveys (nine waves; n = 19,098) and high-resolution well location data to explore the relationship between proximity and both familiarity with and support for hydraulic fracturing. We use two different measures of proximity-respondent distance to the nearest well and the density of wells within a certain radius of the respondent's location. We find that both types of proximity to new development are linked to more familiarity with hydraulic fracturing, even after controlling for various individual and contextual factors, but only distance-based proximity is linked to more support for the practice. When significant, these relationships are similar to or exceed the effects of race, income, gender, and age. We discuss the implications of these findings for effective risk communication as well as the importance of incorporating spatial analysis into public opinion research on perceptions of energy development. © 2018 Society for Risk Analysis.

Utah Heavy Oil Program

DOE Office of Scientific and Technical Information (OSTI.GOV)

J. Bauman; S. Burian; M. Deo

The Utah Heavy Oil Program (UHOP) was established in June 2006 to provide multidisciplinary research support to federal and state constituents for addressing the wide-ranging issues surrounding the creation of an industry for unconventional oil production in the United States. Additionally, UHOP was to serve as an on-going source of unbiased information to the nation surrounding technical, economic, legal and environmental aspects of developing heavy oil, oil sands, and oil shale resources. UHOP fulGilled its role by completing three tasks. First, in response to the Energy Policy Act of 2005 Section 369(p), UHOP published an update report to the 1987more » technical and economic assessment of domestic heavy oil resources that was prepared by the Interstate Oil and Gas Compact Commission. The UHOP report, entitled 'A Technical, Economic, and Legal Assessment of North American Heavy Oil, Oil Sands, and Oil Shale Resources' was published in electronic and hard copy form in October 2007. Second, UHOP developed of a comprehensive, publicly accessible online repository of unconventional oil resources in North America based on the DSpace software platform. An interactive map was also developed as a source of geospatial information and as a means to interact with the repository from a geospatial setting. All documents uploaded to the repository are fully searchable by author, title, and keywords. Third, UHOP sponsored Give research projects related to unconventional fuels development. Two projects looked at issues associated with oil shale production, including oil shale pyrolysis kinetics, resource heterogeneity, and reservoir simulation. One project evaluated in situ production from Utah oil sands. Another project focused on water availability and produced water treatments. The last project considered commercial oil shale leasing from a policy, environmental, and economic perspective.« less

Modeling the Relative GHG Emissions of Conventional and Shale Gas Production

PubMed Central

2011-01-01

Recent reports show growing reserves of unconventional gas are available and that there is an appetite from policy makers, industry, and others to better understand the GHG impact of exploiting reserves such as shale gas. There is little publicly available data comparing unconventional and conventional gas production. Existing studies rely on national inventories, but it is not generally possible to separate emissions from unconventional and conventional sources within these totals. Even if unconventional and conventional sites had been listed separately, it would not be possible to eliminate site-specific factors to compare gas production methods on an equal footing. To address this difficulty, the emissions of gas production have instead been modeled. In this way, parameters common to both methods of production can be held constant, while allowing those parameters which differentiate unconventional gas and conventional gas production to vary. The results are placed into the context of power generation, to give a ″well-to-wire″ (WtW) intensity. It was estimated that shale gas typically has a WtW emissions intensity about 1.8–2.4% higher than conventional gas, arising mainly from higher methane releases in well completion. Even using extreme assumptions, it was found that WtW emissions from shale gas need be no more than 15% higher than conventional gas if flaring or recovery measures are used. In all cases considered, the WtW emissions of shale gas powergen are significantly lower than those of coal. PMID:22085088

Modeling the relative GHG emissions of conventional and shale gas production.

PubMed

Stephenson, Trevor; Valle, Jose Eduardo; Riera-Palou, Xavier

2011-12-15

Recent reports show growing reserves of unconventional gas are available and that there is an appetite from policy makers, industry, and others to better understand the GHG impact of exploiting reserves such as shale gas. There is little publicly available data comparing unconventional and conventional gas production. Existing studies rely on national inventories, but it is not generally possible to separate emissions from unconventional and conventional sources within these totals. Even if unconventional and conventional sites had been listed separately, it would not be possible to eliminate site-specific factors to compare gas production methods on an equal footing. To address this difficulty, the emissions of gas production have instead been modeled. In this way, parameters common to both methods of production can be held constant, while allowing those parameters which differentiate unconventional gas and conventional gas production to vary. The results are placed into the context of power generation, to give a ″well-to-wire″ (WtW) intensity. It was estimated that shale gas typically has a WtW emissions intensity about 1.8-2.4% higher than conventional gas, arising mainly from higher methane releases in well completion. Even using extreme assumptions, it was found that WtW emissions from shale gas need be no more than 15% higher than conventional gas if flaring or recovery measures are used. In all cases considered, the WtW emissions of shale gas powergen are significantly lower than those of coal.

Unconventional therapies for cancer: 1. Essiac

PubMed Central

Kaegi, E

1998-01-01

Physicians and patients have been frustrated by the lack of reliable information on unconventional therapies. To help fill this gap in the area of breast cancer therapy, the Canadian Breast Cancer Research Initiative formed a task force to advise it on how best to promote research into unconventional therapies. As part of the work of the task force, a review of the available literature was carried out for each of the following products: Essiac, green tea, Iscador, hydrazine sulfate, vitamins A, C and E, and 714-X. The first article in this series on unconventional therapies for cancer describes the methodology used to obtain and evaluate the information and provides a summary of the findings on Essiac. Subsequent articles will cover the other products. For most of the products reviewed, there has been some indication of possible benefit but no definitive evidence. Innovative and collaborative research needed to meet the information needs of growing numbers of patients and their physicians is now being sponsored by the Canadian Breast Cancer Research Initiative. Open communication between patients and physicians is also necessary for the maintenance of an appropriate therapeutic partnership and for the identification and control of side effects. The Ontario Division of the Canadian Cancer Society, a partner in the Canadian Breast Cancer Research Initiative, supported the preparation of a patient-information piece on unconventional therapies to accompany the series. This item will assist patients who are considering such therapies and will promote open communication between patients and their physicians. PMID:9559016

Genome-Wide Survey of Host Responses: Use of Computational Analysis to Classify Exposures and Extract Signatures of Unconventional Versus Common Viral Exposures

DTIC Science & Technology

2006-11-01

alpha viruses, among which was Venezuelan equine encephalitis (VEE). The “training sets” were constructed from in vitro exposures to purified...virus and 4 serotypes of Dengue), and the forth group include 2 alpha viruses, among which was Venezuelan equine encephalitis (VEE). We have used...We examined our hypothesis that in vitro exposures can predict exposures in vivo. We have used data from PBMC exposed to Venezuelan equine

Unconventional oil and gas spills: Materials, volumes, and risks to surface waters in four states of the U.S.

PubMed

Maloney, Kelly O; Baruch-Mordo, Sharon; Patterson, Lauren A; Nicot, Jean-Philippe; Entrekin, Sally A; Fargione, Joseph E; Kiesecker, Joseph M; Konschnik, Kate E; Ryan, Joseph N; Trainor, Anne M; Saiers, James E; Wiseman, Hannah J

2017-03-01

Extraction of oil and gas from unconventional sources, such as shale, has dramatically increased over the past ten years, raising the potential for spills or releases of chemicals, waste materials, and oil and gas. We analyzed spill data associated with unconventional wells from Colorado, New Mexico, North Dakota and Pennsylvania from 2005 to 2014, where we defined unconventional wells as horizontally drilled into an unconventional formation. We identified materials spilled by state and for each material we summarized frequency, volumes and spill rates. We evaluated the environmental risk of spills by calculating distance to the nearest stream and compared these distances to existing setback regulations. Finally, we summarized relative importance to drinking water in watersheds where spills occurred. Across all four states, we identified 21,300 unconventional wells and 6622 reported spills. The number of horizontal well bores increased sharply beginning in the late 2000s; spill rates also increased for all states except PA where the rate initially increased, reached a maximum in 2009 and then decreased. Wastewater, crude oil, drilling waste, and hydraulic fracturing fluid were the materials most often spilled; spilled volumes of these materials largely ranged from 100 to 10,000L. Across all states, the average distance of spills to a stream was highest in New Mexico (1379m), followed by Colorado (747m), North Dakota (598m) and then Pennsylvania (268m), and 7.0, 13.3, and 20.4% of spills occurred within existing surface water setback regulations of 30.5, 61.0, and 91.4m, respectively. Pennsylvania spills occurred in watersheds with a higher relative importance to drinking water than the other three states. Results from this study can inform risk assessments by providing improved input parameters on volume and rates of materials spilled, and guide regulations and the management policy of spills. Published by Elsevier B.V.

Unconventional oil and gas spills: Materials, volumes, and risks to surface waters in four states of the U.S.

USGS Publications Warehouse

Maloney, Kelly O.; Baruch-Mordo, Sharon; Patterson, Lauren A.; Nicot, Jean-Philippe; Entrekin, Sally; Fargione, Joe E.; Kiesecker, Joseph M.; Konschnik, Kate E.; Ryan, Joseph N.; Trainor, Anne M.; Saiers, James E.; Wiseman, Hannah J.

2017-01-01

Extraction of oil and gas from unconventional sources, such as shale, has dramatically increased over the past ten years, raising the potential for spills or releases of chemicals, waste materials, and oil and gas. We analyzed spill data associated with unconventional wells from Colorado, New Mexico, North Dakota and Pennsylvania from 2005 to 2014, where we defined unconventional wells as horizontally drilled into an unconventional formation. We identified materials spilled by state and for each material we summarized frequency, volumes and spill rates. We evaluated the environmental risk of spills by calculating distance to the nearest stream and compared these distances to existing setback regulations. Finally, we summarized relative importance to drinking water in watersheds where spills occurred. Across all four states, we identified 21,300 unconventional wells and 6622 reported spills. The number of horizontal well bores increased sharply beginning in the late 2000s; spill rates also increased for all states except PA where the rate initially increased, reached a maximum in 2009 and then decreased. Wastewater, crude oil, drilling waste, and hydraulic fracturing fluid were the materials most often spilled; spilled volumes of these materials largely ranged from 100 to 10,000 L. Across all states, the average distance of spills to a stream was highest in New Mexico (1379 m), followed by Colorado (747 m), North Dakota (598 m) and then Pennsylvania (268 m), and 7.0, 13.3, and 20.4% of spills occurred within existing surface water setback regulations of 30.5, 61.0, and 91.4 m, respectively. Pennsylvania spills occurred in watersheds with a higher relative importance to drinking water than the other three states. Results from this study can inform risk assessments by providing improved input parameters on volume and rates of materials spilled, and guide regulations and the management policy of spills.

Dehydration stress memory genes of Zea mays; comparison with Arabidopsis thaliana

PubMed Central

2014-01-01

Background Pre-exposing plants to diverse abiotic stresses may alter their physiological and transcriptional responses to a subsequent stress, suggesting a form of “stress memory”. Arabidopsis thaliana plants that have experienced multiple exposures to dehydration stress display transcriptional behavior suggesting “memory” from an earlier stress. Genes that respond to a first stress by up-regulating or down-regulating their transcription but in a subsequent stress provide a significantly different response define the ‘memory genes’ category. Genes responding similarly to each stress form the ‘non-memory’ category. It is unknown whether such memory responses exists in other Angiosperm lineages and whether memory is an evolutionarily conserved response to repeated dehydration stresses. Results Here, we determine the transcriptional responses of maize (Zea mays L.) plants that have experienced repeated exposures to dehydration stress in comparison with plants encountering the stress for the first time. Four distinct transcription memory response patterns similar to those displayed by A. thaliana were revealed. The most important contribution is the evidence that monocot and eudicot plants, two lineages that have diverged 140 to 200 M years ago, display similar abilities to ‘remember’ a dehydration stress and to modify their transcriptional responses, accordingly. The highly sensitive RNA-Seq analyses allowed to identify genes that function similarly in the two lineages, as well as genes that function in species-specific ways. Memory transcription patterns indicate that the transcriptional behavior of responding genes under repeated stresses is different from the behavior during an initial dehydration stress, suggesting that stress memory is a complex phenotype resulting from coordinated responses of multiple signaling pathways. Conclusions Structurally related genes displaying the same memory responses in the two species would suggest conservation of the genes’ memory during the evolution of plants’ dehydration stress response systems. On the other hand, divergent transcription memory responses by genes encoding similar functions would suggest occurrence of species-specific memory responses. The results provide novel insights into our current knowledge of how plants respond to multiple dehydration stresses, as compared to a single exposure, and may serve as a reference platform to study the functions of memory genes in adaptive responses to water deficit in monocot and eudicot plants. PMID:24885787

Single-Cell Analysis of Experience-Dependent Transcriptomic States in Mouse Visual Cortex

PubMed Central

Hrvatin, Sinisa; Hochbaum, Daniel R.; Nagy, M. Aurel; Cicconet, Marcelo; Robertson, Keiramarie; Cheadle, Lucas; Zilionis, Rapolas; Ratner, Alex; Borges-Monroy, Rebeca; Klein, Allon M.; Sabatini, Bernardo L.; Greenberg, Michael E.

2017-01-01

Activity-dependent transcriptional responses shape cortical function. However, we lack a comprehensive understanding of the diversity of these responses across the full range of cortical cell types, and how these changes contribute to neuronal plasticity and disease. Here we applied high-throughput single-cell RNA-sequencing to investigate the breadth of transcriptional changes that occur across cell types in mouse visual cortex following exposure to light. We identified significant and divergent transcriptional responses to stimulation in each of the 30 cell types characterized, revealing 611 stimulus-responsive genes. Excitatory pyramidal neurons exhibit inter- and intra-laminar heterogeneity in the induction of stimulus responsive genes. Non-neuronal cells demonstrated clear transcriptional responses that may regulate experience-dependent changes in neurovascular coupling and myelination. Together, these results reveal the dynamic landscape of stimulus-dependent transcriptional changes that occur across cell types in visual cortex, which are likely critical for cortical function and may be sites of de-regulation in developmental brain disorders. PMID:29230054

An integrated approach to characterize transcription factor and microRNA regulatory networks involved in Schwann cell response to peripheral nerve injury

PubMed Central

2013-01-01

Background The regenerative response of Schwann cells after peripheral nerve injury is a critical process directly related to the pathophysiology of a number of neurodegenerative diseases. This SC injury response is dependent on an intricate gene regulatory program coordinated by a number of transcription factors and microRNAs, but the interactions among them remain largely unknown. Uncovering the transcriptional and post-transcriptional regulatory networks governing the Schwann cell injury response is a key step towards a better understanding of Schwann cell biology and may help develop novel therapies for related diseases. Performing such comprehensive network analysis requires systematic bioinformatics methods to integrate multiple genomic datasets. Results In this study we present a computational pipeline to infer transcription factor and microRNA regulatory networks. Our approach combined mRNA and microRNA expression profiling data, ChIP-Seq data of transcription factors, and computational transcription factor and microRNA target prediction. Using mRNA and microRNA expression data collected in a Schwann cell injury model, we constructed a regulatory network and studied regulatory pathways involved in Schwann cell response to injury. Furthermore, we analyzed network motifs and obtained insights on cooperative regulation of transcription factors and microRNAs in Schwann cell injury recovery. Conclusions This work demonstrates a systematic method for gene regulatory network inference that may be used to gain new information on gene regulation by transcription factors and microRNAs. PMID:23387820

Transcriptional regulation of drought response: a tortuous network of transcriptional factors

PubMed Central

Singh, Dhriti; Laxmi, Ashverya

2015-01-01

Drought is one of the leading factors responsible for the reduction in crop yield worldwide. Due to climate change, in future, more areas are going to be affected by drought and for prolonged periods. Therefore, understanding the mechanisms underlying the drought response is one of the major scientific concerns for improving crop yield. Plants deploy diverse strategies and mechanisms to respond and tolerate drought stress. Expression of numerous genes is modulated in different plants under drought stress that help them to optimize their growth and development. Plant hormone abscisic acid (ABA) plays a major role in plant response and tolerance by regulating the expression of many genes under drought stress. Transcription factors being the major regulator of gene expression play a crucial role in stress response. ABA regulates the expression of most of the target genes through ABA-responsive element (ABRE) binding protein/ABRE binding factor (AREB/ABF) transcription factors. Genes regulated by AREB/ABFs constitute a regulon termed as AREB/ABF regulon. In addition to this, drought responsive genes are also regulated by ABA-independent mechanisms. In ABA-independent regulation, dehydration-responsive element binding protein (DREB), NAM, ATAF, and CUC regulons play an important role by regulating many drought-responsive genes. Apart from these major regulons, MYB/MYC, WRKY, and nuclear factor-Y (NF-Y) transcription factors are also involved in drought response and tolerance. Our understanding about transcriptional regulation of drought is still evolving. Recent reports have suggested the existence of crosstalk between different transcription factors operating under drought stress. In this article, we have reviewed various regulons working under drought stress and their crosstalk with each other. PMID:26579147

Designed Transcriptional Regulation in Mammalian Cells Based on TALE- and CRISPR/dCas9.

PubMed

Lebar, Tina; Jerala, Roman

2018-01-01

Transcriptional regulation lies at the center of many cellular processes and is the result of cellular response to different external and internal signals. Control of transcription of selected genes enables an unprecedented access to shape the cellular response. While orthogonal transcription factors from bacteria, yeast, plants, or other cells have been used to introduce new cellular logic into mammalian cells, the discovery of designable modular DNA binding domains, such as Transcription Activator-Like Effectors (TALEs) and the CRISPR system, enable targeting of almost any selected DNA sequence. Fusion or conditional association of DNA targeting domain with transcriptional effector domains enables controlled regulation of almost any endogenous or ectopic gene. Moreover, the designed regulators can be linked into genetic circuits to implement complex responses, such as different types of Boolean functions and switches. In this chapter, we describe the protocols for achieving efficient transcriptional regulation with TALE- and CRISPR-based designed transcription factors in mammalian cells.

Resveratrol regulates gene transcription via activation of stimulus-responsive transcription factors.

PubMed

Thiel, Gerald; Rössler, Oliver G

2017-03-01

Resveratrol (trans-3,4',5-trihydroxystilbene), a polyphenolic phytoalexin of grapes and other fruits and plants, is a common constituent of our diet and of dietary supplements. Many health-promoting benefits have been connected with resveratrol in the treatment of cardiovascular diseases, cancer, diabetes, inflammation, neurodegeneration, and diseases connected with aging. To explain the pleiotropic effects of resveratrol, the molecular targets of this compound have to be identified on the cellular level. Resveratrol induces intracellular signal transduction pathways which ultimately lead to changes in the gene expression pattern of the cells. Here, we review the effect of resveratrol on the activation of the stimulus-responsive transcription factors CREB, AP-1, Egr-1, Elk-1, and Nrf2. Following activation, these transcription factors induce transcription of delayed response genes. The gene products of these delayed response genes are ultimately responsible for the changes in the biochemistry and physiology of resveratrol-treated cells. The activation of stimulus-responsive transcription factors may explain many of the intracellular activities of resveratrol. However, results obtained in vitro may not easily be transferred to in vivo systems. Copyright © 2016 Elsevier Ltd. All rights reserved.

Landscape of post-transcriptional gene regulation during hepatitis C virus infection

PubMed Central

Schwerk, Johannes; Jarret, Abigail P.; Joslyn, Rochelle C.; Savan, Ram

2015-01-01

Post-transcriptional regulation of gene expression plays a pivotal role in various gene regulatory networks including, but not limited to metabolism, embryogenesis and immune responses. Different mechanisms of post-transcriptional regulation, which can act individually, synergistically, or even in an antagonistic manner have been described. Hepatitis C virus (HCV) is notorious for subverting host immune responses and indeed exploits several components of the host’s post-transcriptional regulatory machinery for its own benefit. At the same time, HCV replication is post-transcriptionally targeted by host cell components to blunt viral propagation. This review discusses the interplay of post-transcriptional mechanisms that affect host immune responses in the setting of HCV infection and highlights the sophisticated mechanisms both host and virus have evolved in the race for superiority. PMID:25890065

An unconventional approach to ecosystem unit classification in western North Carolina, USA

Treesearch

W. Henry McNab; Sara A. Browning; Steven A. Simon; Penelope E. Fouts

1999-01-01

The authors used an unconventional combination of data transformation and multivariate analyses to reduce subjectivity in identification of ecosystem units in a mountainous region of western North Carolina, USA. Vegetative cover and environmental variables were measured on 79 stratified, randomly located, 0.1 ha sample plots in a 4000 ha watershed. Binary...

Introduction

USGS Publications Warehouse

Warwick, Peter D.

2011-01-01

The Energy Minerals Division (EMD) of the American Association of Petroleum Geologists (AAPG) is a membership-based, technical interest group having the primary goal of advancing the science of geology, especially as it relates to exploration, discovery, and production of unconventional energy resources. Current research on unconventional energy resources is rapidly changing and exploration and development efforts for these resources are constantly expanding. Nine summaries derived from 2011 committee reports presented at the EMD Annual Meeting in Houston, Texas in April, 2011, are contained in this review. The complete set of committee reports is available to AAPG members at http://emd.aapg.org/members_only/ annual2011/index.cfm. This report updates the 2006 and 2009 EMD unconventional energy review published in this journal (American Association of Petroleum Geologists, Energy Minerals Division 2007, 2009).

From Cytosol to the Apoplast: The Hygromycin Phosphotransferase (HYG(R)) Model in Arabidopsis.

PubMed

Zhang, Haiyan; Li, Jinjin

2016-01-01

The process by which proteins are secreted via endoplasmic reticulum (ER)/Golgi-independent mechanism is conveniently called unconventional protein secretion. Recent studies have revealed that unconventional protein secretion operates in plants, but little is known about its underlying mechanism and function. This chapter provides methods we have used to analyze unconventional character of hygromycin phosphotransferase (HYG(R)) secretion in plant cells. Following isolation of protoplasts from HYG (R) -GFP-transgenic plants and incubation with brefeldin A (BFA), an inhibitor of conventional secretory pathway, we easily obtain protein extracts from protoplasts and culture medium separately. These proteins are separated by sodium dodecyl sulfate-polyacrylamide gel electrophoresis (SDS-PAGE), followed by Western blot analysis with anti-GFP antibodies.

Geckoprinting: assembly of microelectronic devices on unconventional surfaces by transfer printing with isolated gecko setal arrays

PubMed Central

Jeong, Jaeyoung; Kim, Juho; Song, Kwangsun; Autumn, Kellar; Lee, Jongho

2014-01-01

Developing electronics in unconventional forms provides opportunities to expand the use of electronics in diverse applications including bio-integrated or implanted electronics. One of the key challenges lies in integrating semiconductor microdevices onto unconventional substrates without glue, high pressure or temperature that may cause damage to microdevices, substrates or interfaces. This paper describes a solution based on natural gecko setal arrays that switch adhesion mechanically on and off, enabling pick and place manipulation of thin microscale semiconductor materials onto diverse surfaces including plants and insects whose surfaces are usually rough and irregular. A demonstration of functional ‘geckoprinted’ microelectronic devices provides a proof of concept of our results in practical applications. PMID:25056216

Unconventional aspects of electronic transport in delafossite oxides

NASA Astrophysics Data System (ADS)

Daou, Ramzy; Frésard, Raymond; Eyert, Volker; Hébert, Sylvie; Maignan, Antoine

2017-12-01

The electronic transport properties of the delafossite oxides ? are usually understood in terms of two well-separated entities, namely the triangular ? and (? layers. Here, we review several cases among this extensive family of materials where the transport depends on the interlayer coupling and displays unconventional properties. We review the doped thermoelectrics based on ? and ?, which show a high-temperature recovery of Fermi-liquid transport exponents, as well as the highly anisotropic metals ?, ?, and ?, where the sheer simplicity of the Fermi surface leads to unconventional transport. We present some of the theoretical tools that have been used to investigate these transport properties and review what can and cannot be learned from the extensive set of electronic structure calculations that have been performed.

Changes in transcript expression patterns as a result of cryoprotectant treatment and liquid nitrogen exposure in Arabidopsis shoot tips.

PubMed

Gross, Briana L; Henk, Adam D; Bonnart, Remi; Volk, Gayle M

2017-03-01

Transcripts related to abiotic stress, oxidation, and wounding were differentially expressed in Arabidopsis shoot tips in response to cryoprotectant and liquid nitrogen treatment. Cryopreservation methods have been implemented in genebanks as a strategy to back-up plant genetic resource collections that are vegetatively propagated. Cryopreservation is frequently performed using vitrification methods, whereby shoot tips are treated with cryoprotectant solutions, such as Plant Vitrification Solution 2 (PVS2) or Plant Vitrification Solution 3 (PVS3); these solutions remove and/or replace freezable water within the meristem cells. We used the model system Arabidopsis thaliana to identify suites of transcripts that are up- or downregulated in response to PVS2 and PVS3 treatment and liquid nitrogen (LN) exposure. Our results suggest that there are many changes in transcript expression in shoot tips as a result of cryoprotection and that these changes exceed the number detected as a result of LN exposure. In total, 180 transcripts showed significant changes in expression level unique to treatment with either the cryoprotectant or cryopreservation followed by recovery. Of these 180 transcripts, 67 were related to stress, defense, wounding, lipid, carbohydrate, abscisic acid, oxidation, temperature (cold/heat), or osmoregulation. The responses of five transcripts were confirmed using qPCR methods. The transcripts responding to PVS2 + LN suggest an oxidative response to this treatment, whereas the PVS3 + LN treatment invoked a more general metabolic response. This work shows that the choice of cryoprotectant can have a major influence on the patterns of transcript expression, presumably due to the level and extent of stress experienced by the shoot tip. As a result, there may be divergent responses of study systems to PVS2 and PVS3 treatments.

Environmental contaminants and microRNA regulation: Transcription factors as regulators of toxicant-altered microRNA expression

DOE Office of Scientific and Technical Information (OSTI.GOV)

Sollome, James; Martin, Elizabeth

MicroRNAs (miRNAs) regulate gene expression by binding mRNA and inhibiting translation and/or inducing degradation of the associated transcripts. Expression levels of miRNAs have been shown to be altered in response to environmental toxicants, thus impacting cellular function and influencing disease risk. Transcription factors (TFs) are known to be altered in response to environmental toxicants and play a critical role in the regulation of miRNA expression. To date, environmentally-responsive TFs that are important for regulating miRNAs remain understudied. In a state-of-the-art analysis, we utilized an in silico bioinformatic approach to characterize potential transcriptional regulators of environmentally-responsive miRNAs. Using the miRStart database,more » genomic sequences of promoter regions for all available human miRNAs (n = 847) were identified and promoter regions were defined as − 1000/+500 base pairs from the transcription start site. Subsequently, the promoter region sequences of environmentally-responsive miRNAs (n = 128) were analyzed using enrichment analysis to determine overrepresented TF binding sites (TFBS). While most (56/73) TFs differed across environmental contaminants, a set of 17 TFs was enriched for promoter binding among miRNAs responsive to numerous environmental contaminants. Of these, one TF was common to miRNAs altered by the majority of environmental contaminants, namely SWI/SNF-related, matrix-associated, actin-dependent regulator of chromatin, subfamily A, member 3 (SMARCA3). These identified TFs represent candidate common transcriptional regulators of miRNAs perturbed by environmental toxicants. - Highlights: • Transcription factors that regulate environmentally-modulated miRNA expression are understudied • Transcription factor binding sites (TFBS) located within DNA promoter regions of miRNAs were identified. • Specific transcription factors may serve as master regulators of environmentally-mediated microRNA expression.« less

Different gene-specific mechanisms determine the 'revised-response' memory transcription patterns of a subset of A. thaliana dehydration stress responding genes.

PubMed

Liu, Ning; Ding, Yong; Fromm, Michael; Avramova, Zoya

2014-05-01

Plants that have experienced several exposures to dehydration stress show increased resistance to future exposures by producing faster and/or stronger reactions, while many dehydration stress responding genes in Arabidopsis thaliana super-induce their transcription as a 'memory' from the previous encounter. A previously unknown, rather unusual, memory response pattern is displayed by a subset of the dehydration stress response genes. Despite robustly responding to a first stress, these genes return to their initial, pre-stressed, transcript levels during the watered recovery; surprisingly, they do not respond further to subsequent stresses of similar magnitude and duration. This transcriptional behavior defines the 'revised-response' memory genes. Here, we investigate the molecular mechanisms regulating this transcription memory behavior. Potential roles of abscisic acid (ABA), of transcription factors (TFs) from the ABA signaling pathways (ABF2/3/4 and MYC2), and of histone modifications (H3K4me3 and H3K27me3) as factors in the revised-response transcription memory patterns are elucidated. We identify the TF MYC2 as the critical component for the memory behavior of a specific subset of MYC2-dependent genes. © The Author(s) 2014. Published by Oxford University Press on behalf of Nucleic Acids Research.

Water resources and shale gas/oil production in the Appalachian Basin: critical issues and evolving developments

USGS Publications Warehouse

Kappel, William M.; Williams, John H.; Szabo, Zoltan

2013-01-01

Unconventional natural gas and oil resources in the United States are important components of a national energy program. While the Nation seeks greater energy independence and greener sources of energy, Federal agencies with environmental responsibilities, state and local regulators and water-resource agencies, and citizens throughout areas of unconventional shale gas development have concerns about the environmental effects of high volume hydraulic fracturing (HVHF), including those in the Appalachian Basin in the northeastern United States (fig. 1). Environmental concerns posing critical challenges include the availability and use of surface water and groundwater for hydraulic fracturing; the migration of stray gas and potential effects on overlying aquifers; the potential for flowback, formation fluids, and other wastes to contaminate surface water and groundwater; and the effects from drill pads, roads, and pipeline infrastructure on land disturbance in small watersheds and headwater streams (U.S. Government Printing Office, 2012). Federal, state, regional and local agencies, along with the gas industry, are striving to use the best science and technology to develop these unconventional resources in an environmentally safe manner. Some of these concerns were addressed in U.S. Geological Survey (USGS) Fact Sheet 2009–3032 (Soeder and Kappel, 2009) about potential critical effects on water resources associated with the development of gas extraction from the Marcellus Shale of the Hamilton Group (Ver Straeten and others, 1994). Since that time, (1) the extraction process has evolved, (2) environmental awareness related to high-volume hydraulic fracturing process has increased, (3) state regulations concerning gas well drilling have been modified, and (4) the practices used by industry to obtain, transport, recover, treat, recycle, and ultimately dispose of the spent fluids and solid waste materials have evolved. This report updates and expands on Fact Sheet 2009–3032 and presents new information regarding selected aspects of unconventional shale gas development in the Appalachian Basin (primarily Virginia, West Virginia, Maryland, Pennsylvania, Ohio, and New York). This document was prepared by the USGS, in cooperation with the U.S. Department of Energy, and reviews the evolving technical advances and scientific studies made in the Appalachian Basin between 2009 and the present (2013), addressing past and current issues for oil and gas development in the region.

Resveratrol upregulates Egr-1 expression and activity involving extracellular signal-regulated protein kinase and ternary complex factors

DOE Office of Scientific and Technical Information (OSTI.GOV)

Rössler, Oliver G.; Glatzel, Daniel; Thiel, Gerald, E-mail: gerald.thiel@uks.eu

2015-03-01

Many intracellular functions have been attributed to resveratrol, a polyphenolic phytoalexin found in grapes and in other plants. Here, we show that resveratrol induces the expression of the transcription factor Egr-1 in human embryonic kidney cells. Using a chromosomally embedded Egr-1-responsive reporter gene, we show that the Egr-1 activity was significantly elevated in resveratrol-treated cells, indicating that the newly synthesized Egr-1 protein was biologically active. Stimulus-transcription coupling leading to the resveratrol-induced upregulation of Egr-1 expression and activity requires the protein kinases Raf and extracellular signal-regulated protein kinase ERK, while MAP kinase phosphatase-1 functions as a nuclear shut-off device that interruptsmore » the signaling cascade connecting resveratrol stimulation with enhanced Egr-1 expression. On the transcriptional level, Elk-1, a key transcriptional regulator of serum response element-driven gene transcription, connects the intracellular signaling cascade elicited by resveratrol with transcription of the Egr-1 gene. These data were corroborated by the observation that stimulation of the cells with resveratrol increased the transcriptional activation potential of Elk-1. The SRE as well as the GC-rich DNA binding site of Egr-1 function as resveratrol-responsive elements. Thus, resveratrol regulates gene transcription via activation of the stimulus-regulated protein kinases Raf and ERK and the stimulus-responsive transcription factors TCF and Egr-1. - Highlights: • The plant polyphenol resveratrol upregulates Egr-1 expression and activity. • The stimulation of Egr-1 requires the protein kinases ERK and Raf. • Resveratrol treatment upregulates the transcriptional activation potential of Elk-1. • Resveratrol-induced stimulation of Egr-1 requires ternary complex factors. • Two distinct resveratrol-responsive elements were identified.« less

The Smad3 linker region contains a transcriptional activation domain

PubMed Central

2004-01-01

Transforming growth factor-β (TGF-β)/Smads regulate a wide variety of biological responses through transcriptional regulation of target genes. Smad3 plays a key role in TGF-β/Smad-mediated transcriptional responses. Here, we show that the proline-rich linker region of Smad3 contains a transcriptional activation domain. When the linker region is fused to a heterologous DNA-binding domain, it activates transcription. We show that the linker region physically interacts with p300. The adenovirus E1a protein, which binds to p300, inhibits the transcriptional activity of the linker region, and overexpression of p300 can rescue the linker-mediated transcriptional activation. In contrast, an adenovirus E1a mutant, which cannot bind to p300, does not inhibit the linker-mediated transcription. The native Smad3 protein lacking the linker region is unable to mediate TGF-β transcriptional activation responses, although it can be phosphorylated by the TGF-β receptor at the C-terminal tail and has a significantly increased ability to form a heteromeric complex with Smad4. We show further that the linker region and the C-terminal domain of Smad3 synergize for transcriptional activation in the presence of TGF-β. Thus our findings uncover an important function of the Smad3 linker region in Smad-mediated transcriptional control. PMID:15588252

The Smad3 linker region contains a transcriptional activation domain.

PubMed

Wang, Guannan; Long, Jianyin; Matsuura, Isao; He, Dongming; Liu, Fang

2005-02-15

Transforming growth factor-beta (TGF-beta)/Smads regulate a wide variety of biological responses through transcriptional regulation of target genes. Smad3 plays a key role in TGF-beta/Smad-mediated transcriptional responses. Here, we show that the proline-rich linker region of Smad3 contains a transcriptional activation domain. When the linker region is fused to a heterologous DNA-binding domain, it activates transcription. We show that the linker region physically interacts with p300. The adenovirus E1a protein, which binds to p300, inhibits the transcriptional activity of the linker region, and overexpression of p300 can rescue the linker-mediated transcriptional activation. In contrast, an adenovirus E1a mutant, which cannot bind to p300, does not inhibit the linker-mediated transcription. The native Smad3 protein lacking the linker region is unable to mediate TGF-beta transcriptional activation responses, although it can be phosphorylated by the TGF-beta receptor at the C-terminal tail and has a significantly increased ability to form a heteromeric complex with Smad4. We show further that the linker region and the C-terminal domain of Smad3 synergize for transcriptional activation in the presence of TGF-beta. Thus our findings uncover an important function of the Smad3 linker region in Smad-mediated transcriptional control.

Optimizing Water Management for Collocated Conventional and Unconventional Reservoirs

NASA Astrophysics Data System (ADS)

Reedy, R. C.; Scanlon, B. R.; Walsh, M.

2016-12-01

With the U.S. producing much more water than oil from oil and gas reservoirs, managing produced water is becoming a critical issue. Here we quantify water production from collocated conventional and unconventional reservoirs using well by well analysis and evaluate various water management strategies using the U.S. Permian Basin as a case study. Water production during the past 15 years in the Permian Basin totaled 55×109 barrels (bbl), 95% from wells in conventional reservoirs resulting in an average water to oil ratio of 12 compared to ratios of 2-3 in wells in unconventional reservoirs. Some of this water ( 25%) is returned to the reservoir for secondary oil recovery (water flooding) while the remaining water is injected into an average of 18,000 salt water disposal wells. Total water production over the past 15 yr (2000 - 2015) exceeds water used for hydraulic fracturing by almost 40 times. Analyzing water injection into salt water disposal wells relative to water requirements for hydraulic fracturing at a 5 square mile grid scale based on 2014 data indicates that water disposal exceeds water requirements for hydraulic fracturing throughout most of the play. Reusing/recycling of produced water for hydraulic fracturing would reduce sourcing and disposal issues related to hydraulic fracturing. Because shales (unconventional reservoirs) provide the source rocks for many conventional reservoirs, coordinating water management from both conventional and unconventional reservoirs can help resolve issues related to sourcing of water for hydraulic fracturing and disposing of produced water. Reusing/recycling produced water can also help reduce water scarcity concerns in some regions.

Can Unconventional Exercise be Helpful in the Treatment, Management and Prevention of Osteosarcopenic Obesity?

PubMed

Kelly, Owen J; Gilman, Jennifer C

2017-01-01

Body composition changes occur with aging; bone and muscle mass decrease while fat mass increases. The collective term for these changes is osteosarcopenic obesity. It is known that conventional resistance exercise programs build/maintain lean mass and reduce fat mass. However, unconventional (to Western society/medicine) forms of exercise may be viable for the treatment/prevention of osteosarcopenic obesity. The purpose of this review is to assess relatively unconventional exercises for their efficacy in maintaining/improving bone and muscle mass and reducing fat mass. A literature search for unconventional exercise showed Tai Chi, yoga, Pilates, whole body vibration, electrical stimulation of muscle, and the Alexander Technique were considered alternative/ unconventional. A PubMed and Medline search for human data using combinations and synonyms of osteoporosis, sarcopenia and obesity, and each exercise was then conducted. Tai Chi, yoga, and Pilates, in addition to whole body vibration, electrical stimulation of muscle, and the Alexander Technique are all considered low impact. Tai Chi, yoga, and Pilates not only physically support the body, but also increase balance and quality of life. The devices showed promise in reducing or preventing muscle atrophy in older people that are unable to perform conventional exercises. Any exercise, conventional or otherwise, especially in sedentary older people, at risk of, or diagnosed with osteosarcopenic obesity may be better than none. Exercise prescriptions should suit the patient and the desired outcomes; the patient should not be forced to fit an exercise prescription, so all potential forms of exercise should be considered. Copyright© Bentham Science Publishers; For any queries, please email at epub@benthamscience.org.

Assessing the Role of ETHYLENE RESPONSE FACTOR Transcriptional Repressors in Salicylic Acid-Mediated Suppression of Jasmonic Acid-Responsive Genes.

PubMed

Caarls, Lotte; Van der Does, Dieuwertje; Hickman, Richard; Jansen, Wouter; Verk, Marcel C Van; Proietti, Silvia; Lorenzo, Oscar; Solano, Roberto; Pieterse, Corné M J; Van Wees, Saskia C M

2017-02-01

Salicylic acid (SA) and jasmonic acid (JA) cross-communicate in the plant immune signaling network to finely regulate induced defenses. In Arabidopsis, SA antagonizes many JA-responsive genes, partly by targeting the ETHYLENE RESPONSE FACTOR (ERF)-type transcriptional activator ORA59. Members of the ERF transcription factor family typically bind to GCC-box motifs in the promoters of JA- and ethylene-responsive genes, thereby positively or negatively regulating their expression. The GCC-box motif is sufficient for SA-mediated suppression of JA-responsive gene expression. Here, we investigated whether SA-induced ERF-type transcriptional repressors, which may compete with JA-induced ERF-type activators for binding at the GCC-box, play a role in SA/JA antagonism. We selected ERFs that are transcriptionally induced by SA and/or possess an EAR transcriptional repressor motif. Several of the 16 ERFs tested suppressed JA-dependent gene expression, as revealed by enhanced JA-induced PDF1.2 or VSP2 expression levels in the corresponding erf mutants, while others were involved in activation of these genes. However, SA could antagonize JA-induced PDF1.2 or VSP2 in all erf mutants, suggesting that the tested ERF transcriptional repressors are not required for SA/JA cross-talk. Moreover, a mutant in the co-repressor TOPLESS, that showed reduction in repression of JA signaling, still displayed SA-mediated antagonism of PDF1.2 and VSP2. Collectively, these results suggest that SA-regulated ERF transcriptional repressors are not essential for antagonism of JA-responsive gene expression by SA. We further show that de novo SA-induced protein synthesis is required for suppression of JA-induced PDF1.2, pointing to SA-stimulated production of an as yet unknown protein that suppresses JA-induced transcription. © The Author 2016. Published by Oxford University Press on behalf of Japanese Society of Plant Physiologists. All rights reserved. For permissions, please email: journals.permissions@oup.com.

An ABRE promoter sequence is involved in osmotic stress-responsive expression of the DREB2A gene, which encodes a transcription factor regulating drought-inducible genes in Arabidopsis.

PubMed

Kim, June-Sik; Mizoi, Junya; Yoshida, Takuya; Fujita, Yasunari; Nakajima, Jun; Ohori, Teppei; Todaka, Daisuke; Nakashima, Kazuo; Hirayama, Takashi; Shinozaki, Kazuo; Yamaguchi-Shinozaki, Kazuko

2011-12-01

In plants, osmotic stress-responsive transcriptional regulation depends mainly on two major classes of cis-acting elements found in the promoter regions of stress-inducible genes: ABA-responsive elements (ABREs) and dehydration-responsive elements (DREs). ABRE has been shown to perceive ABA-mediated osmotic stress signals, whereas DRE is known to be involved in an ABA-independent pathway. Previously, we reported that the transcription factor DRE-BINDING PROTEIN 2A (DREB2A) regulates DRE-mediated transcription of target genes under osmotic stress conditions in Arabidopsis (Arabidopsis thaliana). However, the transcriptional regulation of DREB2A itself remains largely uncharacterized. To elucidate the transcriptional mechanism associated with the DREB2A gene under osmotic stress conditions, we generated a series of truncated and base-substituted variants of the DREB2A promoter and evaluated their transcriptional activities individually. We found that both ABRE and coupling element 3 (CE3)-like sequences located approximately -100 bp from the transcriptional initiation site are necessary for the dehydration-responsive expression of DREB2A. Coupling our transient expression analyses with yeast one-hybrid and chromatin immunoprecipitation (ChIP) assays indicated that the ABRE-BINDING PROTEIN 1 (AREB1), AREB2 and ABRE-BINDING FACTOR 3 (ABF3) bZIP transcription factors can bind to and activate the DREB2A promoter in an ABRE-dependent manner. Exogenous ABA application induced only a modest accumulation of the DREB2A transcript when compared with the osmotic stress treatment. However, the osmotic stress-induced DREB2A expression was found to be markedly impaired in several ABA-deficient and ABA-insensitive mutants. These results suggest that in addition to an ABA-independent pathway, the ABA-dependent pathway plays a positive role in the osmotic stress-responsive expression of DREB2A.

Natural antisense transcripts associated with salinity response in alfalfa

USDA-ARS?s Scientific Manuscript database

Natural antisense transcripts (NATs) are long non-coding RNAs (lncRNAs) complimentary to the messenger (sense) RNA (Wang et al. 2014). Many of them are involved in regulation of their own sense transcripts thus playing pivotal biological roles in all processes of organismal development and responses...

Acclimation of Saccharomyces cerevisiae to low temperature: a chemostat-based transcriptome analysis.

PubMed

Tai, Siew Leng; Daran-Lapujade, Pascale; Walsh, Michael C; Pronk, Jack T; Daran, Jean-Marc

2007-12-01

Effects of suboptimal temperatures on transcriptional regulation in yeast have been extensively studied in batch cultures. To eliminate indirect effects of specific growth rates that are inherent to batch-cultivation studies, genome-wide transcriptional responses to low temperatures were analyzed in steady-state chemostats, grown at a fixed specific growth rate (0.03 h(-1)). Although in vivo metabolic fluxes were essentially the same in cultures grown at 12 and at 30 degrees C, concentrations of the growth-limiting nutrients (glucose or ammonia) were higher at 12 degrees C. This difference was reflected by transcript levels of genes that encode transporters for the growth-limiting nutrients. Several transcriptional responses to low temperature occurred under both nutrient-limitation regimes. Increased transcription of ribosome-biogenesis genes emphasized the importance of adapting protein-synthesis capacity to low temperature. In contrast to observations in cold-shock and batch-culture studies, transcript levels of environmental stress response genes were reduced at 12 degrees C. Transcription of trehalose-biosynthesis genes and intracellular trehalose levels indicated that, in contrast to its role in cold-shock adaptation, trehalose is not involved in steady-state low-temperature adaptation. Comparison of the chemostat-based transcriptome data with literature data revealed large differences between transcriptional reprogramming during long-term low-temperature acclimation and the transcriptional responses to a rapid transition to low temperature.

Novel gradient-diameter magnetic nanowire arrays with unconventional magnetic anisotropy behaviors.

PubMed

Wang, Jing; Zuo, Zhili; Huang, Liang; Warsi, Muhammad Asif; Xiao, John Q; Hu, Jun

2018-06-21

Fe-Co-Ni gradient-diameter magnetic nanowire arrays were fabricated via direct-current electrodeposition into a tapered anodic aluminium oxide template. In contrast to the magnetic behaviors of uniform-diameter nanowire arrays, these arrays exhibited tailorable magnetic anisotropy that can be used to switch magnetic nanowires easily and unconventional temperature-dependent coercivity with much better thermal stability.

Anomalous Thermal Conductivity and Magnetic Torque Response in the Honeycomb Magnet α -RuCl3

NASA Astrophysics Data System (ADS)

Leahy, Ian A.; Pocs, Christopher A.; Siegfried, Peter E.; Graf, David; Do, S.-H.; Choi, Kwang-Yong; Normand, B.; Lee, Minhyea

2017-05-01

We report on the unusual behavior of the in-plane thermal conductivity κ and torque τ response in the Kitaev-Heisenberg material α -RuCl3 . κ shows a striking enhancement with linear growth beyond H =7 T , where magnetic order disappears, while τ for both of the in-plane symmetry directions shows an anomaly at the same field. The temperature and field dependence of κ are far more complex than conventional phonon and magnon contributions, and require us to invoke the presence of unconventional spin excitations whose properties are characteristic of a field-induced spin-liquid phase related to the enigmatic physics of the Kitaev model in an applied magnetic field.

Food Allergy: Our Evolving Understanding of Its Pathogenesis, Prevention, and Treatment.

PubMed

Iweala, Onyinye I; Burks, A Wesley

2016-05-01

Food allergy is defined as an IgE-mediated hypersensitivity response to ingested food with allergic symptoms ranging from urticaria to life-threatening anaphylaxis. Food allergy is thought to develop because of (1) failed induction of tolerance upon initial exposure to food antigen or (2) breakdown of established tolerance to food antigen. We review current understanding of the pathogenesis, epidemiology, and natural history of food allergy, including the unconventional IgE-mediated food allergy to mammalian meat known as alpha-gal food allergy. We highlight emerging data on food allergy treatment and prevention, emphasizing the growing appeal of manipulating the gut microenvironment using probiotics and helminth products to blunt systemic allergic responses to food.

Unconventional Dentistry in India – An Insight into the Traditional Methods

PubMed Central

Boloor, Vinita Ashutosh; Hosadurga, Rajesh; Rao, Anupama; Jenifer, Haziel; Pratap, Sruthy

2014-01-01

Unconventional medicine (UM) has been known and practised since the recorded history of civilization. Some unconventional practices may be viewed as “the continuity of traditions, religious beliefs, and even quackery that non-specialists practice.” These practices have been associated with religious beliefs and the spiritual domain as well as with the physical domain. In ancient Old World civilizations, UM was performed by skilled experts or wise men; in today's Western civilization, practitioners may or may not be licensed, and some are charlatans. Dentistry, like medicine, is a traditional, science-based, highly regulated healthcare profession that serves increasingly sophisticated and demanding clients. Today, traditional dental practice is dealing with an array of challenges to the established professional system; these challenges are generally termed “alternative” (or complementary, unconventional, or integrative). Genuine alternatives are comparable methods of equal value that have met scientific and regulatory criteria for safety and effectiveness. Because “alternative care” has become politicized and is often a misnomer – referring to practices that are not alternative to, complementary to, or integrating with conventional health care – the more accurate term “unconventional” is used. PMID:25161919

Monitoring radionuclides in subsurface drinking water sources near unconventional drilling operations: a pilot study.

PubMed

Nelson, Andrew W; Knight, Andrew W; Eitrheim, Eric S; Schultz, Michael K

2015-04-01

Unconventional drilling (the combination of hydraulic fracturing and horizontal drilling) to extract oil and natural gas is expanding rapidly around the world. The rate of expansion challenges scientists and regulators to assess the risks of the new technologies on drinking water resources. One concern is the potential for subsurface drinking water resource contamination by naturally occurring radioactive materials co-extracted during unconventional drilling activities. Given the rate of expansion, opportunities to test drinking water resources in the pre- and post-fracturing setting are rare. This pilot study investigated the levels of natural uranium, lead-210, and polonium-210 in private drinking wells within 2000 m of a large-volume hydraulic fracturing operation--before and approximately one-year following the fracturing activities. Observed radionuclide concentrations in well waters tested did not exceed maximum contaminant levels recommended by state and federal agencies. No statistically-significant differences in radionuclide concentrations were observed in well-water samples collected before and after the hydraulic fracturing activities. Expanded monitoring of private drinking wells before and after hydraulic fracturing activities is needed to develop understanding of the potential for drinking water resource contamination from unconventional drilling and gas extraction activities. Copyright © 2015 Elsevier Ltd. All rights reserved.

Is automatic speech-to-text transcription ready for use in psychological experiments?

PubMed

Ziman, Kirsten; Heusser, Andrew C; Fitzpatrick, Paxton C; Field, Campbell E; Manning, Jeremy R

2018-04-23

Verbal responses are a convenient and naturalistic way for participants to provide data in psychological experiments (Salzinger, The Journal of General Psychology, 61(1),65-94:1959). However, audio recordings of verbal responses typically require additional processing, such as transcribing the recordings into text, as compared with other behavioral response modalities (e.g., typed responses, button presses, etc.). Further, the transcription process is often tedious and time-intensive, requiring human listeners to manually examine each moment of recorded speech. Here we evaluate the performance of a state-of-the-art speech recognition algorithm (Halpern et al., 2016) in transcribing audio data into text during a list-learning experiment. We compare transcripts made by human annotators to the computer-generated transcripts. Both sets of transcripts matched to a high degree and exhibited similar statistical properties, in terms of the participants' recall performance and recall dynamics that the transcripts captured. This proof-of-concept study suggests that speech-to-text engines could provide a cheap, reliable, and rapid means of automatically transcribing speech data in psychological experiments. Further, our findings open the door for verbal response experiments that scale to thousands of participants (e.g., administered online), as well as a new generation of experiments that decode speech on the fly and adapt experimental parameters based on participants' prior responses.

An overview of transcriptional regulation in response to toxicological insult.

PubMed

Jennings, Paul; Limonciel, Alice; Felice, Luca; Leonard, Martin O

2013-01-01

The completion of the human genome project and the subsequent advent of DNA microarray and high-throughput sequencing technologies have led to a renaissance in molecular toxicology. Toxicogenomic data sets, from both in vivo and in vitro studies, are growing exponentially, providing a wealth of information on regulation of stress pathways at the transcriptome level. Through such studies, we are now beginning to appreciate the diversity and complexity of biological responses to xenobiotics. In this review, we aim to consolidate and summarise the major toxicologically relevant transcription factor-governed molecular pathways. It is becoming clear that different chemical entities can cause oxidative, genotoxic and proteotoxic stress, which induce cellular responses in an effort to restore homoeostasis. Primary among the response pathways involved are NFE2L2 (Nrf2), NFE2L1 (Nrf1), p53, heat shock factor and the unfolded protein response. Additionally, more specific mechanisms exist where xenobiotics act as ligands, including the aryl hydrocarbon receptor, metal-responsive transcription factor-1 and the nuclear receptor family of transcription factors. Other pathways including the immunomodulatory transcription factors NF-κB and STAT together with the hypoxia-inducible transcription factor HIF are also implicated in cellular responses to xenobiotic exposure. A less specific but equally important aspect to cellular injury controlled by transcriptional activity is loss of tissue-specific gene expression, resulting in dedifferentiation of target cells and compromise of tissue function. Here, we review these pathways and the genes they regulate in order to provide an overview of this growing field of molecular toxicology.

The Fast and Transient Transcriptional Network of Gravity and Mechanical Stimulation in the Arabidopsis Root Apex1[w

PubMed Central

Kimbrough, Jeffery M.; Salinas-Mondragon, Raul; Boss, Wendy F.; Brown, Christopher S.; Sederoff, Heike Winter

2004-01-01

Plant root growth is affected by both gravity and mechanical stimulation (Massa GD, Gilroy S [2003] Plant J 33: 435–445). A coordinated response to both stimuli requires specific and common elements. To delineate the transcriptional response mechanisms, we carried out whole-genome microarray analysis of Arabidopsis root apices after gravity stimulation (reorientation) and mechanical stimulation and monitored transcript levels of 22,744 genes in a time course during the first hour after either stimulus. Rapid, transient changes in the relative abundance of specific transcripts occurred in response to gravity or mechanical stimulation, and these transcript level changes reveal clusters of coordinated events. Transcriptional regulation occurs in the root apices within less than 2 min after either stimulus. We identified genes responding specifically to each stimulus as well as transcripts regulated in both signal transduction pathways. Several unknown genes were specifically induced only during gravitropic stimulation (gravity induced genes). We also analyzed the network of transcriptional regulation during the early stages of gravitropism and mechanical stimulation. PMID:15347791

Anoxia-responsive regulation of the FoxO transcription factors in freshwater turtles, Trachemys scripta elegans.

PubMed

Krivoruchko, Anastasia; Storey, Kenneth B

2013-11-01

The forkhead class O (FoxO) transcription factors are important regulators of multiple aspects of cellular metabolism. We hypothesized that activation of these transcription factors could play crucial roles in low oxygen survival in the anoxia-tolerant turtle, Trachemys scripta elegans. Two FoxOs, FoxO1 and FoxO3, were examined in turtle tissues in response to 5 and 20h of anoxic submergence using techniques of RT-PCR, western immunoblotting and DNA-binding assays to assess activation. Transcript levels of FoxO-responsive genes were also quantified using RT-PCR. FoxO1 was anoxia-responsive in the liver, with increases in transcript levels, protein levels, nuclear levels and DNA-binding of 1.7-4.8fold in response to anoxia. Levels of phosphorylated FoxO1 also decreased to 57% of control values in response to 5h of anoxia, indicating activation. FoxO3 was activated in the heart, kidney and liver in response to anoxia, with nuclear levels increasing by 1.5-3.7fold and DNA-binding activity increasing by 1.3-2.9fold. Transcript levels of two FoxO-target genes, p27kip1 and catalase, also rose by 2.4-2.5fold in the turtle liver under anoxia. The results suggest that the FoxO transcription factors are activated in response to anoxia in T. scripta elegans, potentially contributing to the regulation of stress resistance and metabolic depression. This study provides the first demonstration of activation of FoxOs in a natural model for vertebrate anoxia tolerance, further improving understanding of how tissues can survive without oxygen. © 2013.

Systematic analysis of phloem-feeding insect-induced transcriptional reprogramming in Arabidopsis highlights common features and reveals distinct responses to specialist and generalist insects.

PubMed

Foyer, Christine H; Verrall, Susan R; Hancock, Robert D

2015-02-01

Phloem-feeding insects (PFIs), of which aphids are the largest group, are major agricultural pests causing extensive damage to crop plants. In contrast to chewing insects, the nature of the plant response to PFIs remains poorly characterized. Scrutiny of the literature concerning transcriptional responses of model and crop plant species to PFIs reveals surprisingly little consensus with respect to the transcripts showing altered abundance following infestation. Nevertheless, core features of the transcriptional response to PFIs can be defined in Arabidopsis thaliana. This comparison of the PFI-associated transcriptional response observed in A. thaliana infested by the generalists Myzus persicae and Bemisia tabaci with the specialist Brevicoryne brassicae highlights the importance of calcium-dependent and receptor kinase-associated signalling. We discuss these findings within the context of the complex cross-talk between the different hormones regulating basal immune response mechanisms in plants. We identify PFI-responsive genes, highlighting the importance of cell wall-associated kinases in plant-PFI interactions, as well as the significant role of kinases containing the domain of unknown function 26. A common feature of plant-PFI interaction is enhanced abundance of transcripts encoding WRKY transcription factors. However, significant divergence was observed with respect to secondary metabolism dependent upon the insect attacker. Transcripts encoding enzymes and proteins associated with glucosinolate metabolism were decreased following attack by the generalist M. persicae but not by the specialist B. brassicae. This analysis provides a comprehensive overview of the molecular patterns associated with the plant response to PFIs and suggests that plants recognize and respond to perturbations in the cell wall occurring during PFI infestation. © The Author 2014. Published by Oxford University Press on behalf of the Society for Experimental Biology. All rights reserved. For permissions, please email: journals.permissions@oup.com.

A critical role for topoisomerase IIb and DNA double strand breaks in transcription

PubMed Central

Calderwood, Stuart K.

2016-01-01

ABSTRACT Recent studies have indicated a novel role for topoisomerase IIb in transcription. Transcription of heat shock genes, serum-induced immediate early genes and nuclear receptor-activated genes, each required DNA double strands generated by topoisomerase IIb. Such strand breaks seemed both necessary and sufficient for transcriptional activation. In addition, such transcription was associated with initiation of the DNA damage response pathways, including the activation of the enzymes: ataxia-telangiectasia mutated (ATM), DNA-dependent protein kinase and poly (ADP ribose) polymerase 1. DNA damage response signaling was involved both in transcription and in repair of DNA breaks generated by topoisomerase IIb. PMID:27100743

A critical role for topoisomerase IIb and DNA double strand breaks in transcription.

PubMed

Calderwood, Stuart K

2016-05-26

Recent studies have indicated a novel role for topoisomerase IIb in transcription. Transcription of heat shock genes, serum-induced immediate early genes and nuclear receptor-activated genes, each required DNA double strands generated by topoisomerase IIb. Such strand breaks seemed both necessary and sufficient for transcriptional activation. In addition, such transcription was associated with initiation of the DNA damage response pathways, including the activation of the enzymes: ataxia-telangiectasia mutated (ATM), DNA-dependent protein kinase and poly (ADP ribose) polymerase 1. DNA damage response signaling was involved both in transcription and in repair of DNA breaks generated by topoisomerase IIb.

STAT3 precedes HIF1α transcriptional responses to oxygen and oxygen and glucose deprivation in human brain pericytes.

PubMed

Carlsson, Robert; Özen, Ilknur; Barbariga, Marco; Gaceb, Abderahim; Roth, Michaela; Paul, Gesine

2018-01-01

Brain pericytes are important to maintain vascular integrity of the neurovascular unit under both physiological and ischemic conditions. Ischemic stroke is known to induce an inflammatory and hypoxic response due to the lack of oxygen and glucose in the brain tissue. How this early response to ischemia is molecularly regulated in pericytes is largely unknown and may be of importance for future therapeutic targets. Here we evaluate the transcriptional responses in in vitro cultured human brain pericytes after oxygen and/or glucose deprivation. Hypoxia has been widely known to stabilise the transcription factor hypoxia inducible factor 1-alpha (HIF1α) and mediate the induction of hypoxic transcriptional programs after ischemia. However, we find that the transcription factors Jun Proto-Oncogene (c-JUN), Nuclear Factor Of Kappa Light Polypeptide Gene Enhancer In B-Cells (NFκB) and signal transducer and activator of transcription 3 (STAT3) bind genes regulated after 2hours (hs) of omitted glucose and oxygen before HIF1α. Potent HIF1α responses require 6hs of hypoxia to substantiate transcriptional regulation comparable to either c-JUN or STAT3. Phosphorylated STAT3 protein is at its highest after 5 min of oxygen and glucose (OGD) deprivation, whereas maximum HIF1α stabilisation requires 120 min. We show that STAT3 regulates angiogenic and metabolic pathways before HIF1α, suggesting that HIF1α is not the initiating trans-acting factor in the response of pericytes to ischemia.

Analyzing the dose-dependence of the Saccharomyces cerevisiae global transcriptional response to methyl methanesulfonate and ionizing radiation.

PubMed

Benton, Michael G; Somasundaram, Swetha; Glasner, Jeremy D; Palecek, Sean P

2006-12-01

One of the most crucial tasks for a cell to ensure its long term survival is preserving the integrity of its genetic heritage via maintenance of DNA structure and sequence. While the DNA damage response in the yeast Saccharomyces cerevisiae, a model eukaryotic organism, has been extensively studied, much remains to be elucidated about how the organism senses and responds to different types and doses of DNA damage. We have measured the global transcriptional response of S. cerevisiae to multiple doses of two representative DNA damaging agents, methyl methanesulfonate (MMS) and gamma radiation. Hierarchical clustering of genes with a statistically significant change in transcription illustrated the differences in the cellular responses to MMS and gamma radiation. Overall, MMS produced a larger transcriptional response than gamma radiation, and many of the genes modulated in response to MMS are involved in protein and translational regulation. Several clusters of coregulated genes whose responses varied with DNA damaging agent dose were identified. Perhaps the most interesting cluster contained four genes exhibiting biphasic induction in response to MMS dose. All of the genes (DUN1, RNR2, RNR4, and HUG1) are involved in the Mec1p kinase pathway known to respond to MMS, presumably due to stalled DNA replication forks. The biphasic responses of these genes suggest that the pathway is induced at lower levels as MMS dose increases. The genes in this cluster with a threefold or greater transcriptional response to gamma radiation all showed an increased induction with increasing gamma radiation dosage. Analyzing genome-wide transcriptional changes to multiple doses of external stresses enabled the identification of cellular responses that are modulated by magnitude of the stress, providing insights into how a cell deals with genotoxicity.

"Hit-and-Run" transcription: de novo transcription initiated by a transient bZIP1 "hit" persists after the "run".

PubMed

Doidy, Joan; Li, Ying; Neymotin, Benjamin; Edwards, Molly B; Varala, Kranthi; Gresham, David; Coruzzi, Gloria M

2016-02-03

Dynamic transcriptional regulation is critical for an organism's response to environmental signals and yet remains elusive to capture. Such transcriptional regulation is mediated by master transcription factors (TF) that control large gene regulatory networks. Recently, we described a dynamic mode of TF regulation named "hit-and-run". This model proposes that master TF can interact transiently with a set of targets, but the transcription of these transient targets continues after the TF dissociation from the target promoter. However, experimental evidence validating active transcription of the transient TF-targets is still lacking. Here, we show that active transcription continues after transient TF-target interactions by tracking de novo synthesis of RNAs made in response to TF nuclear import. To do this, we introduced an affinity-labeled 4-thiouracil (4tU) nucleobase to specifically isolate newly synthesized transcripts following conditional TF nuclear import. Thus, we extended the TARGET system (Transient Assay Reporting Genome-wide Effects of Transcription factors) to include 4tU-labeling and named this new technology TARGET-tU. Our proof-of-principle example is the master TF Basic Leucine Zipper 1 (bZIP1), a central integrator of metabolic signaling in plants. Using TARGET-tU, we captured newly synthesized mRNAs made in response to bZIP1 nuclear import at a time when bZIP1 is no longer detectably bound to its target. Thus, the analysis of de novo transcripomics demonstrates that bZIP1 may act as a catalyst TF to initiate a transcriptional complex ("hit"), after which active transcription by RNA polymerase continues without the TF being bound to the gene promoter ("run"). Our findings provide experimental proof for active transcription of transient TF-targets supporting a "hit-and-run" mode of action. This dynamic regulatory model allows a master TF to catalytically propagate rapid and broad transcriptional responses to changes in environment. Thus, the functional read-out of de novo transcripts produced by transient TF-target interactions allowed us to capture new models for genome-wide transcriptional control.

Evaluation of Potential Damage to Unconventional Structures by Sonic Booms

DTIC Science & Technology

1990-05-01

plaster and gypsum board caused by sonic boom is broken...on wood lath 3.3 5.6 2. Plaster on gyplath 7.5 16 3. Plaster on expanded metal lath 16 16 4. Plaster on concrete block 16 16 5. Gypsum board (new) 16... wallboard (also called plasterboard or drywall), it is assumed that interior walls of unconventional historic wood frame buildings used plaster instead.

How to Survive and Prosper in the Real World after Graduation: An Unconventional Approach to Achieving Your Success.

ERIC Educational Resources Information Center

Connors, Shawn M.

Unconventional advice to help college graduates be successful is offered. Ways to find sources of money (i.e., jobs) are described, including: using services or products offered through the mail, making phone calls to build a network of contacts in a particular industry, attending seminars to further one's knowledge of a field, learning about…

Unconventional Cyber Warfare: Cyber Opportunities in Unconventional Warfare

DTIC Science & Technology

2014-06-01

thanks to Tunisia’s modern communications infrastructure , pervasive Internet, and mobile phone network.”151 Although the use of information and...and physical space. Tunisia had a well-developed mobile phone and Internet infrastructure with nearly nine out of 10 Tunisians owning a mobile phone...OF TABLES Table 1. Top 20 countries of mobile phones per 100 people .........................................60 Table 2. Top 20 countries by number

Unconventional signal detection techniques with Gaussian probability mixtures adaptation in non-AWGN channels: full resolution receiver

NASA Astrophysics Data System (ADS)

Chabdarov, Shamil M.; Nadeev, Adel F.; Chickrin, Dmitry E.; Faizullin, Rashid R.

2011-04-01

In this paper we discuss unconventional detection technique also known as «full resolution receiver». This receiver uses Gaussian probability mixtures for interference structure adaptation. Full resolution receiver is alternative to conventional matched filter receivers in the case of non-Gaussian interferences. For the DS-CDMA forward channel with presence of complex interferences sufficient performance increasing was shown.

Unconventional Warfare in the American Civil War

DTIC Science & Technology

2004-06-18

Miller Thesis Title: Unconventional Warfare in the American Civil War Approved by: , Thesis Committee Chair LTC ( R ) Gregory T. Beck...M.A. , Member LTC ( R ) Richard Barbuto, Ph.D. , Consulting Faculty LTC ( R ) James B. Martin, Ph.D. Accepted this 18th day of...troops and supplies to forward areas. In official correspondence dated 26 May 1864 from Captain A. V. Barringer , Chief Quartermaster, Department of West

Genomic and transcriptomic characterization of the transcription factor family R2R3-MYB in soybean and its involvement in the resistance responses to Phakopsora pachyrhizi.

PubMed

Aoyagi, Luciano N; Lopes-Caitar, Valéria S; de Carvalho, Mayra C C G; Darben, Luana M; Polizel-Podanosqui, Adriana; Kuwahara, Marcia K; Nepomuceno, Alexandre L; Abdelnoor, Ricardo V; Marcelino-Guimarães, Francismar C

2014-12-01

Myb genes constitute one of the largest transcription factor families in the plant kingdom. Soybean MYB transcription factors have been related to the plant response to biotic stresses. Their involvement in response to Phakopsora pachyrhizi infection has been reported by several transcriptional studies. Due to their apparently highly diverse functions, these genes are promising targets for developing crop varieties resistant to diseases. In the present study, the identification and phylogenetic analysis of the soybean R2R3-MYB (GmMYB) transcription factor family was performed and the expression profiles of these genes under biotic stress were determined. GmMYBs were identified from the soybean genome using bioinformatic tools, and their putative functions were determined based on the phylogenetic tree and classified into subfamilies using guides AtMYBs describing known functions. The transcriptional profiles of GmMYBs upon infection with different pathogen were revealed by in vivo and in silico analyses. Selected target genes potentially involved in disease responses were assessed by RT-qPCR after different times of inoculation with P. pachyrhizi using different genetic backgrounds related to resistance genes (Rpp2 and Rpp5). R2R3-MYB transcription factors related to lignin synthesis and genes responsive to chitin were significantly induced in the resistant genotypes. Copyright © 2014 Elsevier Ireland Ltd. All rights reserved.

Transcriptional and chromatin regulation during fasting – The genomic era

PubMed Central

Goldstein, Ido; Hager, Gordon L.

2015-01-01

An elaborate metabolic response to fasting is orchestrated by the liver and is heavily reliant upon transcriptional regulation. In response to hormones (glucagon, glucocorticoids) many transcription factors (TFs) are activated and regulate various genes involved in metabolic pathways aimed at restoring homeostasis: gluconeogenesis, fatty acid oxidation, ketogenesis and amino acid shuttling. We summarize the recent discoveries regarding fasting-related TFs with an emphasis on genome-wide binding patterns. Collectively, the summarized findings reveal a large degree of co-operation between TFs during fasting which occurs at motif-rich DNA sites bound by a combination of TFs. These new findings implicate transcriptional and chromatin regulation as major determinants of the response to fasting and unravels the complex, multi-TF nature of this response. PMID:26520657

Tissue- and stage-specific Wnt target gene expression is controlled subsequent to β-catenin recruitment to cis-regulatory modules.

PubMed

Nakamura, Yukio; de Paiva Alves, Eduardo; Veenstra, Gert Jan C; Hoppler, Stefan

2016-06-01

Key signalling pathways, such as canonical Wnt/β-catenin signalling, operate repeatedly to regulate tissue- and stage-specific transcriptional responses during development. Although recruitment of nuclear β-catenin to target genomic loci serves as the hallmark of canonical Wnt signalling, mechanisms controlling stage- or tissue-specific transcriptional responses remain elusive. Here, a direct comparison of genome-wide occupancy of β-catenin with a stage-matched Wnt-regulated transcriptome reveals that only a subset of β-catenin-bound genomic loci are transcriptionally regulated by Wnt signalling. We demonstrate that Wnt signalling regulates β-catenin binding to Wnt target genes not only when they are transcriptionally regulated, but also in contexts in which their transcription remains unaffected. The transcriptional response to Wnt signalling depends on additional mechanisms, such as BMP or FGF signalling for the particular genes we investigated, which do not influence β-catenin recruitment. Our findings suggest a more general paradigm for Wnt-regulated transcriptional mechanisms, which is relevant for tissue-specific functions of Wnt/β-catenin signalling in embryonic development but also for stem cell-mediated homeostasis and cancer. Chromatin association of β-catenin, even to functional Wnt-response elements, can no longer be considered a proxy for identifying transcriptionally Wnt-regulated genes. Context-dependent mechanisms are crucial for transcriptional activation of Wnt/β-catenin target genes subsequent to β-catenin recruitment. Our conclusions therefore also imply that Wnt-regulated β-catenin binding in one context can mark Wnt-regulated transcriptional target genes for different contexts. © 2016. Published by The Company of Biologists Ltd.

Transcriptional Response of Nitrifying Communities to Wetting of Dry Soil

PubMed Central

Firestone, Mary K.

2013-01-01

The first rainfall following a severe dry period provides an abrupt water potential change that is both an acute physiological stress and a defined stimulus for the reawakening of soil microbial communities. We followed the responses of indigenous communities of ammonia-oxidizing bacteria, ammonia-oxidizing archaea, and nitrite-oxidizing bacteria to the addition of water to laboratory incubations of soils taken from two California annual grasslands following a typically dry Mediterranean summer. By quantifying transcripts for a subunit of bacterial and archaeal ammonia monooxygenases (amoA) and a bacterial nitrite oxidoreductase (nxrA) in soil from 15 min to 72 h after water addition, we identified transcriptional response patterns for each of these three groups of nitrifiers. An increase in quantity of bacterial amoA transcripts was detectable within 1 h of wet-up and continued until the size of the ammonium pool began to decrease, reflecting a possible role of transcription in upregulation of nitrification after drought-induced stasis. In one soil, the pulse of amoA transcription lasted for less than 24 h, demonstrating the transience of transcriptional pools and the tight coupling of transcription to the local soil environment. Analysis of 16S rRNA using a high-density microarray suggested that nitrite-oxidizing Nitrobacter spp. respond in tandem with ammonia-oxidizing bacteria while nitrite-oxidizing Nitrospina spp. and Nitrospira bacteria may not. Archaeal ammonia oxidizers may respond slightly later than bacterial ammonia oxidizers but may maintain elevated transcription longer. Despite months of desiccation-induced inactivation, we found rapid transcriptional response by all three groups of soil nitrifiers. PMID:23524666

Myonuclear transcription is responsive to mechanical load and DNA content but uncoupled from cell size during hypertrophy.

PubMed

Kirby, Tyler J; Patel, Rooshil M; McClintock, Timothy S; Dupont-Versteegden, Esther E; Peterson, Charlotte A; McCarthy, John J

2016-03-01

Myofibers increase size and DNA content in response to a hypertrophic stimulus, thus providing a physiological model with which to study how these factors affect global transcription. Using 5-ethynyl uridine (EU) to metabolically label nascent RNA, we measured a sevenfold increase in myofiber transcription during early hypertrophy before a change in cell size and DNA content. The typical increase in myofiber DNA content observed at the later stage of hypertrophy was associated with a significant decrease in the percentage of EU-positive myonuclei; however, when DNA content was held constant by preventing myonuclear accretion via satellite cell depletion, both the number of transcriptionally active myonuclei and the amount of RNA generated by each myonucleus increased. During late hypertrophy, transcription did not scale with cell size, as smaller myofibers (<1000 μm(2)) demonstrated the highest transcriptional activity. Finally, transcription was primarily responsible for changes in the expression of genes known to regulate myofiber size. These findings show that resident myonuclei possess a significant reserve capacity to up-regulate transcription during hypertrophy and that myofiber transcription is responsive to DNA content but uncoupled from cell size during hypertrophy. © 2016 Kirby et al. This article is distributed by The American Society for Cell Biology under license from the author(s). Two months after publication it is available to the public under an Attribution–Noncommercial–Share Alike 3.0 Unported Creative Commons License (http://creativecommons.org/licenses/by-nc-sa/3.0).

Unconventional plasticity of HIV-1 reverse transcriptase: how inhibitors could open a connection "gate" between allosteric and catalytic sites.

PubMed

Bellucci, Luca; Angeli, Lucilla; Tafi, Andrea; Radi, Marco; Botta, Maurizio

2013-12-23

Targeted molecular dynamics (TMD) simulations allowed for identifying the chemical/structural features of the nucleotide-competitive HIV-1 inhibitor DAVP-1, which is responsible for the disruption of the T-shape motif between Try183 and Trp229 of the reverse transcriptase (RT). DAVP-1 promoted the opening of a connection "gate" between allosteric and catalytic sites of HIV-1 RT, thus explaining its peculiar mechanism of action and providing useful insights to develop novel nucleotide-competitive RT inhibitors.

Brevicoryne brassicae aphids interfere with transcriptome responses of Arabidopsis thaliana to feeding by Plutella xylostella caterpillars in a density-dependent manner.

PubMed

Kroes, Anneke; Broekgaarden, Colette; Castellanos Uribe, Marcos; May, Sean; van Loon, Joop J A; Dicke, Marcel

2017-01-01

Plants are commonly attacked by multiple herbivorous species. Yet, little is known about transcriptional patterns underlying plant responses to multiple insect attackers feeding simultaneously. Here, we assessed transcriptomic responses of Arabidopsis thaliana plants to simultaneous feeding by Plutella xylostella caterpillars and Brevicoryne brassicae aphids in comparison to plants infested by P. xylostella caterpillars alone, using microarray analysis. We particularly investigated how aphid feeding interferes with the transcriptomic response to P. xylostella caterpillars and whether this interference is dependent on aphid density and time since aphid attack. Various JA-responsive genes were up-regulated in response to feeding by P. xylostella caterpillars. The additional presence of aphids, both at low and high densities, clearly affected the transcriptional plant response to caterpillars. Interestingly, some important modulators of plant defense signalling, including WRKY transcription factor genes and ABA-dependent genes, were differentially induced in response to simultaneous aphid feeding at low or high density compared with responses to P. xylostella caterpillars feeding alone. Furthermore, aphids affected the P. xylostella-induced transcriptomic response in a density-dependent manner, which caused an acceleration in plant response against dual insect attack at high aphid density compared to dual insect attack at low aphid density. In conclusion, our study provides evidence that aphids influence the caterpillar-induced transcriptional response of A. thaliana in a density-dependent manner. It highlights the importance of addressing insect density to understand how plant responses to single attackers interfere with responses to other attackers and thus underlines the importance of the dynamics of transcriptional plant responses to multiple herbivory.

Unconventional gas development facilitates plant invasions.

PubMed

Barlow, Kathryn M; Mortensen, David A; Drohan, Patrick J; Averill, Kristine M

2017-11-01

Vegetation removal and soil disturbance from natural resource development, combined with invasive plant propagule pressure, can increase vulnerability to plant invasions. Unconventional oil and gas development produces surface disturbance by way of well pad, road, and pipeline construction, and increased traffic. Little is known about the resulting impacts on plant community assembly, including the spread of invasive plants. Our work was conducted in Pennsylvania forests that overlay the Marcellus and Utica shale formations to determine if invasive plants have spread to edge habitat created by unconventional gas development and to investigate factors associated with their presence. A piecewise structural equation model was used to determine the direct and indirect factors associated with invasive plant establishment on well pads. The model included the following measured or calculated variables: current propagule pressure on local access roads, the spatial extent of the pre-development road network (potential source of invasive propagules), the number of wells per pad (indicator of traffic density), and pad age. Sixty-one percent of the 127 well pads surveyed had at least one invasive plant species present. Invasive plant presence on well pads was positively correlated with local propagule pressure on access roads and indirectly with road density pre-development, the number of wells, and age of the well pad. The vast reserves of unconventional oil and gas are in the early stages of development in the US. Continued development of this underground resource must be paired with careful monitoring and management of surface ecological impacts, including the spread of invasive plants. Prioritizing invasive plant monitoring in unconventional oil and gas development areas with existing roads and multi-well pads could improve early detection and control of invasive plants. Copyright © 2017 Elsevier Ltd. All rights reserved.

Longitudinal pathways from unconventional personal attributes in the late 20s to cannabis use prior to sexual intercourse in the late 30s.

PubMed

Lee, Jung Yeon; Brook, Judith S; Pahl, Kerstin; Brook, David W

2017-11-01

A quarter of people living with human immunodeficiency virus (HIV) infection in the United States are women. Furthermore, African American and Hispanic/Latina women continue to be disproportionately affected by HIV, compared with women of other races/ethnicities. Cannabis use prior to intercourse may be associated with increased risky sexual behaviors which are highly related to HIV. The ultimate goal of this research is to better understand the relationships between unconventional personal attributes (e.g., risk-taking behaviors) in the late 20s, substance use (e.g., alcohol) in the mid 30s, and cannabis use prior to intercourse in the late 30s using a community sample; such an understanding may inform interventions. This study employing data from the Harlem Longitudinal Development Study includes 343 female participants (50% African Americans, 50% Puerto Ricans). Structural equation modeling indicated that unconventional personal attributes in the late 20s were associated with substance use in the mid 30s (β=0.32, p<0.001), which in turn, was associated with cannabis use prior to sexual intercourse in the late 30s (β=0.64, p<0.001). Unconventional personal attributes in the late 20s were also directly related to cannabis use prior to sexual intercourse in the late 30s (β=0.39, p<0.01). The findings of this study suggest that interventions focused on decreasing unconventional personal attributes as well as substance use may reduce sexual risk behaviors among urban African American and Puerto Rican women. Also, the implications of this study for health care providers and researchers working in HIV prevention are that these precursors may be useful as patient screening tools. Copyright © 2017 Elsevier Ltd. All rights reserved.

Sarcomeric Myosin Expression in the Tongue Body of Humans, Macaques and Rats

PubMed Central

Rahnert, Jill A.; Sokoloff, Alan J.; Burkholder, Thomas J.

2010-01-01

Expression of developmental and unconventional myosin heavy chain (MHC) isoforms in some adult head and neck muscles is thought to reflect specific contractile demands of muscle fibers active during kinematically complex movements. Mammalian tongue muscles are active during oromotor behaviors that encompass a wide range of tongue movement speeds and tongue shape changes (e.g. respiration, oral transport, swallowing, rejection), but the extent to which tongue muscles express developmental and unconventional MHC is not known. Quantitative PCR was used to determine the mRNA content of conventional MHC-beta, MHC-2a, MHC-2b and MHC-2x, the developmental isoforms embryonic MHC and neonatal MHC and the unconventional isoforms atrial/cardiac-α MHC (MHC-alpha), extraocular MHC, masseter MHC and slow tonic MHC in tongue body muscles of the rat, macaque and human. In all species, conventional MHC isoforms predominate. MHC-2b and MHC-2x account for 98% of total MHC mRNA in the rat. MHC-2a, MHC-2x and MHC-beta account for 94% of total MHC mRNA in humans and 96% of total MHC mRNA in macaque. With the exception of MHC-alpha in humans (5%), developmental and unconventional MHC mRNA represents less than 0.3% of total MHC mRNA. We conclude that in these species, there is limited expression of developmental and unconventional MHC and that diversity of tongue body muscle fiber contractile properties is achieved primarily by MHC-beta, MHC-2a, MHC-2x and MHC-2b. Whether expression of MHC-alpha mRNA in tongue is unique to humans or present in other hominoids awaits further investigation. PMID:19907142

Water Issues Associated with Increasing Unconventional Oil Production in the Permian Basin

NASA Astrophysics Data System (ADS)

Reedy, R. C.; Scanlon, B. R.; Male, F.; Walsh, M.

2017-12-01

The Permian Basin is being transformed from a major conventional oil play to the world's largest unconventional play; however, managing water for this transition is critical in this semiarid region. The study included quantifying produced water volumes with oil and gas production along with water demands for hydraulic fracturing using a detailed well-by-well analysis. Our results show that oil wells in conventional reservoirs generate large volumes of produced water relative to oil production with produced water to oil ratios of 13 (i.e. 13 barrels [bbl] of water relative to a bbl of oil). However, produced water from conventional reservoirs has been mostly injected back into the pressure-depleted oil-producing reservoirs for enhanced oil recovery using water flooding. Unconventional horizontal wells use large volumes of water for hydraulic fracturing that has been markedly increasing by factors of 10 - 16 per well and by factors of 7-10 after dividing by lateral well length (2008-2015). Although unconventional wells generate less produced water relative to oil ( 3 bbl of water relative to oil) than conventional wells, the main difference is that this produced water cannot be reinjected into the low permeability shale reservoirs. Instead, the produced water is disposed into non-producing geologic zones that could result in overpressuring and induced seismicity. There is a high potential for reusing produced water from unconventional wells in the Permian Basin because the produced water volumes can support the hydraulic fracturing water demand based on 2014 data. Reusing produced water with minimal water treatment (clean brine) could partially mitigate produced water injection concerns while reducing water demand for hydraulic fracturing.

Mongolian Almond (Prunus mongolica Maxim): The Morpho-Physiological, Biochemical and Transcriptomic Response to Drought Stress

PubMed Central

Bai, Shulan; Gao, Xiaomin; Liu, Min; Yan, Wei

2015-01-01

Prunus mongolica Maxim, which is widely established in the Gobi Desert, shows extreme tolerance to drought. However, there is a lack of available transcriptomic resources for this species related to its response to water deficiency. To investigate the mechanisms that allow P. mongolica to maintain growth in extremely arid environments, the response of P. mongolica seedlings to drought stress was analyzed using morphological, physiological, biochemical and high-throughput sequencing approaches. We generated 28,713,735 and 26,650,133 raw reads from no-stress control and drought-stressed P. mongolica seedlings, respectively. In total, we obtained 67,352 transcripts with an average length of 874.44 bp. Compared with the no-stress control, 3,365 transcripts were differentially expressed in the drought-stressed seedlings, including 55.75% (1,876 transcripts) up-regulated and 44.25% (1,489 transcripts) down-regulated transcripts. The photosynthesis response showed a decreasing tendency under drought stress, but the changes in the levels of hormones (auxins, cytokinins and abscisic acid) resulted in the closing of stomata and decreased cell enlargement and division; these changes were effective for promoting P. mongolica survival in Gobi Desert. Next, we analyzed the aquaporin and superoxide dismutase gene families due to their importance in plant resistance to drought stress. We found that all of the plasma membrane intrinsic protein transcripts were down-regulated in the drought-stressed treatment, whereas drought did not affect the expression of nodulin intrinsic protein or small basic intrinsic protein transcripts in P. mongolica seedlings. In addition, activation of iron superoxide dismutase transcription and enhanced transcription of manganese superoxide dismutase were observed in P. mongolica to promote tolerance of drought stress. This study identified drought response genes in P. mongolica seedlings. Our results provide a significant contribution to the understanding of how P. mongolica responds to drought stress at the transcriptome level, which may help to elucidate molecular mechanisms associated with the drought response of almond plants. PMID:25893685

Fatigue and gene expression in human leukocytes: Increased NF-κB and decreased glucocorticoid signaling in breast cancer survivors with persistent fatigue

PubMed Central

Bower, Julienne E.; Ganz, Patricia A.; Irwin, Michael R.; Arevalo, Jesusa M.G.; Cole, Steve W.

2013-01-01

Fatigue is highly prevalent in the general population and is one of the most common side effects of cancer treatment. There is growing evidence that pro-inflammatory cytokines play a role in cancer-related fatigue, although the molecular mechanisms for chronic inflammation and fatigue have not been determined. The current study utilized genome-wide expression microarrays to identify differences in gene expression and associated alterations in transcriptional activity in leukocytes from breast cancer survivors with persistent fatigue (n = 11) and non-fatigued controls (n = 10). We focused on transcription of inflammation-related genes, particularly those responsive to the pro-inflammatory NF-κB transcription control pathway. Further, given the role of glucocorticoids as key regulators of inflammatory processes, we examined transcription of glucocorticoid-responsive genes indicative of potential glucocorticoid receptor (GR) desensitization. Plasma levels of cortisol were also assessed. Consistent with hypotheses, results showed increased expression of transcripts with response elements for NF-κB, and reduced expression of transcripts with response elements for glucocorticoids (p < .05) in fatigued breast cancer survivors. No differences in plasma levels of cortisol were observed. These data indicate that increased activity of pro-inflammatory transcription factors may contribute to persistent cancer-related fatigue and provide insight into potential mechanisms for tonic increases in NF-κB activity, specifically decreased expression of GR anti-inflammatory transcription factors. PMID:20854893

Overlapping Podospora anserina Transcriptional Responses to Bacterial and Fungal Non Self Indicate a Multilayered Innate Immune Response

PubMed Central

Lamacchia, Marina; Dyrka, Witold; Breton, Annick; Saupe, Sven J.; Paoletti, Mathieu

2016-01-01

Recognition and response to non self is essential to development and survival of all organisms. It can occur between individuals of the same species or between different organisms. Fungi are established models for conspecific non self recognition in the form of vegetative incompatibility (VI), a genetically controlled process initiating a programmed cell death (PCD) leading to the rejection of a fusion cell between genetically different isolates of the same species. In Podospora anserina VI is controlled by members of the hnwd gene family encoding for proteins analogous to NOD Like Receptors (NLR) immune receptors in eukaryotes. It was hypothesized that the hnwd controlled VI reaction was derived from the fungal innate immune response. Here we analyze the P. anserina transcriptional responses to two bacterial species, Serratia fonticola to which P. anserina survives and S. marcescens to which P. anserina succumbs, and compare these to the transcriptional response induced under VI conditions. Transcriptional responses to both bacteria largely overlap, however the number of genes regulated and magnitude of regulation is more important when P. anserina survives. Transcriptional responses to bacteria also overlap with the VI reaction for both up or down regulated gene sets. Genes up regulated tend to be clustered in the genome, and display limited phylogenetic distribution. In all three responses we observed genes related to autophagy to be up-regulated. Autophagy contributes to the fungal survival in all three conditions. Genes encoding for secondary metabolites and histidine kinase signaling are also up regulated in all three conditions. Transcriptional responses also display differences. Genes involved in response to oxidative stress, or encoding small secreted proteins are essentially expressed in response to bacteria, while genes encoding NLR proteins are expressed during VI. Most functions encoded in response to bacteria favor survival of the fungus while most functions up regulated during VI would lead to cell death. These differences are discussed in the frame of a multilayered response to non self in fungi. PMID:27148175

Downstream promoter interactions of TFIID TAFs facilitate transcription reinitiation

PubMed Central

Joo, Yoo Jin; Ficarro, Scott B.; Soares, Luis M.; Chun, Yujin; Marto, Jarrod A.; Buratowski, Stephen

2017-01-01

TFIID binds promoter DNA to recruit RNA polymerase II and other basal factors for transcription. Although the TATA-binding protein (TBP) subunit of TFIID is necessary and sufficient for in vitro transcription, the TBP-associated factor (TAF) subunits recognize downstream promoter elements, act as coactivators, and interact with nucleosomes. In yeast nuclear extracts, transcription induces stable TAF binding to downstream promoter DNA, promoting subsequent activator-independent transcription reinitiation. In vivo, promoter responses to TAF mutations correlate with the level of downstream, rather than overall, Taf1 cross-linking. We propose a new model in which TAFs function as reinitiation factors, accounting for the differential responses of promoters to various transcription factor mutations. PMID:29203645

Mining whole genomes and transcriptomes of Jatropha (Jatropha curcas) and Castor bean (Ricinus communis) for NBS-LRR genes and defense response associated transcription factors.

PubMed

Sood, Archit; Jaiswal, Varun; Chanumolu, Sree Krishna; Malhotra, Nikhil; Pal, Tarun; Chauhan, Rajinder Singh

2014-11-01

Jatropha (Jatropha curcas L.) and Castor bean (Ricinus communis) are oilseed crops of family Euphorbiaceae with the potential of producing high quality biodiesel and having industrial value. Both the bioenergy plants are becoming susceptible to various biotic stresses directly affecting the oil quality and content. No report exists as of today on analysis of Nucleotide Binding Site-Leucine Rich Repeat (NBS-LRR) gene repertoire and defense response transcription factors in both the plant species. In silico analysis of whole genomes and transcriptomes identified 47 new NBS-LRR genes in both the species and 122 and 318 defense response related transcription factors in Jatropha and Castor bean, respectively. The identified NBS-LRR genes and defense response transcription factors were mapped onto the respective genomes. Common and unique NBS-LRR genes and defense related transcription factors were identified in both the plant species. All NBS-LRR genes in both the species were characterized into Toll/interleukin-1 receptor NBS-LRRs (TNLs) and coiled-coil NBS-LRRs (CNLs), position on contigs, gene clusters and motifs and domains distribution. Transcript abundance or expression values were measured for all NBS-LRR genes and defense response transcription factors, suggesting their functional role. The current study provides a repertoire of NBS-LRR genes and transcription factors which can be used in not only dissecting the molecular basis of disease resistance phenotype but also in developing disease resistant genotypes in Jatropha and Castor bean through transgenic or molecular breeding approaches.

The legume miR1514a modulates a NAC transcription factor transcript to trigger phasiRNA formation in response to drought

PubMed Central

Sosa-Valencia, Guadalupe; Palomar, Miguel; Covarrubias, Alejandra A.

2017-01-01

Abstract Recent studies have identified microRNAs as post-transcriptional regulators involved in stress responses. miR1514a is a legume microRNA that is induced in response to drought stress in Phaseolus vulgaris (common bean) and shows differential accumulation levels in roots during water deficit in two cultivars with different drought tolerance phenotypes. A recent degradome analysis revealed that miR1514a targets the transcripts of two NAC transcription factors (TFs), Phvul.010g121000 and Phvul.010g120700. Furthermore, expression studies and small RNA-seq data indicate that only Phvul.010g120700 generates phasiRNAs, which also accumulate under water deficit conditions. To confirm these results, we over-expressed miR1514a in transgenic hairy roots, and observed a reduced accumulation of Phvul.010g120700 and an increase in NAC-derived phasiRNAs; inhibition of miR1514a activity resulted in the opposite effect. Moreover, we determined that a NAC-derived phasiRNA associates with ARGONAUTE 1 (AGO1), suggesting that it is functional. In addition, a transcriptome analysis of transgenic hairy roots with reduced miR1514a levels revealed several differentially expressed transcripts, mainly involved in metabolism and stress responses, suggesting they are regulated by the NAC TF and/or by phasiRNAs. This work therefore demonstrates the participation of miR1514 in the regulation of a NAC transcription factor transcript through phasiRNA production during the plant response to water deficit. PMID:28338719

Unconventional energy resources: 2007-2008 review

USGS Publications Warehouse

Warwick, Peter D.; ,

2009-01-01

This paper summarizes five 2007–2008 resource commodity committee reports prepared by the Energy Minerals Division (EMD) of the American Association of Petroleum Geologists. Current United States and global research and development activities related to gas hydrates, gas shales, geothermal resources, oil sands, and uranium resources are included in this review. These commodity reports were written to advise EMD leadership and membership of the current status of research and development of unconventional energy resources. Unconventional energy resources are defined as those resources other than conventional oil and natural gas that typically occur in sandstone and carbonate rocks. Gas hydrate resources are potentially enormous; however, production technologies are still under development. Gas shale, geothermal, oil sand, and uranium resources are now increasing targets of exploration and development, and are rapidly becoming important energy resources that will continue to be developed in the future.

Magnetic Field Enhanced Superconductivity in Epitaxial Thin Film WTe2.

PubMed

Asaba, Tomoya; Wang, Yongjie; Li, Gang; Xiang, Ziji; Tinsman, Colin; Chen, Lu; Zhou, Shangnan; Zhao, Songrui; Laleyan, David; Li, Yi; Mi, Zetian; Li, Lu

2018-04-25

In conventional superconductors an external magnetic field generally suppresses superconductivity. This results from a simple thermodynamic competition of the superconducting and magnetic free energies. In this study, we report the unconventional features in the superconducting epitaxial thin film tungsten telluride (WTe 2 ). Measuring the electrical transport properties of Molecular Beam Epitaxy (MBE) grown WTe 2 thin films with a high precision rotation stage, we map the upper critical field H c2 at different temperatures T. We observe the superconducting transition temperature T c is enhanced by in-plane magnetic fields. The upper critical field H c2 is observed to establish an unconventional non-monotonic dependence on temperature. We suggest that this unconventional feature is due to the lifting of inversion symmetry, which leads to the enhancement of H c2 in Ising superconductors.

Water deficit modulates the response of Vitis vinifera to the Pierce's disease pathogen Xylella fastidiosa.

PubMed

Choi, Hong-Kyu; Iandolino, Alberto; da Silva, Francisco Goes; Cook, Douglas R

2013-06-01

Pierce's disease, caused by the bacterium Xylella fastidiosa, is one of the most devastating diseases of cultivated grape, currently restricted to the Americas. To test the long-standing hypothesis that Pierce's disease results from pathogen-induced drought stress, we used the Affymetrix Vitis GeneChip to compare the transcriptional response of Vitis vinifera to Xylella infection, water deficit, or a combination of the two stresses. The results reveal a redirection of gene transcription involving 822 genes with a minimum twofold change (P < 0.05), including the upregulation of transcripts for phenylpropanoid and flavonoid biosynthesis, pathogenesis-related proteins, abscisic acid- and jasmonic acid-responsive biosynthesis, and downregulation of transcripts related to photosynthesis, growth, and nutrition. Although the transcriptional response of plants to Xylella infection was largely distinct from the response of healthy plants to water stress, we find that 138 of the pathogen-induced genes exhibited a significantly stronger transcriptional response when plants were simultaneously exposed to infection and drought stress, suggesting a strong interaction between disease and water deficit. This interaction between drought stress and disease was mirrored in planta at the physiological level for aspects of water relations and photosynthesis and in terms of the severity of disease symptoms and the extent of pathogen colonization, providing a molecular correlate of the classical concept of the disease triangle in which environment impacts disease severity.

De-repression of CSP-1 activates adaptive responses to antifungal azoles

PubMed Central

Chen, Xi; Xue, Wei; Zhou, Jun; Zhang, Zhenying; Wei, Shiping; Liu, Xingyu; Sun, Xianyun; Wang, Wenzhao; Li, Shaojie

2016-01-01

Antifungal azoles are the major drugs that are used to treat fungal infections. This study found that in response to antifungal azole stress, Neurospora crassa could activate the transcriptional responses of many genes and increase azole resistance by reducing the level of conidial separation 1 (CSP-1), a global transcription repressor, at azole-responsive genes. The expression of csp-1 was directly activated by the transcription factors WC-1 and WC-2. Upon ketoconazole (KTC) stress, the transcript levels of wc-1 and wc-2 were not changed, but csp-1 transcription rapidly declined. A chromatin immunoprecipitation-quantitative polymerase chain reaction analysis revealed a rapid reduction in the WC-2 enrichment at the csp-1 promoter upon KTC treatment, which might be responsible for the KTC-induced csp-1 downregulation. Deletion of csp-1 increased resistance to KTC and voriconazole, while csp-1 overexpression increased KTC susceptibility. CSP-1 transcriptionally repressed a number of azole-responsive genes, including genes encoding the azole target ERG11, the azole efflux pump CDR4, and the sterol C-22 desaturase ERG5. Deletion of csp-1 also reduced the KTC-induced accumulation of ergosterol intermediates, eburicol, and 14α-methyl-3,6-diol. CSP-1 orthologs are widely present in filamentous fungi, and an Aspergillus fumigatus mutant in which the csp-1 was deleted was resistant to itraconazole. PMID:26781458

An ABA-responsive DRE-binding protein gene from Setaria italica, SiARDP, the target gene of SiAREB, plays a critical role under drought stress.

PubMed

Li, Cong; Yue, Jing; Wu, Xiaowei; Xu, Cong; Yu, Jingjuan

2014-10-01

The DREB (dehydration-responsive element binding)-type transcription factors regulate the expression of stress-inducible genes by binding the DRE/CRT cis-elements in promoter regions. The upstream transcription factors that regulate the transcription of DREB transcription factors have not been clearly defined, although the function of DREB transcription factors in abiotic stress is known. In this study, an abscisic acid (ABA)-responsive DREB-binding protein gene (SiARDP) was cloned from foxtail millet (Setaria italica). The transcript level of SiARDP increased not only after drought, high salt, and low temperature stresses, but also after an ABA treatment in foxtail millet seedlings. Two ABA-responsive elements (ABRE1: ACGTGTC; ABRE2: ACGTGGC) exist in the promoter of SiARDP. Further analyses showed that two ABA-responsive element binding (AREB)-type transcription factors, SiAREB1 and SiAREB2, could physically bind to the ABRE core element in vitro and in vivo. The constitutive expression of SiARDP in Arabidopsis thaliana enhanced drought and salt tolerance during seed germination and seedling development, and overexpression of SiARDP in foxtail millet improved drought tolerance. The expression levels of target genes of SiARDP were upregulated in transgenic Arabidopsis and foxtail millet. These results reveal that SiARDP, one of the target genes of SiAREB, is involved in ABA-dependent signal pathways and plays a critical role in the abiotic stress response in plants. © The Author 2014. Published by Oxford University Press on behalf of the Society for Experimental Biology.

Transcriptomic response of the insect vector, Peregrinus maidis, to Maize mosaic rhabdovirus and identification of conserved responses to propagative viruses in hopper vectors.

PubMed

Martin, Kathleen M; Barandoc-Alviar, Karen; Schneweis, Derek J; Stewart, Catherine L; Rotenberg, Dorith; Whitfield, Anna E

2017-09-01

Maize mosaic virus (MMV) is a plant-pathogenic rhabdovirus that is transmitted by the corn planthopper, Peregrinus maidis, in a propagative manner. P. maidis supports long-term MMV infections with no negative effects on insect performance. To elucidate whole-body transcriptome responses to virus infection, RNA-Seq was used to examine differential gene expression of virus-infected adult insects, and libraries were prepared from replicated groups of virus-exposed insects and non-exposed insects. From the 68,003 de novo-assembled transcripts, 144 were differentially-expressed (DE) during viral infection with comparable numbers up- and down-regulated. DE transcripts with similarity to genes associated with transposable elements (i.e., RNA-directed DNA polymerases) were enriched and may represent a mechanisim for modulating virus infection. Comparison of the P. maidis DE transcripts to published propagative virus-responsive transcript databases for two other hopper vectors revealed that 16% of the DE transcripts were shared across the three systems and may represent conserved responses to propagative viruses. Copyright © 2017 Elsevier Inc. All rights reserved.

Tunable regulation of CREB DNA binding activity couples genotoxic stress response and metabolism

PubMed Central

Kim, Sang Hwa; Trinh, Anthony T.; Larsen, Michele Campaigne; Mastrocola, Adam S.; Jefcoate, Colin R.; Bushel, Pierre R.; Tibbetts, Randal S.

2016-01-01

cAMP response element binding protein (CREB) is a key regulator of glucose metabolism and synaptic plasticity that is canonically regulated through recruitment of transcriptional coactivators. Here we show that phosphorylation of CREB on a conserved cluster of Ser residues (the ATM/CK cluster) by the DNA damage-activated protein kinase ataxia-telangiectasia-mutated (ATM) and casein kinase1 (CK1) and casein kinase2 (CK2) positively and negatively regulates CREB-mediated transcription in a signal dependent manner. In response to genotoxic stress, phosphorylation of the ATM/CK cluster inhibited CREB-mediated gene expression, DNA binding activity and chromatin occupancy proportional to the number of modified Ser residues. Paradoxically, substoichiometric, ATM-independent, phosphorylation of the ATM/CK cluster potentiated bursts in CREB-mediated transcription by promoting recruitment of the CREB coactivator, cAMP-regulated transcriptional coactivators (CRTC2). Livers from mice expressing a non-phosphorylatable CREB allele failed to attenuate gluconeogenic genes in response to DNA damage or fully activate the same genes in response to glucagon. We propose that phosphorylation-dependent regulation of DNA binding activity evolved as a tunable mechanism to control CREB transcriptional output and promote metabolic homeostasis in response to rapidly changing environmental conditions. PMID:27431323

Bio-inspired Ni2+-polyphenol hydrophilic network to achieve unconventional high-flux nanofiltration membranes for environmental remediation.

PubMed

You, Fangjie; Xu, Yanchao; Yang, Xiaobin; Zhang, Yanqiu; Shao, Lu

2017-06-01

A novel Ni 2+ -polyphenol network was designed as an excellent bio-coating by a one-step strategy to obtain nanofiltration membranes, possessing unconventional high water flux up to 56.1 L m -2 h -1 bar -1 with rose bengal (RB) rejection above 95%. This study provides a facile approach to prepare highly-efficient nanofiltration membranes for wastewater remediation.

Sub state Unconventional Warfare: Expanding United States Military Political Options

DTIC Science & Technology

2016-05-26

phases due to competing incumbent efforts. Giap was influenced in his understanding of revolutionary war phasing by Sun Tzu who Giap called one of his...Challenge of Unconventional Warfare. London: Routledge, 2012. Ames, Roger T. Sun - Tzu The Art of Warfare. New York: Ballantine Books, 1993. Amin, Samir...Guerrilla: Insurgents, Patriots, and Terrorists from Sun Tzu to Bin Laden. London: Brassey’s Inc., 2004. Rosenau, William, Subversion and Insurgency

Transcriptome Analysis of Kiwifruit (Actinidia chinensis) Bark in Response to Armoured Scale Insect (Hemiberlesia lataniae) Feeding

PubMed Central

Hill, M. Garry; Wurms, Kirstin V.; Davy, Marcus W.; Gould, Elaine; Allan, Andrew; Mauchline, Nicola A.; Luo, Zhiwei; Ah Chee, Annette; Stannard, Kate; Storey, Roy D.; Rikkerink, Erik H.

2015-01-01

The kiwifruit cultivar Actinidia chinensis ‘Hort16A’ is resistant to the polyphagous armoured scale insect pest Hemiberlesia lataniae (Hemiptera: Diaspididae). A cDNA microarray consisting of 17,512 unigenes selected from over 132,000 expressed sequence tags (ESTs) was used to measure the transcriptomic profile of the A. chinensis ‘Hort16A’ canes in response to a controlled infestation of H. lataniae. After 2 days, 272 transcripts were differentially expressed. After 7 days, 5,284 (30%) transcripts were differentially expressed. The transcripts were grouped into 22 major functional categories using MapMan software. After 7 days, transcripts associated with photosynthesis (photosystem II) were significantly down-regulated, while those associated with secondary metabolism were significantly up-regulated. A total of 643 transcripts associated with response to stress were differentially expressed. This included biotic stress-related transcripts orthologous with pathogenesis related proteins, the phenylpropanoid pathway, NBS-LRR (R) genes, and receptor-like kinase–leucine rich repeat signalling proteins. While transcriptional studies are not conclusive in their own right, results were suggestive of a defence response involving both ETI and PTI, with predominance of the SA signalling pathway. Exogenous application of an SA-mimic decreased H. lataniae growth on A. chinensis ‘Hort16A’ plants in two laboratory experiments. PMID:26571404

Unconventional high-Tc superconductivity in fullerides.

PubMed

Takabayashi, Yasuhiro; Prassides, Kosmas

2016-09-13

A3C60 molecular superconductors share a common electronic phase diagram with unconventional high-temperature superconductors such as the cuprates: superconductivity emerges from an antiferromagnetic strongly correlated Mott-insulating state upon tuning a parameter such as pressure (bandwidth control) accompanied by a dome-shaped dependence of the critical temperature, Tc However, unlike atom-based superconductors, the parent state from which superconductivity emerges solely by changing an electronic parameter-the overlap between the outer wave functions of the constituent molecules-is controlled by the C60 (3-) molecular electronic structure via the on-molecule Jahn-Teller effect influence of molecular geometry and spin state. Destruction of the parent Mott-Jahn-Teller state through chemical or physical pressurization yields an unconventional Jahn-Teller metal, where quasi-localized and itinerant electron behaviours coexist. Localized features gradually disappear with lattice contraction and conventional Fermi liquid behaviour is recovered. The nature of the underlying (correlated versus weak-coupling Bardeen-Cooper-Schrieffer theory) s-wave superconducting states mirrors the unconventional/conventional metal dichotomy: the highest superconducting critical temperature occurs at the crossover between Jahn-Teller and Fermi liquid metal when the Jahn-Teller distortion melts.This article is part of the themed issue 'Fullerenes: past, present and future, celebrating the 30th anniversary of Buckminster Fullerene'. © 2016 The Author(s).

Unconventional high-Tc superconductivity in fullerides

PubMed Central

Takabayashi, Yasuhiro; Prassides, Kosmas

2016-01-01

A3C60 molecular superconductors share a common electronic phase diagram with unconventional high-temperature superconductors such as the cuprates: superconductivity emerges from an antiferromagnetic strongly correlated Mott-insulating state upon tuning a parameter such as pressure (bandwidth control) accompanied by a dome-shaped dependence of the critical temperature, Tc. However, unlike atom-based superconductors, the parent state from which superconductivity emerges solely by changing an electronic parameter—the overlap between the outer wave functions of the constituent molecules—is controlled by the C603− molecular electronic structure via the on-molecule Jahn–Teller effect influence of molecular geometry and spin state. Destruction of the parent Mott–Jahn–Teller state through chemical or physical pressurization yields an unconventional Jahn–Teller metal, where quasi-localized and itinerant electron behaviours coexist. Localized features gradually disappear with lattice contraction and conventional Fermi liquid behaviour is recovered. The nature of the underlying (correlated versus weak-coupling Bardeen–Cooper–Schrieffer theory) s-wave superconducting states mirrors the unconventional/conventional metal dichotomy: the highest superconducting critical temperature occurs at the crossover between Jahn–Teller and Fermi liquid metal when the Jahn–Teller distortion melts. This article is part of the themed issue ‘Fullerenes: past, present and future, celebrating the 30th anniversary of Buckminster Fullerene’. PMID:27501971

Quantitative mass spectrometry of unconventional human biological matrices

NASA Astrophysics Data System (ADS)

Dutkiewicz, Ewelina P.; Urban, Pawel L.

2016-10-01

The development of sensitive and versatile mass spectrometric methodology has fuelled interest in the analysis of metabolites and drugs in unconventional biological specimens. Here, we discuss the analysis of eight human matrices-hair, nail, breath, saliva, tears, meibum, nasal mucus and skin excretions (including sweat)-by mass spectrometry (MS). The use of such specimens brings a number of advantages, the most important being non-invasive sampling, the limited risk of adulteration and the ability to obtain information that complements blood and urine tests. The most often studied matrices are hair, breath and saliva. This review primarily focuses on endogenous (e.g. potential biomarkers, hormones) and exogenous (e.g. drugs, environmental contaminants) small molecules. The majority of analytical methods used chromatographic separation prior to MS; however, such a hyphenated methodology greatly limits analytical throughput. On the other hand, the mass spectrometric methods that exclude chromatographic separation are fast but suffer from matrix interferences. To enable development of quantitative assays for unconventional matrices, it is desirable to standardize the protocols for the analysis of each specimen and create appropriate certified reference materials. Overcoming these challenges will make analysis of unconventional human biological matrices more common in a clinical setting. This article is part of the themed issue 'Quantitative mass spectrometry'.

Staying alive in adversity: transcriptome dynamics in the stress-resistant dauer larva.

PubMed

Holt, Suzan J

2006-10-01

In response to food depletion and overcrowding, the soil nematode Caenorhabditis elegans can arrest development and form an alternate third larval stage called the dauer. Though nonfeeding, the dauer larva is long lived and stress resistant. Metabolic and transcription rates are lowered but the transcriptome of the dauer is complex. In this study, distribution analysis of transcript profiles generated by Serial Analysis of Gene Expression (SAGE) in dauer larvae and in mixed developmental stages is presented. An inverse relationship was observed between frequency and abundance/copy number of SAGE tag types (transcripts) in both profiles. In the dauer profile, a relatively greater proportion of highly abundant transcripts was counterbalanced by a smaller fraction of low to moderately abundant transcripts. Comparisons of abundant tag counts between the two profiles revealed relative enrichment in the dauer profile of transcripts with predicted or known involvement in ribosome biogenesis and protein synthesis, membrane transport, and immune responses. Translation-coupled mRNA decay is proposed as part of an immune-like stress response in the dauer larva. An influence of genomic region on transcript level may reflect the coordination of transcription and mRNA turnover.

ABA signaling is necessary but not sufficient for RD29B transcriptional memory during successive dehydration stresses in Arabidopsis thaliana.

PubMed

Virlouvet, Laetitia; Ding, Yong; Fujii, Hiroaki; Avramova, Zoya; Fromm, Michael

2014-07-01

Plants subjected to a prior dehydration stress were seen to have altered transcriptional responses during a subsequent dehydration stress for up to 5 days after the initial stress. The abscisic acid (ABA) inducible RD29B gene of Arabidopsis thaliana was strongly induced after the first stress and displayed transcriptional memory with transcript levels nine-fold higher during the second dehydration stress. These increased transcript levels were due to an increased rate of transcription and are associated with an altered chromatin template during the recovery interval between the dehydration stresses. Here we use a combination of promoter deletion/substitutions, mutants in the trans-acting transcription factors and their upstream protein kinases, and treatments with exogenous ABA or dehydration stress to advance our understanding of the features required for transcriptional memory of RD29B. ABA Response Elements (ABREs) are sufficient to confer transcriptional memory on a minimal promoter, although there is a context effect from flanking sequences. Different mutations in Snf1 Related Protein Kinase 2 (SnRK2) genes positively and negatively affected the response, suggesting that this effect is important for transcriptional memory. Although exogenous ABA treatments could prime transcriptional memory, a second ABA treatment was not sufficient to activate transcriptional memory. Therefore, we concluded that transcriptional memory requires ABA and an ABA-independent factor that is induced or activated by a subsequent dehydration stress and directly or indirectly results in a more active RD29B chromatin template. These results advance our knowledge of the cis- and trans-acting factors that are required for transcriptional memory of RD29B. © 2014 The Authors The Plant Journal © 2014 John Wiley & Sons Ltd.

Integration of light and circadian signals that regulate chloroplast transcription by a nuclear-encoded sigma factor.

PubMed

Belbin, Fiona E; Noordally, Zeenat B; Wetherill, Sarah J; Atkins, Kelly A; Franklin, Keara A; Dodd, Antony N

2017-01-01

We investigated the signalling pathways that regulate chloroplast transcription in response to environmental signals. One mechanism controlling plastid transcription involves nuclear-encoded sigma subunits of plastid-encoded plastid RNA polymerase. Transcripts encoding the sigma factor SIG5 are regulated by light and the circadian clock. However, the extent to which a chloroplast target of SIG5 is regulated by light-induced changes in SIG5 expression is unknown. Moreover, the photoreceptor signalling pathways underlying the circadian regulation of chloroplast transcription by SIG5 are unidentified. We monitored the regulation of chloroplast transcription in photoreceptor and sigma factor mutants under controlled light regimes in Arabidopsis thaliana. We established that a chloroplast transcriptional response to light intensity was mediated by SIG5; a chloroplast transcriptional response to the relative proportions of red and far red light was regulated by SIG5 through phytochrome and photosynthetic signals; and the circadian regulation of chloroplast transcription by SIG5 was predominantly dependent on blue light and cryptochrome. Our experiments reveal the extensive integration of signals concerning the light environment by a single sigma factor to regulate chloroplast transcription. This may originate from an evolutionarily ancient mechanism that protects photosynthetic bacteria from high light stress, which subsequently became integrated with higher plant phototransduction networks. © 2016 The Authors. New Phytologist © 2016 New Phytologist Trust.

Teaching resources. Model of the TIR1 pathway for auxin-mediated gene expression.

PubMed

Laskowski, Marta

2006-02-14

Auxin mediates numerous plant responses, some of which have been shown to require transcriptional regulation. One auxin response pathway, which depends on the relief of transcriptional repression, is mediated by TIR1 (transport inhibitor response protein 1). TIR1 is an auxin receptor and also a subunit of an SCF-type ubiquitin ligase. In the presence of a low concentration of auxin in the nucleus, members of the Aux/IAA family of transcriptional repressors bind to ARF proteins and inhibit the transcription of specific auxin response genes. Increased nuclear concentrations of auxin promote auxin binding to TIR1, causing the Aux/IAA proteins to associate with TIR1 and leading to their degradation by a proteasome-mediated pathway. This decreases the concentration of Aux/IAA proteins in the nucleus and thereby enables the expression of certain auxin response genes.

Versatility of Cooperative Transcriptional Activation: A Thermodynamical Modeling Analysis for Greater-Than-Additive and Less-Than-Additive Effects

PubMed Central

Frank, Till D.; Carmody, Aimée M.; Kholodenko, Boris N.

2012-01-01

We derive a statistical model of transcriptional activation using equilibrium thermodynamics of chemical reactions. We examine to what extent this statistical model predicts synergy effects of cooperative activation of gene expression. We determine parameter domains in which greater-than-additive and less-than-additive effects are predicted for cooperative regulation by two activators. We show that the statistical approach can be used to identify different causes of synergistic greater-than-additive effects: nonlinearities of the thermostatistical transcriptional machinery and three-body interactions between RNA polymerase and two activators. In particular, our model-based analysis suggests that at low transcription factor concentrations cooperative activation cannot yield synergistic greater-than-additive effects, i.e., DNA transcription can only exhibit less-than-additive effects. Accordingly, transcriptional activity turns from synergistic greater-than-additive responses at relatively high transcription factor concentrations into less-than-additive responses at relatively low concentrations. In addition, two types of re-entrant phenomena are predicted. First, our analysis predicts that under particular circumstances transcriptional activity will feature a sequence of less-than-additive, greater-than-additive, and eventually less-than-additive effects when for fixed activator concentrations the regulatory impact of activators on the binding of RNA polymerase to the promoter increases from weak, to moderate, to strong. Second, for appropriate promoter conditions when activator concentrations are increased then the aforementioned re-entrant sequence of less-than-additive, greater-than-additive, and less-than-additive effects is predicted as well. Finally, our model-based analysis suggests that even for weak activators that individually induce only negligible increases in promoter activity, promoter activity can exhibit greater-than-additive responses when transcription factors and RNA polymerase interact by means of three-body interactions. Overall, we show that versatility of transcriptional activation is brought about by nonlinearities of transcriptional response functions and interactions between transcription factors, RNA polymerase and DNA. PMID:22506020

Frequency Modulation of Transcriptional Bursting Enables Sensitive and Rapid Gene Regulation.

PubMed

Li, Congxin; Cesbron, François; Oehler, Michael; Brunner, Michael; Höfer, Thomas

2018-04-25

Gene regulation is a complex non-equilibrium process. Here, we show that quantitating the temporal regulation of key gene states (transcriptionally inactive, active, and refractory) provides a parsimonious framework for analyzing gene regulation. Our theory makes two non-intuitive predictions. First, for transcription factors (TFs) that regulate transcription burst frequency, as opposed to amplitude or duration, weak TF binding is sufficient to elicit strong transcriptional responses. Second, refractoriness of a gene after a transcription burst enables rapid responses to stimuli. We validate both predictions experimentally by exploiting the natural, optogenetic-like responsiveness of the Neurospora GATA-type TF White Collar Complex (WCC) to blue light. Further, we demonstrate that differential regulation of WCC target genes is caused by different gene activation rates, not different TF occupancy, and that these rates are tuned by both the core promoter and the distance between TF-binding site and core promoter. In total, our work demonstrates the relevance of a kinetic, non-equilibrium framework for understanding transcriptional regulation. Copyright © 2018 The Authors. Published by Elsevier Inc. All rights reserved.

Dual Roles for Ikaros in Regulation of Macrophage Chromatin State and Inflammatory Gene Expression.

PubMed

Oh, Kyu-Seon; Gottschalk, Rachel A; Lounsbury, Nicolas W; Sun, Jing; Dorrington, Michael G; Baek, Songjoon; Sun, Guangping; Wang, Ze; Krauss, Kathleen S; Milner, Joshua D; Dutta, Bhaskar; Hager, Gordon L; Sung, Myong-Hee; Fraser, Iain D C

2018-06-13

Macrophage activation by bacterial LPS leads to induction of a complex inflammatory gene program dependent on numerous transcription factor families. The transcription factor Ikaros has been shown to play a critical role in lymphoid cell development and differentiation; however, its function in myeloid cells and innate immune responses is less appreciated. Using comprehensive genomic analysis of Ikaros-dependent transcription, DNA binding, and chromatin accessibility, we describe unexpected dual repressor and activator functions for Ikaros in the LPS response of murine macrophages. Consistent with the described function of Ikaros as transcriptional repressor, Ikzf1 -/- macrophages showed enhanced induction for select responses. In contrast, we observed a dramatic defect in expression of many delayed LPS response genes, and chromatin immunoprecipitation sequencing analyses support a key role for Ikaros in sustained NF-κB chromatin binding. Decreased Ikaros expression in Ikzf1 +/- mice and human cells dampens these Ikaros-enhanced inflammatory responses, highlighting the importance of quantitative control of Ikaros protein level for its activator function. In the absence of Ikaros, a constitutively open chromatin state was coincident with dysregulation of LPS-induced chromatin remodeling, gene expression, and cytokine responses. Together, our data suggest a central role for Ikaros in coordinating the complex macrophage transcriptional program in response to pathogen challenge.

Role for Human Mediator Subunit MED25 in Recruitment of Mediator to Promoters by Endoplasmic Reticulum Stress-responsive Transcription Factor ATF6α*

PubMed Central

Sela, Dotan; Conkright, Juliana J.; Chen, Lu; Gilmore, Joshua; Washburn, Michael P.; Florens, Laurence; Conaway, Ronald C.; Conaway, Joan Weliky

2013-01-01

Transcription factor ATF6α functions as a master regulator of endoplasmic reticulum (ER) stress response genes. In response to ER stress, ATF6α translocates from its site of latency in the ER membrane to the nucleus, where it activates RNA polymerase II transcription of ER stress response genes upon binding sequence-specifically to ER stress response enhancer elements (ERSEs) in their promoter-regulatory regions. In a recent study, we demonstrated that ATF6α activates transcription of ER stress response genes by a mechanism involving recruitment to ERSEs of the multisubunit Mediator and several histone acetyltransferase (HAT) complexes, including Spt-Ada-Gcn5 (SAGA) and Ada-Two-A-containing (ATAC) (Sela, D., Chen, L., Martin-Brown, S., Washburn, M.P., Florens, L., Conaway, J.W., and Conaway, R.C. (2012) J. Biol. Chem. 287, 23035–23045). In this study, we extend our investigation of the mechanism by which ATF6α supports recruitment of Mediator to ER stress response genes. We present findings arguing that Mediator subunit MED25 plays a critical role in this process and identify a MED25 domain that serves as a docking site on Mediator for the ATF6α transcription activation domain. PMID:23864652

Transcriptomic profiling-based mutant screen reveals three new transcription factors mediating menadione resistance in Neurospora crassa.

PubMed

Zhu, Jufen; Yu, Xinxu; Xie, Baogui; Gu, Xiaokui; Zhang, Zhenying; Li, Shaojie

2013-06-01

To gain insight into the regulatory mechanisms of oxidative stress responses in filamentous fungi, the genome-wide transcriptional response of Neurospora crassa to menadione was analysed by digital gene expression (DGE) profiling, which identified 779 upregulated genes and 576 downregulated genes. Knockout mutants affecting 130 highly-upregulated genes were tested for menadione sensitivity, which revealed that loss of the transcription factor siderophore regulation (SRE) (a transcriptional repressor for siderophore biosynthesis), catatase-3, cytochrome c peroxidase or superoxide dismutase 1 copper chaperone causes hypersensitivity to menadione. Deletion of sre dramatically increased transcription of the siderophore biosynthesis gene ono and the siderophore iron transporter gene sit during menadione stress, suggesting that SRE is required for repression of iron uptake under oxidative stress conditions. Contrary to its phenotype, the sre deletion mutant showed higher transcriptional levels of genes encoding reactive oxygen species (ROS) scavengers than wild type during menadione stress, which implies that the mutant suffers a higher level of oxidative stress than wild type. Uncontrolled iron uptake in the sre mutant might exacerbate cellular oxidative stress. This is the first report of a negative regulator of iron assimilation participating in the fungal oxidative stress response. In addition to SRE, eight other transcription factor genes were also menadione-responsive but their single gene knockout mutants showed wild-type menadione sensitivity. Two of them, named as mit-2 (menadione induced transcription factor-2) and mit-4 (menadione induced transcription factor-4), were selected for double mutant analysis. The double mutant was hypersensitive to menadione. Similarly, the double mutation of mit-2 and sre also had additive effects on menadione sensitivity, suggesting multiple transcription factors mediate oxidative stress resistance in an additive manner. Copyright © 2013 The British Mycological Society. Published by Elsevier Ltd. All rights reserved.

Comparative transcriptome and gene co-expression network analysis reveal genes and signaling pathways adaptively responsive to varied adverse stresses in the insect fungal pathogen, Beauveria bassiana.

PubMed

He, Zhangjiang; Zhao, Xin; Lu, Zhuoyue; Wang, Huifang; Liu, Pengfei; Zeng, Fanqin; Zhang, Yongjun

2018-01-01

Sensing, responding, and adapting to the surrounding environment are crucial for all living organisms to survive, proliferate, and differentiate in their biological niches. Beauveria bassiana is an economically important insect-pathogenic fungus which is widely used as a biocontrol agent to control a variety of insect pests. The fungal pathogen unavoidably encounters a variety of adverse environmental stresses and defense response from the host insects during application of the fungal agents. However, few are known about the transcription response of the fungus to respond or adapt varied adverse stresses. Here, we comparatively analyzed the transcriptome of B. bassiana in globe genome under the varied stationary-phase stresses including osmotic agent (0.8 M NaCl), high temperature (32 °C), cell wall-perturbing agent (Congo red), and oxidative agents (H 2 O 2 or menadione). Total of 12,412 reads were obtained, and mapped to the 6767 genes of the B. bassiana. All of these stresses caused transcription responses involved in basal metabolism, cell wall construction, stress response or cell rescue/detoxification, signaling transduction and gene transcription regulation, and likely other cellular processes. An array of genes displayed similar transcription patterns in response to at least two of the five stresses, suggesting a shared transcription response to varied adverse stresses. Gene co-expression network analysis revealed that mTOR signaling pathway, but not HOG1 MAP kinase pathway, played a central role in regulation the varied adverse stress responses, which was verified by RNAi-mediated knockdown of TOR1. Our findings provided an insight of transcription response and gene co-expression network of B. bassiana in adaptation to varied environments. Copyright © 2017 Elsevier Inc. All rights reserved.

Elucidation of biocontrol mechanisms of Trichoderma harzianum against different plant fungal pathogens: Universal yet host specific response.

PubMed

Sharma, Vivek; Salwan, Richa; Sharma, Prem N; Kanwar, S S

2017-02-01

In the present study, different transcripts of Trichoderma harzianum ThHP-3 were evaluated for their response against four fungal pathogens Fusarium oxysporum, Colletotrichum capsici, Colletotrichum truncatum and Gloesercospora sorghi using RT-qPCR. The time course study of T. harzianum transcripts related to signal transduction, lytic enzymes, secondary metabolites and various transporters revealed variation in expression against four fungal pathogens. In a broader term, the transcripts were upregulated at various time intervals but the optimum expression of cyp3, abc, nrp, tga1, pmk, ech42 and glh20 varied with respect to host fungi. Additionally, the expression of transcripts related to transporters/cytochromes was also observed against Fusarium oxysporum after 96h whereas transcripts related to secondary metabolites and lytic enzymes showed significant difference in expression against Colletotrichum spp. from 72 to 96h. This is first study on transcriptomic response of T. harzianum against pathogenic fungi which shows their host specific response. Copyright © 2016 Elsevier B.V. All rights reserved.

Transcriptional and catalytic responses of antioxidant and biotransformation pathways in mussels, Mytilus galloprovincialis, exposed to chemical mixtures.

PubMed

Giuliani, Maria Elisa; Benedetti, Maura; Arukwe, Augustine; Regoli, Francesco

2013-06-15

Antioxidant and biotransformation pathways are widely studied in marine organisms exposed to environmental stressors. However, mechanisms of responses and links between different intracellular levels are not always easy to elucidate and conflicting results are frequently observed between molecular and enzymatic data. In this study, transcriptional and catalytic responses of antioxidant and biotransformation parameters were analyzed after a 4-week exposure of a marine invertebrate, Mytilus galloprovincialis, to chemical mixtures from low polluted and highly polluted sediments. A significant, dose-dependent bioaccumulation was observed for polycyclic aromatic hydrocarbons, especially low molecular weight compounds. Among antioxidant defences, catalase and glutathione peroxidases did not exhibit variations in enzymatic activity, while the corresponding gene transcriptions were up- and down-regulated, respectively; unchanged mRNA levels of superoxide dismutase confirmed the non-synchronous pathways of variations for such antioxidants. Biotransformation responses also revealed inconsistent trends between transcriptional and catalytic variations of glutathione S-transferases, and a significant increase in mRNA levels for cytochrome P450 3A1. The overall results indicated that transcriptional responses might be sensitive but do not necessarily correspond to functional changes, being more useful as "exposure" rather than "effect" biomarkers. Data on gene transcription and catalytic activities should be carefully interpreted when assessing the impact of chemical pollutants and additional studies are needed on modulation of post-transcriptional mechanisms by environmental stressors. Copyright © 2013 Elsevier B.V. All rights reserved.

Functional architecture of Escherichia coli: new insights provided by a natural decomposition approach.

PubMed

Freyre-González, Julio A; Alonso-Pavón, José A; Treviño-Quintanilla, Luis G; Collado-Vides, Julio

2008-10-27

Previous studies have used different methods in an effort to extract the modular organization of transcriptional regulatory networks. However, these approaches are not natural, as they try to cluster strongly connected genes into a module or locate known pleiotropic transcription factors in lower hierarchical layers. Here, we unravel the transcriptional regulatory network of Escherichia coli by separating it into its key elements, thus revealing its natural organization. We also present a mathematical criterion, based on the topological features of the transcriptional regulatory network, to classify the network elements into one of two possible classes: hierarchical or modular genes. We found that modular genes are clustered into physiologically correlated groups validated by a statistical analysis of the enrichment of the functional classes. Hierarchical genes encode transcription factors responsible for coordinating module responses based on general interest signals. Hierarchical elements correlate highly with the previously studied global regulators, suggesting that this could be the first mathematical method to identify global regulators. We identified a new element in transcriptional regulatory networks never described before: intermodular genes. These are structural genes that integrate, at the promoter level, signals coming from different modules, and therefore from different physiological responses. Using the concept of pleiotropy, we have reconstructed the hierarchy of the network and discuss the role of feedforward motifs in shaping the hierarchical backbone of the transcriptional regulatory network. This study sheds new light on the design principles underpinning the organization of transcriptional regulatory networks, showing a novel nonpyramidal architecture composed of independent modules globally governed by hierarchical transcription factors, whose responses are integrated by intermodular genes.

Chronic nicotine treatment leads to induction of tyrosine hydroxylase in locus ceruleus neurons: the role of transcriptional activation.

PubMed

Sun, Baoyong; Chen, Xiqun; Xu, Lu; Sterling, Carol; Tank, A William

2004-10-01

Chronic nicotine treatment (two daily subcutaneous injections administered approximately 12 h apart for 14 days) is associated with long-term inductions of tyrosine hydroxylase (TH) protein and TH mRNA in locus ceruleus (LC) neurons. These increases persist for at least 3 days after the final nicotine injection in LC cell bodies and for at least 7 to 10 days in LC nerve terminal regions. We tested whether this long-term response is due to sustained stimulation of TH gene transcription rate. A semiquantitative reverse transcription-polymerase chain reaction assay was developed to assess changes in the levels of TH RNA primary transcripts; these changes are an indirect measurement of changes in TH gene transcription rate. TH RNA primary transcript levels increase rapidly in the LC after a single nicotine administration and return to basal levels by 24 h. A similar rapid and transient induction of LC TH RNA primary transcripts occurs after chronic nicotine administration. In contrast, TH RNA primary transcript levels remain elevated for a sustained period of time (at least 1 day) in the adrenal medulla after chronic nicotine administration. Similar rapid, but transient changes in LC TH RNA primary transcript levels are observed after repeated immobilization stress. These results suggest that TH gene transcription rate in the LC is stimulated rapidly after each nicotine injection; however, in contrast to the adrenal medulla, there is no sustained transcriptional response elicited by chronic nicotine treatment or repeated immobilization stress in the LC, suggesting that post-transcriptional mechanisms may also play a role in these long-term responses.

Popular epidemiology and "fracking": citizens' concerns regarding the economic, environmental, health and social impacts of unconventional natural gas drilling operations.

PubMed

Powers, Martha; Saberi, Poune; Pepino, Richard; Strupp, Emily; Bugos, Eva; Cannuscio, Carolyn C

2015-06-01

Pennsylvania sits atop the Marcellus Shale, a reservoir of natural gas that was untapped until the 2004 introduction of unconventional natural gas drilling operations (UNGDO) in the state. Colloquially known as fracking, UNGDO is a controversial process that employs large volumes of water to fracture the shale and capture gas; it has become a multi-billion dollar industry in Pennsylvania. We analyzed letters to the editor of the most widely circulated local newspaper in the most heavily drilled county in Pennsylvania (Bradford County) in order to characterize residents' concerns and their involvement in popular epidemiology--the process by which citizens investigate risks associated with a perceived environmental threat. We reviewed 215 letters to the editor that referenced natural gas operations and were published by The Daily Review between January 1, 2008 and June 8, 2013. We used NVivo 10 to code and analyze letters and identify major themes. Nvivo is qualitative data analysis software (http://www.qsrinternational.com/products_nvivo.aspx) that allows researchers to code and analyze "unstructured" data, including text files of any type (e.g., interview transcripts, news articles, letters, archival materials) as well as photographs and videos. Nvivo can be used to classify, sort, query, comment on, and share data across a research group. Letters demonstrated citizen engagement in beginning and intermediate stages of lay epidemiology, as well as discord and stress regarding four main issues: socio-economic impacts, perceived threats to water, population growth and implications, and changes to the rural landscape. Residents called for stronger scientific evidence and a balance of economic development and health and environmental protections. Citizens' distress regarding UNGDO appeared to be exacerbated by a dearth of information to guide economic growth and health, environmental, and social concerns. This analysis proposes locally informed questions to guide future surveillance and research.

Casein Kinase II Regulation of the Hot1 Transcription Factor Promotes Stochastic Gene Expression*

PubMed Central

Burns, Laura T.; Wente, Susan R.

2014-01-01

In Saccharomyces cerevisiae, Hog1 MAPK is activated and induces a transcriptional program in response to hyperosmotic stress. Several Hog1-responsive genes exhibit stochastic transcription, resulting in cell-to-cell variability in mRNA and protein levels. However, the mechanisms governing stochastic gene activity are not fully defined. Here we uncover a novel role for casein kinase II (CK2) in the cellular response to hyperosmotic stress. CK2 interacts with and phosphorylates the Hot1 transcription factor; however, Hot1 phosphorylation is not sufficient for controlling the stochastic response. The CK2 protein itself is required to negatively regulate mRNA expression of Hot1-responsive genes and Hot1 enrichment at target promoters. Single-cell gene expression analysis reveals altered activation of Hot1-targeted STL1 in ck2 mutants, resulting in a bimodal to unimodal shift in expression. Together, this work reveals a novel CK2 function during the hyperosmotic stress response that promotes cell-to-cell variability in gene expression. PMID:24817120

Direct transcriptional activation of BT genes by NLP transcription factors is a key component of the nitrate response in Arabidopsis.

PubMed

Sato, Takeo; Maekawa, Shugo; Konishi, Mineko; Yoshioka, Nozomi; Sasaki, Yuki; Maeda, Haruna; Ishida, Tetsuya; Kato, Yuki; Yamaguchi, Junji; Yanagisawa, Shuichi

2017-01-29

Nitrate modulates growth and development, functioning as a nutrient signal in plants. Although many changes in physiological processes in response to nitrate have been well characterized as nitrate responses, the molecular mechanisms underlying the nitrate response are not yet fully understood. Here, we show that NLP transcription factors, which are key regulators of the nitrate response, directly activate the nitrate-inducible expression of BT1 and BT2 encoding putative scaffold proteins with a plant-specific domain structure in Arabidopsis. Interestingly, the 35S promoter-driven expression of BT2 partially rescued growth inhibition caused by reductions in NLP activity in Arabidopsis. Furthermore, simultaneous disruption of BT1 and BT2 affected nitrate-dependent lateral root development. These results suggest that direct activation of BT1 and BT2 by NLP transcriptional activators is a key component of the molecular mechanism underlying the nitrate response in Arabidopsis. Copyright © 2016 Elsevier Inc. All rights reserved.

Transcriptomic response of the red tide dinoflagellate, Karenia brevis, to nitrogen and phosphorus depletion and addition.

PubMed

Morey, Jeanine S; Monroe, Emily A; Kinney, Amanda L; Beal, Marion; Johnson, Jillian G; Hitchcock, Gary L; Van Dolah, Frances M

2011-07-05

The role of coastal nutrient sources in the persistence of Karenia brevis red tides in coastal waters of Florida is a contentious issue that warrants investigation into the regulation of nutrient responses in this dinoflagellate. In other phytoplankton studied, nutrient status is reflected by the expression levels of N- and P-responsive gene transcripts. In dinoflagellates, however, many processes are regulated post-transcriptionally. All nuclear encoded gene transcripts studied to date possess a 5' trans-spliced leader (SL) sequence suggestive, based on the trypanosome model, of post-transcriptional regulation. The current study therefore sought to determine if the transcriptome of K. brevis is responsive to nitrogen and phosphorus and is informative of nutrient status. Microarray analysis of N-depleted K. brevis cultures revealed an increase in the expression of transcripts involved in N-assimilation (nitrate and ammonium transporters, glutamine synthetases) relative to nutrient replete cells. In contrast, a transcriptional signal of P-starvation was not apparent despite evidence of P-starvation based on their rapid growth response to P-addition. To study transcriptome responses to nutrient addition, the limiting nutrient was added to depleted cells and changes in global gene expression were assessed over the first 48 hours following nutrient addition. Both N- and P-addition resulted in significant changes in approximately 4% of genes on the microarray, using a significance cutoff of 1.7-fold and p ≤ 10-4. By far, the earliest responding genes were dominated in both nutrient treatments by pentatricopeptide repeat (PPR) proteins, which increased in expression up to 3-fold by 1 h following nutrient addition. PPR proteins are nuclear encoded proteins involved in chloroplast and mitochondria RNA processing. Correspondingly, other functions enriched in response to both nutrients were photosystem and ribosomal genes. Microarray analysis provided transcriptomic evidence for N- but not P-limitation in K. brevis. Transcriptomic responses to the addition of either N or P suggest a concerted program leading to the reactivation of chloroplast functions. Even the earliest responding PPR protein transcripts possess a 5' SL sequence that suggests post-transcriptional control. Given the current state of knowledge of dinoflagellate gene regulation, it is currently unclear how these rapid changes in such transcript levels are achieved.

The capacity of states to govern shale gas development risks.

PubMed

Wiseman, Hannah J

2014-01-01

The development of natural gas and oil from unconventional formations in the United States has grown substantially in recent years and has created governance challenges. In light of this recent growth, and increasing attention to global shale gas resources, the successes and failures of governance efforts in this country serve as important lessons for other nations that have their own unconventional petroleum resources and are beginning to move forward with development, thus calling for a more in-depth examination of the laws governing shale gas development and their implementation. Governance includes both the substance of laws and the activities of entities that implement and influence laws, and in the case of oil and gas, states are primarily responsible for risk governance. Nongovernmental actors and industry also work with states to shape and implement regulations and standards. This Policy Analysis introduces the role of various actors in U.S. shale gas governance, explaining why the states are primarily responsible for risk governance, and explores the capacity of states to conduct governance, examining the content of their laws and the strength of their regulatory entities. The Analysis concludes that states are, to a degree, addressing the changing risks of development. Gaps remain in the substance of regulations, however, and many states appear to lack adequate support or policies for training industry in compliance matters, monitoring activity at sites, prioritizing certain types of regulatory violations that pose the highest risks, enforcing laws, and ensuring that the public is aware of inspections and enforcement and can therefore monitor state activity.

A Role for Iron-Sulfur Clusters in the Regulation of Transcription Factor Yap5-dependent High Iron Transcriptional Responses in Yeast*

PubMed Central

Li, Liangtao; Miao, Ren; Bertram, Sophie; Jia, Xuan; Ward, Diane M.; Kaplan, Jerry

2012-01-01

Yeast respond to increased cytosolic iron by activating the transcription factor Yap5 increasing transcription of CCC1, which encodes a vacuolar iron importer. Using a genetic screen to identify genes involved in Yap5 iron sensing, we discovered that a mutation in SSQ1, which encodes a mitochondrial chaperone involved in iron-sulfur cluster synthesis, prevented expression of Yap5 target genes. We demonstrated that mutation or reduced expression of other genes involved in mitochondrial iron-sulfur cluster synthesis (YFH1, ISU1) prevented induction of the Yap5 response. We took advantage of the iron-dependent catalytic activity of Pseudaminobacter salicylatoxidans gentisate 1,2-dioxygenase expressed in yeast to measure changes in cytosolic iron. We determined that reductions in iron-sulfur cluster synthesis did not affect the activity of cytosolic gentisate 1,2-dioxygenase. We show that loss of activity of the cytosolic iron-sulfur cluster assembly complex proteins or deletion of cytosolic glutaredoxins did not reduce expression of Yap5 target genes. These results suggest that the high iron transcriptional response, as well as the low iron transcriptional response, senses iron-sulfur clusters. PMID:22915593

Genetic variation of transgenerational plasticity of offspring germination in response to salinity stress and the seed transcriptome of Medicago truncatula.

PubMed

Vu, Wendy T; Chang, Peter L; Moriuchi, Ken S; Friesen, Maren L

2015-04-01

Transgenerational plasticity provides phenotypic variation that contributes to adaptation. For plants, the timing of seed germination is critical for offspring survival in stressful environments, as germination timing can alter the environmental conditions a seedling experiences. Stored seed transcripts are important determinants of seed germination, but have not previously been linked with transgenerational plasticity of germination behavior. In this study we used RNAseq and growth chamber experiments of the model legume M. trucantula to test whether parental exposure to salinity stress influences the expression of stored seed transcripts and early offspring traits and test for genetic variation. We detected genotype-dependent parental environmental effects (transgenerational plasticity) on the expression levels of stored seed transcripts, seed size, and germination behavior of four M. truncatula genotypes. More than 50% of the transcripts detected in the mature, ungerminated seed transcriptome were annotated as regulating seed germination, some of which are involved in abiotic stress response and post-embryonic development. Some genotypes showed increased seed size in response to parental exposure to salinity stress, but no parental environmental influence on germination timing. In contrast, other genotypes showed no seed size differences across contrasting parental conditions but displayed transgenerational plasticity for germimation timing, with significantly delayed germination in saline conditions when parental plants were exposed to salinity. In genotypes that show significant transgenerational plastic germination response, we found significant coexpression networks derived from salt responsive transcripts involved in post-transcriptional regulation of the germination pathway. Consistent with the delayed germination response to saline conditions in these genotypes, we found genes associated with dormancy and up-regulation of abscisic acid (ABA). Our results demonstrate genetic variation in transgenerational plasticity within M. truncatula and show that parental exposure to salinity stress influences the expression of stored seed transcripts, seed weight, and germination behavior. Furthermore, we show that the parental environment influences gene expression to modulate biological pathways that are likely responsible for offspring germination responses to salinity stress.

Fatigue and gene expression in human leukocytes: increased NF-κB and decreased glucocorticoid signaling in breast cancer survivors with persistent fatigue.

PubMed

Bower, Julienne E; Ganz, Patricia A; Irwin, Michael R; Arevalo, Jesusa M G; Cole, Steve W

2011-01-01

Fatigue is highly prevalent in the general population and is one of the most common side effects of cancer treatment. There is growing evidence that pro-inflammatory cytokines play a role in cancer-related fatigue, although the molecular mechanisms for chronic inflammation and fatigue have not been determined. The current study utilized genome-wide expression microarrays to identify differences in gene expression and associated alterations in transcriptional activity in leukocytes from breast cancer survivors with persistent fatigue (n=11) and non-fatigued controls (n=10). We focused on transcription of inflammation-related genes, particularly those responsive to the pro-inflammatory NF-κB transcription control pathway. Further, given the role of glucocorticoids as key regulators of inflammatory processes, we examined transcription of glucocorticoid-responsive genes indicative of potential glucocorticoid receptor (GR) desensitization. Plasma levels of cortisol were also assessed. Consistent with hypotheses, results showed increased expression of transcripts with response elements for NF-κB, and reduced expression of transcripts with response elements for glucocorticoids (p<.05) in fatigued breast cancer survivors. No differences in plasma levels of cortisol were observed. These data indicate that increased activity of pro-inflammatory transcription factors may contribute to persistent cancer-related fatigue and provide insight into potential mechanisms for tonic increases in NF-κB activity, specifically decreased expression of GR anti-inflammatory transcription factors. Copyright © 2010 Elsevier Inc. All rights reserved.

Hepcidin mediates transcriptional changes that modulate acute cytokine-induced inflammatory responses in mice

PubMed Central

De Domenico, Ivana; Zhang, Tian Y.; Koening, Curry L.; Branch, Ryan W.; London, Nyall; Lo, Eric; Daynes, Raymond A.; Kushner, James P.; Li, Dean; Ward, Diane M.; Kaplan, Jerry

2010-01-01

Hepcidin is a peptide hormone that regulates iron homeostasis and acts as an antimicrobial peptide. It is expressed and secreted by a variety of cell types in response to iron loading and inflammation. Hepcidin mediates iron homeostasis by binding to the iron exporter ferroportin, inducing its internalization and degradation via activation of the protein kinase Jak2 and the subsequent phosphorylation of ferroportin. Here we have shown that hepcidin-activated Jak2 also phosphorylates the transcription factor Stat3, resulting in a transcriptional response. Hepcidin treatment of ferroportin-expressing mouse macrophages showed changes in mRNA expression levels of a wide variety of genes. The changes in transcript levels for half of these genes were a direct effect of hepcidin, as shown by cycloheximide insensitivity, and dependent on the presence of Stat3. Hepcidin-mediated transcriptional changes modulated LPS-induced transcription in both cultured macrophages and in vivo mouse models, as demonstrated by suppression of IL-6 and TNF-α transcript and secreted protein. Hepcidin-mediated transcription in mice also suppressed toxicity and morbidity due to single doses of LPS, poly(I:C), and turpentine, which is used to model chronic inflammatory disease. Most notably, we demonstrated that hepcidin pretreatment protected mice from a lethal dose of LPS and that hepcidin-knockout mice could be rescued from LPS toxicity by injection of hepcidin. The results of our study suggest a new function for hepcidin in modulating acute inflammatory responses. PMID:20530874

Role of ART-27, a Novel Androgen Receptor Coactivator, in Normal Prostate and Prostate Cancer

DTIC Science & Technology

2005-04-01

associates with pro- teins that include RBP5, a subunit shared by RNA polymerases I, II , and Ill, an RBP5 binding protein called unconventional prefoldin ...of a large multiprotein complex that contains RNA polymerase II subunit 5, a subunit shared by all three RNA polymerases; unconventional prefoldin ...dithiothreitol; GRIP, glucocorticoid re- ceptor Interacting p rotein; HA, hemagglutinin; MMTV, mouse mamm ary tumor virus ; PAIS, partial AIS; SDS

Psychological and Unconventional Warfare, 1941-1952: Origins of a Special Warfare Capability for the United States Army

DTIC Science & Technology

1979-11-01

nic -,L-dant orer unconventional wsr:fare? In shnrt, wfiat were-the pre-1952 roots of tbe’ P9ych𔃺rg1.ca1 WArfArPg Contme" artx], cMocom~tant y, the...General Robert A. McClure, 30 March 1948, from Co’.onel William S. Biddle , Assistant Chief, Plans and Policy Group, 1, 319, Plans and Operations Division

Breakdown of Landau Fermi liquid theory: Restrictions on the degrees of freedom of quantum electrons

NASA Astrophysics Data System (ADS)

Su, Yue-Hua; Lu, Han-Tao

2018-04-01

One challenge in contemporary condensed matter physics is to understand unconventional electronic physics beyond the paradigm of Landau Fermi-liquid theory. Here, we present a perspective that posits that most such examples of unconventional electronic physics stem from restrictions on the degrees of freedom of quantum electrons in Landau Fermi liquids. Since the degrees of freedom are deeply connected to the system's symmetries and topology, these restrictions can thus be realized by external constraints or by interaction-driven processes via the following mechanisms: (i) symmetry breaking, (ii) new emergent symmetries, and (iii) nontrivial topology. Various examples of unconventional electronic physics beyond the reach of traditional Landau Fermi liquid theory are extensively investigated from this point of view. Our perspective yields basic pathways to study the breakdown of Landau Fermi liquids and also provides a guiding principle in the search for novel electronic systems and devices.

Unconventional treatments for chronic inflammatory demyelinating polyneuropathy.

PubMed

Rajabally, Yusuf A

2017-10-01

This article focuses on the unconventional treatments used in chronic inflammatory demyelinating polyneuropathy (CIDP). First line, evidence-based treatments for CIDP include corticosteroids, immunoglobulins and plasma exchanges. Several unproven treatments are however given in treatment-refractory disease or to reduce requirements in validated therapies for reasons of side effects/practical delivery/cost. Despite methodological issues, IFN-α, azathioprine and methotrexate have not been shown to be useful in randomized controlled trials. Cyclophosphamide, rituximab and, as final resort in highly selected cases, hematopoietic stem cell transplant may be options considered in severely disabled refractory patients. Debatably, azathioprine, methotrexate, cyclosporine and mycophenolate mofetil are still occasionally used, among others, in milder disease. Physical therapy may be of benefit in CIDP but is not systematically considered as an integral part of management strategies. Current literature relating to unconventional therapies in CIDP is reviewed here and the possible avenues that require consideration in severe refractory disease and less disabling forms are discussed.

Unconventional Superconductivity in the BiS_{2}-Based Layered Superconductor NdO_{0.71}F_{0.29}BiS_{2}.

PubMed

Ota, Yuichi; Okazaki, Kozo; Yamamoto, Haruyoshi Q; Yamamoto, Takashi; Watanabe, Shuntaro; Chen, Chuangtian; Nagao, Masanori; Watauchi, Satoshi; Tanaka, Isao; Takano, Yoshihiko; Shin, Shik

2017-04-21

We investigate the superconducting-gap anisotropy in one of the recently discovered BiS_{2}-based superconductors, NdO_{0.71}F_{0.29}BiS_{2} (T_{c}∼5  K), using laser-based angle-resolved photoemission spectroscopy. Whereas the previously discovered high-T_{c} superconductors such as copper oxides and iron-based superconductors, which are believed to have unconventional superconducting mechanisms, have 3d electrons in their conduction bands, the conduction band of BiS_{2}-based superconductors mainly consists of Bi 6p electrons, and, hence, the conventional superconducting mechanism might be expected. Contrary to this expectation, we observe a strongly anisotropic superconducting gap. This result strongly suggests that the pairing mechanism for NdO_{0.71}F_{0.29}BiS_{2} is an unconventional one and we attribute the observed anisotropy to competitive or cooperative multiple paring interactions.

Superconductivity and Competing Ordered Phase in RuPn (Pn = As, P)

NASA Astrophysics Data System (ADS)

Hirai, Daigorou; Takayama, Tomohiro; Hashizume, Daisuke; Yamamoto, Ayako; Takagi, Hidenori

2011-03-01

Unconventional superconductivity likely manifests itself when some competing electronic phases are suppressed down to zero temperature such as cuprates and iron-pnictide superconductors. Therefore, the correlated metallic state neighboring a competing electronic ordering can be a promising playground for unconventional superconductivity. Here we report superconductivity emerging adjacent to electronically ordered phases of RuPn (Pn = As, P). We found that RuAs(P) exhibits phase transitions at 240 (265) K, which is discerned as a drop of magnetic susceptibility or a resistivity upturn. Such anomalies can be suppressed by substituting Rh to the Ru site. Accompanied by the disappearance of the electronic order, superconductivity was found to emerge below 1.8 K and 3.8 K for RuAs and RuP, respectively. The superconductivity in Rh substituted RuPn, which neighbors a competing electronic order, might exhibit an exotic pairing state as seen in the unconventional superconductors known to date.

'Beautiful' unconventional synthesis and processing technologies of superconductors and some other materials.

PubMed

Badica, Petre; Crisan, Adrian; Aldica, Gheorghe; Endo, Kazuhiro; Borodianska, Hanna; Togano, Kazumasa; Awaji, Satoshi; Watanabe, Kazuo; Sakka, Yoshio; Vasylkiv, Oleg

2011-02-01

Superconducting materials have contributed significantly to the development of modern materials science and engineering. Specific technological solutions for their synthesis and processing helped in understanding the principles and approaches to the design, fabrication and application of many other materials. In this review, we explore the bidirectional relationship between the general and particular synthesis concepts. The analysis is mostly based on our studies where some unconventional technologies were applied to different superconductors and some other materials. These technologies include spray-frozen freeze-drying, fast pyrolysis, field-assisted sintering (or spark plasma sintering), nanoblasting, processing in high magnetic fields, methods of control of supersaturation and migration during film growth, and mechanical treatments of composite wires. The analysis provides future research directions and some key elements to define the concept of 'beautiful' technology in materials science. It also reconfirms the key position and importance of superconductors in the development of new materials and unconventional synthesis approaches.

H2S and polysulfide metabolism: Conventional and unconventional pathways.

PubMed

Olson, Kenneth R

2018-03-01

It is now well established that hydrogen sulfide (H 2 S) is an effector of a wide variety of physiological processes. It is also clear that many of the effects of H 2 S are mediated through reactions with cysteine sulfur on regulatory proteins and most of these are not mediated directly by H 2 S but require prior oxidation of H 2 S and the formation of per- and polysulfides (H 2 S n , n = 2-8). Attendant with understanding the regulatory functions of H 2 S and H 2 S n is an appreciation of the mechanisms that control, i.e., both increase and decrease, their production and catabolism. Although a number of standard "conventional" pathways have been described and well characterized, novel "unconventional" pathways are continuously being identified. This review summarizes our current knowledge of both the conventional and unconventional. Copyright © 2017 Elsevier Inc. All rights reserved.

Index theorem for the flat Andreev bound states at a dirty surface of a nodal superconductor

NASA Astrophysics Data System (ADS)

Ikegaya, Satoshi; Asano, Yasuhiro

2018-03-01

We discuss the stability of at-band Andreev bound states appearing at a surface of a nodal unconventional superconductor. In the clean limit, the existence of the surface bound states is topologically characterized by a momentum-dependent topological invariant: one-dimensional winding number de ned in the restricted Brillouin zone. Thus, such topological invariant is ill-defined in the presence of potential disorder which is inevitable in experiments. By paying attention to chiral symmetry of the Hamiltonian, we provide an alternative topological index N ZES that predicts the number of Andreev bound states at a dirty surface of an unconventional superconductor. Moreover, we demonstrate that the zero-bias differential conductance in a normal metal/unconventional superconductor junction is quantized at (4e 2 /h)|N ZES | in the limit of strong impurity scattering in the normal metal.

Unconventional energy resources: 2015 review. Shale gas and liquids

USGS Publications Warehouse

Fishman, Neil S.; Bowker, Kent; Cander, Harris; Cardott, Brian; Charette, Marc; Chew, Kenneth; Chidsey, Thomas; Dubiel, Russell F.; Egenhoff, Sven O.; Enomoto, Catherine B.; Hammes, Ursula; Harrison, William; Jiang, Shu; LeFever, Julie A.; McCracken, Jock; Nordeng, Stephen; Nyahay, Richard; Sonnenberg, Stephen; Vanden Berg, Michael; ,

2015-01-01

Introduction As the source rocks from which petroleum is generated, organic-rich shales have always been considered an important component of petroleum systems. Over the last few years, it has been realized that in some mudrocks, sufficient hydrocarbons remain in place to allow for commercial development, although advanced drilling and completion technology is typically required to access hydrocarbons from these reservoirs. Tight oil reservoirs (also referred to as continuous oil accumulations) contain hydrocarbons migrated from source rocks that are geologically/stratigraphically interbedded with or occur immediately overlying/underlying them. Migration is minimal in charging these tight oil accumulations (Gaswirth and Marra 2014). Companies around the world are now successfully exploiting organic-rich shales and tight rocks for contained hydrocarbons, and the search for these types of unconventional petroleum reservoirs is growing. Unconventional reservoirs range in geologic age from Ordovician to Tertiary (Silverman et al. 2005; EIA 2013a). 

Unconventional oil and gas extraction and animal health.

PubMed

Bamberger, M; Oswald, R E

2014-08-01

The extraction of hydrocarbons from shale formations using horizontal drilling with high volume hydraulic fracturing (unconventional shale gas and tight oil extraction), while derived from methods that have been used for decades, is a relatively new innovation that was introduced first in the United States and has more recently spread worldwide. Although this has led to the availability of new sources of fossil fuels for domestic consumption and export, important issues have been raised concerning the safety of the process relative to public health, animal health, and our food supply. Because of the multiple toxicants used and generated, and because of the complexity of the drilling, hydraulic fracturing, and completion processes including associated infrastructure such as pipelines, compressor stations and processing plants, impacts on the health of humans and animals are difficult to assess definitively. We discuss here findings concerning the safety of unconventional oil and gas extraction from the perspectives of public health, veterinary medicine, and food safety.

Hydro-mechanical coupled simulation of hydraulic fracturing using the eXtended Finite Element Method (XFEM)

NASA Astrophysics Data System (ADS)

Youn, Dong Joon

This thesis presents the development and validation of an advanced hydro-mechanical coupled finite element program analyzing hydraulic fracture propagation within unconventional hydrocarbon formations under various conditions. The realistic modeling of hydraulic fracturing is necessarily required to improve the understanding and efficiency of the stimulation technique. Such modeling remains highly challenging, however, due to factors including the complexity of fracture propagation mechanisms, the coupled behavior of fracture displacement and fluid pressure, the interactions between pre-existing natural and initiated hydraulic fractures and the formation heterogeneity of the target reservoir. In this research, an eXtended Finite Element Method (XFEM) scheme is developed allowing for representation of single or multiple fracture propagations without any need for re-meshing. Also, the coupled flows through the fracture are considered in the program to account for their influence on stresses and deformations along the hydraulic fracture. In this research, a sequential coupling scheme is applied to estimate fracture aperture and fluid pressure with the XFEM. Later, the coupled XFEM program is used to estimate wellbore bottomhole pressure during fracture propagation, and the pressure variations are analyzed to determine the geometry and performance of the hydraulic fracturing as pressure leak-off test. Finally, material heterogeneity is included into the XFEM program to check the effect of random formation property distributions to the hydraulic fracture geometry. Random field theory is used to create the random realization of the material heterogeneity with the consideration of mean, standard deviation, and property correlation length. These analyses lead to probabilistic information on the response of unconventional reservoirs and offer a more scientific approach regarding risk management for the unconventional reservoir stimulation. The new stochastic approach combining XFEM and random field is named as eXtended Random Finite Element Method (XRFEM). All the numerical analysis codes in this thesis are written in Fortran 2003, and these codes are applicable as a series of sub-modules within a suite of finite element codes developed by Smith and Griffiths (2004).

The transcriptional response of microbial communities in thawing Alaskan permafrost soils.

PubMed

Coolen, Marco J L; Orsi, William D

2015-01-01

Thawing of permafrost soils is expected to stimulate microbial decomposition and respiration of sequestered carbon. This could, in turn, increase atmospheric concentrations of greenhouse gasses, such as carbon dioxide and methane, and create a positive feedback to climate warming. Recent metagenomic studies suggest that permafrost has a large metabolic potential for carbon processing, including pathways for fermentation and methanogenesis. Here, we performed a pilot study using ultrahigh throughput Illumina HiSeq sequencing of reverse transcribed messenger RNA to obtain a detailed overview of active metabolic pathways and responsible organisms in up to 70 cm deep permafrost soils at a moist acidic tundra location in Arctic Alaska. The transcriptional response of the permafrost microbial community was compared before and after 11 days of thaw. In general, the transcriptional profile under frozen conditions suggests a dominance of stress responses, survival strategies, and maintenance processes, whereas upon thaw a rapid enzymatic response to decomposing soil organic matter (SOM) was observed. Bacteroidetes, Firmicutes, ascomycete fungi, and methanogens were responsible for largest transcriptional response upon thaw. Transcripts indicative of heterotrophic methanogenic pathways utilizing acetate, methanol, and methylamine were found predominantly in the permafrost table after thaw. Furthermore, transcripts involved in acetogenesis were expressed exclusively after thaw suggesting that acetogenic bacteria are a potential source of acetate for acetoclastic methanogenesis in freshly thawed permafrost. Metatranscriptomics is shown here to be a useful approach for inferring the activity of permafrost microbes that has potential to improve our understanding of permafrost SOM bioavailability and biogeochemical mechanisms contributing to greenhouse gas emissions as a result of permafrost thaw.

The transcriptional response of microbial communities in thawing Alaskan permafrost soils

PubMed Central

Coolen, Marco J. L.; Orsi, William D.

2015-01-01

Thawing of permafrost soils is expected to stimulate microbial decomposition and respiration of sequestered carbon. This could, in turn, increase atmospheric concentrations of greenhouse gasses, such as carbon dioxide and methane, and create a positive feedback to climate warming. Recent metagenomic studies suggest that permafrost has a large metabolic potential for carbon processing, including pathways for fermentation and methanogenesis. Here, we performed a pilot study using ultrahigh throughput Illumina HiSeq sequencing of reverse transcribed messenger RNA to obtain a detailed overview of active metabolic pathways and responsible organisms in up to 70 cm deep permafrost soils at a moist acidic tundra location in Arctic Alaska. The transcriptional response of the permafrost microbial community was compared before and after 11 days of thaw. In general, the transcriptional profile under frozen conditions suggests a dominance of stress responses, survival strategies, and maintenance processes, whereas upon thaw a rapid enzymatic response to decomposing soil organic matter (SOM) was observed. Bacteroidetes, Firmicutes, ascomycete fungi, and methanogens were responsible for largest transcriptional response upon thaw. Transcripts indicative of heterotrophic methanogenic pathways utilizing acetate, methanol, and methylamine were found predominantly in the permafrost table after thaw. Furthermore, transcripts involved in acetogenesis were expressed exclusively after thaw suggesting that acetogenic bacteria are a potential source of acetate for acetoclastic methanogenesis in freshly thawed permafrost. Metatranscriptomics is shown here to be a useful approach for inferring the activity of permafrost microbes that has potential to improve our understanding of permafrost SOM bioavailability and biogeochemical mechanisms contributing to greenhouse gas emissions as a result of permafrost thaw. PMID:25852660

Gravity-regulated gene expression in Arabidopsis thaliana

NASA Astrophysics Data System (ADS)

Sederoff, Heike; Brown, Christopher S.; Heber, Steffen; Kajla, Jyoti D.; Kumar, Sandeep; Lomax, Terri L.; Wheeler, Benjamin; Yalamanchili, Roopa

Plant growth and development is regulated by changes in environmental signals. Plants sense environmental changes and respond to them by modifying gene expression programs to ad-just cell growth, differentiation, and metabolism. Functional expression of genes comprises many different processes including transcription, translation, post-transcriptional and post-translational modifications, as well as the degradation of RNA and proteins. Recently, it was discovered that small RNAs (sRNA, 18-24 nucleotides long), which are heritable and systemic, are key elements in regulating gene expression in response to biotic and abiotic changes. Sev-eral different classes of sRNAs have been identified that are part of a non-cell autonomous and phloem-mobile network of regulators affecting transcript stability, translational kinetics, and DNA methylation patterns responsible for heritable transcriptional silencing (epigenetics). Our research has focused on gene expression changes in response to gravistimulation of Arabidopsis roots. Using high-throughput technologies including microarrays and 454 sequencing, we iden-tified rapid changes in transcript abundance of genes as well as differential expression of small RNA in Arabidopsis root apices after minutes of reorientation. Some of the differentially regu-lated transcripts are encoded by genes that are important for the bending response. Functional mutants of those genes respond faster to reorientation than the respective wild type plants, indicating that these proteins are repressors of differential cell elongation. We compared the gravity responsive sRNAs to the changes in transcript abundances of their putative targets and identified several potential miRNA: target pairs. Currently, we are using mutant and transgenic Arabidopsis plants to characterize the function of those miRNAs and their putative targets in gravitropic and phototropic responses in Arabidopsis.

MEDIATOR25 Acts as an Integrative Hub for the Regulation of Jasmonate-Responsive Gene Expression in Arabidopsis1[C][W

PubMed Central

Çevik, Volkan; Kidd, Brendan N.; Zhang, Peijun; Hill, Claire; Kiddle, Steve; Denby, Katherine J.; Holub, Eric B.; Cahill, David M.; Manners, John M.; Schenk, Peer M.; Beynon, Jim; Kazan, Kemal

2012-01-01

The PHYTOCHROME AND FLOWERING TIME1 gene encoding the MEDIATOR25 (MED25) subunit of the eukaryotic Mediator complex is a positive regulator of jasmonate (JA)-responsive gene expression in Arabidopsis (Arabidopsis thaliana). Based on the function of the Mediator complex as a bridge between DNA-bound transcriptional activators and the RNA polymerase II complex, MED25 has been hypothesized to function in association with transcriptional regulators of the JA pathway. However, it is currently not known mechanistically how MED25 functions to regulate JA-responsive gene expression. In this study, we show that MED25 physically interacts with several key transcriptional regulators of the JA signaling pathway, including the APETALA2 (AP2)/ETHYLENE RESPONSE FACTOR (ERF) transcription factors OCTADECANOID-RESPONSIVE ARABIDOPSIS AP2/ERF59 and ERF1 as well as the master regulator MYC2. Physical interaction detected between MED25 and four group IX AP2/ERF transcription factors was shown to require the activator interaction domain of MED25 as well as the recently discovered Conserved Motif IX-1/EDLL transcription activation motif of MED25-interacting AP2/ERFs. Using transcriptional activation experiments, we also show that OCTADECANOID-RESPONSIVE ARABIDOPSIS AP2/ERF59- and ERF1-dependent activation of PLANT DEFENSIN1.2 as well as MYC2-dependent activation of VEGETATIVE STORAGE PROTEIN1 requires a functional MED25. In addition, MED25 is required for MYC2-dependent repression of pathogen defense genes. These results suggest an important role for MED25 as an integrative hub within the Mediator complex during the regulation of JA-associated gene expression. PMID:22822211

Abiotic and Biotic Stressors Causing Equivalent Mortality Induce Highly Variable Transcriptional Responses in the Soybean Aphid

PubMed Central

Enders, Laramy S.; Bickel, Ryan D.; Brisson, Jennifer A.; Heng-Moss, Tiffany M.; Siegfried, Blair D.; Zera, Anthony J.; Miller, Nicholas J.

2014-01-01

Environmental stress affects basic organismal functioning and can cause physiological, developmental, and reproductive impairment. However, in many nonmodel organisms, the core molecular stress response remains poorly characterized and the extent to which stress-induced transcriptional changes differ across qualitatively different stress types is largely unexplored. The current study examines the molecular stress response of the soybean aphid (Aphis glycines) using RNA sequencing and compares transcriptional responses to multiple stressors (heat, starvation, and plant defenses) at a standardized stress level (27% adult mortality). Stress-induced transcriptional changes showed remarkable variation, with starvation, heat, and plant defensive stress altering the expression of 3985, 510, and 12 genes, respectively. Molecular responses showed little overlap across all three stressors. However, a common transcriptional stress response was identified under heat and starvation, involved with up-regulation of glycogen biosynthesis and molecular chaperones and down-regulation of bacterial endosymbiont cellular and insect cuticular components. Stressor-specific responses indicated heat affected expression of heat shock proteins and cuticular components, whereas starvation altered a diverse set of genes involved in primary metabolism, oxidative reductive processes, nucleosome and histone assembly, and the regulation of DNA repair and replication. Exposure to host plant defenses elicited the weakest response, of which half of the genes were of unknown function. This study highlights the need for standardizing stress levels when comparing across stress types and provides a basis for understanding the role of general vs. stressor specific molecular responses in aphids. PMID:25538100

The Role of the Transcriptional Response to DNA Replication Stress

PubMed Central

Herlihy, Anna E.; de Bruin, Robertus A.M.

2017-01-01

During DNA replication many factors can result in DNA replication stress. The DNA replication stress checkpoint prevents the accumulation of replication stress-induced DNA damage and the potential ensuing genome instability. A critical role for post-translational modifications, such as phosphorylation, in the replication stress checkpoint response has been well established. However, recent work has revealed an important role for transcription in the cellular response to DNA replication stress. In this review, we will provide an overview of current knowledge of the cellular response to DNA replication stress with a specific focus on the DNA replication stress checkpoint transcriptional response and its role in the prevention of replication stress-induced DNA damage. PMID:28257104

The Role of the Transcriptional Response to DNA Replication Stress.

PubMed

Herlihy, Anna E; de Bruin, Robertus A M

2017-03-02

During DNA replication many factors can result in DNA replication stress. The DNA replication stress checkpoint prevents the accumulation of replication stress-induced DNA damage and the potential ensuing genome instability. A critical role for post-translational modifications, such as phosphorylation, in the replication stress checkpoint response has been well established. However, recent work has revealed an important role for transcription in the cellular response to DNA replication stress. In this review, we will provide an overview of current knowledge of the cellular response to DNA replication stress with a specific focus on the DNA replication stress checkpoint transcriptional response and its role in the prevention of replication stress-induced DNA damage.

Comparative transcriptional and translational analysis of leptospiral outer membrane protein expression in response to temperature.

PubMed

Lo, Miranda; Cordwell, Stuart J; Bulach, Dieter M; Adler, Ben

2009-12-08

Leptospirosis is a global zoonosis affecting millions of people annually. Transcriptional changes in response to temperature were previously investigated using microarrays to identify genes potentially expressed upon host entry. Past studies found that various leptospiral outer membrane proteins are differentially expressed at different temperatures. However, our microarray studies highlighted a divergence between protein abundance and transcript levels for some proteins. Given the abundance of post-transcriptional expression control mechanisms, this finding highlighted the importance of global protein analysis systems. To complement our previous transcription study, we evaluated differences in the proteins of the leptospiral outer membrane fraction in response to temperature upshift. Outer membrane protein-enriched fractions from Leptospira interrogans grown at 30 degrees C or overnight upshift to 37 degrees C were isolated and the relative abundance of each protein was determined by iTRAQ analysis coupled with two-dimensional liquid chromatography and tandem mass spectrometry (2-DLC/MS-MS). We identified 1026 proteins with 99% confidence; 27 and 66 were present at elevated and reduced abundance respectively. Protein abundance changes were compared with transcriptional differences determined from the microarray studies. While there was some correlation between the microarray and iTRAQ data, a subset of genes that showed no differential expression by microarray was found to encode temperature-regulated proteins. This set of genes is of particular interest as it is likely that regulation of their expression occurs post-transcriptionally, providing an opportunity to develop hypotheses about the molecular dynamics of the outer membrane of Leptospira in response to changing environments. This is the first study to compare transcriptional and translational responses to temperature shift in L. interrogans. The results thus provide an insight into the mechanisms used by L. interrogans to adapt to conditions encountered in the host and to cause disease. Our results suggest down-regulation of protein expression in response to temperature, and decreased expression of outer membrane proteins may facilitate minimal interaction with host immune mechanisms.

Defining the microbial transcriptional response to colitis through integrated host and microbiome profiling

PubMed Central

Ilott, Nicholas Edward; Bollrath, Julia; Danne, Camille; Schiering, Chris; Shale, Matthew; Adelmann, Krista; Krausgruber, Thomas; Heger, Andreas; Sims, David; Powrie, Fiona

2016-01-01

The gut microbiome is significantly altered in inflammatory bowel diseases, but the basis of these changes is not well understood. We have combined metagenomic and metatranscriptomic profiling of the gut microbiome to assess modifications to both bacterial community structure and transcriptional activity in a mouse model of colitis. By using transcriptomic analysis of colonic tissue and luminal RNA derived from the host, we have also characterised how host transcription relates to the microbial transcriptional response in inflammation. In colitis, increased abundance and transcription of diverse microbial gene families involved in responses to nutrient deprivation, antimicrobial peptide production and oxidative stress support an adaptation of multiple commensal genera to withstand a diverse set of environmental stressors in the inflammatory environment. These data are supported by a transcriptional signature of activated macrophages and granulocytes in the gut lumen during colitis, a signature that includes the transcription of the key antimicrobial genes S100a8 and S100a9 (calprotectin). Genes involved in microbial resistance to oxidative stress, including Dps/ferritin, Fe-dependent peroxidase and glutathione S-transferase were identified as changing to a greater extent at the level of transcription than would be predicted by DNA abundance changes, implicating a role for increased oxygen tension and/or host-derived reactive oxygen species in driving transcriptional changes in commensal microbes. PMID:27003245

Inflammation response at the transcriptional level of HepG2 cells induced by multi-walled carbon nanotubes

NASA Astrophysics Data System (ADS)

Piret, Jean-Pascal; Vankoningsloo, Sébastien; Noël, Florence; Mejia Mendoza, Jorge; Lucas, Stéphane; Saout, Christelle; Toussaint, Olivier

2011-07-01

Poor information are currently available about the biological effects of multi-walled carbon nanotubes (MWCNT) on the liver. In this study, we evaluated the effects of MWCNT at the transcriptional level on the classical in vitro model of HepG2 hepatocarcinoma cells. The expression levels of 96 transcript species implicated in the inflammatory and immune responses was studied after a 24h incubation of HepG2 cells in presence of raw MWCNT dispersed in water by stirring. Among the 46 transcript species detected, only a few transcripts including mRNA coding for interleukine-7, chemokines receptor of the C-C families CCR7, as well as Endothelin-1, were statistically more abundant after treatment with MWCNT. Altogether, these data indicate that MWCNT can only induce a weak inflammatory response in HepG2 cells.

Integrated analysis of rice transcriptomic and metabolomic responses to elevated night temperatures identifies sensitivity- and tolerance-related profiles.

PubMed

Glaubitz, Ulrike; Li, Xia; Schaedel, Sandra; Erban, Alexander; Sulpice, Ronan; Kopka, Joachim; Hincha, Dirk K; Zuther, Ellen

2017-01-01

Transcript and metabolite profiling were performed on leaves from six rice cultivars under high night temperature (HNT) condition. Six genes were identified as central for HNT response encoding proteins involved in transcription regulation, signal transduction, protein-protein interactions, jasmonate response and the biosynthesis of secondary metabolites. Sensitive cultivars showed specific changes in transcript abundance including abiotic stress responses, changes of cell wall-related genes, of ABA signaling and secondary metabolism. Additionally, metabolite profiles revealed a highly activated TCA cycle under HNT and concomitantly increased levels in pathways branching off that could be corroborated by enzyme activity measurements. Integrated data analysis using clustering based on one-dimensional self-organizing maps identified two profiles highly correlated with HNT sensitivity. The sensitivity profile included genes of the functional bins abiotic stress, hormone metabolism, cell wall, signaling, redox state, transcription factors, secondary metabolites and defence genes. In the tolerance profile, similar bins were affected with slight differences in hormone metabolism and transcription factor responses. Metabolites of the two profiles revealed involvement of GABA signaling, thus providing a link to the TCA cycle status in sensitive cultivars and of myo-inositol as precursor for inositol phosphates linking jasmonate signaling to the HNT response specifically in tolerant cultivars. © 2016 John Wiley & Sons Ltd.

Identification of bovine leukemia virus tax function associated with host cell transcription, signaling, stress response and immune response pathway by microarray-based gene expression analysis

PubMed Central

2012-01-01

Background Bovine leukemia virus (BLV) is associated with enzootic bovine leukosis and is closely related to human T-cell leukemia virus type I. The Tax protein of BLV is a transcriptional activator of viral replication and a key contributor to oncogenic potential. We previously identified interesting mutant forms of Tax with elevated (TaxD247G) or reduced (TaxS240P) transactivation effects on BLV replication and propagation. However, the effects of these mutations on functions other than transcriptional activation are unknown. In this study, to identify genes that play a role in the cascade of signal events regulated by wild-type and mutant Tax proteins, we used a large-scale host cell gene-profiling approach. Results Using a microarray containing approximately 18,400 human mRNA transcripts, we found several alterations after the expression of Tax proteins in genes involved in many cellular functions such as transcription, signal transduction, cell growth, apoptosis, stress response, and immune response, indicating that Tax protein has multiple biological effects on various cellular environments. We also found that TaxD247G strongly regulated more genes involved in transcription, signal transduction, and cell growth functions, contrary to TaxS240P, which regulated fewer genes. In addition, the expression of genes related to stress response significantly increased in the presence of TaxS240P as compared to wild-type Tax and TaxD247G. By contrast, the largest group of downregulated genes was related to immune response, and the majority of these genes belonged to the interferon family. However, no significant difference in the expression level of downregulated genes was observed among the Tax proteins. Finally, the expression of important cellular factors obtained from the human microarray results were validated at the RNA and protein levels by real-time quantitative reverse transcription-polymerase chain reaction and western blotting, respectively, after transfecting Tax proteins into bovine cells and human HeLa cells. Conclusion A comparative analysis of wild-type and mutant Tax proteins indicates that Tax protein exerts a significant impact on cellular functions as diverse as transcription, signal transduction, cell growth, stress response and immune response. Importantly, our study is the first report that shows the extent to which BLV Tax regulates the innate immune response. PMID:22455445

Assessment of the Noise Reduction Potential of Advanced Subsonic Transport Concepts for NASA's Environmentally Responsible Aviation Project

NASA Technical Reports Server (NTRS)

Thomas, Russell H.; Burley, Casey L.; Nickol, Craig L.

2016-01-01

Aircraft system noise is predicted for a portfolio of NASA advanced concepts with 2025 entry-into-service technology assumptions. The subsonic transport concepts include tube-and-wing configurations with engines mounted under the wing, over the wing nacelle integration, and a double deck fuselage with engines at a mid-fuselage location. Also included are hybrid wing body aircraft with engines upstream of the fuselage trailing edge. Both advanced direct drive engines and geared turbofan engines are modeled. Recent acoustic experimental information was utilized in the prediction for several key technologies. The 301-passenger class hybrid wing body with geared ultra high bypass engines is assessed at 40.3 EPNLdB cumulative below the Stage 4 certification level. Other hybrid wing body and unconventional tube-and-wing configurations reach levels of 33 EPNLdB or more below the certification level. Many factors contribute to the system level result; however, the hybrid wing body in the 301-passenger class, as compared to a tubeand- wing with conventional engine under wing installation, has 11.9 EPNLdB of noise reduction due to replacing reflection with acoustic shielding of engine noise sources. Therefore, the propulsion airframe aeroacoustic interaction effects clearly differentiate the unconventional configurations that approach levels close to or exceed the 42 EPNLdB goal.

Memory responses of jasmonic acid-associated Arabidopsis genes to a repeated dehydration stress.

PubMed

Liu, Ning; Staswick, Paul E; Avramova, Zoya

2016-11-01

Dehydration stress activates numerous genes co-regulated by diverse signaling pathways. Upon repeated exposures, however, a subset of these genes does not respond maintaining instead transcription at their initial pre-stressed levels ('revised-response' genes). Most of these genes are involved in jasmonic acid (JA) biosynthesis, JA-signaling and JA-mediated stress responses. How these JA-associated genes are regulated to provide different responses to similar dehydration stresses is an enigma. Here, we investigate molecular mechanisms that contribute to this transcriptional behavior. The memory-mechanism is stress-specific: one exposure to dehydration stress or to abscisic acid (ABA) is required to prevent transcription in the second. Both ABA-mediated and JA-mediated pathways are critical for the activation of these genes, but the two signaling pathways interact differently during a single or multiple encounters with dehydration stress. Synthesis of JA during the first (S1) but not the second dehydration stress (S2) accounts for the altered transcriptional responses. We propose a model for these memory responses, wherein lack of MYC2 and of JA synthesis in S2 is responsible for the lack of expression of downstream genes. The similar length of the memory displayed by different memory-type genes suggests biological relevance for transcriptional memory as a gene-regulating mechanism during recurring bouts of drought. © 2016 John Wiley & Sons Ltd.

Link between epigenomic alterations and genome-wide aberrant transcriptional response to allergen in dendritic cells conveying maternal asthma risk.

PubMed

Mikhaylova, Lyudmila; Zhang, Yiming; Kobzik, Lester; Fedulov, Alexey V

2013-01-01

We investigated the link between epigenome-wide methylation aberrations at birth and genomic transcriptional changes upon allergen sensitization that occur in the neonatal dendritic cells (DC) due to maternal asthma. We previously demonstrated that neonates of asthmatic mothers are born with a functional skew in splenic DCs that can be seen even in allergen-naïve pups and can convey allergy responses to normal recipients. However, minimal-to-no transcriptional or phenotypic changes were found to explain this alteration. Here we provide in-depth analysis of genome-wide DNA methylation profiles and RNA transcriptional (microarray) profiles before and after allergen sensitization. We identified differentially methylated and differentially expressed loci and performed manually-curated matching of methylation status of the key regulatory sequences (promoters and CpG islands) to expression of their respective transcripts before and after sensitization. We found that while allergen-naive DCs from asthma-at-risk neonates have minimal transcriptional change compared to controls, the methylation changes are extensive. The substantial transcriptional change only becomes evident upon allergen sensitization, when it occurs in multiple genes with the pre-existing epigenetic alterations. We demonstrate that maternal asthma leads to both hyper- and hypomethylation in neonatal DCs, and that both types of events at various loci significantly overlap with transcriptional responses to allergen. Pathway analysis indicates that approximately 1/2 of differentially expressed and differentially methylated genes directly interact in known networks involved in allergy and asthma processes. We conclude that congenital epigenetic changes in DCs are strongly linked to altered transcriptional responses to allergen and to early-life asthma origin. The findings are consistent with the emerging paradigm that asthma is a disease with underlying epigenetic changes.

Parathyroid hormone induces transcription of collagenase in rat osteoblastic cells by a mechanism using cyclic adenosine 3',5'-monophosphate and requiring protein synthesis

NASA Technical Reports Server (NTRS)

Scott, D. K.; Brakenhoff, K. D.; Clohisy, J. C.; Quinn, C. O.; Partridge, N. C.

1992-01-01

Collagenase is synthesized and secreted by rat osteoblastic cells in response to PTH. We have previously demonstrated that this effect involves a substantial increase in collagenase mRNA via transcription. Northern blots and nuclear run-on assays were performed to further investigate the induction of collagenase by PTH in the rat osteoblastic cell line UMR 106-01. Detectable amounts of collagenase mRNA were not apparent until 2 h of PTH treatment, showed the greatest abundance at 4 h, and declined to approximately 30% of maximum by 8 h. The changes in the rate of transcription of the collagenase gene in response to PTH paralleled and preceded the changes in the steady state mRNA levels. After an initial lag period of about 1 h, collagenase transcription rates increased from very low levels to a maximal response at 2 h, returning to about 50% of maximum by 10 h. The increased transcriptional rate of the collagenase gene was found to be dependent on the concentration of PTH, with a half-maximal response at approximately 7 x 10(-10) M rat PTH-(1-34) and a maximal effect with a dose of 10(-8) M. The PTH-mediated induction of collagenase transcriptional activity was completely abolished by cycloheximide, while transcription of the beta-actin gene was unaffected by the translation inhibitor. These data suggest that a protein factor(s) is required for PTH-mediated transcriptional induction of collagenase. Since PTH increases intracellular levels of several potential second messengers, agents that mimic these substances were employed to determine which signal transduction pathway is predominant in the PTH-mediated stimulation of collagenase transcription.(ABSTRACT TRUNCATED AT 250 WORDS).

Identification of PEG-induced water stress responsive transcripts using co-expression network in Eucalyptus grandis.

PubMed

Ghosh Dasgupta, Modhumita; Dharanishanthi, Veeramuthu

2017-09-05

Ecophysiological studies in Eucalyptus have shown that water is the principal factor limiting stem growth. Effect of water deficit conditions on physiological and biochemical parameters has been extensively reported in Eucalyptus. The present study was conducted to identify major polyethylene glycol induced water stress responsive transcripts in Eucalyptus grandis using gene co-expression network. A customized array representing 3359 water stress responsive genes was designed to document their expression in leaves of E. grandis cuttings subjected to -0.225MPa of PEG treatment. The differentially expressed transcripts were documented and significantly co-expressed transcripts were used for construction of network. The co-expression network was constructed with 915 nodes and 3454 edges with degree ranging from 2 to 45. Ninety four GO categories and 117 functional pathways were identified in the network. MCODE analysis generated 27 modules and module 6 with 479 nodes and 1005 edges was identified as the biologically relevant network. The major water responsive transcripts represented in the module included dehydrin, osmotin, LEA protein, expansin, arabinogalactans, heat shock proteins, major facilitator proteins, ARM repeat proteins, raffinose synthase, tonoplast intrinsic protein and transcription factors like DREB2A, ARF9, AGL24, UNE12, WLIM1 and MYB66, MYB70, MYB 55, MYB 16 and MYB 103. The coordinated analysis of gene expression patterns and coexpression networks developed in this study identified an array of transcripts that may regulate PEG induced water stress responses in E. grandis. Copyright © 2017 Elsevier B.V. All rights reserved.

Intrinsic transcriptional heterogeneity in B cells controls early class switching to IgE

PubMed Central

Wu, Yee Ling; Teichmann, Sarah A.

2017-01-01

Noncoding transcripts originating upstream of the immunoglobulin constant region (I transcripts) are required to direct activation-induced deaminase to initiate class switching in B cells. Differential regulation of Iε and Iγ1 transcription in response to interleukin 4 (IL-4), hence class switching to IgE and IgG1, is not fully understood. In this study, we combine novel mouse reporters and single-cell RNA sequencing to reveal the heterogeneity in IL-4–induced I transcription. We identify an early population of cells expressing Iε but not Iγ1 and demonstrate that early Iε transcription leads to switching to IgE and occurs at lower activation levels than Iγ1. Our results reveal how probabilistic transcription with a lower activation threshold for Iε directs the early choice of IgE versus IgG1, a key physiological response against parasitic infestations and a mediator of allergy and asthma. PMID:27994069

Cytokines and their STATs in cutaneous and visceral leishmaniasis.

PubMed

Cummings, Hannah E; Tuladhar, Rashmi; Satoskar, Abhay R

2010-01-01

Cytokines play a critical role in shaping the host immune response to Leishmania infection and directing the development of protective and non-protective immunities during infection. Cytokines exert their biological activities through the activation and translocation of transcription factors into the nucleus whether they drive the expression of specific cytokine-responsive genes. Signal transducer and activator of transcription (STATs) are transcription factors which play a critical role in mediating signaling downstream of cytokine receptors and are important for shaping the host immune response during Leishmania infection. Here we discuss the signature cytokines and their associated STATs involved in the host immune response during cutaneous and visceral leishmaniasis.

Transcriptional responses of Arabidopsis thaliana to chewing and sucking insect herbivores

DOE PAGES

Appel, Heidi M.; Fescemyer, Howard; Ehlting, Juergen; ...

2014-11-14

We tested the hypothesis that Arabidopsis can recognize and respond differentially to insect species at the transcriptional level using a genome wide microarray. Transcriptional reprogramming was characterized using co-expression analysis in damaged and undamaged leaves at two times in response to mechanical wounding and four insect species. In all, 2778 (10.6%) of annotated genes on the array were differentially expressed in at least one treatment. Responses differed mainly between aphid and caterpillar and sampling times. Responses to aphids and caterpillars shared only 10% of up-regulated and 8% of down-regulated genes. Responses to two caterpillars shared 21 and 12% of up-more » and down-regulated genes, whereas responses to the two aphids shared only 7 and 4% of up-regulated and down-regulated genes. Overlap in genes expressed between 6 and 24 h was 3–15%, and depended on the insect species. Responses in attacked and unattacked leaves differed at 6 h but converged by 24 h. Genes responding to the insects are also responsive to many stressors and included primary metabolism. Aphids down-regulated amino acid catabolism; caterpillars stimulated production of amino acids involved in glucosinolate synthesis. Co-expression analysis revealed 17 response networks. Transcription factors were a major portion of differentially expressed genes throughout and responsive genes shared most of the known or postulated binding sites. However, cis-element composition of genes down regulated by the aphid M. persicae was unique, as were those of genes down-regulated by caterpillars. As many as 20 cis-elements were over-represented in one or more treatments, including some from well-characterized classes and others as yet uncharacterized. We suggest that transcriptional changes elicited by wounding and insects are heavily influenced by transcription factors and involve both enrichment of a common set of cis-elements and a unique enrichment of a few cis-elements in responding genes.« less

Transcriptional responses of Arabidopsis thaliana to chewing and sucking insect herbivores

DOE Office of Scientific and Technical Information (OSTI.GOV)

Appel, Heidi M.; Fescemyer, Howard; Ehlting, Juergen

We tested the hypothesis that Arabidopsis can recognize and respond differentially to insect species at the transcriptional level using a genome wide microarray. Transcriptional reprogramming was characterized using co-expression analysis in damaged and undamaged leaves at two times in response to mechanical wounding and four insect species. In all, 2778 (10.6%) of annotated genes on the array were differentially expressed in at least one treatment. Responses differed mainly between aphid and caterpillar and sampling times. Responses to aphids and caterpillars shared only 10% of up-regulated and 8% of down-regulated genes. Responses to two caterpillars shared 21 and 12% of up-more » and down-regulated genes, whereas responses to the two aphids shared only 7 and 4% of up-regulated and down-regulated genes. Overlap in genes expressed between 6 and 24 h was 3–15%, and depended on the insect species. Responses in attacked and unattacked leaves differed at 6 h but converged by 24 h. Genes responding to the insects are also responsive to many stressors and included primary metabolism. Aphids down-regulated amino acid catabolism; caterpillars stimulated production of amino acids involved in glucosinolate synthesis. Co-expression analysis revealed 17 response networks. Transcription factors were a major portion of differentially expressed genes throughout and responsive genes shared most of the known or postulated binding sites. However, cis-element composition of genes down regulated by the aphid M. persicae was unique, as were those of genes down-regulated by caterpillars. As many as 20 cis-elements were over-represented in one or more treatments, including some from well-characterized classes and others as yet uncharacterized. We suggest that transcriptional changes elicited by wounding and insects are heavily influenced by transcription factors and involve both enrichment of a common set of cis-elements and a unique enrichment of a few cis-elements in responding genes.« less

Prostate Cell Specific Regulation of Androgen Receptor Phosphorylation in Vivo

DTIC Science & Technology

2009-11-01

includes both Rpb5, a subunit shared by RNA polymerase (Pol) I, II , and III, and the corepressor, Unconventional prefoldin Rpb5-Interactor (URI/C19orf2...complex that contains RNA polymerase II subunit 5, a subunit shared by all three RNA polymerases; unconventional prefoldin RPB5-in- teractor (URI), which...sequence of ART-27 is conserved throughout evolution from worms to humans and its predicted protein structure is homologous to the prefoldin -a family of

Ending the Debate: Unconventional Warfare, Foreign Internal Defense, and Why Words Matter

DTIC Science & Technology

2006-06-01

JCS] apparently was fearful of what it perceived to be the stigma of having the military accused of engaging in subrosa [sic], cloak -and­ dagger ...was fearful of what it perceived to be the stigma of having the military accused of engaging in sub-rosa, cloak - and- dagger activities in the event of...disrupted by the terrorist attacks of 11 September. Less than two years later, Special Forces had successfully prosecuted two unconventional warfare

U.S. Geological Survey assessments of continuous (unconventional) oil and gas resources, 2000 to 2011

USGS Publications Warehouse

,

2015-10-20

From 2000 to 2011, the U.S. Geological Survey conducted 139 quantitative assessments of continuous (unconventional) oil and gas accumulations within the United States. This report documents those assessments more fully than previously done by providing detailed documentation of both the assessment input and output. This report also compiles the data into spreadsheet tables that can be more readily used to provide analogs for future assessments, especially for hypothetical continuous accumulations.

Study of unconventional aircraft engines designed for low energy consumption

NASA Technical Reports Server (NTRS)

Gray, D. E.

1976-01-01

Declining U.S. oil reserves and escalating energy costs underline the need for reducing fuel consumption in aircraft engines. The most promising unconventional aircraft engines based on their potential for fuel savings and improved economics are identified. The engines installed in both a long-range and medium-range aircraft were evaluated. Projected technology advances are identified and evaluated for their state-of-readiness for application to a commercial transport. Programs are recommended for developing the necessary technology.

The endoplasmic reticulum is a hub to sort proteins toward unconventional traffic pathways and endosymbiotic organelles.

PubMed

Bellucci, Michele; De Marchis, Francesca; Pompa, Andrea

2017-12-18

The discovery that much of the extracellular proteome in eukaryotic cells consists of proteins lacking a signal peptide, which cannot therefore enter the secretory pathway, has led to the identification of alternative protein secretion routes bypassing the Golgi apparatus. However, proteins harboring a signal peptide for translocation into the endoplasmic reticulum can also be transported along these alternative routes, which are still far from being well elucidated in terms of the molecular machineries and subcellular/intermediate compartments involved. In this review, we first try to provide a definition of all the unconventional protein secretion pathways in eukaryotic cells, as those pathways followed by proteins directed to an 'external space' bypassing the Golgi, where 'external space' refers to the extracellular space plus the lumen of the secretory route compartments and the inner space of mitochondria and plastids. Then, we discuss the role of the endoplasmic reticulum in sorting proteins toward unconventional traffic pathways in plants. In this regard, various unconventional pathways exporting proteins from the endoplasmic reticulum to the vacuole, plasma membrane, apoplast, mitochondria, and plastids are described, including the short routes followed by the proteins resident in the endoplasmic reticulum. © The Author(s) 2017. Published by Oxford University Press on behalf of the Society for Experimental Biology. All rights reserved. For permissions, please email: journals.permissions@oup.com.

Unconventional spin distributions in thick Ni{sub 80}Fe{sub 20} nanodisks

DOE Office of Scientific and Technical Information (OSTI.GOV)

Kumar, D.; Lupo, P.; Haldar, A.

2016-05-09

We study the spin distributions in permalloy (Py: Ni{sub 80}Fe{sub 20}) nanodisks as a function of diameter D (300 nm ≤ D ≤ 1 μm) and thickness L (30 nm ≤ L ≤ 100 nm). We observed that beyond a certain thickness, for a fixed disk diameter, an unconventional spin topology precipitates which is marked by the presence of a divergence field within the magnetic vortex curl. The strength of this divergence changes anti-symmetrically from negative to positive—depending on the core polarity—along the axis of the cylindrical nanodisk. This is also accompanied by a skyrmion-like out-of-plane bending of the spin vectors farther away from the disk center. Additionally, the vortex core dilatesmore » significantly when compared to its typical size. This has been directly observed using magnetic force microscopy. We determined from the ferromagnetic resonance spectroscopy measurements that the unconventional topology in the thicker nanodisks gyrated at a frequency, which is significantly lower than what is predicted by a magnetic vortex based analytical model. Micromagnetic simulations involving dipolar and exchange interactions appear to satisfactorily reproduce the experimentally observed static and dynamic behaviors. Besides providing a physical example of an unconventional topology, these results can also aid the design of topologically protected memory elements.« less

Landscape disturbance from unconventional and conventional oil and gas development in the Marcellus Shale region of Pennsylvania, USA

USGS Publications Warehouse

Slonecker, Terry E.; Milheim, Lesley E.

2015-01-01

The spatial footprint of unconventional (hydraulic fracturing) and conventional oil and gas development in the Marcellus Shale region of the State of Pennsylvania was digitized from high-resolution, ortho-rectified, digital aerial photography, from 2004 to 2010. We used these data to measure the spatial extent of oil and gas development and to assess the exposure of the extant natural resources across the landscape of the watersheds in the study area. We found that either form of development: (1) occurred in ~50% of the 930 watersheds that defined the study area; (2) was closer to streams than the recommended safe distance in ~50% of the watersheds; (3) was in some places closer to impaired streams and state-defined wildland trout streams than the recommended safe distance; (4) was within 10 upstream kilometers of surface drinking water intakes in ~45% of the watersheds that had surface drinking water intakes; (5) occurred in ~10% of state-defined exceptional value watersheds; (6) occurred in ~30% of the watersheds with resident populations defined as disproportionately exposed to pollutants; (7) tended to occur at interior forest locations; and (8) had >100 residents within 3 km for ~30% of the unconventional oil and gas development sites. Further, we found that exposure to the potential effects of landscape disturbance attributable to conventional oil and gas development was more prevalent than its unconventional counterpart.

An overview on exploration and environmental impact of unconventional gas sources and treatment options for produced water.

PubMed

Silva, Tânia L S; Morales-Torres, Sergio; Castro-Silva, Sérgio; Figueiredo, José L; Silva, Adrián M T

2017-09-15

Rising global energy demands associated to unbalanced allocation of water resources highlight the importance of water management solutions for the gas industry. Advanced drilling, completion and stimulation techniques for gas extraction, allow more economical access to unconventional gas reserves. This stimulated a shale gas revolution, besides tight gas and coalbed methane, also causing escalating water handling challenges in order to avoid a major impact on the environment. Hydraulic fracturing allied to horizontal drilling is gaining higher relevance in the exploration of unconventional gas reserves, but a large amount of wastewater (known as "produced water") is generated. Its variable chemical composition and flow rates, together with more severe regulations and public concern, have promoted the development of solutions for the treatment and reuse of such produced water. This work intends to provide an overview on the exploration and subsequent environmental implications of unconventional gas sources, as well as the technologies for treatment of produced water, describing the main results and drawbacks, together with some cost estimates. In particular, the growing volumes of produced water from shale gas plays are creating an interesting market opportunity for water technology and service providers. Membrane-based technologies (membrane distillation, forward osmosis, membrane bioreactors and pervaporation) and advanced oxidation processes (ozonation, Fenton, photocatalysis) are claimed to be adequate treatment solutions. Copyright © 2017 Elsevier Ltd. All rights reserved.

The postman always rings twice: two cases of shotgun deaths associated with an unconventional home security alarm system.

PubMed

Asirdizer, Mahmut; Turkmen, Nursel; Akan, Okan; Yavuz, Mehmet Sunay

2014-06-01

Injury and death cases caused by booby traps are not common in forensic medicine practice. Besides, installation of booby traps including firearms is generally for suicidal and rarely for homicidal purposes. Although few patents were described about home security alarm system that were created by firearms in the United States, 1 sample of injury with a similar unconventional mechanism of home safety system was reported by Asirdizer and Yavuz in 2009. In the published case report, the story of an electrical technician who was invited to a summer house by the homeowner to check the home security alarm system was reported. In the so-called report, he was stated to be injured by the shotgun attached to the unconventional home security alarm system while checking the system. As a result, the homeowner was convicted of a possible intent to cause a life-threatening injury to the technician.The so-called homeowner and his wife died by the same shotgun attached to the same unconventional home security alarm system 4 years on from the first event. In the present case report, we have aimed to present the findings of the crime scene and the autopsies of these unusual 2 deaths and to discuss individual and legal factors in paving the way for the deaths of 2 people.

Heat shock factor-1 modulates p53 activity in the transcriptional response to DNA damage

PubMed Central

Logan, Ian R.; McNeill, Hesta V.; Cook, Susan; Lu, Xiaohong; Meek, David W.; Fuller-Pace, Frances V.; Lunec, John; Robson, Craig N.

2009-01-01

Here we define an important role for heat shock factor 1 (HSF1) in the cellular response to genotoxic agents. We demonstrate for the first time that HSF1 can complex with nuclear p53 and that both proteins are co-operatively recruited to p53-responsive genes such as p21. Analysis of natural and synthetic cis elements demonstrates that HSF1 can enhance p53-mediated transcription, whilst depletion of HSF1 reduces the expression of p53-responsive transcripts. We find that HSF1 is required for optimal p21 expression and p53-mediated cell-cycle arrest in response to genotoxins while loss of HSF1 attenuates apoptosis in response to these agents. To explain these novel properties of HSF1 we show that HSF1 can complex with DNA damage kinases ATR and Chk1 to effect p53 phosphorylation in response to DNA damage. Our data reveal HSF1 as a key transcriptional regulator in response to genotoxic compounds widely used in the clinical setting, and suggest that HSF1 will contribute to the efficacy of these agents. PMID:19295133

Transcription of Biotic Stress Associated Genes in White Clover (Trifolium repens L.) Differs in Response to Cyst and Root-Knot Nematode Infection

PubMed Central

Islam, Afsana; Mercer, Chris F.; Leung, Susanna; Dijkwel, Paul P.

2015-01-01

The transcription of four members of the Kunitz proteinase inhibitor (KPI) gene family of white clover (Trifolium repens L.), designated as Tr-KPI1, Tr-KPI2, Tr-KPI4 and Tr-KPI5, was investigated at both local infection (roots) and systemic (leaf tissue) sites in white clover in response to infection with the clover root knot nematode (CRKN) Meloidogyne trifoliophila and the clover cyst nematode (CCN) Heterodera trifolii. Invasion by the CRKN resulted in a significant decrease in transcript abundance of Tr-KPI4 locally at both 4 days post-infection (dpi) and at 8 dpi, and an increase in transcription of Tr-KPI1 systemically at 8 dpi. In contrast, an increase in transcript abundance of all four Tr-KPI genes locally at 4 and 8 dpi, and an increase of Tr-KPI1, Tr-KPI2, and Tr-KPI5 at 8 dpi systemically was observed in response to infection with the CCN. Challenge of a resistant (R) genotype and a susceptible (S) genotype of white clover with the CCN revealed a significant increase in transcript abundance of all four Tr-KPI genes locally in the R genotype, while an increase in abundance of only Tr-KPI1, Tr-KPI2, and Tr-KPI5 was observed in the S genotype, and only at 4 dpi. The transcript abundance of a member of the1-AMINOCYCLOPROPANE-1-CARBOXYLATE (ACC) SYNTHASE gene family from white clover (Tr-ACS1) was significantly down-regulated locally in response to CRKN infection at 4 and 8 dpi and at 4 dpi, systemically, while abundance increased locally and systemically at 8 dpi in response to CCN challenge. Conversely, the abundance of the jasmonic acid (JA) signalling gene, CORONATINE-INSENSITIVE PROTEIN 1 from white clover (Tr-COI1) increased significantly at 8 dpi locally in response to CRKN infection, but decreased at 8 dpi in response to CCN infection. The significance of this differential regulation of transcription is discussed with respect to differences in infection strategy of the two nematode species. PMID:26393362

Transcription of Biotic Stress Associated Genes in White Clover (Trifolium repens L.) Differs in Response to Cyst and Root-Knot Nematode Infection.

PubMed

Islam, Afsana; Mercer, Chris F; Leung, Susanna; Dijkwel, Paul P; McManus, Michael T

2015-01-01

The transcription of four members of the Kunitz proteinase inhibitor (KPI) gene family of white clover (Trifolium repens L.), designated as Tr-KPI1, Tr-KPI2, Tr-KPI4 and Tr-KPI5, was investigated at both local infection (roots) and systemic (leaf tissue) sites in white clover in response to infection with the clover root knot nematode (CRKN) Meloidogyne trifoliophila and the clover cyst nematode (CCN) Heterodera trifolii. Invasion by the CRKN resulted in a significant decrease in transcript abundance of Tr-KPI4 locally at both 4 days post-infection (dpi) and at 8 dpi, and an increase in transcription of Tr-KPI1 systemically at 8 dpi. In contrast, an increase in transcript abundance of all four Tr-KPI genes locally at 4 and 8 dpi, and an increase of Tr-KPI1, Tr-KPI2, and Tr-KPI5 at 8 dpi systemically was observed in response to infection with the CCN. Challenge of a resistant (R) genotype and a susceptible (S) genotype of white clover with the CCN revealed a significant increase in transcript abundance of all four Tr-KPI genes locally in the R genotype, while an increase in abundance of only Tr-KPI1, Tr-KPI2, and Tr-KPI5 was observed in the S genotype, and only at 4 dpi. The transcript abundance of a member of the1-AMINOCYCLOPROPANE-1-CARBOXYLATE (ACC) SYNTHASE gene family from white clover (Tr-ACS1) was significantly down-regulated locally in response to CRKN infection at 4 and 8 dpi and at 4 dpi, systemically, while abundance increased locally and systemically at 8 dpi in response to CCN challenge. Conversely, the abundance of the jasmonic acid (JA) signalling gene, CORONATINE-INSENSITIVE PROTEIN 1 from white clover (Tr-COI1) increased significantly at 8 dpi locally in response to CRKN infection, but decreased at 8 dpi in response to CCN infection. The significance of this differential regulation of transcription is discussed with respect to differences in infection strategy of the two nematode species.

Genome-scale cold stress response regulatory networks in ten Arabidopsis thaliana ecotypes

PubMed Central

2013-01-01

Background Low temperature leads to major crop losses every year. Although several studies have been conducted focusing on diversity of cold tolerance level in multiple phenotypically divergent Arabidopsis thaliana (A. thaliana) ecotypes, genome-scale molecular understanding is still lacking. Results In this study, we report genome-scale transcript response diversity of 10 A. thaliana ecotypes originating from different geographical locations to non-freezing cold stress (10°C). To analyze the transcriptional response diversity, we initially compared transcriptome changes in all 10 ecotypes using Arabidopsis NimbleGen ATH6 microarrays. In total 6061 transcripts were significantly cold regulated (p < 0.01) in 10 ecotypes, including 498 transcription factors and 315 transposable elements. The majority of the transcripts (75%) showed ecotype specific expression pattern. By using sequence data available from Arabidopsis thaliana 1001 genome project, we further investigated sequence polymorphisms in the core cold stress regulon genes. Significant numbers of non-synonymous amino acid changes were observed in the coding region of the CBF regulon genes. Considering the limited knowledge about regulatory interactions between transcription factors and their target genes in the model plant A. thaliana, we have adopted a powerful systems genetics approach- Network Component Analysis (NCA) to construct an in-silico transcriptional regulatory network model during response to cold stress. The resulting regulatory network contained 1,275 nodes and 7,720 connections, with 178 transcription factors and 1,331 target genes. Conclusions A. thaliana ecotypes exhibit considerable variation in transcriptome level responses to non-freezing cold stress treatment. Ecotype specific transcripts and related gene ontology (GO) categories were identified to delineate natural variation of cold stress regulated differential gene expression in the model plant A. thaliana. The predicted regulatory network model was able to identify new ecotype specific transcription factors and their regulatory interactions, which might be crucial for their local geographic adaptation to cold temperature. Additionally, since the approach presented here is general, it could be adapted to study networks regulating biological process in any biological systems. PMID:24148294

Exposure to chorioamnionitis alters the monocyte transcriptional response to the neonatal pathogen Staphylococcus epidermidis.

PubMed

de Jong, Emma; Hancock, David G; Wells, Christine; Richmond, Peter; Simmer, Karen; Burgner, David; Strunk, Tobias; Currie, Andrew J

2018-03-13

Preterm infants are uniquely susceptible to late-onset sepsis that is frequently caused by the skin commensal Staphylococcus epidermidis. Innate immune responses, particularly from monocytes, are a key protective mechanism. Impaired cytokine production by preterm infant monocytes is well described, but few studies have comprehensively assessed the corresponding monocyte transcriptional response. Innate immune responses in preterm infants may be modulated by inflammation such as prenatal exposure to histologic chorioamnionitis which complicates 40-70% of preterm pregnancies. Chorioamnionitis alters the risk of late-onset sepsis, but its effect on monocyte function is largely unknown. Here, we aimed to determine the impact of exposure to chorioamnionitis on the proportions and phenotype of cord blood monocytes using flow cytometry, as well as their transcriptional response to live S. epidermidis. RNA-seq was performed on purified cord blood monocytes from very preterm infants (<32 weeks gestation, with and without chorioamnionitis-exposure) and term infants (37-40 weeks), pre- and postchallenge with live S. epidermidis. Preterm monocytes from infants without chorioamnionitis-exposure did not exhibit an intrinsically deficient transcriptional response to S. epidermidis compared to term infants. In contrast, chorioamnionitis-exposure was associated with hypo-responsive transcriptional phenotype regarding a subset of genes involved in antigen presentation and adaptive immunity. Overall, our findings suggest that prenatal exposure to inflammation may alter the risk of sepsis in preterm infants partly by modulation of monocyte responses to pathogens. © 2018 Australasian Society for Immunology Inc.

The transcription factor Cabut coordinates energy metabolism and the circadian clock in response to sugar sensing

PubMed Central

Bartok, Osnat; Teesalu, Mari; Ashwall-Fluss, Reut; Pandey, Varun; Hanan, Mor; Rovenko, Bohdana M; Poukkula, Minna; Havula, Essi; Moussaieff, Arieh; Vodala, Sadanand; Nahmias, Yaakov; Kadener, Sebastian; Hietakangas, Ville

2015-01-01

Nutrient sensing pathways adjust metabolism and physiological functions in response to food intake. For example, sugar feeding promotes lipogenesis by activating glycolytic and lipogenic genes through the Mondo/ChREBP-Mlx transcription factor complex. Concomitantly, other metabolic routes are inhibited, but the mechanisms of transcriptional repression upon sugar sensing have remained elusive. Here, we characterize cabut (cbt), a transcription factor responsible for the repressive branch of the sugar sensing transcriptional network in Drosophila. We demonstrate that cbt is rapidly induced upon sugar feeding through direct regulation by Mondo-Mlx. We found that CBT represses several metabolic targets in response to sugar feeding, including both isoforms of phosphoenolpyruvate carboxykinase (pepck). Deregulation of pepck1 (CG17725) in mlx mutants underlies imbalance of glycerol and glucose metabolism as well as developmental lethality. Furthermore, we demonstrate that cbt provides a regulatory link between nutrient sensing and the circadian clock. Specifically, we show that a subset of genes regulated by the circadian clock are also targets of CBT. Moreover, perturbation of CBT levels leads to deregulation of the circadian transcriptome and circadian behavioral patterns. PMID:25916830

Identification of a novel trafficking pathway exporting a replication protein, Orc2 to nucleus via classical secretory pathway in Plasmodium falciparum.

PubMed

Sharma, Rahul; Sharma, Bhumika; Gupta, Ashish; Dhar, Suman Kumar

2018-05-01

Malaria parasites use an extensive secretory pathway to traffic a number of proteins within itself and beyond. In higher eukaryotes, Endoplasmic Reticulum (ER) membrane bound transcription factors such as SREBP are reported to get processed en route and migrate to nucleus under the influence of specific cues. However, a protein constitutively trafficked to the nucleus via classical secretory pathway has not been reported. Herein, we report the presence of a novel trafficking pathway in an apicomplexan, Plasmodium falciparum where a homologue of an Origin Recognition Complex 2 (Orc2) goes to the nucleus following its association with the ER. Our work highlights the unconventional role of ER in protein trafficking and reports for the first time an ORC homologue getting trafficked through such a pathway to the nucleus where it may be involved in DNA replication and other ancillary functions. Such trafficking pathways may have a profound impact on the cell biology of a malaria parasite and have significant implications in strategizing new antimalarials. Copyright © 2018 Elsevier B.V. All rights reserved.

MCAK and Stathmin Upregulation in Breast Cancer Cells: Etiology and Response to Pharmacologic Reagents

DTIC Science & Technology

2004-07-01

and the affinity for MTs are cells (Maney et al., 2001). Finally, the neck domain is not molecular refinements that adapt motile kinesins for specific...1,500 nM taxol-stabilized MTs in 80 p.I of BRB80 (80 mM molecular motor. Nature. 389:93-96. Pipes, pH 6.8, 1 mM EGTA, and 1 mM MgCI2), 12.5 p.M taxol, 1...summarizes the biological functions and examines the possible molecular the r egio immeiatel iete mt core mechanisms of Kin C and Kin I unconventional

Unconventional Rotor Power Response to Yaw Error Variations

DOE PAGES

Schreck, S. J.; Schepers, J. G.

2014-12-16

Continued inquiry into rotor and blade aerodynamics remains crucial for achieving accurate, reliable prediction of wind turbine power performance under yawed conditions. To exploit key advantages conferred by controlled inflow conditions, we used EU-JOULE DATA Project and UAE Phase VI experimental data to characterize rotor power production under yawed conditions. Anomalies in rotor power variation with yaw error were observed, and the underlying fluid dynamic interactions were isolated. Unlike currently recognized influences caused by angled inflow and skewed wake, which may be considered potential flow interactions, these anomalies were linked to pronounced viscous and unsteady effects.

Statement of Rear Admiral Nevin P. Carr, Jr., United States Navy Chief of Naval Research before the Terrorism, Unconventional Threats and Capabilities Subcommittee of the House Armed Services Committee on The Fiscal year 2011 Budget Request

DTIC Science & Technology

2010-03-23

foundation of our S&T portfolio by developing a broad base of scientific knowledge from which INP, FNC, and quick reaction efforts are generated...optimally tailoring experiences, in real-time, to current cognitive and physiological states of the learner. A unique human systems design approach is...efforts include modeling human responses to blast, ballistic, and blunt trauma, as well as modeling physical and cognitive effects of blast exposure and

Comparison of unusual carbon-based working electrodes for electrochemiluminescence sensors.

PubMed

Noman, Muhammad; Sanginario, Alessandro; Jagadale, Pravin; Demarchi, Danilo; Tagliaferro, Alberto

2017-06-01

In this work, unconventional carbon-based materials were investigated for use in electrochemiluminescence (ECL) working electrodes. Precursors such as bamboo, pistachio shells, kevlar ® fibers and camphor were differently treated and used as working electrodes in ECL experiments. After a proper process they were assembled as electrodes and tested in an electrochemical cell. Comparison among them and with a commercial glassy carbon electrode (GCE) shows a very good response for all of them thus demonstrating their potential use as disposable low-cost electrodes for early detection electrochemical analysis. Copyright © 2017 Elsevier B.V. All rights reserved.

A systems biology perspective on the role of WRKY transcription factors in drought responses in plants.

PubMed

Tripathi, Prateek; Rabara, Roel C; Rushton, Paul J

2014-02-01

Drought is one of the major challenges affecting crop productivity and yield. However, water stress responses are notoriously multigenic and quantitative with strong environmental effects on phenotypes. It is also clear that water stress often does not occur alone under field conditions but rather in conjunction with other abiotic stresses such as high temperature and high light intensities. A multidisciplinary approach with successful integration of a whole range of -omics technologies will not only define the system, but also provide new gene targets for both transgenic approaches and marker-assisted selection. Transcription factors are major players in water stress signaling and some constitute major hubs in the signaling webs. The main transcription factors in this network include MYB, bHLH, bZIP, ERF, NAC, and WRKY transcription factors. The role of WRKY transcription factors in abiotic stress signaling networks is just becoming apparent and systems biology approaches are starting to define their places in the signaling network. Using systems biology approaches, there are now many transcriptomic analyses and promoter analyses that concern WRKY transcription factors. In addition, reports on nuclear proteomics have identified WRKY proteins that are up-regulated at the protein level by water stress. Interactomics has started to identify different classes of WRKY-interacting proteins. What are often lacking are connections between metabolomics, WRKY transcription factors, promoters, biosynthetic pathways, fluxes and downstream responses. As more levels of the system are characterized, a more detailed understanding of the roles of WRKY transcription factors in drought responses in crops will be obtained.

Transcriptional Control in Marine Copiotrophic and Oligotrophic Bacteria with Streamlined Genomes.

PubMed

Cottrell, Matthew T; Kirchman, David L

2016-10-01

Bacteria often respond to environmental stimuli using transcriptional control, but this may not be the case for marine bacteria such as "Candidatus Pelagibacter ubique," a cultivated representative of the SAR11 clade, the most abundant organism in the ocean. This bacterium has a small, streamlined genome and an unusually low number of transcriptional regulators, suggesting that transcriptional control is low in Pelagibacter and limits its response to environmental conditions. Transcriptome sequencing during batch culture growth revealed that only 0.1% of protein-encoding genes appear to be under transcriptional control in Pelagibacter and in another oligotroph (SAR92) whereas >10% of genes were under transcriptional control in the copiotrophs Polaribacter sp. strain MED152 and Ruegeria pomeroyi When growth levels changed, transcript levels remained steady in Pelagibacter and SAR92 but shifted in MED152 and R. pomeroyi Transcript abundances per cell, determined using an internal RNA sequencing standard, were low (<1 transcript per cell) for all but a few of the most highly transcribed genes in all four taxa, and there was no correlation between transcript abundances per cell and shifts in the levels of transcription. These results suggest that low transcriptional control contributes to the success of Pelagibacter and possibly other oligotrophic microbes that dominate microbial communities in the oceans. Diverse heterotrophic bacteria drive biogeochemical cycling in the ocean. The most abundant types of marine bacteria are oligotrophs with small, streamlined genomes. The metabolic controls that regulate the response of oligotrophic bacteria to environmental conditions remain unclear. Our results reveal that transcriptional control is lower in marine oligotrophic bacteria than in marine copiotrophic bacteria. Although responses of bacteria to environmental conditions are commonly regulated at the level of transcription, metabolism in the most abundant bacteria in the ocean appears to be regulated by other mechanisms. Copyright © 2016, American Society for Microbiology. All Rights Reserved.

Msn2p/Msn4p act as a key transcriptional activator of yeast cytoplasmic thiol peroxidase II.

PubMed

Hong, Seung-Keun; Cha, Mee-Kyung; Choi, Yong-Soo; Kim, Won-Cheol; Kim, Il-Han

2002-04-05

We observed that the transcription of Saccharomyces cerevisiae cytoplasmic thiol peroxidase type II (cTPx II) (YDR453C) is regulated in response to various stresses (e.g. oxidative stress, carbon starvation, and heat-shock). It has been suggested that both transcription-activating proteins, Yap1p and Skn7p, regulate the transcription of cTPx II upon exposure to oxidative stress. However, a dramatic loss of transcriptional response to various stresses in yeast mutant strains lacking both Msn2p and Msn4p suggests that the transcription factors act as a principal transcriptional activator. In addition to two Yap1p response elements (YREs), TTACTAA and TTAGTAA, the presence of two stress response elements (STREs) (CCCCT) in the upstream sequence of cTPx II also suggests that Msn2p/Msn4p could control stress-induced expression of cTPx II. Analysis of the transcriptional activity of site-directed mutagenesis of the putative STREs (STRE1 and STRE2) and YREs (TRE1 and YRE2) in terms of the activity of a lacZ reporter gene under control of the cTPx II promoter indicates that STRE2 acts as a principal binding element essential for transactivation of the cTPx II promoter. The transcriptional activity of the cTPx II promoter was exponentially increased after postdiauxic growth. The transcriptional activity of the cTPx II promoter is greatly increased by rapamycin. Deletion of Tor1, Tor2, Ras1, and Ras2 resulted in a considerable induction when compared with their parent strains, suggesting that the transcription of cTPx II is under negative control of the Ras/cAMP and target of rapamycin signaling pathways. Taken together, these results suggest that cTPx II is a target of Msn2p/Msn4p transcription factors under negative control of the Ras-protein kinase A and target of rapamycin signaling pathways. Furthermore, the accumulation of cTPx II upon exposure to oxidative stress and during the postdiauxic shift suggests an important antioxidant role in stationary phase yeast cells.

Modulation of yeast genome expression in response to defective RNA polymerase III-dependent transcription.

PubMed

Conesa, Christine; Ruotolo, Roberta; Soularue, Pascal; Simms, Tiffany A; Donze, David; Sentenac, André; Dieci, Giorgio

2005-10-01

We used genome-wide expression analysis in Saccharomyces cerevisiae to explore whether and how the expression of protein-coding, RNA polymerase (Pol) II-transcribed genes is influenced by a decrease in RNA Pol III-dependent transcription. The Pol II transcriptome was characterized in four thermosensitive, slow-growth mutants affected in different components of the RNA Pol III transcription machinery. Unexpectedly, we found only a modest correlation between altered expression of Pol II-transcribed genes and their proximity to class III genes, a result also confirmed by the analysis of single tRNA gene deletants. Instead, the transcriptome of all of the four mutants was characterized by increased expression of genes known to be under the control of the Gcn4p transcriptional activator. Indeed, GCN4 was found to be translationally induced in the mutants, and deleting the GCN4 gene eliminated the response. The Gcn4p-dependent expression changes did not require the Gcn2 protein kinase and could be specifically counteracted by an increased gene dosage of initiator tRNA(Met). Initiator tRNA(Met) depletion thus triggers a GCN4-dependent reprogramming of genome expression in response to decreased Pol III transcription. Such an effect might represent a key element in the coordinated transcriptional response of yeast cells to environmental changes.

Changes in DnaA-dependent gene expression contribute to the transcriptional and developmental response of Bacillus subtilis to manganese limitation in Luria-Bertani medium.

PubMed

Hoover, Sharon E; Xu, Weihong; Xiao, Wenzhong; Burkholder, William F

2010-08-01

The SOS response to DNA damage in bacteria is a well-known component of the complex transcriptional responses to genotoxic environmental stresses such as exposure to reactive oxygen species, alkylating agents, and many of the antibiotics targeting DNA replication. However, bacteria such as Bacillus subtilis also respond to conditions that perturb DNA replication via a transcriptional response mediated by the replication initiation protein DnaA. In addition to regulating the initiation of DNA replication, DnaA directly regulates the transcription of specific genes. Conditions that perturb DNA replication can trigger the accumulation of active DnaA, activating or repressing the transcription of genes in the DnaA regulon. We report here that simply growing B. subtilis in LB medium altered DnaA-dependent gene expression in a manner consistent with the accumulation of active DnaA and that this was part of a general transcriptional response to manganese limitation. The SOS response to DNA damage was not induced under these conditions. One of the genes positively regulated by DnaA in Bacillus subtilis encodes a protein that inhibits the initiation of sporulation, Sda. Sda expression was induced as cells entered stationary phase in LB medium but not in LB medium supplemented with manganese, and the induction of Sda inhibited sporulation-specific gene expression and the onset of spore morphogenesis. In the absence of Sda, manganese-limited cells initiated spore development but failed to form mature spores. These data highlight that DnaA-dependent gene expression may influence the response of bacteria to a range of environmental conditions, including conditions that are not obviously associated with genotoxic stress.

Changes in DnaA-Dependent Gene Expression Contribute to the Transcriptional and Developmental Response of Bacillus subtilis to Manganese Limitation in Luria-Bertani Medium▿ †

PubMed Central

Hoover, Sharon E.; Xu, Weihong; Xiao, Wenzhong; Burkholder, William F.

2010-01-01

The SOS response to DNA damage in bacteria is a well-known component of the complex transcriptional responses to genotoxic environmental stresses such as exposure to reactive oxygen species, alkylating agents, and many of the antibiotics targeting DNA replication. However, bacteria such as Bacillus subtilis also respond to conditions that perturb DNA replication via a transcriptional response mediated by the replication initiation protein DnaA. In addition to regulating the initiation of DNA replication, DnaA directly regulates the transcription of specific genes. Conditions that perturb DNA replication can trigger the accumulation of active DnaA, activating or repressing the transcription of genes in the DnaA regulon. We report here that simply growing B. subtilis in LB medium altered DnaA-dependent gene expression in a manner consistent with the accumulation of active DnaA and that this was part of a general transcriptional response to manganese limitation. The SOS response to DNA damage was not induced under these conditions. One of the genes positively regulated by DnaA in Bacillus subtilis encodes a protein that inhibits the initiation of sporulation, Sda. Sda expression was induced as cells entered stationary phase in LB medium but not in LB medium supplemented with manganese, and the induction of Sda inhibited sporulation-specific gene expression and the onset of spore morphogenesis. In the absence of Sda, manganese-limited cells initiated spore development but failed to form mature spores. These data highlight that DnaA-dependent gene expression may influence the response of bacteria to a range of environmental conditions, including conditions that are not obviously associated with genotoxic stress. PMID:20511500

Deciphering molecular circuits from genetic variation underlying transcriptional responsiveness to stimuli

PubMed Central

Gat-Viks, Irit; Chevrier, Nicolas; Wilentzik, Roni; Eisenhaure, Thomas; Raychowdhury, Raktima; Steuerman, Yael; Shalek, Alex; Hacohen, Nir; Amit, Ido; Regev, Aviv

2013-01-01

Individual genetic variation affects gene expression in response to stimuli, often by influencing complex molecular circuits. Here we combine genomic and intermediate-scale transcriptional profiling with computational methods to identify variants that affect the responsiveness of genes to stimuli (responsiveness QTLs; reQTLs) and to position these variants in molecular circuit diagrams. We apply this approach to study variation in transcriptional responsiveness to pathogen components in dendritic cells from recombinant inbred mouse strains. We identify reQTLs that correlate with particular stimuli and position them in known pathways. For example, in response to a virus-like stimulus, a trans-acting variant acts as an activator of the antiviral response; using RNAi, we identify Rgs16 as the likely causal gene. Our approach charts an experimental and analytic path to decipher the mechanisms underlying genetic variation in circuits that control responses to stimuli. PMID:23503680

Deciphering molecular circuits from genetic variation underlying transcriptional responsiveness to stimuli.

PubMed

Gat-Viks, Irit; Chevrier, Nicolas; Wilentzik, Roni; Eisenhaure, Thomas; Raychowdhury, Raktima; Steuerman, Yael; Shalek, Alex K; Hacohen, Nir; Amit, Ido; Regev, Aviv

2013-04-01

Individual genetic variation affects gene responsiveness to stimuli, often by influencing complex molecular circuits. Here we combine genomic and intermediate-scale transcriptional profiling with computational methods to identify variants that affect the responsiveness of genes to stimuli (responsiveness quantitative trait loci or reQTLs) and to position these variants in molecular circuit diagrams. We apply this approach to study variation in transcriptional responsiveness to pathogen components in dendritic cells from recombinant inbred mouse strains. We identify reQTLs that correlate with particular stimuli and position them in known pathways. For example, in response to a virus-like stimulus, a trans-acting variant responds as an activator of the antiviral response; using RNA interference, we identify Rgs16 as the likely causal gene. Our approach charts an experimental and analytic path to decipher the mechanisms underlying genetic variation in circuits that control responses to stimuli.

Architecture, Assembly, and Emerging Applications of Branched Functional Polyelectrolytes and Poly(ionic liquid)s.

PubMed

Xu, Weinan; Ledin, Petr A; Shevchenko, Valery V; Tsukruk, Vladimir V

2015-06-17

Branched polyelectrolytes with cylindrical brush, dendritic, hyperbranched, grafted, and star architectures bearing ionizable functional groups possess complex and unique assembly behavior in solution at surfaces and interfaces as compared to their linear counterparts. This review summarizes the recent developments in the introduction of various architectures and understanding of the assembly behavior of branched polyelectrolytes with a focus on functional polyelectrolytes and poly(ionic liquid)s with responsive properties. The branched polyelectrolytes and poly(ionic liquid)s interact electrostatically with small molecules, linear polyelectrolytes, or other branched polyelectrolytes to form assemblies of hybrid nanoparticles, multilayer thin films, responsive microcapsules, and ion-conductive membranes. The branched structures lead to unconventional assemblies and complex hierarchical structures with responsive properties as summarized in this review. Finally, we discuss prospectives for emerging applications of branched polyelectrolytes and poly(ionic liquid)s for energy harvesting and storage, controlled delivery, chemical microreactors, adaptive surfaces, and ion-exchange membranes.

Unconventional quantum criticality emerging as a new common language of transition-metal compounds, heavy-fermion systems, and organic conductors.

PubMed

Imada, Masatoshi; Misawa, Takahiro; Yamaji, Youhei

2010-04-28

We analyze and overview some of the different types of unconventional quantum criticalities by focusing on two origins. One origin of the unconventionality is the proximity to first-order transitions. The border between the first-order and continuous transitions is described by a quantum tricritical point (QTCP) for symmetry breaking transitions. One of the characteristic features of the quantum tricriticality is the concomitant divergence of an order parameter and uniform fluctuations, in contrast to the conventional quantum critical point (QCP). The interplay of these two fluctuations generates unconventionality. Several puzzling non-Fermi-liquid properties in experiments are taken to be accounted for by the resultant universality, as in the cases of Y bRh(2)Si(2), CeRu(2)Si(2) and β-Y bAlB(4). Another more dramatic unconventionality appears again at the border of the first-order and continuous transitions, but in this case for topological transitions such as metal-insulator and Lifshitz transitions. This border, the marginal quantum critical point (MQCP), belongs to an unprecedented universality class with diverging uniform fluctuations at zero temperature. The Ising universality at the critical end point of the first-order transition at nonzero temperatures transforms to the marginal quantum criticality when the critical temperature is suppressed to zero. The MQCP has a unique feature with a combined character of symmetry breaking and topological transitions. In the metal-insulator transitions, the theoretical results are supported by experimental indications for V(2 - x)Cr(x)O(3) and an organic conductor κ-(ET)(2)Cu[N(CN)(2)]Cl. Identifying topological transitions also reveals how non-Fermi liquid appears as a phase in metals. The theory also accounts for the criticality of a metamagnetic transition in ZrZn(2), by interpreting it as an interplay of Lifshitz transition and correlation effects. We discuss the common underlying physics in these examples.

Unconventional supercapacitors from nanocarbon-based electrode materials to device configurations.

PubMed

Liu, Lili; Niu, Zhiqiang; Chen, Jun

2016-07-25

As energy storage devices, supercapacitors that are also called electrochemical capacitors possess high power density, excellent reversibility and long cycle life. The recent boom in electronic devices with different functions in transparent LED displays, stretchable electronic systems and artificial skin has increased the demand for supercapacitors to move towards light, thin, integrated macro- and micro-devices with transparent, flexible, stretchable, compressible and/or wearable abilities. The successful fabrication of such supercapacitors depends mainly on the preparation of innovative electrode materials and the design of unconventional supercapacitor configurations. Tremendous research efforts have been recently made to design and construct innovative nanocarbon-based electrode materials and supercapacitors with unconventional configurations. We review here recent developments in supercapacitors from nanocarbon-based electrode materials to device configurations. The advances in nanocarbon-based electrode materials mainly include the assembly technologies of macroscopic nanostructured electrodes with different dimensions of carbon nanotubes/nanofibers, graphene, mesoporous carbon, activated carbon, and their composites. The electrodes with macroscopic nanostructured carbon-based materials overcome the issues of low conductivity, poor mechanical properties, and limited dimensions that are faced by conventional methods. The configurational design of advanced supercapacitor devices is presented with six types of unconventional supercapacitor devices: flexible, micro-, stretchable, compressible, transparent and fiber supercapacitors. Such supercapacitors display unique configurations and excellent electrochemical performance at different states such as bending, stretching, compressing and/or folding. For example, all-solid-state simplified supercapacitors that are based on nanostructured graphene composite paper are able to maintain 95% of the original capacity at a 180° folding state. The progress made so far will guide further developments in the structural design of nanocarbon-based electrode materials and the configurational diversity of supercapacitor devices. Future developments and prospects in the controllable assembly of macroscopic nanostructured electrodes and the innovation of unconventional supercapacitor configurations are also discussed. This should shed light on the R&D of supercapacitors.

Transcriptional regulation of the operon encoding stress-responsive ECF sigma factor SigH and its anti-sigma factor RshA, and control of its regulatory network in Corynebacterium glutamicum

PubMed Central

2012-01-01

Background The expression of genes in Corynebacterium glutamicum, a Gram-positive non-pathogenic bacterium used mainly for the industrial production of amino acids, is regulated by seven different sigma factors of RNA polymerase, including the stress-responsive ECF-sigma factor SigH. The sigH gene is located in a gene cluster together with the rshA gene, putatively encoding an anti-sigma factor. The aim of this study was to analyze the transcriptional regulation of the sigH and rshA gene cluster and the effects of RshA on the SigH regulon, in order to refine the model describing the role of SigH and RshA during stress response. Results Transcription analyses revealed that the sigH gene and rshA gene are cotranscribed from four sigH housekeeping promoters in C. glutamicum. In addition, a SigH-controlled rshA promoter was found to only drive the transcription of the rshA gene. To test the role of the putative anti-sigma factor gene rshA under normal growth conditions, a C. glutamicum rshA deletion strain was constructed and used for genome-wide transcription profiling with DNA microarrays. In total, 83 genes organized in 61 putative transcriptional units, including those previously detected using sigH mutant strains, exhibited increased transcript levels in the rshA deletion mutant compared to its parental strain. The genes encoding proteins related to disulphide stress response, heat stress proteins, components of the SOS-response to DNA damage and proteasome components were the most markedly upregulated gene groups. Altogether six SigH-dependent promoters upstream of the identified genes were determined by primer extension and a refined consensus promoter consisting of 45 original promoter sequences was constructed. Conclusions The rshA gene codes for an anti-sigma factor controlling the function of the stress-responsive sigma factor SigH in C. glutamicum. Transcription of rshA from a SigH-dependent promoter may serve to quickly shutdown the SigH-dependent stress response after the cells have overcome the stress condition. Here we propose a model of the regulation of oxidative and heat stress response including redox homeostasis by SigH, RshA and the thioredoxin system. PMID:22943411

Transcriptional regulation of the operon encoding stress-responsive ECF sigma factor SigH and its anti-sigma factor RshA, and control of its regulatory network in Corynebacterium glutamicum.

PubMed

Busche, Tobias; Silar, Radoslav; Pičmanová, Martina; Pátek, Miroslav; Kalinowski, Jörn

2012-09-03

The expression of genes in Corynebacterium glutamicum, a Gram-positive non-pathogenic bacterium used mainly for the industrial production of amino acids, is regulated by seven different sigma factors of RNA polymerase, including the stress-responsive ECF-sigma factor SigH. The sigH gene is located in a gene cluster together with the rshA gene, putatively encoding an anti-sigma factor. The aim of this study was to analyze the transcriptional regulation of the sigH and rshA gene cluster and the effects of RshA on the SigH regulon, in order to refine the model describing the role of SigH and RshA during stress response. Transcription analyses revealed that the sigH gene and rshA gene are cotranscribed from four sigH housekeeping promoters in C. glutamicum. In addition, a SigH-controlled rshA promoter was found to only drive the transcription of the rshA gene. To test the role of the putative anti-sigma factor gene rshA under normal growth conditions, a C. glutamicum rshA deletion strain was constructed and used for genome-wide transcription profiling with DNA microarrays. In total, 83 genes organized in 61 putative transcriptional units, including those previously detected using sigH mutant strains, exhibited increased transcript levels in the rshA deletion mutant compared to its parental strain. The genes encoding proteins related to disulphide stress response, heat stress proteins, components of the SOS-response to DNA damage and proteasome components were the most markedly upregulated gene groups. Altogether six SigH-dependent promoters upstream of the identified genes were determined by primer extension and a refined consensus promoter consisting of 45 original promoter sequences was constructed. The rshA gene codes for an anti-sigma factor controlling the function of the stress-responsive sigma factor SigH in C. glutamicum. Transcription of rshA from a SigH-dependent promoter may serve to quickly shutdown the SigH-dependent stress response after the cells have overcome the stress condition. Here we propose a model of the regulation of oxidative and heat stress response including redox homeostasis by SigH, RshA and the thioredoxin system.

Identification and expression analysis of WRKY transcription factor genes in canola (Brassica napus L.) in response to fungal pathogens and hormone treatments.

PubMed

Yang, Bo; Jiang, Yuanqing; Rahman, Muhammad H; Deyholos, Michael K; Kav, Nat N V

2009-06-03

Members of plant WRKY transcription factor families are widely implicated in defense responses and various other physiological processes. For canola (Brassica napus L.), no WRKY genes have been described in detail. Because of the economic importance of this crop, and its evolutionary relationship to Arabidopsis thaliana, we sought to characterize a subset of canola WRKY genes in the context of pathogen and hormone responses. In this study, we identified 46 WRKY genes from canola by mining the expressed sequence tag (EST) database and cloned cDNA sequences of 38 BnWRKYs. A phylogenetic tree was constructed using the conserved WRKY domain amino acid sequences, which demonstrated that BnWRKYs can be divided into three major groups. We further compared BnWRKYs to the 72 WRKY genes from Arabidopsis and 91 WRKY from rice, and we identified 46 presumptive orthologs of AtWRKY genes. We examined the subcellular localization of four BnWRKY proteins using green fluorescent protein (GFP) and we observed the fluorescent green signals in the nucleus only.The responses of 16 selected BnWRKY genes to two fungal pathogens, Sclerotinia sclerotiorum and Alternaria brassicae, were analyzed by quantitative real time-PCR (qRT-PCR). Transcript abundance of 13 BnWRKY genes changed significantly following pathogen challenge: transcripts of 10 WRKYs increased in abundance, two WRKY transcripts decreased after infection, and one decreased at 12 h post-infection but increased later on (72 h). We also observed that transcript abundance of 13/16 BnWRKY genes was responsive to one or more hormones, including abscisic acid (ABA), and cytokinin (6-benzylaminopurine, BAP) and the defense signaling molecules jasmonic acid (JA), salicylic acid (SA), and ethylene (ET). We compared these transcript expression patterns to those previously described for presumptive orthologs of these genes in Arabidopsis and rice, and observed both similarities and differences in expression patterns. We identified a set of 13 BnWRKY genes from among 16 BnWRKY genes assayed, that are responsive to both fungal pathogens and hormone treatments, suggesting shared signaling mechanisms for these responses. This study suggests that a large number of BnWRKY proteins are involved in the transcriptional regulation of defense-related genes in response to fungal pathogens and hormone stimuli.

Alternative Splicing in Plant Genes: A Means of Regulating the Environmental Fitness of Plants.

PubMed

Shang, Xudong; Cao, Ying; Ma, Ligeng

2017-02-20

Gene expression can be regulated through transcriptional and post-transcriptional mechanisms. Transcription in eukaryotes produces pre-mRNA molecules, which are processed and spliced post-transcriptionally to create translatable mRNAs. More than one mRNA may be produced from a single pre-mRNA by alternative splicing (AS); thus, AS serves to diversify an organism's transcriptome and proteome. Previous studies of gene expression in plants have focused on the role of transcriptional regulation in response to environmental changes. However, recent data suggest that post-transcriptional regulation, especially AS, is necessary for plants to adapt to a changing environment. In this review, we summarize recent advances in our understanding of AS during plant development in response to environmental changes. We suggest that alternative gene splicing is a novel means of regulating the environmental fitness of plants.

Ubiquitin ligase activity of TFIIH and the transcriptional response to DNA damage.

PubMed

Takagi, Yuichiro; Masuda, Claudio A; Chang, Wei-Hau; Komori, Hirofumi; Wang, Dong; Hunter, Tony; Joazeiro, Claudio A P; Kornberg, Roger D

2005-04-15

Core transcription factor (TF) IIH purified from yeast possesses an E3 ubiquitin (Ub) ligase activity, which resides, at least in part, in a RING finger (RNF) domain of the Ssl1 subunit. Yeast strains mutated in the Ssl1 RNF domain are sensitive to ultraviolet (UV) light and to methyl methanesulfonate (MMS). This increased sensitivity to DNA-damaging agents does not reflect a deficiency in nucleotide excision repair. Rather, it correlates with reduced transcriptional induction of genes involved in DNA repair, suggesting that the E3 Ub ligase activity of TFIIH mediates the transcriptional response to DNA damage.

Future Propulsion Opportunities for Commuter Airplanes

NASA Technical Reports Server (NTRS)

Strack, W. C.

1982-01-01

Commuter airplane propulsion opportunities are summarized. Consideration is given to advanced technology conventional turboprop engines, advanced propellers, and several unconventional alternatives: regenerative turboprops, rotaries, and diesels. Advanced versions of conventional turboprops (including propellers) offer 15-20 percent savings in fuel and 10-15 percent in DOC compared to the new crop of 1500-2000 SHP engines currently in development. Unconventional engines could boost the fuel savings to 30-40 percent. The conclusion is that several important opportunities exist and, therefore, powerplant technology need not plateau.

Russian-Soviet Unconventional Wars in the Caucasus, Central Asia, and Afghanistan (Leavenworth Papers, Number 20)

DTIC Science & Technology

1993-04-01

offers important new perspectives on elements of continuity and change in combat over two centuries. This is the first study to provide an in-depth...examination of the evolution of the Russian and Soviet unconventional experience on the predominantly Muslim southern periphery of the former empire. There...include not only adjustment to the tactics of an unfamiliar enemy but the adaptation of one·s own tactics and equipment to constraints imposed on

Set Up for Failure: The Use of US Security Force Assistance to Prepare Foreign Security Forces for Traditional Combat Operations

DTIC Science & Technology

2017-05-17

Do the SFA lessons drawn from the unconventional warfare focus of the post-9-11 paradigm hold true across the spectrum of conflict, or are there...relevance. Do the SFA lessons drawn from the unconventional warfare focus of the post-9-11 paradigm hold true across the spectrum of conflict, or...traditional warfare is fought changes from epoch to epoch as technology, armament, and other factors change, but certain immutable principles hold true

Searches for dark matter and new physics with unconventional signatures

NASA Astrophysics Data System (ADS)

Wulz, C.-E.; CMS Collaboration

2017-07-01

Selected results on searches for dark matter and unconventional signatures with the CMS detector are presented. Dark matter searches in channels with one or two jets, single photons, vector bosons, or top and bottom quarks combined with missing momentum in the final states are described. Unusual signatures such as displaced objects, disappearing or kinked tracks, delayed or stopped particles have also been explored. The analyses were performed with proton-proton data recorded at LHC centre-of-mass energies up to 13TeV.

Notes on implementation of sparsely distributed memory

NASA Technical Reports Server (NTRS)

Keeler, J. D.; Denning, P. J.

1986-01-01

The Sparsely Distributed Memory (SDM) developed by Kanerva is an unconventional memory design with very interesting and desirable properties. The memory works in a manner that is closely related to modern theories of human memory. The SDM model is discussed in terms of its implementation in hardware. Two appendices discuss the unconventional approaches of the SDM: Appendix A treats a resistive circuit for fast, parallel address decoding; and Appendix B treats a systolic array for high throughput read and write operations.

Flight experience with manually controlled unconventional aircraft motions

NASA Technical Reports Server (NTRS)

Barfield, A. F.

1978-01-01

A modified YF-16 aircraft was used to flight demonstrate decoupled modes under the USAF Fighter Control Configured Vehicle (CCV) Program. The direct force capabilities were used to implement seven manually controlled unconventional modes on the aircraft, allowing flat turns, decoupled normal acceleration control, independent longitudinal and lateral translations, uncoupled elevation and azimuth aiming, and blended direct lift. This paper describes the design, development, and flight testing of these control modes. The need for task-tailored mode authorities, gain-scheduling and selected closed-loop design is discussed.

Minimal Conductance Quantization in a Normal-Metal/Unconventional-Superconductor Junction

NASA Astrophysics Data System (ADS)

Ikegaya, Satoshi; Asano, Yasuhiro

2018-04-01

We discuss the minimum value of the zero-bias differential conductance in a normal-metal/unconventional-superconductor junction. A numerical simulation demonstrates that the zero-bias conductance is quantized at (4e^2/h) N_ZES in the limit of strong impurity scatterings in the normal-metal. The integer N_ZES represents the number of perfect transmission channels through the junction. By focusing on the chiral symmetry of Hamiltonian, we prove the existence of N_ZES-fold degenerate resonant states in the dirty normal segment.

The Basic Leucine Zipper Transcription Factor ABSCISIC ACID RESPONSE ELEMENT-BINDING FACTOR2 Is an Important Transcriptional Regulator of Abscisic Acid-Dependent Grape Berry Ripening Processes1[W][OPEN

PubMed Central

Nicolas, Philippe; Lecourieux, David; Kappel, Christian; Cluzet, Stéphanie; Cramer, Grant; Delrot, Serge; Lecourieux, Fatma

2014-01-01

In grape (Vitis vinifera), abscisic acid (ABA) accumulates during fruit ripening and is thought to play a pivotal role in this process, but the molecular basis of this control is poorly understood. This work characterizes ABSCISIC ACID RESPONSE ELEMENT-BINDING FACTOR2 (VvABF2), a grape basic leucine zipper transcription factor belonging to a phylogenetic subgroup previously shown to be involved in ABA and abiotic stress signaling in other plant species. VvABF2 transcripts mainly accumulated in the berry, from the onset of ripening to the harvesting stage, and were up-regulated by ABA. Microarray analysis of transgenic grape cells overexpressing VvABF2 showed that this transcription factor up-regulates and/or modifies existing networks related to ABA responses. In addition, grape cells overexpressing VvABF2 exhibited enhanced responses to ABA treatment compared with control cells. Among the VvABF2-mediated responses highlighted in this study, the synthesis of phenolic compounds and cell wall softening were the most strongly affected. VvABF2 overexpression strongly increased the accumulation of stilbenes that play a role in plant defense and human health (resveratrol and piceid). In addition, the firmness of fruits from tomato (Solanum lycopersicum) plants overexpressing VvABF2 was strongly reduced. These data indicate that VvABF2 is an important transcriptional regulator of ABA-dependent grape berry ripening. PMID:24276949

A nuclear factor I-like activity and a liver-specific repressor govern estrogen-regulated in vitro transcription from the Xenopus laevis vitellogenin B1 promoter.

PubMed

Corthésy, B; Cardinaux, J R; Claret, F X; Wahli, W

1989-12-01

A hormone-controlled in vitro transcription system derived from Xenopus liver nuclear extracts was exploited to identify novel cis-acting elements within the vitellogenin gene B1 promoter region. In addition to the already well-documented estrogen-responsive element (ERE), two elements were found within the 140 base pairs upstream of the transcription initiation site. One of them, a negative regulatory element, is responsible for the lack of promoter activity in the absence of the hormone and, as demonstrated by DNA-binding assays, interacts with a liver-specific transcription factor. The second is required in association with the estrogen-responsive element to mediate hormonal induction and is recognized by the Xenopus liver homolog of nuclear factor I.

A Member of the p38 Mitogen-Activated Protein Kinase Family Is Responsible for Transcriptional Induction of Dopa decarboxylase in the Epidermis of Drosophila melanogaster during the Innate Immune Response▿ †

PubMed Central

Davis, Monica M.; Primrose, David A.; Hodgetts, Ross B.

2008-01-01

Drosophila innate immunity is controlled primarily by the activation of IMD (immune deficiency) or Toll signaling leading to the production of antimicrobial peptides (AMPs). IMD signaling also activates the JUN N-terminal kinase (JNK) cascade, which is responsible for immune induction of non-antimicrobial peptide immune gene transcription though the transcription factor AP-1. Transcription of the Dopa decarboxylase (Ddc) gene is induced in response to gram-negative and gram-positive septic injury, but not aseptic wounding. Transcription is induced throughout the epidermis and not specifically at the site of infection. Ddc transcripts are detectible within 2 h and remain high for several hours following infection with either gram-negative or gram-positive bacteria. Using Ddc-green fluorescent protein (GFP) reporter gene constructs, we show that a conserved consensus AP-1 binding site upstream of the Ddc transcription start site is required for induction. However, neither the Toll, IMD, nor JNK pathway is involved. Rather, Ddc transcription depends on a previously uncharacterized member of the p38 mitogen-activated protein kinase family, p38c. We propose that the involvement of DDC in a new pathway involved in Drosophila immunity increases the levels of dopamine, which is metabolized to produce reactive quinones that exert an antimicrobial effect on invading bacteria. PMID:18519585

Transcriptional regulatory networks controlling woolliness in peach in response to preharvest gibberellin application and cold storage.

PubMed

Pegoraro, Camila; Tadiello, Alice; Girardi, César L; Chaves, Fábio C; Quecini, Vera; de Oliveira, Antonio Costa; Trainotti, Livio; Rombaldi, Cesar Valmor

2015-11-18

Postharvest fruit conservation relies on low temperatures and manipulations of hormone metabolism to maintain sensory properties. Peaches are susceptible to chilling injuries, such as 'woolliness' that is caused by juice loss leading to a 'wooly' fruit texture. Application of gibberellic acid at the initial stages of pit hardening impairs woolliness incidence, however the mechanisms controlling the response remain unknown. We have employed genome wide transcriptional profiling to investigate the effects of gibberellic acid application and cold storage on harvested peaches. Approximately half of the investigated genes exhibited significant differential expression in response to the treatments. Cellular and developmental process gene ontologies were overrepresented among the differentially regulated genes, whereas sequences in cell death and immune response categories were underrepresented. Gene set enrichment demonstrated a predominant role of cold storage in repressing the transcription of genes associated to cell wall metabolism. In contrast, genes involved in hormone responses exhibited a more complex transcriptional response, indicating an extensive network of crosstalk between hormone signaling and low temperatures. Time course transcriptional analyses demonstrate the large contribution of gene expression regulation on the biochemical changes leading to woolliness in peach. Overall, our results provide insights on the mechanisms controlling the complex phenotypes associated to postharvest textural changes in peach and suggest that hormone mediated reprogramming previous to pit hardening affects the onset of chilling injuries.

Mitochondrial and Chloroplast Stress Responses Are Modulated in Distinct Touch and Chemical Inhibition Phases1[OPEN

PubMed Central

Ivanova, Aneta; Millar, A. Harvey; Whelan, James

2016-01-01

Previous studies have identified a range of transcription factors that modulate retrograde regulation of mitochondrial and chloroplast functions in Arabidopsis (Arabidopsis thaliana). However, the relative importance of these regulators and whether they act downstream of separate or overlapping signaling cascades is still unclear. Here, we demonstrate that multiple stress-related signaling pathways, with distinct kinetic signatures, converge on overlapping gene sets involved in energy organelle function. The transcription factor ANAC017 is almost solely responsible for transcript induction of marker genes around 3 to 6 h after chemical inhibition of organelle function and is a key regulator of mitochondrial and specific types of chloroplast retrograde signaling. However, an independent and highly transient gene expression phase, initiated within 10 to 30 min after treatment, also targets energy organelle functions, and is related to touch and wounding responses. Metabolite analysis demonstrates that this early response is concurrent with rapid changes in tricarboxylic acid cycle intermediates and large changes in transcript abundance of genes encoding mitochondrial dicarboxylate carrier proteins. It was further demonstrated that transcription factors AtWRKY15 and AtWRKY40 have repressive regulatory roles in this touch-responsive gene expression. Together, our results show that several regulatory systems can independently affect energy organelle function in response to stress, providing different means to exert operational control. PMID:27208304

Rapid Myeloid Cell Transcriptional and Proteomic Responses to Periodontopathogenic Porphyromonas gingivalis

PubMed Central

Nares, Salvador; Moutsopoulos, Niki M.; Angelov, Nikola; Rangel, Zoila G.; Munson, Peter J.; Sinha, Neha; Wahl, Sharon M.

2009-01-01

Long-lived monocytes, macrophages, and dendritic cells (DCs) are Toll-like receptor-expressing, antigen-presenting cells derived from a common myeloid lineage that play key roles in innate and adaptive immune responses. Based on immunohistochemical and molecular analyses of inflamed tissues from patients with chronic destructive periodontal disease, these cells, found in the inflammatory infiltrate, may drive the progressive periodontal pathogenesis. To investigate early transcriptional signatures and subsequent proteomic responses to the periodontal pathogen, Porphyromonas gingivalis, donor-matched human blood monocytes, differentiated DCs, and macrophages were exposed to P. gingivalis lipopolysaccharide (LPS) and gene expression levels were measured by oligonucleotide microarrays. In addition to striking differences in constitutive transcriptional profiles between these myeloid populations, we identify a P. gingivalis LPS-inducible convergent, transcriptional core response of more than 400 annotated genes/ESTs among these populations, reflected by a shared, but quantitatively distinct, proteomic response. Nonetheless, clear differences emerged between the monocytes, DCs, and macrophages. The finding that long-lived myeloid inflammatory cells, particularly DCs, rapidly and aggressively respond to P. gingivalis LPS by generating chemokines, proteases, and cytokines capable of driving T-helper cell lineage polarization without evidence of corresponding immunosuppressive pathways highlights their prominent role in host defense and progressive tissue pathogenesis. The shared, unique, and/or complementary transcriptional and proteomic profiles may frame the context of the host response to P. gingivalis, contributing to the destructive nature of periodontal inflammation. PMID:19264901

Long noncoding RNAs responsive to Fusarium oxysporum infection in Arabidopsis thaliana.

PubMed

Zhu, Qian-Hao; Stephen, Stuart; Taylor, Jennifer; Helliwell, Chris A; Wang, Ming-Bo

2014-01-01

Short noncoding RNAs have been demonstrated to play important roles in regulation of gene expression and stress responses, but the repertoire and functions of long noncoding RNAs (lncRNAs) remain largely unexplored, particularly in plants. To explore the role of lncRNAs in disease resistance, we used a strand-specific RNA-sequencing approach to identify lncRNAs responsive to Fusarium oxysporum infection in Arabidopsis thaliana. Antisense transcription was found in c. 20% of the annotated A. thaliana genes. Several noncoding natural antisense transcripts responsive to F. oxysporum infection were found in genes implicated in disease defense. While the majority of the novel transcriptionally active regions (TARs) were adjacent to annotated genes and could be an extension of the annotated transcripts, 159 novel intergenic TARs, including 20 F. oxysporum-responsive lncTARs, were identified. Ten F. oxysporum-induced lncTARs were functionally characterized using T-DNA insertion or RNA-interference knockdown lines, and five were demonstrated to be related to disease development. Promoter analysis suggests that some of the F. oxysporum-induced lncTARs are direct targets of transcription factor(s) responsive to pathogen attack. Our results demonstrated that strand-specific RNA sequencing is a powerful tool for uncovering hidden levels of transcriptome and that IncRNAs are important components of the antifungal networks in A. thaliana. © 2013 The Authors. New Phytologist © 2013 New Phytologist Trust.

Transcriptional Regulation of Arabidopsis MIR168a and ARGONAUTE1 Homeostasis in Abscisic Acid and Abiotic Stress Responses1[W

PubMed Central

Li, Wei; Cui, Xiao; Meng, Zhaolu; Huang, Xiahe; Xie, Qi; Wu, Heng; Jin, Hailing; Zhang, Dabing; Liang, Wanqi

2012-01-01

The accumulation of a number of small RNAs in plants is affected by abscisic acid (ABA) and abiotic stresses, but the underlying mechanisms are poorly understood. The miR168-mediated feedback regulatory loop regulates ARGONAUTE1 (AGO1) homeostasis, which is crucial for gene expression modulation and plant development. Here, we reveal a transcriptional regulatory mechanism by which MIR168 controls AGO1 homeostasis during ABA treatment and abiotic stress responses in Arabidopsis (Arabidopsis thaliana). Plants overexpressing MIR168a and the AGO1 loss-of-function mutant ago1-27 display ABA hypersensitivity and drought tolerance, while the mir168a-2 mutant shows ABA hyposensitivity and drought hypersensitivity. Both the precursor and mature miR168 were induced under ABA and several abiotic stress treatments, but no obvious decrease for the target of miR168, AGO1, was shown under the same conditions. However, promoter activity analysis indicated that AGO1 transcription activity was increased under ABA and drought treatments, suggesting that transcriptional elevation of MIR168a is required for maintaining a stable AGO1 transcript level during the stress response. Furthermore, we showed both in vitro and in vivo that the transcription of MIR168a is directly regulated by four abscisic acid-responsive element (ABRE) binding factors, which bind to the ABRE cis-element within the MIR168a promoter. This ABRE motif is also found in the promoter of MIR168a homologs in diverse plant species. Our findings suggest that transcriptional regulation of miR168 and posttranscriptional control of AGO1 homeostasis may play an important and conserved role in stress response and signal transduction in plants. PMID:22247272

Transcriptional regulation of Arabidopsis MIR168a and argonaute1 homeostasis in abscisic acid and abiotic stress responses.

PubMed

Li, Wei; Cui, Xiao; Meng, Zhaolu; Huang, Xiahe; Xie, Qi; Wu, Heng; Jin, Hailing; Zhang, Dabing; Liang, Wanqi

2012-03-01

The accumulation of a number of small RNAs in plants is affected by abscisic acid (ABA) and abiotic stresses, but the underlying mechanisms are poorly understood. The miR168-mediated feedback regulatory loop regulates ARGONAUTE1 (AGO1) homeostasis, which is crucial for gene expression modulation and plant development. Here, we reveal a transcriptional regulatory mechanism by which MIR168 controls AGO1 homeostasis during ABA treatment and abiotic stress responses in Arabidopsis (Arabidopsis thaliana). Plants overexpressing MIR168a and the AGO1 loss-of-function mutant ago1-27 display ABA hypersensitivity and drought tolerance, while the mir168a-2 mutant shows ABA hyposensitivity and drought hypersensitivity. Both the precursor and mature miR168 were induced under ABA and several abiotic stress treatments, but no obvious decrease for the target of miR168, AGO1, was shown under the same conditions. However, promoter activity analysis indicated that AGO1 transcription activity was increased under ABA and drought treatments, suggesting that transcriptional elevation of MIR168a is required for maintaining a stable AGO1 transcript level during the stress response. Furthermore, we showed both in vitro and in vivo that the transcription of MIR168a is directly regulated by four abscisic acid-responsive element (ABRE) binding factors, which bind to the ABRE cis-element within the MIR168a promoter. This ABRE motif is also found in the promoter of MIR168a homologs in diverse plant species. Our findings suggest that transcriptional regulation of miR168 and posttranscriptional control of AGO1 homeostasis may play an important and conserved role in stress response and signal transduction in plants.

Resveratrol stimulates c-Fos gene transcription via activation of ERK1/2 involving multiple genetic elements.

PubMed

Thiel, Gerald; Rössler, Oliver G

2018-06-05

The polyphenol resveratrol is found in many plant and fruits and is a constituent of our diet. Resveratrol has been proposed to have chemopreventive and anti-inflammatory activities. On the cellular level, resveratrol activates stimulus-regulated transcription factors. To identify resveratrol-responsive elements within a natural gene promoter, the molecular pathway leading to c-Fos gene expression by resveratrol was dissected. The c-Fos gene encodes a basic region leucine zipper transcription factor and is a prototype of an immediate-early gene that is regulated by a wide range of signaling molecules. We analyzed chromatin-integrated c-Fos promoter-luciferase reporter genes where transcription factor binding sites were destroyed by point mutations or deletion mutagenesis. The results show that mutation of the binding sites for serum response factor (SRF), activator protein-1 (AP-1) and cAMP response element binding protein (CREB) significantly reduced reporter gene transcription following stimulation of the cells with resveratrol. Inactivation of the binding sites for signal transducer and activator of transcription (STAT) or ternary complex factors did not influence resveratrol-regulated c-Fos promoter activity. Thus, the c-Fos promoter contains three resveratrol-responsive elements, the cAMP response element (CRE), and the binding sites for SRF and AP-1. Moreover, we show that the transcriptional activation potential of the c-Fos protein is increased in resveratrol-stimulated cells, indicating that the biological activity of c-Fos is elevated by resveratrol stimulation. Pharmacological and genetic experiments revealed that the protein kinase ERK1/2 is the signal transducer that connects resveratrol treatment with the c-Fos gene. Copyright © 2018 Elsevier B.V. All rights reserved.

Post-Transcriptional Coordination of the Arabidopsis Iron Deficiency Response is Partially Dependent on the E3 Ligases RING DOMAIN LIGASE1 (RGLG1) and RING DOMAIN LIGASE2 (RGLG2)*

PubMed Central

Pan, I-Chun; Tsai, Huei-Hsuan; Cheng, Ya-Tan; Wen, Tuan-Nan; Buckhout, Thomas J.; Schmidt, Wolfgang

2015-01-01

Acclimation to changing environmental conditions is mediated by proteins, the abundance of which is carefully tuned by an elaborate interplay of DNA-templated and post-transcriptional processes. To dissect the mechanisms that control and mediate cellular iron homeostasis, we conducted quantitative high-resolution iTRAQ proteomics and microarray-based transcriptomic profiling of iron-deficient Arabidopsis thaliana plants. A total of 13,706 and 12,124 proteins was identified with a quadrupole-Orbitrap hybrid mass spectrometer in roots and leaves, respectively. This deep proteomic coverage allowed accurate estimates of post-transcriptional regulation in response to iron deficiency. Similarly regulated transcripts were detected in only 13% (roots) and 11% (leaves) of the 886 proteins that differentially accumulated between iron-sufficient and iron-deficient plants, indicating that the majority of the iron-responsive proteins was post-transcriptionally regulated. Mutants harboring defects in the RING DOMAIN LIGASE1 (RGLG1)1 and RING DOMAIN LIGASE2 (RGLG2) showed a pleiotropic phenotype that resembled iron-deficient plants with reduced trichome density and the formation of branched root hairs. Proteomic and transcriptomic profiling of rglg1 rglg2 double mutants revealed that the functional RGLG protein is required for the regulation of a large set of iron-responsive proteins including the coordinated expression of ribosomal proteins. This integrative analysis provides a detailed catalog of post-transcriptionally regulated proteins and allows the concept of a chiefly transcriptionally regulated iron deficiency response to be revisited. Protein data are available via ProteomeXchange with identifier PXD002126. PMID:26253232

Circulating RNA transcripts identify therapeutic response in cystic fibrosis lung disease.

PubMed

Saavedra, Milene T; Hughes, Grant J; Sanders, Linda A; Carr, Michelle; Rodman, David M; Coldren, Christopher D; Geraci, Mark W; Sagel, Scott D; Accurso, Frank J; West, James; Nick, Jerry A

2008-11-01

Circulating leukocyte RNA transcripts are systemic markers of inflammation, which have not been studied in cystic fibrosis (CF) lung disease. Although the standard assessment of pulmonary treatment response is FEV(1), a measure of airflow limitation, the lack of systemic markers to reflect changes in lung inflammation critically limits the testing of proposed therapeutics. We sought to prospectively identify and validate peripheral blood leukocyte genes that could mark resolution of pulmonary infection and inflammation using a model by which RNA transcripts could increase the predictive value of spirometry. Peripheral blood mononuclear cells were isolated from 10 patients with CF and acute pulmonary exacerbations before and after therapy. RNA expression profiling revealed that 10 genes significantly changed with treatment when compared with matched non-CF and control subjects with stable CF to establish baseline transcript abundance. Peripheral blood mononuclear cell RNA transcripts were prospectively validated, using real-time polymerase chain reaction amplification, in an independent cohort of acutely ill patients with CF (n = 14). Patients who responded to therapy were analyzed using general estimating equations and multiple logistic regression, such that changes in FEV(1)% predicted were regressed with transcript changes. Three genes, CD64, ADAM9, and CD36, were significant and independent predictors of a therapeutic response beyond that of FEV(1) alone (P < 0.05). In both cohorts, receiver operating characteristic analysis revealed greater accuracy when genes were combined with FEV(1). Circulating mononuclear cell transcripts characterize a response to the treatment of pulmonary exacerbations. Even in small patient cohorts, changes in gene expression in conjunction with FEV(1) may enhance current outcomes measures for treatment response.

Plant Mediator complex and its critical functions in transcription regulation.

PubMed

Yang, Yan; Li, Ling; Qu, Li-Jia

2016-02-01

The Mediator complex is an important component of the eukaryotic transcriptional machinery. As an essential link between transcription factors and RNA polymerase II, the Mediator complex transduces diverse signals to genes involved in different pathways. The plant Mediator complex was recently purified and comprises conserved and specific subunits. It functions in concert with transcription factors to modulate various responses. In this review, we summarize the recent advances in understanding the plant Mediator complex and its diverse roles in plant growth, development, defense, non-coding RNA production, response to abiotic stresses, flowering, genomic stability and metabolic homeostasis. In addition, the transcription factors interacting with the Mediator complex are also highlighted. © 2015 Institute of Botany, Chinese Academy of Sciences.

The Small Ethylene Response Factor ERF96 is Involved in the Regulation of the Abscisic Acid Response in Arabidopsis

DOE Office of Scientific and Technical Information (OSTI.GOV)

Wang, Xiaoping; Liu, Shanda; Tian, Hainan

We report that ethylene regulates many aspects of plant growth and development including seed germination, leaf senescence, and fruit ripening, and of plant responses to environmental stimuli including both biotic and abiotic stresses. Ethylene response factors (ERFs) are plant-specific transcription factors and are a subfamily of the AP2 (APETALA2)/ERF transcription factor family. The function of many members in this large gene family remains largely unknown. ERF96, a member of the Group IX ERF family transcription factors, has recently been shown to be a transcriptional activator that is involved in plant defense response in Arabidopsis. Here we provide evidence that ERF96more » is a positive regulator of abscisic acid (ABA) responses. Bioinformatics analysis indicated that there are a total four small ERFs in Arabidopsis including ERF95, ERF96, ERF97, and ERF98, and that ERF96 forms a cluster with ERF95 and ERF97. By using quantitative RT-PCR, we found that ERF96 is expressed in all tissues and organs examined except roots, with relatively high expression in flowers and seeds. Results from the protoplast transfection assay indicated that the EDLL motif-containing C-terminal domain is responsible for ERF96’s transcriptional activity. Although loss-of-function mutant of ERF96 was morphologically similar to wild type plants, transgenic plants overexpressing ERF96 had smaller rosette size and were delayed in flowering time. In ABA sensitivity assays, we found that ERF96 overexpression plants were hypersensitive to ABA in terms of ABA inhibition of seed germination, early seedling development and root elongation. Consistent with these observations, elevated transcript levels of some ABA-responsive genes including RD29A, ABI5, ABF3, ABF4, P5CS, and COR15A were observed in the transgenic plants in the presence of ABA. However, in the absence of ABA treatment, the transcript levels of these ABA-responsive genes remained largely unchanged. Our experiments also showed that water loss in ERF96 overexpression plants was slower than that in Col wild type plants. Stomatal closure assays indicated that ERF96 overexpression plants had reduced stomatal aperture in the presence of ABA. In conclusion, taken together, our results suggest that ERF96 positively regulates ABA responses in Arabidopsis.« less

The Small Ethylene Response Factor ERF96 is Involved in the Regulation of the Abscisic Acid Response in Arabidopsis

DOE PAGES

Wang, Xiaoping; Liu, Shanda; Tian, Hainan; ...

2015-11-26

We report that ethylene regulates many aspects of plant growth and development including seed germination, leaf senescence, and fruit ripening, and of plant responses to environmental stimuli including both biotic and abiotic stresses. Ethylene response factors (ERFs) are plant-specific transcription factors and are a subfamily of the AP2 (APETALA2)/ERF transcription factor family. The function of many members in this large gene family remains largely unknown. ERF96, a member of the Group IX ERF family transcription factors, has recently been shown to be a transcriptional activator that is involved in plant defense response in Arabidopsis. Here we provide evidence that ERF96more » is a positive regulator of abscisic acid (ABA) responses. Bioinformatics analysis indicated that there are a total four small ERFs in Arabidopsis including ERF95, ERF96, ERF97, and ERF98, and that ERF96 forms a cluster with ERF95 and ERF97. By using quantitative RT-PCR, we found that ERF96 is expressed in all tissues and organs examined except roots, with relatively high expression in flowers and seeds. Results from the protoplast transfection assay indicated that the EDLL motif-containing C-terminal domain is responsible for ERF96’s transcriptional activity. Although loss-of-function mutant of ERF96 was morphologically similar to wild type plants, transgenic plants overexpressing ERF96 had smaller rosette size and were delayed in flowering time. In ABA sensitivity assays, we found that ERF96 overexpression plants were hypersensitive to ABA in terms of ABA inhibition of seed germination, early seedling development and root elongation. Consistent with these observations, elevated transcript levels of some ABA-responsive genes including RD29A, ABI5, ABF3, ABF4, P5CS, and COR15A were observed in the transgenic plants in the presence of ABA. However, in the absence of ABA treatment, the transcript levels of these ABA-responsive genes remained largely unchanged. Our experiments also showed that water loss in ERF96 overexpression plants was slower than that in Col wild type plants. Stomatal closure assays indicated that ERF96 overexpression plants had reduced stomatal aperture in the presence of ABA. In conclusion, taken together, our results suggest that ERF96 positively regulates ABA responses in Arabidopsis.« less

Molecular predictors of therapeutic response to specific anti-cancer agents

DOEpatents

Spellman, Paul T.; Gray, Joe W.; Sadanandam, Anguraj; Heiser, Laura M.; Gibb, William J.; Kuo, Wen-lin; Wang, Nicholas J.

2016-11-29

Herein is described the use of a collection of 50 breast cancer cell lines to match responses to 77 conventional and experimental therapeutic agents with transcriptional, proteomic and genomic subtypes found in primary tumors. Almost all compounds produced strong differential responses across the cell lines produced responses that were associated with transcriptional and proteomic subtypes and produced responses that were associated with recurrent genome copy number abnormalities. These associations can now be incorporated into clinical trials that test subtype markers and clinical responses simultaneously.

Osmotic stress response in Acinetobacter baylyi: identification of a glycine-betaine biosynthesis pathway and regulation of osmoadaptive choline uptake and glycine-betaine synthesis through a choline-responsive BetI repressor.

PubMed

Scholz, Anica; Stahl, Julia; de Berardinis, Veronique; Müller, Volker; Averhoff, Beate

2016-04-01

Acinetobacter baylyi, a ubiquitous soil bacterium, can cope with high salinity by uptake of choline as precursor of the compatible solute glycine betaine. Here, we report on the identification of a choline dehydrogenase (BetA) and a glycine betaine aldehyde dehydrogenase (BetB) mediating the oxidation of choline to glycine betaine. The betAB genes were found to form an operon together with the potential transcriptional regulator betI. The transcription of the betIBA operon and the two recently identified choline transporters was upregulated in response to choline and choline plus salt. The finding that the osmo-independent transporter BetT1 undergoes a higher upregulation in response to choline alone than betT2 suggests that BetT1 does not primarily function in osmoadaptation. Electrophoretic mobility shift assays led to the conclusion that BetI mediates transcriptional regulation of both, the betIBA gene operon and the choline transporters. BetI was released from the DNA in response to choline which together with the transcriptional upregulation of the bet genes in the presence of choline suggests that BetI is a choline sensing transcriptional repressor. © 2016 Society for Applied Microbiology and John Wiley & Sons Ltd.

Mechanisms of specificity in neuronal activity-regulated gene transcription

PubMed Central

Lyons, Michelle R.; West, Anne E.

2011-01-01

The brain is a highly adaptable organ that is capable of converting sensory information into changes in neuronal function. This plasticity allows behavior to be accommodated to the environment, providing an important evolutionary advantage. Neurons convert environmental stimuli into long-lasting changes in their physiology in part through the synaptic activity-regulated transcription of new gene products. Since the neurotransmitter-dependent regulation of Fos transcription was first discovered nearly 25 years ago, a wealth of studies have enriched our understanding of the molecular pathways that mediate activity-regulated changes in gene transcription. These findings show that a broad range of signaling pathways and transcriptional regulators can be engaged by neuronal activity to sculpt complex programs of stimulus-regulated gene transcription. However, the shear scope of the transcriptional pathways engaged by neuronal activity raises the question of how specificity in the nature of the transcriptional response is achieved in order to encode physiologically relevant responses to divergent stimuli. Here we summarize the general paradigms by which neuronal activity regulates transcription while focusing on the molecular mechanisms that confer differential stimulus-, cell-type-, and developmental-specificity upon activity-regulated programs of neuronal gene transcription. In addition, we preview some of the new technologies that will advance our future understanding of the mechanisms and consequences of activity-regulated gene transcription in the brain. PMID:21620929

MUTATIONAL AND TRANSCRIPTIONAL RESPONSES OF SAMMONELLA TO MX: CORRELATION OF MUTATIONAL DOSE RESPONSE TO CHANGES IN GENE EXPRESSION

EPA Science Inventory

We measured the mutational and transcriptional response of Salmonella TA 100 to 3 concentrations of a drinking water mutagen -chloro-4-(dichloromethyl)-5-hydroxy2(5H)-furanone (MX). The mutagenicity of MX in strain TA100 was evaluated in a 30min suspension assay, and the mutageni...

A new age in AquaMedicine: unconventional approach in studying aquatic diseases.

PubMed

Gotesman, Michael; Menanteau-Ledouble, Simon; Saleh, Mona; Bergmann, Sven M; El-Matbouli, Mansour

2018-06-08

Marine and aquaculture industries are important sectors of the food production and global trade. Unfortunately, the fish food industry is challenged with a plethora of infectious pathogens. The freshwater and marine fish communities are rapidly incorporating novel and most up to date techniques for detection, characterization and treatment strategies. Rapid detection of infectious diseases is important in preventing large disease outbreaks. One hundred forty-six articles including reviews papers were analyzed and their conclusions evaluated in the present paper. This allowed us to describe the most recent development research regarding the control of diseases in the aquatic environment as well as promising avenues that may result in beneficial developments. For the characterization of diseases, traditional sequencing and histological based methods have been augmented with transcriptional and proteomic studies. Recent studies have demonstrated that transcriptional based approaches using qPCR are often synergistic to expression based studies that rely on proteomic-based techniques to better understand pathogen-host interactions. Preventative therapies that rely on prophylactics such as vaccination with protein antigens or attenuated viruses are not always feasible and therefore, the development of therapies based on small nucleotide based medicine is on the horizon. Of those, RNAi or CRISPR/Cas- based therapies show great promise in combating various types of diseases caused by viral and parasitic agents that effect aquatic and fish medicine. In our modern times, when the marine industry has become so vital for feed and economic stability, even the most extreme alternative treatment strategies such as the use of small molecules or even the use of disease to control invasive species populations should be considered.

HIF-1 and SKN-1 coordinate the transcriptional response to hydrogen sulfide in Caenorhabditis elegans.

PubMed

Miller, Dana L; Budde, Mark W; Roth, Mark B

2011-01-01

Hydrogen sulfide (H₂S) has dramatic physiological effects on animals that are associated with improved survival. C. elegans grown in H₂S are long-lived and thermotolerant. To identify mechanisms by which adaptation to H₂S effects physiological functions, we have measured transcriptional responses to H₂S exposure. Using microarray analysis we observe rapid changes in the abundance of specific mRNAs. The number and magnitude of transcriptional changes increased with the duration of H₂S exposure. Functional annotation suggests that genes associated with protein homeostasis are upregulated upon prolonged exposure to H₂S. Previous work has shown that the hypoxia-inducible transcription factor, HIF-1, is required for survival in H₂S. In fact, we show that hif-1 is required for most, if not all, early transcriptional changes in H₂S. Moreover, our data demonstrate that SKN-1, the C. elegans homologue of NRF2, also contributes to H₂S-dependent changes in transcription. We show that these results are functionally important, as skn-1 is essential to survive exposure to H₂S. Our results suggest a model in which HIF-1 and SKN-1 coordinate a broad transcriptional response to H₂S that culminates in a global reorganization of protein homeostasis networks.

Two novel male-associated peroxinectin genes are downregulated by exposure to delousing drugs in Caligus rogercresseyi.

PubMed

Núñez-Acuña, Gustavo; Gallardo-Escárate, Cristian

2015-02-15

Peroxinectin (PX) is a protein involved in cell adhesion, peroxidase activities, and the encapsulation of invaders in diverse species, including parasitic copepods. Recently, a transcript denoted peroxinectin-like was identified in the salmon louse Lepeophtheirus salmonis, and this was significantly correlated with the immune response of host fish. Thus, the PX gene is a potential candidate to evaluate host-parasite interactions, as well as to analyze responses to delousing drugs used in the salmon aquaculture industry worldwide. The objective of this study was to identify Peroxinectin transcripts in the Chilean salmon louse Caligus rogercresseyi, and to determine expression levels after exposition to the antiparasitics deltamethrin and azamethiphos. Two novel transcript homologs to peroxinectins were identified from a transcriptomic library of C. rogercresseyi. Moreover, in silico gene transcription levels were evaluated through RNA-seq analyses based on unique gene read levels in transcriptomic libraries that were constructed from sea lice exposed to delousing drugs. The identified transcripts were named Peroxinectin-Cr1 and Peroxinectin-Cr2, which, respectively, had lengths of 2543 and 2555 base pairs. Both PX transcripts were highly associated with male adults, and transcription levels were significantly reduced by deltamethrin and azamethiphos. This result suggests a modulation of peroxinectin in response to delousing drugs. Copyright © 2014 Elsevier B.V. All rights reserved.

A Framework for Fracture Network Formation in Overpressurised Impermeable Shale: Deformability Versus Diagenesis

NASA Astrophysics Data System (ADS)

Alevizos, Sotiris; Poulet, Thomas; Sari, Mustafa; Lesueur, Martin; Regenauer-Lieb, Klaus; Veveakis, Manolis

2017-03-01

Understanding the formation, geometry and fluid connectivity of nominally impermeable unconventional shale gas and oil reservoirs is crucial for safe unlocking of these vast energy resources. We present a recent discovery of volumetric instabilities of ductile materials that may explain why impermeable formations become permeable. Here, we present the fundamental mechanisms, the critical parameters and the applicability of the novel theory to unconventional reservoirs. We show that for a reservoir under compaction, there exist certain ambient and permeability conditions at which diagenetic (fluid-release) reactions may provoke channelling localisation instabilities. These channels are periodically interspersed in the matrix and represent areas where the excess fluid from the reaction is segregated at high velocity. We find that channelling instabilities are favoured from pore collapse features for extremely low-permeability formations and fluid-release diagenetic reactions, therefore providing a natural, periodic network of efficient fluid pathways in an otherwise impermeable matrix (i.e. fractures). Such an outcome is of extreme importance the for exploration and extraction phases of unconventional reservoirs.

Unconventional fermionic pairing states in a monochromatically tilted optical lattice

DOE PAGES

Nocera, Alberto; Polkovnikov, Anatoli; Feiguin, Adrian E.

2017-02-01

We study the one-dimensional attractive fermionic Hubbard model under the influence of periodic driving with the time-dependent density matrix renormalization group method. We show that the system can be driven into an unconventional pairing state characterized by a condensate made of Cooper pairs with a finite center-of-mass momentum similar to a Fulde-Ferrell state. We obtain results both in the laboratory and the rotating reference frames demonstrating that the momentum of the condensate can be finely tuned by changing the ratio between the amplitude and the frequency of the driving. In particular, by quenching this ratio to the value corresponding tomore » suppression of the tunneling and the Coulomb interaction strength to zero, we are able to “freeze” the condensate. We finally study the effects of different initial conditions and compare our numerical results to those obtained from a time-independent Floquet theory in the large frequency regime. Lastly, our work offers the possibility of engineering and controlling unconventional pairing states in fermionic condensates.« less

Superconductivity in the vicinity of antiferromagnetic order in CrAs.

PubMed

Wu, Wei; Cheng, Jinguang; Matsubayashi, Kazuyuki; Kong, Panpan; Lin, Fukun; Jin, Changqing; Wang, Nanlin; Uwatoko, Yoshiya; Luo, Jianlin

2014-11-19

One of the common features of unconventional superconducting systems such as the heavy-fermion, high transition-temperature cuprate and iron-pnictide superconductors is that the superconductivity emerges in the vicinity of long-range antiferromagnetically ordered state. In addition to doping charge carriers, the application of external pressure is an effective and clean approach to induce unconventional superconductivity near a magnetic quantum critical point. Here we report on the discovery of superconductivity on the verge of antiferromagnetic order in CrAs via the application of external pressure. Bulk superconductivity with Tc≈2 K emerges at the critical pressure Pc≈8 kbar, where the first-order antiferromagnetic transition at T(N)≈265 K under ambient pressure is completely suppressed. The close proximity of superconductivity to an antiferromagnetic order suggests an unconventional pairing mechanism for CrAs. The present finding opens a new avenue for searching novel superconductors in the Cr and other transition metal-based systems.

Unconventional Protein Secretion in Animal Cells.

PubMed

Ng, Fanny; Tang, Bor Luen

2016-01-01

All eukaryotic cells secrete a range of proteins in a constitutive or regulated manner through the conventional or canonical exocytic/secretory pathway characterized by vesicular traffic from the endoplasmic reticulum, through the Golgi apparatus, and towards the plasma membrane. However, a number of proteins are secreted in an unconventional manner, which are insensitive to inhibitors of conventional exocytosis and use a route that bypasses the Golgi apparatus. These include cytosolic proteins such as fibroblast growth factor 2 (FGF2) and interleukin-1β (IL-1β), and membrane proteins that are known to also traverse to the plasma membrane by a conventional process of exocytosis, such as α integrin and the cystic fibrosis transmembrane conductor (CFTR). Mechanisms underlying unconventional protein secretion (UPS) are actively being analyzed and deciphered, and these range from an unusual form of plasma membrane translocation to vesicular processes involving the generation of exosomes and other extracellular microvesicles. In this chapter, we provide an overview on what is currently known about UPS in animal cells.

Novel unconventional therapeutic approaches to atopic eczema.

PubMed

Worm, M; Henz, B M

2000-01-01

Atopic eczema is a chronic, recurrent, multifactorial skin disease, and, accordingly, there are numerous therapeutic options for its symptomatic treatment. Conventional medications are however often unsatisfactory for many patients because of adverse effects on long-term use. For this reason, patients often readily welcome unconventional therapeutic approaches. We present here a selected number of such treatment modalities, namely gamma-linolenic acid, Chinese herbal tea, diets eliminating allergens, pseudoallergens, metal salts and sodium, and bioresonance. When stringent scientific criteria are applied in the evaluation of such study results, none of the reviewed alternative treatments provides unequivocal, convincing evidence of its efficacy, even when double-blind, placebo-controlled studies are available. With Chinese herbal tea, potentially serious adverse effects should be considered as well. Any new type of unconventional therapy should thus be thoroughly evaluated and shown to be equal or superior to conventional treatments with regard to both efficacy and tolerability before it is recommended for use in clinical practice. Copyright 2000 S. Karger AG, Basel.

Ketamine and Imipramine Reverse Transcriptional Signatures of Susceptibility and Induce Resilience-Specific Gene Expression Profiles.

PubMed

Bagot, Rosemary C; Cates, Hannah M; Purushothaman, Immanuel; Vialou, Vincent; Heller, Elizabeth A; Yieh, Lynn; LaBonté, Benoit; Peña, Catherine J; Shen, Li; Wittenberg, Gayle M; Nestler, Eric J

2017-02-15

Examining transcriptional regulation by antidepressants in key neural circuits implicated in depression and understanding the relation to transcriptional mechanisms of susceptibility and natural resilience may help in the search for new therapeutic agents. Given the heterogeneity of treatment response in human populations, examining both treatment response and nonresponse is critical. We compared the effects of a conventional monoamine-based tricyclic antidepressant, imipramine, and a rapidly acting, non-monoamine-based antidepressant, ketamine, in mice subjected to chronic social defeat stress, a validated depression model, and used RNA sequencing to analyze transcriptional profiles associated with susceptibility, resilience, and antidepressant response and nonresponse in the prefrontal cortex (PFC), nucleus accumbens, hippocampus, and amygdala. We identified similar numbers of responders and nonresponders after ketamine or imipramine treatment. Ketamine induced more expression changes in the hippocampus; imipramine induced more expression changes in the nucleus accumbens and amygdala. Transcriptional profiles in treatment responders were most similar in the PFC. Nonresponse reflected both the lack of response-associated gene expression changes and unique gene regulation. In responders, both drugs reversed susceptibility-associated transcriptional changes and induced resilience-associated transcription in the PFC. We generated a uniquely large resource of gene expression data in four interconnected limbic brain regions implicated in depression and its treatment with imipramine or ketamine. Our analyses highlight the PFC as a key site of common transcriptional regulation by antidepressant drugs and in both reversing susceptibility- and inducing resilience-associated molecular adaptations. In addition, we found region-specific effects of each drug, suggesting both common and unique effects of imipramine versus ketamine. Copyright © 2016 Society of Biological Psychiatry. Published by Elsevier Inc. All rights reserved.

Hyperforin activates gene transcription involving transient receptor potential C6 channels.

PubMed

Thiel, Gerald; Rössler, Oliver G

2017-04-01

Hypericum perforatum is one of the most prominent medical plants. Hyperforin, a main ingredient of H. perforatum, has been shown to activate transient receptor potential canonical C6 (TRPC6) channels. Alternatively, it has been proposed that hyperforin functions as a protonophore in a TRPC6-independent manner. Here, we show that hyperforin stimulation activates the transcription factor AP-1 in HEK293 cells expressing TRPC6 (T6.11 cells), but did not substantially change the AP-1 activity in HEK293 cells lacking TRPC6. We identified the AP-1 binding site as a hyperforin-responsive element. AP-1 is composed of the transcription factors c-Jun and c-Fos, or other members of the c-Jun and c-Fos families of proteins. Hyperforin stimulation increased c-Jun and c-Fos promoter activities in T6.11 cells and induced an upregulation of c-Jun and c-Fos biosynthesis. The analysis of the c-Fos promoter revealed that the cAMP-response element also functions as a hyperforin-responsive element. Hyperforin-induced upregulation of AP-1 in T6.11 cells was attenuated by preincubation of the cells with either pregnenolone or progesterone, indicating that gene regulation via TRPC6 is under control of hormones or hormonal precursors. The signal transduction of hyperforin-induced AP-1 gene transcription required an influx of Ca 2+ ions into the cells, the activation of MAP kinases, and the activation of the transcription factors c-Jun and ternary complex factor. We conclude that hyperforin regulates gene transcription via activation of TRPC6 channels, involving stimulus-regulated protein kinases and stimulus-responsive transcription factors. The fact that hyperforin regulates gene transcription may explain many of the intracellular alterations induced by this compound. Copyright © 2017 Elsevier Inc. All rights reserved.

Deciphering the role of the signal- and Sty1 kinase-dependent phosphorylation of the stress-responsive transcription factor Atf1 on gene activation.

PubMed

Salat-Canela, Clàudia; Paulo, Esther; Sánchez-Mir, Laura; Carmona, Mercè; Ayté, José; Oliva, Baldo; Hidalgo, Elena

2017-08-18

Adaptation to stress triggers the most dramatic shift in gene expression in fission yeast ( Schizosaccharomyces pombe ), and this response is driven by signaling via the MAPK Sty1. Upon activation, Sty1 accumulates in the nucleus and stimulates expression of hundreds of genes via the nuclear transcription factor Atf1, including expression of atf1 itself. However, the role of stress-induced, Sty1-mediated Atf1 phosphorylation in transcriptional activation is unclear. To this end, we expressed Atf1 phosphorylation mutants from a constitutive promoter to uncouple Atf1 activity from endogenous, stress-activated Atf1 expression. We found that cells expressing a nonphosphorylatable Atf1 variant are sensitive to oxidative stress because of impaired transcription of a subset of stress genes whose expression is also controlled by another transcription factor, Pap1. Furthermore, cells expressing a phospho-mimicking Atf1 mutant display enhanced stress resistance, and although expression of the Pap1-dependent genes still relied on stress induction, another subset of stress-responsive genes was constitutively expressed in these cells. We also observed that, in cells expressing the phospho-mimicking Atf1 mutant, the presence of Sty1 was completely dispensable, with all stress defects of Sty1-deficient cells being suppressed by expression of the Atf1 mutant. We further demonstrated that Sty1-mediated Atf1 phosphorylation does not stimulate binding of Atf1 to DNA but, rather, establishes a platform of interactions with the basal transcriptional machinery to facilitate transcription initiation. In summary, our results provide evidence that Atf1 phosphorylation by the MAPK Sty1 is required for oxidative stress responses in fission yeast cells by promoting transcription initiation. © 2017 by The American Society for Biochemistry and Molecular Biology, Inc.

Alternative Splicing Control of Abiotic Stress Responses.

PubMed

Laloum, Tom; Martín, Guiomar; Duque, Paula

2018-02-01

Alternative splicing, which generates multiple transcripts from the same gene, is an important modulator of gene expression that can increase proteome diversity and regulate mRNA levels. In plants, this post-transcriptional mechanism is markedly induced in response to environmental stress, and recent studies have identified alternative splicing events that allow rapid adjustment of the abundance and function of key stress-response components. In agreement, plant mutants defective in splicing factors are severely impaired in their response to abiotic stress. Notably, mounting evidence indicates that alternative splicing regulates stress responses largely by targeting the abscisic acid (ABA) pathway. We review here current understanding of post-transcriptional control of plant stress tolerance via alternative splicing and discuss research challenges for the near future. Copyright © 2017 Elsevier Ltd. All rights reserved.

Auxin-Mediated Transcriptional System with a Minimal Set of Components Is Critical for Morphogenesis through the Life Cycle in Marchantia polymorpha

PubMed Central

Kato, Hirotaka; Ishizaki, Kimitsune; Kouno, Masaru; Shirakawa, Makoto; Bowman, John L.; Nishihama, Ryuichi; Kohchi, Takayuki

2015-01-01

The plant hormone auxin regulates many aspects of plant growth and development. Recent progress in Arabidopsis provided a scheme that auxin receptors, TIR1/AFBs, target transcriptional co-repressors, AUX/IAAs, for degradation, allowing ARFs to regulate transcription of auxin responsive genes. The mechanism of auxin-mediated transcriptional regulation is considered to have evolved around the time plants adapted to land. However, little is known about the role of auxin-mediated transcription in basal land plant lineages. We focused on the liverwort Marchantia polymorpha, which belongs to the earliest diverging lineage of land plants. M. polymorpha has only a single TIR1/AFB (MpTIR1), a single AUX/IAA (MpIAA), and three ARFs (MpARF1, MpARF2, and MpARF3) in the genome. Expression of a dominant allele of MpIAA with mutations in its putative degron sequence conferred an auxin resistant phenotype and repressed auxin-dependent expression of the auxin response reporter proGH3:GUS. We next established a system for DEX-inducible auxin-response repression by expressing the putatively stabilized MpIAA protein fused with the glucocorticoid receptor domain (MpIAAmDII-GR). Repression of auxin responses in proMpIAA:MpIAAmDII-GR plants caused severe defects in various developmental processes, including gemmaling development, dorsiventrality, organogenesis, and tropic responses. Transient transactivation assays showed that the three MpARFs had different transcriptional activities, each corresponding to their phylogenetic classifications. Moreover, MpIAA and MpARF proteins interacted with each other with different affinities. This study provides evidence that pleiotropic auxin responses can be achieved by a minimal set of auxin signaling factors and suggests that the transcriptional regulation mediated by TIR1/AFB, AUX/IAA, and three types of ARFs might have been a key invention to establish body plans of land plants. We propose that M. polymorpha is a good model to investigate the principles and the evolution of auxin-mediated transcriptional regulation and its roles in land plant morphogenesis. PMID:26020919

Auxin-Mediated Transcriptional System with a Minimal Set of Components Is Critical for Morphogenesis through the Life Cycle in Marchantia polymorpha.

PubMed

Kato, Hirotaka; Ishizaki, Kimitsune; Kouno, Masaru; Shirakawa, Makoto; Bowman, John L; Nishihama, Ryuichi; Kohchi, Takayuki

2015-05-01

The plant hormone auxin regulates many aspects of plant growth and development. Recent progress in Arabidopsis provided a scheme that auxin receptors, TIR1/AFBs, target transcriptional co-repressors, AUX/IAAs, for degradation, allowing ARFs to regulate transcription of auxin responsive genes. The mechanism of auxin-mediated transcriptional regulation is considered to have evolved around the time plants adapted to land. However, little is known about the role of auxin-mediated transcription in basal land plant lineages. We focused on the liverwort Marchantia polymorpha, which belongs to the earliest diverging lineage of land plants. M. polymorpha has only a single TIR1/AFB (MpTIR1), a single AUX/IAA (MpIAA), and three ARFs (MpARF1, MpARF2, and MpARF3) in the genome. Expression of a dominant allele of MpIAA with mutations in its putative degron sequence conferred an auxin resistant phenotype and repressed auxin-dependent expression of the auxin response reporter proGH3:GUS. We next established a system for DEX-inducible auxin-response repression by expressing the putatively stabilized MpIAA protein fused with the glucocorticoid receptor domain (MpIAA(mDII)-GR). Repression of auxin responses in (pro)MpIAA:MpIAA(mDII)-GR plants caused severe defects in various developmental processes, including gemmaling development, dorsiventrality, organogenesis, and tropic responses. Transient transactivation assays showed that the three MpARFs had different transcriptional activities, each corresponding to their phylogenetic classifications. Moreover, MpIAA and MpARF proteins interacted with each other with different affinities. This study provides evidence that pleiotropic auxin responses can be achieved by a minimal set of auxin signaling factors and suggests that the transcriptional regulation mediated by TIR1/AFB, AUX/IAA, and three types of ARFs might have been a key invention to establish body plans of land plants. We propose that M. polymorpha is a good model to investigate the principles and the evolution of auxin-mediated transcriptional regulation and its roles in land plant morphogenesis.

Transcriptional Repression of ATF4 Gene by CCAAT/Enhancer-binding Protein β (C/EBPβ) Differentially Regulates Integrated Stress Response*

PubMed Central

Dey, Souvik; Savant, Sudha; Teske, Brian F.; Hatzoglou, Maria; Calkhoven, Cornelis F.; Wek, Ronald C.

2012-01-01

Different environmental stresses induce the phosphorylation of eIF2 (eIF2∼P), repressing global protein synthesis coincident with preferential translation of ATF4. ATF4 is a transcriptional activator of genes involved in metabolism and nutrient uptake, antioxidation, and regulation of apoptosis. Because ATF4 is a common downstream target that integrates signaling from different eIF2 kinases and their respective stress signals, the eIF2∼P/ATF4 pathway is collectively referred to as the integrated stress response. Although eIF2∼P elicits translational control in response to many different stresses, there are selected stresses, such as exposure to UV irradiation, that do not increase ATF4 expression despite robust eIF2∼P. The rationale for this discordant induction of ATF4 expression and eIF2∼P in response to UV irradiation is that transcription of ATF4 is repressed, and therefore ATF4 mRNA is not available for preferential translation. In this study, we show that C/EBPβ is a transcriptional repressor of ATF4 during UV stress. C/EBPβ binds to critical elements in the ATF4 promoter, resulting in its transcriptional repression. Expression of C/EBPβ increases in response to UV stress, and the liver-enriched inhibitory protein (LIP) isoform of C/EBPβ, but not the liver-enriched activating protein (LAP) version, represses ATF4 transcription. Loss of the liver-enriched inhibitory protein isoform results in increased ATF4 mRNA levels in response to UV irradiation and subsequent recovery of ATF4 translation, leading to enhanced expression of its target genes. Together these results illustrate how eIF2∼P and translational control combined with transcription factors regulated by alternative signaling pathways can direct programs of gene expression that are specifically tailored to each environmental stress. PMID:22556424

Shale gas development effects on the songbird community in a central Appalachian forest

USGS Publications Warehouse

Farwell, Laura S.; Wood, Petra; Sheehan, James; George, Gregory A.

2016-01-01

In the last decade, unconventional drilling for natural gas from the Marcellus-Utica shale has increased exponentially in the central Appalachians. This heavily forested region contains important breeding habitat for many neotropical migratory songbirds, including several species of conservation concern. Our goal was to examine effects of unconventional gas development on forest habitat and breeding songbirds at a predominantly forested site from 2008 to 2015. Construction of gas well pads and infrastructure (e.g., roads, pipelines) contributed to an overall 4.5% loss in forest cover at the site, a 12.4% loss in core forest, and a 51.7% increase in forest edge density. We evaluated the relationship between land-cover metrics and species richness within three avian guilds: forest-interior, early-successional, and synanthropic, in addition to abundances of 21 focal species. Land-cover impacts were evaluated at two spatial extents: a point-level within 100-m and 500-m buffers of each avian survey station, and a landscape-level across the study area (4326 ha). Although we observed variability in species-specific responses, we found distinct trends in long-term response among the three avian guilds. Forest-interior guild richness declined at all points across the site and at points impacted within 100 m by shale gas but did not change at unimpacted points. Early-successional and synanthropic guild richness increased at all points and at impacted points. Our results suggest that shale gas development has the potential to fragment regional forests and alter avian communities, and that efforts to minimize new development in core forests will reduce negative impacts to forest dependent species.

Assessment of the Performance Potential of Advanced Subsonic Transport Concepts for NASA's Environmentally Responsible Aviation Project

NASA Technical Reports Server (NTRS)

Nickol, Craig L.; Haller, William J.

2016-01-01

NASA's Environmentally Responsible Aviation (ERA) project has matured technologies to enable simultaneous reductions in fuel burn, noise, and nitrogen oxide (NOx) emissions for future subsonic commercial transport aircraft. The fuel burn reduction target was a 50% reduction in block fuel burn (relative to a 2005 best-in-class baseline aircraft), utilizing technologies with an estimated Technology Readiness Level (TRL) of 4-6 by 2020. Progress towards this fuel burn reduction target was measured through the conceptual design and analysis of advanced subsonic commercial transport concepts spanning vehicle size classes from regional jet (98 passengers) to very large twin aisle size (400 passengers). Both conventional tube-and-wing (T+W) concepts and unconventional (over-wing-nacelle (OWN), hybrid wing body (HWB), mid-fuselage nacelle (MFN)) concepts were developed. A set of propulsion and airframe technologies were defined and integrated onto these advanced concepts which were then sized to meet the baseline mission requirements. Block fuel burn performance was then estimated, resulting in reductions relative to the 2005 best-in-class baseline performance ranging from 39% to 49%. The advanced single-aisle and large twin aisle T+W concepts had reductions of 43% and 41%, respectively, relative to the 737-800 and 777-200LR aircraft. The single-aisle OWN concept and the large twin aisle class HWB concept had reductions of 45% and 47%, respectively. In addition to their estimated fuel burn reduction performance, these unconventional concepts have the potential to provide significant noise reductions due, in part, to engine shielding provided by the airframe. Finally, all of the advanced concepts also have the potential for significant NOx emissions reductions due to the use of advanced combustor technology. Noise and NOx emissions reduction estimates were also generated for these concepts as part of the ERA project.

Arabidopsis transcriptional responses differentiating closely related chemicals (herbicides) and cross-species extrapolation to Brassica

EPA Science Inventory

Using whole genome Affymetrix ATH1 GeneChips we characterized the transcriptional response of Arabidopsis thaliana Columbia 24 hours after treatment with five different herbicides. Four of them (chloransulam, imazapyr, primisulfuron, sulfometuron) inhibit acetolactate synthase (A...

TRANSCRIPTIONAL RESPONSES OF MOUSE EMBRYO CULTURES EXPOSED TO BROMOCHLOROACETIC ACID

EPA Science Inventory

Transcriptional responses of mouse embryo cultures exposed to bromochloroacetic acid

Edward D. Karoly?*, Judith E. Schmid* and E. Sidney Hunter III*
?Curriculum in Toxicology, University of North Carolina at Chapel Hill, Chapel Hill, North Carolina and *Reproductive Tox...

The NAC transcription factor family in maritime pine (Pinus Pinaster): molecular regulation of two genes involved in stress responses.

PubMed

Pascual, Ma Belén; Cánovas, Francisco M; Ávila, Concepción

2015-10-24

NAC transcription factors comprise a large plant-specific gene family involved in the regulation of diverse biological processes. Despite the growing number of studies on NAC transcription factors in various species, little information is available about this family in conifers. The goal of this study was to identify the NAC transcription family in maritime pine (Pinus pinaster), to characterize ATAF-like genes in response to various stresses and to study their molecular regulation. We have isolated two maritime pine NAC genes and using a transient expression assay in N. benthamiana leaves estudied the promoter jasmonate response. In this study, we identified 37 NAC genes from maritime pine and classified them into six main subfamilies. The largest group includes 12 sequences corresponding to stress-related genes. Two of these NAC genes, PpNAC2 and PpNAC3, were isolated and their expression profiles were examined at various developmental stages and in response to various types of stress. The expression of both genes was strongly induced by methyl jasmonate (MeJA), mechanical wounding, and high salinity. The promoter regions of these genes were shown to contain cis-elements involved in the stress response and plant hormonal regulation, including E-boxes, which are commonly found in the promoters of genes that respond to jasmonate, and binding sites for bHLH proteins. Using a transient expression assay in N. benthamiana leaves, we found that the promoter of PpNAC3 was rapidly induced upon MeJA treatment, while this response disappeared in plants in which the transcription factor NbbHLH2 was silenced. Our results suggest that PpNAC2 and PpNAC3 encode stress-responsive NAC transcription factors involved in the jasmonate response in pine. Furthermore, these data also suggest that the jasmonate signaling pathway is conserved between angiosperms and gymnosperms. These findings may be useful for engineering stress tolerance in pine via biotechnological approaches.

Long Non-Coding RNAs Responsive to Salt and Boron Stress in the Hyper-Arid Lluteño Maize from Atacama Desert.

PubMed

Huanca-Mamani, Wilson; Arias-Carrasco, Raúl; Cárdenas-Ninasivincha, Steffany; Rojas-Herrera, Marcelo; Sepúlveda-Hermosilla, Gonzalo; Caris-Maldonado, José Carlos; Bastías, Elizabeth; Maracaja-Coutinho, Vinicius

2018-03-20

Long non-coding RNAs (lncRNAs) have been defined as transcripts longer than 200 nucleotides, which lack significant protein coding potential and possess critical roles in diverse cellular processes. Long non-coding RNAs have recently been functionally characterized in plant stress-response mechanisms. In the present study, we perform a comprehensive identification of lncRNAs in response to combined stress induced by salinity and excess of boron in the Lluteño maize, a tolerant maize landrace from Atacama Desert, Chile. We use deep RNA sequencing to identify a set of 48,345 different lncRNAs, of which 28,012 (58.1%) are conserved with other maize (B73, Mo17 or Palomero), with the remaining 41.9% belonging to potentially Lluteño exclusive lncRNA transcripts. According to B73 maize reference genome sequence, most Lluteño lncRNAs correspond to intergenic transcripts. Interestingly, Lluteño lncRNAs presents an unusual overall higher expression compared to protein coding genes under exposure to stressed conditions. In total, we identified 1710 putatively responsive to the combined stressed conditions of salt and boron exposure. We also identified a set of 848 stress responsive potential trans natural antisense transcripts ( trans -NAT) lncRNAs, which seems to be regulating genes associated with regulation of transcription, response to stress, response to abiotic stimulus and participating of the nicotianamine metabolic process. Reverse transcription-quantitative PCR (RT-qPCR) experiments were performed in a subset of lncRNAs, validating their existence and expression patterns. Our results suggest that a diverse set of maize lncRNAs from leaves and roots is responsive to combined salt and boron stress, being the first effort to identify lncRNAs from a maize landrace adapted to extreme conditions such as the Atacama Desert. The information generated is a starting point to understand the genomic adaptabilities suffered by this maize to surpass this extremely stressed environment.

Long Non-Coding RNAs Responsive to Salt and Boron Stress in the Hyper-Arid Lluteño Maize from Atacama Desert

PubMed Central

Huanca-Mamani, Wilson; Arias-Carrasco, Raúl; Cárdenas-Ninasivincha, Steffany; Rojas-Herrera, Marcelo; Sepúlveda-Hermosilla, Gonzalo; Caris-Maldonado, José Carlos; Bastías, Elizabeth; Maracaja-Coutinho, Vinicius

2018-01-01

Long non-coding RNAs (lncRNAs) have been defined as transcripts longer than 200 nucleotides, which lack significant protein coding potential and possess critical roles in diverse cellular processes. Long non-coding RNAs have recently been functionally characterized in plant stress–response mechanisms. In the present study, we perform a comprehensive identification of lncRNAs in response to combined stress induced by salinity and excess of boron in the Lluteño maize, a tolerant maize landrace from Atacama Desert, Chile. We use deep RNA sequencing to identify a set of 48,345 different lncRNAs, of which 28,012 (58.1%) are conserved with other maize (B73, Mo17 or Palomero), with the remaining 41.9% belonging to potentially Lluteño exclusive lncRNA transcripts. According to B73 maize reference genome sequence, most Lluteño lncRNAs correspond to intergenic transcripts. Interestingly, Lluteño lncRNAs presents an unusual overall higher expression compared to protein coding genes under exposure to stressed conditions. In total, we identified 1710 putatively responsive to the combined stressed conditions of salt and boron exposure. We also identified a set of 848 stress responsive potential trans natural antisense transcripts (trans-NAT) lncRNAs, which seems to be regulating genes associated with regulation of transcription, response to stress, response to abiotic stimulus and participating of the nicotianamine metabolic process. Reverse transcription-quantitative PCR (RT-qPCR) experiments were performed in a subset of lncRNAs, validating their existence and expression patterns. Our results suggest that a diverse set of maize lncRNAs from leaves and roots is responsive to combined salt and boron stress, being the first effort to identify lncRNAs from a maize landrace adapted to extreme conditions such as the Atacama Desert. The information generated is a starting point to understand the genomic adaptabilities suffered by this maize to surpass this extremely stressed environment. PMID:29558449

Bipartite functions of the CREB co-activators selectively direct alternative splicing or transcriptional activation

PubMed Central

Amelio, Antonio L; Caputi, Massimo; Conkright, Michael D

2009-01-01

The CREB regulated transcription co-activators (CRTCs) regulate many biological processes by integrating and converting environmental inputs into transcriptional responses. Although the mechanisms by which CRTCs sense cellular signals are characterized, little is known regarding how CRTCs contribute to the regulation of cAMP inducible genes. Here we show that these dynamic regulators, unlike other co-activators, independently direct either pre-mRNA splice-site selection or transcriptional activation depending on the cell type or promoter context. Moreover, in other scenarios, the CRTC co-activators coordinately regulate transcription and splicing. Mutational analyses showed that CRTCs possess distinct functional domains responsible for regulating either pre-mRNA splicing or transcriptional activation. Interestingly, the CRTC1–MAML2 oncoprotein lacks the splicing domain and is incapable of altering splice-site selection despite robustly activating transcription. The differential usage of these distinct domains allows CRTCs to selectively mediate multiple facets of gene regulation, indicating that co-activators are not solely restricted to coordinating alternative splicing with increase in transcriptional activity. PMID:19644446

Photochromic molecular implementations of universal computation.

PubMed

Chaplin, Jack C; Krasnogor, Natalio; Russell, Noah A

2014-12-01

Unconventional computing is an area of research in which novel materials and paradigms are utilised to implement computation. Previously we have demonstrated how registers, logic gates and logic circuits can be implemented, unconventionally, with a biocompatible molecular switch, NitroBIPS, embedded in a polymer matrix. NitroBIPS and related molecules have been shown elsewhere to be capable of modifying many biological processes in a manner that is dependent on its molecular form. Thus, one possible application of this type of unconventional computing is to embed computational processes into biological systems. Here we expand on our earlier proof-of-principle work and demonstrate that universal computation can be implemented using NitroBIPS. We have previously shown that spatially localised computational elements, including registers and logic gates, can be produced. We explain how parallel registers can be implemented, then demonstrate an application of parallel registers in the form of Turing machine tapes, and demonstrate both parallel registers and logic circuits in the form of elementary cellular automata. The Turing machines and elementary cellular automata utilise the same samples and same hardware to implement their registers, logic gates and logic circuits; and both represent examples of universal computing paradigms. This shows that homogenous photochromic computational devices can be dynamically repurposed without invasive reconfiguration. The result represents an important, necessary step towards demonstrating the general feasibility of interfacial computation embedded in biological systems or other unconventional materials and environments. Copyright © 2014 The Authors. Published by Elsevier Ireland Ltd.. All rights reserved.

Cigarette smokers' use of unconventional tobacco products and associations with quitting activity: findings from the ITC-4 U.S. cohort.

PubMed

Kasza, Karin A; Bansal-Travers, Maansi; O'Connor, Richard J; Compton, Wilson M; Kettermann, Anna; Borek, Nicolette; Fong, Geoffrey T; Cummings, K Michael; Hyland, Andrew J

2014-06-01

The purpose of this study was to evaluate the prevalence and correlates of use of nicotine-containing tobacco products such as cigars, pipe tobacco, and cigarettes that promise less exposure to toxins; e-cigarettes; and smokeless tobacco products among a cohort of conventional cigarette smokers followed over the past decade. We also evaluated associations between use of such products and cigarette quitting. Participants were 6,110 adult smokers in the United States, who were interviewed as part of the International Tobacco Control Four Country Survey between 2002 and 2011. Respondents reported their concurrent use of other smoked tobacco products (including cigars, pipe tobacco, and cigarillos), smokeless tobacco products (including chewing tobacco, snus, and snuff), unconventional cigarettes (including Omni, Accord, and Eclipse), and electronic cigarettes. Prevalence and correlates of use and associations between use and cigarette quitting were assessed using regression analyses via generalized estimating equations. Most cigarette smokers did not use unconventional tobacco products, although use of any of these products started to rise at the end of the study period (2011). For each type of tobacco product evaluated, use was most prevalent among those aged 18-24 years. Smokers who did use unconventional tobacco products did not experience a clear cessation advantage. During the past decade, relatively few cigarette smokers reported also using other tobacco products. Those that did use such products were no more likely to stop using conventional cigarettes compared with those who did not use such products.

DNA replication checkpoint promotes G1-S transcription by inactivating the MBF repressor Nrm1

PubMed Central

de Bruin, R. A. M.; Kalashnikova, T. I.; Aslanian, A.; Wohlschlegel, J.; Chahwan, C.; Yates, J. R.; Russell, P.; Wittenberg, C.

2008-01-01

The cell cycle transcriptional program imposes order on events of the cell-cycle and is a target for signals that regulate cell-cycle progression, including checkpoints required to maintain genome integrity. Neither the mechanism nor functional significance of checkpoint regulation of the cell-cycle transcription program are established. We show that Nrm1, an MBF-specific transcriptional repressor acting at the transition from G1 to S phase of the cell cycle, is at the nexus between the cell cycle transcriptional program and the DNA replication checkpoint in fission yeast. Phosphorylation of Nrm1 by the Cds1 (Chk2) checkpoint protein kinase, which is activated in response to DNA replication stress, promotes its dissociation from the MBF transcription factor. This leads to the expression of genes encoding components that function in DNA replication and repair pathways important for cell survival in response to arrested DNA replication. PMID:18682565

Hypercholesterolemia potentiates aortic endothelial response to inhaled diesel exhaust

PubMed Central

Maresh, J. Gregory; Campen, Matthew J.; Reed, Matthew D.; Darrow, April L.; Shohet, Ralph V.

2012-01-01

Background Inhalation of diesel exhaust induces vascular effects including impaired endothelial function and increased atherosclerosis. Objective To examine the in vivo effects of subchronic diesel exhaust exposure on endothelial cell transcriptional responses in the presence of hypercholesterolemia. Methods ApoE (−/−) and ApoE (+/+) mice inhaled diesel exhaust diluted to particulate matter levels of 300 or 1000 μg/m3 vs. filtered air. After 30 days, endothelial cells were harvested from dispersed aortic cells by fluorescent-activated cell sorting (FACS). Relative mRNA abundance was evaluated by microarray analysis to measure strain-specific transcriptional responses in mice exposed to dilute diesel exhaust vs. filtered air. Results Forty-nine transcripts were significantly dysregulated by >2.8-fold in the endothelium of ApoE (−/−) mice receiving diesel exhaust at 300 or 1000 μg/m3. These included transcripts with roles in plasminogen activation, endothelial permeability, inflammation, genomic stability, and atherosclerosis; similar responses were not observed in ApoE (+/+) mice. Conclusions The potentiation of diesel exhaust-related endothelial gene regulation by hypercholesterolemia helps to explain air pollution-induced vascular effects in animals and humans. The observed regulated transcripts implicate pathways important in the acceleration of atherosclerosis by air pollution. PMID:21222557

Cross-talk between freezing response and signaling for regulatory transcriptions of MIR475b and its targets by miR475b promoter in Populus suaveolens

PubMed Central

Niu, Jun; Wang, Jia; Hu, Huiwen; Chen, Yinlei; An, Jiyong; Cai, Jian; Sun, Runze; Sheng, Zhongting; Liu, Xieping; Lin, Shanzhi

2016-01-01

MicroRNAs (miRNAs) are small, non-coding RNAs that play important roles in post-transcriptional regulation of their target genes, yet the transcriptional regulation of plant miRNAs by promoter is poorly understood. Here, we firstly clone pri-miR475b cDNA and its native promoter from P. suaveolens, and characterize Psu-MIR475b as class-II gene transcribed by RNA polymerase II. By 5′ deletion analysis of Psu-miR475b promoter in a series of promoter-GUS chimeric vectors, we functionally identify three positive regulatory regions and multiple cis-acting elements responsible for Psu-miR475b promoter activity in response to freezing stress and exogenous hormone treatment. Moreover, the Psu-miR475b promoter activity displays a tissue-specific manner, negatively regulated by freezing stress and positively by MeJA, SA or GA treatment. Importantly, we comparatively analyze the time-course transcriptional profiles of Psu-miR475b and its targets in Psu-miR475b over-expression transgenic plants controlled by Psu-miR475b-specific promoter or CaMV 35S constitutive promoter, and explore the regulatory mechanism of Psu-miR475b promoter controlling transcriptional expressions of Psu-MIR475b and its targets in response to freezing stress and exogenous hormone treatment. Our results reveal that Psu-miR475b promoter-mediated transcriptions of Psu-MIR475b and its targets in response to freezing stress may be involved in a cross-talk between freezing response and stress signaling process. PMID:26853706

Differential epigenetic and transcriptional response of the skeletal muscle carnitine palmitoyltransferase 1B (CPT1B) gene to lipid exposure with obesity

PubMed Central

Maples, Jill M.; Brault, Jeffrey J.; Witczak, Carol A.; Park, Sanghee; Hubal, Monica J.; Weber, Todd M.; Houmard, Joseph A.

2015-01-01

The ability to increase fatty acid oxidation (FAO) in response to dietary lipid is impaired in the skeletal muscle of obese individuals, which is associated with a failure to coordinately upregulate genes involved with FAO. While the molecular mechanisms contributing to this metabolic inflexibility are not evident, a possible candidate is carnitine palmitoyltransferase-1B (CPT1B), which is a rate-limiting step in FAO. The present study was undertaken to determine if the differential response of skeletal muscle CPT1B gene transcription to lipid between lean and severely obese subjects is linked to epigenetic modifications (DNA methylation and histone acetylation) that impact transcriptional activation. In primary human skeletal muscle cultures the expression of CPT1B was blunted in severely obese women compared with their lean counterparts in response to lipid, which was accompanied by changes in CpG methylation, H3/H4 histone acetylation, and peroxisome proliferator-activated receptor-δ and hepatocyte nuclear factor 4α transcription factor occupancy at the CPT1B promoter. Methylation of specific CpG sites in the CPT1B promoter that correlated with CPT1B transcript level blocked the binding of the transcription factor upstream stimulatory factor, suggesting a potential causal mechanism. These findings indicate that epigenetic modifications may play important roles in the regulation of CPT1B in response to a physiologically relevant lipid mixture in human skeletal muscle, a major site of fatty acid catabolism, and that differential DNA methylation may underlie the depressed expression of CPT1B in response to lipid, contributing to the metabolic inflexibility associated with severe obesity. PMID:26058865

Transcriptional Dynamics Driving MAMP-Triggered Immunity and Pathogen Effector-Mediated Immunosuppression in Arabidopsis Leaves Following Infection with Pseudomonas syringae pv tomato DC3000[OPEN

PubMed Central

Lewis, Laura A.; Polanski, Krzysztof; de Torres-Zabala, Marta; Bowden, Laura; Jenkins, Dafyd J.; Hill, Claire; Baxter, Laura; Truman, William; Prusinska, Justyna; Hickman, Richard; Wild, David L.; Ott, Sascha; Buchanan-Wollaston, Vicky; Beynon, Jim

2015-01-01

Transcriptional reprogramming is integral to effective plant defense. Pathogen effectors act transcriptionally and posttranscriptionally to suppress defense responses. A major challenge to understanding disease and defense responses is discriminating between transcriptional reprogramming associated with microbial-associated molecular pattern (MAMP)-triggered immunity (MTI) and that orchestrated by effectors. A high-resolution time course of genome-wide expression changes following challenge with Pseudomonas syringae pv tomato DC3000 and the nonpathogenic mutant strain DC3000hrpA- allowed us to establish causal links between the activities of pathogen effectors and suppression of MTI and infer with high confidence a range of processes specifically targeted by effectors. Analysis of this information-rich data set with a range of computational tools provided insights into the earliest transcriptional events triggered by effector delivery, regulatory mechanisms recruited, and biological processes targeted. We show that the majority of genes contributing to disease or defense are induced within 6 h postinfection, significantly before pathogen multiplication. Suppression of chloroplast-associated genes is a rapid MAMP-triggered defense response, and suppression of genes involved in chromatin assembly and induction of ubiquitin-related genes coincide with pathogen-induced abscisic acid accumulation. Specific combinations of promoter motifs are engaged in fine-tuning the MTI response and active transcriptional suppression at specific promoter configurations by P. syringae. PMID:26566919

Transcriptional Dynamics Driving MAMP-Triggered Immunity and Pathogen Effector-Mediated Immunosuppression in Arabidopsis Leaves Following Infection with Pseudomonas syringae pv tomato DC3000.

PubMed

Lewis, Laura A; Polanski, Krzysztof; de Torres-Zabala, Marta; Jayaraman, Siddharth; Bowden, Laura; Moore, Jonathan; Penfold, Christopher A; Jenkins, Dafyd J; Hill, Claire; Baxter, Laura; Kulasekaran, Satish; Truman, William; Littlejohn, George; Prusinska, Justyna; Mead, Andrew; Steinbrenner, Jens; Hickman, Richard; Rand, David; Wild, David L; Ott, Sascha; Buchanan-Wollaston, Vicky; Smirnoff, Nick; Beynon, Jim; Denby, Katherine; Grant, Murray

2015-11-01

Transcriptional reprogramming is integral to effective plant defense. Pathogen effectors act transcriptionally and posttranscriptionally to suppress defense responses. A major challenge to understanding disease and defense responses is discriminating between transcriptional reprogramming associated with microbial-associated molecular pattern (MAMP)-triggered immunity (MTI) and that orchestrated by effectors. A high-resolution time course of genome-wide expression changes following challenge with Pseudomonas syringae pv tomato DC3000 and the nonpathogenic mutant strain DC3000hrpA- allowed us to establish causal links between the activities of pathogen effectors and suppression of MTI and infer with high confidence a range of processes specifically targeted by effectors. Analysis of this information-rich data set with a range of computational tools provided insights into the earliest transcriptional events triggered by effector delivery, regulatory mechanisms recruited, and biological processes targeted. We show that the majority of genes contributing to disease or defense are induced within 6 h postinfection, significantly before pathogen multiplication. Suppression of chloroplast-associated genes is a rapid MAMP-triggered defense response, and suppression of genes involved in chromatin assembly and induction of ubiquitin-related genes coincide with pathogen-induced abscisic acid accumulation. Specific combinations of promoter motifs are engaged in fine-tuning the MTI response and active transcriptional suppression at specific promoter configurations by P. syringae. © 2015 American Society of Plant Biologists. All rights reserved.

DNA Methylation and Demethylation in Plant Immunity.

PubMed

Deleris, A; Halter, T; Navarro, L

2016-08-04

Detection of plant and animal pathogens triggers a massive transcriptional reprogramming, which is directed by chromatin-based processes, and ultimately results in antimicrobial immunity. Although the implication of histone modifications in orchestrating biotic stress-induced transcriptional reprogramming has been well characterized, very little was known, until recently, about the role of DNA methylation and demethylation in this process. In this review, we summarize recent findings on the dynamics and biological relevance of DNA methylation and demethylation in plant immunity against nonviral pathogens. In particular, we report the implications of these epigenetic regulatory processes in the transcriptional and co-transcriptional control of immune-responsive genes and discuss their relevance in fine-tuning antimicrobial immune responses. Finally, we discuss the possible yet elusive role of DNA methylation and demethylation in systemic immune responses, transgenerational immune priming, and de novo epiallelism, which could be adaptive.

Transcriptional and post-transcriptional regulation of the ionizing radiation response by ATM and p53

PubMed Central

Venkata Narayanan, Ishwarya; Paulsen, Michelle T.; Bedi, Karan; Berg, Nathan; Ljungman, Emily A.; Francia, Sofia; Veloso, Artur; Magnuson, Brian; di Fagagna, Fabrizio d’Adda; Wilson, Thomas E.; Ljungman, Mats

2017-01-01

In response to ionizing radiation (IR), cells activate a DNA damage response (DDR) pathway to re-program gene expression. Previous studies using total cellular RNA analyses have shown that the stress kinase ATM and the transcription factor p53 are integral components required for induction of IR-induced gene expression. These studies did not distinguish between changes in RNA synthesis and RNA turnover and did not address the role of enhancer elements in DDR-mediated transcriptional regulation. To determine the contribution of synthesis and degradation of RNA and monitor the activity of enhancer elements following exposure to IR, we used the recently developed Bru-seq, BruChase-seq and BruUV-seq techniques. Our results show that ATM and p53 regulate both RNA synthesis and stability as well as enhancer element activity following exposure to IR. Importantly, many genes in the p53-signaling pathway were coordinately up-regulated by both increased synthesis and RNA stability while down-regulated genes were suppressed either by reduced synthesis or stability. Our study is the first of its kind that independently assessed the effects of ionizing radiation on transcription and post-transcriptional regulation in normal human cells. PMID:28256581

GmSBH1, a homeobox transcription factor gene, relates to growth and development and involves in response to high temperature and humidity stress in soybean.

PubMed

Shu, Yingjie; Tao, Yuan; Wang, Shuang; Huang, Liyan; Yu, Xingwang; Wang, Zhankui; Chen, Ming; Gu, Weihong; Ma, Hao

2015-11-01

GmSBH1 involves in response to high temperature and humidity stress. Homeobox transcription factors are key switches that control plant development processes. Glycine max H1 Sbh1 (GmSBH1) was the first homeobox gene isolated from soybean. In the present study, the full ORF of GmSBH1 was isolated, and the encoded protein was found to be a typical class I KNOX homeobox transcription factor. Subcellular localization and transcriptional activation assays showed that GmSBH1 is a nuclear protein and possesses transcriptional activation activity in the homeodomain. The KNOX1 domain was found to play a clear role in suppressing the transcriptional activation activity of GmSBH1. GmSBH1 showed different expression levels among different soybean tissues and was involved in response to high temperature and humidity (HTH) stress in developing soybean seeds. The overexpression of GmSBH1 in Arabidopsis altered leaf and stoma phenotypes and enhanced seed tolerance to HTH stress. Overall, our results indicated that GmSBH1 is involved in growth, development, and enhances tolerance to pre-harvest seed deterioration caused by HTH stress in soybean.

MUTATIONAL AND TRANSCRIPTIONAL RESPONSE OF SALMONELLA TO MX: CORRELATION OF MUTATIONAL DOSE RESPONSE TO CHANGES IN GENE EXPRESSION

EPA Science Inventory

We measured the mutational and transcriptional response of Salmonella TA100 to 3 concentrations of the drinking water mutagen 3-chloro-4-(dichloromethyl)-5-hydroxy2(5H)-furanone (MX). The mutagenicity of MX in strain TA100 was evaluated in a 30min suspension assay, and the mutage...

MUTATIONAL AND TRANSCRIPTIONAL RESPONSES OF STATIONARY- AND LOGARITHMIC-PHASE SALMONELLA TO MX: CORRELATION OF MUTATIONAL RESPONSE TO CHANGES IN GENE EXPRESSION

EPA Science Inventory

We measured the mutational and transcriptional response of stationary-phase and logarithmic-phase S. typhimurium TA100 to 3 concentrations of the drinking water mutagen 3-chloro-4-(dichloromethyl)-5-hydroxy-2(5H)-furanone (MX). The mutagenicity of MX in strain TA100 was evaluated...

The Serum Response Factor and a Putative Novel Transcription Factor Regulate Expression of the Immediate-Early Gene Arc/Arg3.1 in Cultured Cortical Neurons

PubMed Central

Pintchovski, Sean A.; Peebles, Carol L.; Kim, Hong Joo; Verdin, Eric; Finkbeiner, Steven

2010-01-01

The immediate-early effector gene Arc/Arg3.1 is robustly upregulated by synaptic activity associated with learning and memory. Here we show in primary cortical neuron culture that diverse stimuli induce Arc expression through new transcription. Searching for regulatory regions important for Arc transcription, we found nine DNaseI-sensitive nucleosome-depleted sites at this genomic locus. A reporter gene encompassing these sites responded to synaptic activity in an NMDA receptor–dependent manner, consistent with endogenous Arc mRNA. Responsiveness mapped to two enhancer regions ∼6.5 kb and ∼1.4 kb upstream of Arc. We dissected these regions further and found that the proximal enhancer contains a functional and conserved “Zeste-like” response element that binds a putative novel nuclear protein in neurons. Therefore, activity regulates Arc transcription partly by a novel signaling pathway. We also found that the distal enhancer has a functional and highly conserved serum response element. This element binds serum response factor, which is recruited by synaptic activity to regulate Arc. Thus, Arc is the first target of serum response factor that functions at synapses to mediate plasticity. PMID:19193899

Recent behavioral history modifies coupling between cell activity and Arc gene transcription in hippocampal CA1 neurons.

PubMed

Guzowski, John F; Miyashita, Teiko; Chawla, Monica K; Sanderson, Jennifer; Maes, Levi I; Houston, Frank P; Lipa, Peter; McNaughton, Bruce L; Worley, Paul F; Barnes, Carol A

2006-01-24

The ability of neurons to alter their transcriptional programs in response to synaptic input is of fundamental importance to the neuroplastic mechanisms underlying learning and memory. Because of technical limitations of conventional gene detection methods, the current view of activity-dependent neural transcription derives from experiments in which neurons are assumed quiescent until a signaling stimulus is given. The present study was designed to move beyond this static model by examining how earlier episodes of neural activity influence transcription of the immediate-early gene Arc. Using a sensitive FISH method that detects primary transcript at genomic alleles, the proportion of hippocampal CA1 neurons that activate transcription of Arc RNA was constant at approximately 40% in response to both a single novel exploration session and daily sessions repeated over 9 days. This proportion is similar to the percentage of active neurons defined electrophysiologically. However, this close correspondence was disrupted in rats exposed briefly, but repeatedly, to the same environment within a single day. Arc transcription in CA1 neurons declined dramatically after as few as four 5-min sessions, despite stable electrophysiological activity during all sessions. Additional experiments indicate that the decrement in Arc transcription occurred at the cellular, rather than synaptic level, and was not simply linked to habituation to novelty. Thus, the neural genomic response is governed by recent, but not remote, cell firing history in the behaving animal. This state-dependence of neuronal transcriptional coupling provides a mechanism of metaplasticity and may regulate capacity for synaptic modification in neural networks.

Arabidopsis transcriptional responses differentiate between O3 and herbicides

EPA Science Inventory

Using published data based on Affymetrix ATH1 Gene-Chips we characterized the transcriptional response of Arabidopsis thaliana Columbia to O3 and a few other major environmental stresses including oxidative stress . A set of 101 markers could be extracted which provided a compo...

Genome-wide analysis of alternative splicing during dendritic cell response to a bacterial challenge.

PubMed

Rodrigues, Raquel; Grosso, Ana Rita; Moita, Luís

2013-01-01

The immune system relies on the plasticity of its components to produce appropriate responses to frequent environmental challenges. Dendritic cells (DCs) are critical initiators of innate immunity and orchestrate the later and more specific adaptive immunity. The generation of diversity in transcriptional programs is central for effective immune responses. Alternative splicing is widely considered a key generator of transcriptional and proteomic complexity, but its role has been rarely addressed systematically in immune cells. Here we used splicing-sensitive arrays to assess genome-wide gene- and exon-level expression profiles in human DCs in response to a bacterial challenge. We find widespread alternative splicing events and splicing factor transcriptional signatures induced by an E. coli challenge to human DCs. Alternative splicing acts in concert with transcriptional modulation, but these two mechanisms of gene regulation affect primarily distinct functional gene groups. Alternative splicing is likely to have an important role in DC immunobiology because it affects genes known to be involved in DC development, endocytosis, antigen presentation and cell cycle arrest.

Transcriptional regulation of PIN genes by FOUR LIPS and MYB88 during Arabidopsis root gravitropism.

PubMed

Wang, Hong-Zhe; Yang, Ke-Zhen; Zou, Jun-Jie; Zhu, Ling-Ling; Xie, Zi Dian; Morita, Miyo Terao; Tasaka, Masao; Friml, Jiří; Grotewold, Erich; Beeckman, Tom; Vanneste, Steffen; Sack, Fred; Le, Jie

2015-11-18

PIN proteins are auxin export carriers that direct intercellular auxin flow and in turn regulate many aspects of plant growth and development including responses to environmental changes. The Arabidopsis R2R3-MYB transcription factor FOUR LIPS (FLP) and its paralogue MYB88 regulate terminal divisions during stomatal development, as well as female reproductive development and stress responses. Here we show that FLP and MYB88 act redundantly but differentially in regulating the transcription of PIN3 and PIN7 in gravity-sensing cells of primary and lateral roots. On the one hand, FLP is involved in responses to gravity stimulation in primary roots, whereas on the other, FLP and MYB88 function complementarily in establishing the gravitropic set-point angles of lateral roots. Our results support a model in which FLP and MYB88 expression specifically determines the temporal-spatial patterns of PIN3 and PIN7 transcription that are closely associated with their preferential functions during root responses to gravity.

Meta-analysis of published transcriptional and translational fold changes reveals a preference for low-fold inductions.

PubMed

Wren, Jonathan D; Conway, Tyrrell

2006-01-01

The goals of this study were to gain a better quantitative understanding of the dynamic range of transcriptional and translational response observed in biological systems and to examine the reporting of regulatory events for trends and biases. A straightforward pattern-matching routine extracted 3,408 independent observations regarding transcriptional fold-changes and 1,125 regarding translational fold-changes from over 15 million MEDLINE abstracts. Approximately 95% of reported changes were > or =2-fold. Further, the historical trend of reporting individual fold-changes is declining in favor of high-throughput methods for transcription but not translation. Where it was possible to compare the average fold-changes in transcription and translation for the same gene/product (203 examples), approximately 53% were a < or =2-fold difference, suggesting a loose tendency for the two to be coupled in magnitude. We found also that approximately three-fourths of reported regulatory events have been at the transcriptional level. The frequency distribution appears to be normally distributed and peaks near 2-fold, suggesting that nature selects for a low-energy solution to regulatory responses. Because high-throughput technologies ordinarily sacrifice measurement quality for quantity, this also suggests that many regulatory events may not be reliably detectable by such technologies. Text mining of regulatory events and responses provides additional information incorporable into microarray analysis, such as prior fold-change observations and flagging genes that are regulated post-transcription. All extracted regulation and response patterns can be downloaded at the following website: www.ou.edu/microarray/ oumcf/Meta_analysis.xls.

Global transcriptomic analysis of the response of Corynebacterium glutamicum to ferulic acid.

PubMed

Chen, Can; Pan, Junfeng; Yang, Xiaobing; Xiao, He; Zhang, Yaoling; Si, Meiru; Shen, Xihui; Wang, Yao

2017-03-01

Corynebacterium glutamicum can survive by using ferulic acid as the sole carbon source. In this study, we assessed the response of C. glutamicum to ferulic acid stress by means of a global transcriptional response analysis. The transcriptional data showed that several genes involved in degradation of ferulic acid were affected. Moreover, several genes related to the stress response; protein protection or degradation and DNA repair; replication, transcription and translation; and the cell envelope were differentially expressed. Deletion of the katA or sigE gene in C. glutamicum resulted in a decrease in cell viability under ferulic acid stress. These insights will facilitate further engineering of model industrial strains, with enhanced tolerance to ferulic acid to enable easy production of biofuels from lignocellulose.

Uncovering the Role of RNA-Binding Proteins in Gene Expression in the Immune System.

PubMed

Díaz-Muñoz, Manuel D; Turner, Martin

2018-01-01

Fighting external pathogens requires an ever-changing immune system that relies on tight regulation of gene expression. Transcriptional control is the first step to build efficient responses while preventing immunodeficiencies and autoimmunity. Post-transcriptional regulation of RNA editing, location, stability, and translation are the other key steps for final gene expression, and they are all controlled by RNA-binding proteins (RBPs). Nowadays we have a deep understanding of how transcription factors control the immune system but recent evidences suggest that post-transcriptional regulation by RBPs is equally important for both development and activation of immune responses. Here, we review current knowledge about how post-transcriptional control by RBPs shapes our immune system and discuss the perspective of RBPs being the key players of a hidden immune cell epitranscriptome.

HSP70 and heat shock factor 1 cooperate to repress Ras-induced transcriptional activation of the c-fos gene.

PubMed

He, H; Chen, C; Xie, Y; Asea, A; Calderwood, S K

2000-11-01

Heat shock protein 70 (HSP70) is a molecular chaperone involved in protein folding and resistance to the deleterious effects of stress. Here we show that HSP70 suppresses transcription of c-fos, an early response gene that is a key component of the ubiquitous AP-1 transcription factor complex. HSP70 repressed Ras-induced c-fos transcription only in the presence of functional heat shock factor1 (HSF1). This suggests that HSP70 functions as a corepressor with HSF1 to inhibit c-fos gene transcription. Therefore, besides its known function in the stress response, HSP70 also has the property of a corepressor and combines with HSF1 to antagonize Fos expression and may thus impact multiple aspects of cell regulation.

Nitrogen stress response and stringent response are coupled in Escherichia coli

PubMed Central

Brown, Daniel R.; Barton, Geraint; Pan, Zhensheng; Buck, Martin; Wigneshweraraj, Sivaramesh

2014-01-01

Assimilation of nitrogen is an essential process in bacteria. The nitrogen regulation stress response is an adaptive mechanism used by nitrogen-starved Escherichia coli to scavenge for alternative nitrogen sources and requires the global transcriptional regulator NtrC. In addition, nitrogen-starved E. coli cells synthesize a signal molecule, guanosine tetraphosphate (ppGpp), which serves as an effector molecule of many processes including transcription to initiate global physiological changes, collectively termed the stringent response. The regulatory mechanisms leading to elevated ppGpp levels during nutritional stresses remain elusive. Here, we show that transcription of relA, a key gene responsible for the synthesis of ppGpp, is activated by NtrC during nitrogen starvation. The results reveal that NtrC couples these two major bacterial stress responses to manage conditions of nitrogen limitation, and provide novel mechanistic insights into how a specific nutritional stress leads to elevating ppGpp levels in bacteria. PMID:24947454

Bacteria-Triggered Systemic Immunity in Barley Is Associated with WRKY and ETHYLENE RESPONSIVE FACTORs But Not with Salicylic Acid1[C][W

PubMed Central

Dey, Sanjukta; Wenig, Marion; Langen, Gregor; Sharma, Sapna; Kugler, Karl G.; Knappe, Claudia; Hause, Bettina; Bichlmeier, Marlies; Babaeizad, Valiollah; Imani, Jafargholi; Janzik, Ingar; Stempfl, Thomas; Hückelhoven, Ralph; Kogel, Karl-Heinz; Mayer, Klaus F.X.

2014-01-01

Leaf-to-leaf systemic immune signaling known as systemic acquired resistance is poorly understood in monocotyledonous plants. Here, we characterize systemic immunity in barley (Hordeum vulgare) triggered after primary leaf infection with either Pseudomonas syringae pathovar japonica (Psj) or Xanthomonas translucens pathovar cerealis (Xtc). Both pathogens induced resistance in systemic, uninfected leaves against a subsequent challenge infection with Xtc. In contrast to systemic acquired resistance in Arabidopsis (Arabidopsis thaliana), systemic immunity in barley was not associated with NONEXPRESSOR OF PATHOGENESIS-RELATED GENES1 or the local or systemic accumulation of salicylic acid. Instead, we documented a moderate local but not systemic induction of abscisic acid after infection of leaves with Psj. In contrast to salicylic acid or its functional analog benzothiadiazole, local applications of the jasmonic acid methyl ester or abscisic acid triggered systemic immunity to Xtc. RNA sequencing analysis of local and systemic transcript accumulation revealed unique gene expression changes in response to both Psj and Xtc and a clear separation of local from systemic responses. The systemic response appeared relatively modest, and quantitative reverse transcription-polymerase chain reaction associated systemic immunity with the local and systemic induction of two WRKY and two ETHYLENE RESPONSIVE FACTOR (ERF)-like transcription factors. Systemic immunity against Xtc was further associated with transcriptional changes after a secondary/systemic Xtc challenge infection; these changes were dependent on the primary treatment. Taken together, bacteria-induced systemic immunity in barley may be mediated in part by WRKY and ERF-like transcription factors, possibly facilitating transcriptional reprogramming to potentiate immunity. PMID:25332505

Genome-wide microarray analysis of tomato roots showed defined responses to iron deficiency

PubMed Central

2012-01-01

Background Plants react to iron deficiency stress adopting different kind of adaptive responses. Tomato, a Strategy I plant, improves iron uptake through acidification of rhizosphere, reduction of Fe3+ to Fe2+ and transport of Fe2+ into the cells. Large-scale transcriptional analyses of roots under iron deficiency are only available for a very limited number of plant species with particular emphasis for Arabidopsis thaliana. Regarding tomato, an interesting model species for Strategy I plants and an economically important crop, physiological responses to Fe-deficiency have been thoroughly described and molecular analyses have provided evidence for genes involved in iron uptake mechanisms and their regulation. However, no detailed transcriptome analysis has been described so far. Results A genome-wide transcriptional analysis, performed with a chip that allows to monitor the expression of more than 25,000 tomato transcripts, identified 97 differentially expressed transcripts by comparing roots of Fe-deficient and Fe-sufficient tomato plants. These transcripts are related to the physiological responses of tomato roots to the nutrient stress resulting in an improved iron uptake, including regulatory aspects, translocation, root morphological modification and adaptation in primary metabolic pathways, such as glycolysis and TCA cycle. Other genes play a role in flavonoid biosynthesis and hormonal metabolism. Conclusions The transcriptional characterization confirmed the presence of the previously described mechanisms to adapt to iron starvation in tomato, but also allowed to identify other genes potentially playing a role in this process, thus opening new research perspectives to improve the knowledge on the tomato root response to the nutrient deficiency. PMID:22433273

H3K27me3 and H3K4me3 chromatin environment at super-induced dehydration stress memory genes of Arabidopsis thaliana.

PubMed

Liu, Ning; Fromm, Michael; Avramova, Zoya

2014-03-01

Pre-exposure to a stress may alter the plant's cellular, biochemical, and/or transcriptional responses during future encounters as a 'memory' from the previous stress. Genes increasing transcription in response to a first dehydration stress, but producing much higher transcript levels in a subsequent stress, represent the super-induced 'transcription memory' genes in Arabidopsis thaliana. The chromatin environment (histone H3 tri-methylations of Lys 4 and Lys 27, H3K4me3, and H3K27me3) studied at five dehydration stress memory genes revealed existence of distinct memory-response subclasses that responded differently to CLF deficiency and displayed different transcriptional activities during the watered recovery periods. Among the most important findings is the novel aspect of the H3K27me3 function observed at specific dehydration stress memory genes. In contrast to its well-known role as a chromatin repressive mechanism at developmentally regulated genes, H3K27me3 did not prevent transcription from the dehydration stress-responding genes. The high H3K27me3 levels present during transcriptionally inactive states did not interfere with the transition to active transcription and with H3K4me3 accumulation. H3K4me3 and H3K27me3 marks function independently and are not mutually exclusive at the dehydration stress-responding memory genes.

Basic helix-loop-helix transcription factors JASMONATE-ASSOCIATED MYC2-LIKE1 (JAM1), JAM2, and JAM3 are negative regulators of jasmonate responses in Arabidopsis.

PubMed

Sasaki-Sekimoto, Yuko; Jikumaru, Yusuke; Obayashi, Takeshi; Saito, Hikaru; Masuda, Shinji; Kamiya, Yuji; Ohta, Hiroyuki; Shirasu, Ken

2013-09-01

Jasmonates regulate transcriptional reprogramming during growth, development, and defense responses. Jasmonoyl-isoleucine, an amino acid conjugate of jasmonic acid (JA), is perceived by the protein complex composed of the F-box protein CORONATINE INSENSITIVE1 (COI1) and JASMONATE ZIM DOMAIN (JAZ) proteins, leading to the ubiquitin-dependent degradation of JAZ proteins. This activates basic helix-loop-helix-type MYC transcription factors to regulate JA-responsive genes. Here, we show that the expression of genes encoding other basic helix-loop-helix transcription factors, JASMONATE ASSOCIATED MYC2-LIKE1 (JAM1), JAM2, and JAM3, is positively regulated in a COI1- and MYC2-dependent manner in Arabidopsis (Arabidopsis thaliana). However, contrary to myc2, the jam1jam2jam3 triple mutant exhibited shorter roots when treated with methyl jasmonate (MJ), indicating enhanced responsiveness to JA. Our genome-wide expression analyses revealed that key jasmonate metabolic genes as well as a set of genes encoding transcription factors that regulate the JA-responsive metabolic genes are negatively regulated by JAMs after MJ treatment. Consistently, loss of JAM genes resulted in higher accumulation of anthocyanin in MJ-treated plants as well as higher accumulation of JA and 12-hydroxyjasmonic acid in wounded plants. These results show that JAMs negatively regulate the JA responses in a manner that is mostly antagonistic to MYC2.

Basic Helix-Loop-Helix Transcription Factors JASMONATE-ASSOCIATED MYC2-LIKE1 (JAM1), JAM2, and JAM3 Are Negative Regulators of Jasmonate Responses in Arabidopsis1[W][OPEN

PubMed Central

Sasaki-Sekimoto, Yuko; Jikumaru, Yusuke; Obayashi, Takeshi; Saito, Hikaru; Masuda, Shinji; Kamiya, Yuji; Ohta, Hiroyuki; Shirasu, Ken

2013-01-01

Jasmonates regulate transcriptional reprogramming during growth, development, and defense responses. Jasmonoyl-isoleucine, an amino acid conjugate of jasmonic acid (JA), is perceived by the protein complex composed of the F-box protein CORONATINE INSENSITIVE1 (COI1) and JASMONATE ZIM DOMAIN (JAZ) proteins, leading to the ubiquitin-dependent degradation of JAZ proteins. This activates basic helix-loop-helix-type MYC transcription factors to regulate JA-responsive genes. Here, we show that the expression of genes encoding other basic helix-loop-helix transcription factors, JASMONATE ASSOCIATED MYC2-LIKE1 (JAM1), JAM2, and JAM3, is positively regulated in a COI1- and MYC2-dependent manner in Arabidopsis (Arabidopsis thaliana). However, contrary to myc2, the jam1jam2jam3 triple mutant exhibited shorter roots when treated with methyl jasmonate (MJ), indicating enhanced responsiveness to JA. Our genome-wide expression analyses revealed that key jasmonate metabolic genes as well as a set of genes encoding transcription factors that regulate the JA-responsive metabolic genes are negatively regulated by JAMs after MJ treatment. Consistently, loss of JAM genes resulted in higher accumulation of anthocyanin in MJ-treated plants as well as higher accumulation of JA and 12-hydroxyjasmonic acid in wounded plants. These results show that JAMs negatively regulate the JA responses in a manner that is mostly antagonistic to MYC2. PMID:23852442

Heat shock cognate 71 (HSC71) regulates cellular antiviral response by impairing formation of VISA aggregates.

PubMed

Liu, Zhigang; Wu, Shu-Wen; Lei, Cao-Qi; Zhou, Qian; Li, Shu; Shu, Hong-Bing; Wang, Yan-Yi

2013-05-01

In response to viral infection, RIG-I-like RNA helicases detect viral RNA and signal through the mitochondrial adapter protein VISA. VISA activation leads to rapid activation of transcription factors IRF3 and NF-κB, which collaborate to induce transcription of type I interferon (IFN) genes and cellular antiviral response. It has been demonstrated that VISA is activated by forming prion-like aggregates. However, how this process is regulated remains unknown. Here we show that overexpression of HSC71 resulted in potent inhibition of virus-triggered transcription of IFNB1 gene and cellular antiviral response. Consistently, knockdown of HSC71 had opposite effects. HSC71 interacted with VISA, and negatively regulated virus-triggered VISA aggregation. These findings suggest that HSC71 functions as a check against VISA-mediated antiviral response.

ALTERED TRANSCRIPTIONAL RESPONSES OF MOUSE EMBRYO CULTURES EXPOSED TO BISINDOLYLMALEIMIDE (BIS L)

EPA Science Inventory

Altered transcriptional responses in mouse embryos exposed to bisindolylmaleimide I (Bis I) in whole embryo culture

Edward D. Karoly?*, Judith E. Schmid*, Maria R. Blanton*and E. Sidney Hunter III*
?Curriculum in Toxicology, University of North Carolina at Chapel Hill, ...

SAGE ANALYSIS OF TRANSCRIPTOME RESPONSES IN ARABIDOPSIS ROOTS EXPOSED TO 2,4,6-TRINITROTOLUENE

EPA Science Inventory

Serial Analysis of Gene Expression (SAGE) was used to profile transcript levels in Arabidopsis thaliana roots and assess their responses to 2,4,6-trinitrotoluene (TNT) exposure. SAGE libraries representing control and TNT-exposed seedling root transcripts were constructed, and ea...

Transcriptional switches in the control of macronutrient metabolism.

PubMed

Wise, Alan

2008-06-01

This review shows how some transcription factors respond to alterations in macronutrients. Carbohydrates induce enzymes for their metabolism and fatty acid synthesis. Fatty acids reduce carbohydrate processing, induce enzymes for their metabolism, and increase both gluconeogenesis and storage of fat. Fat stores help control carbohydrate uptake by other cells. The following main transcription factors are discussed: carbohydrate response element-binding protein; sterol regulatory element-binding protein-1c, cyclic AMP response element-binding protein, peroxisome proliferator-activated receptor-alpha, and peroxisome proliferator-activated receptor-gamma.

Use of DNA Microarrays to Identify Diagnostic Signature Transcription Profiles for Host Responses to Infectious Agents

DTIC Science & Technology

2004-10-01

informative in this regard. Key signature genes will serve as the basis for rapid diagnostic approaches that could be accessed when an outbreak is suspected...AD Award Number: DAMD17-01-1-0787 TITLE: Use of DNA Microarrays to Identify Diagnostic Signature Transcription Profiles for Host Responses to...Sep 2004) 4. TITLE AND SUBTITLE 5. FUNDING NUMBERS Use of DNA Microarrays to Identify Diagnostic Signature DAMD17-01-1-0787 Transcription Profiles for

Tapping methane hydrates for unconventional natural gas

USGS Publications Warehouse

Ruppel, Carolyn

2007-01-01

Methane hydrate is an icelike form of concentrated methane and water found in the sediments of permafrost regions and marine continental margins at depths far shallower than conventional oil and gas. Despite their relative accessibility and widespread occurrence, methane hydrates have never been tapped to meet increasing global energy demands. With rising natural gas prices, production from these unconventional gas deposits is becoming economically viable, particularly in permafrost areas already being exploited for conventional oil and gas. This article provides an overview of gas hydrate occurrence, resource assessment, exploration, production technologies, renewability, and future challenges.

Water quality studied in areas of unconventional oil and gas development, including areas where hydraulic fracturing techniques are used, in the United States

USGS Publications Warehouse

Susong, David D.; Gallegos, Tanya J.; Oelsner, Gretchen P.

2012-01-01

The U.S. Geological Survey (USGS) John Wesley Powell Center for Analysis and Synthesis is hosting an interdisciplinary working group of USGS scientists to conduct a temporal and spatial analysis of surface-water and groundwater quality in areas of unconventional oil and gas development. The analysis uses existing national and regional datasets to describe water quality, evaluate water-quality changes over time where there are sufficient data, and evaluate spatial and temporal data gaps.

NR and High-Throughput Screening: Putting the Pieces Together Chemicals

EPA Science Inventory

Nuclear receptors (NR) are one of the most abundant classes of transcriptional regulators in animals and function as ligand-activated transcription factors. They provide a direct link between signaling molecules and transcriptional responses that impact diverse functions includin...

Genome-wide characterization and expression analysis enables identification of abiotic stress-responsive MYB transcription factors in cassava (Manihot esculenta).

PubMed

Ruan, Meng-Bin; Guo, Xin; Wang, Bin; Yang, Yi-Ling; Li, Wen-Qi; Yu, Xiao-Ling; Zhang, Peng; Peng, Ming

2017-06-15

The myeloblastosis (MYB) transcription factor superfamily is the largest transcription factor family in plants, playing different roles during stress response. However, abiotic stress-responsive MYB transcription factors have not been systematically studied in cassava (Manihot esculenta), an important tropical tuber root crop. In this study, we used a genome-wide transcriptome analysis to predict 299 putative MeMYB genes in the cassava genome. Under drought and cold stresses, many MeMYB genes exhibited different expression patterns in cassava leaves, indicating that these genes might play a role in abiotic stress responses. We found that several stress-responsive MeMYB genes responded to abscisic acid (ABA) in cassava leaves. We characterize four MeMYBs, namely MeMYB1, MeMYB2, MeMYB4, and MeMYB9, as R2R3-MYB transcription factors. Furthermore, RNAi-driven repression of MeMYB2 resulted in drought and cold tolerance in transgenic cassava. Gene expression assays in wild-type and MeMYB2-RNAi cassava plants revealed that MeMYB2 may affect other MeMYBs as well as MeWRKYs under drought and cold stress, suggesting crosstalk between MYB and WRKY family genes under stress conditions in cassava. © The Author 2017. Published by Oxford University Press on behalf of the Society for Experimental Biology. All rights reserved. For permissions, please email: journals.permissions@oup.com.

Bartonella quintana Deploys Host and Vector Temperature-Specific Transcriptomes

PubMed Central

Previte, Domenic; Yoon, Kyong S.; Clark, J. Marshall; DeRisi, Joseph L.; Koehler, Jane E.

2013-01-01

The bacterial pathogen Bartonella quintana is passed between humans by body lice. B. quintana has adapted to both the human host and body louse vector niches, producing persistent infection with high titer bacterial loads in both the host (up to 105 colony-forming units [CFU]/ml) and vector (more than 108 CFU/ml). Using a novel custom microarray platform, we analyzed bacterial transcription at temperatures corresponding to the host (37°C) and vector (28°C), to probe for temperature-specific and growth phase-specific transcriptomes. We observed that transcription of 7% (93 genes) of the B. quintana genome is modified in response to change in growth phase, and that 5% (68 genes) of the genome is temperature-responsive. Among these transcriptional changes in response to temperature shift and growth phase was the induction of known B. quintana virulence genes and several previously unannotated genes. Hemin binding proteins, secretion systems, response regulators, and genes for invasion and cell attachment were prominent among the differentially-regulated B. quintana genes. This study represents the first analysis of global transcriptional responses by B. quintana. In addition, the in vivo experiments provide novel insight into the B. quintana transcriptional program within the body louse environment. These data and approaches will facilitate study of the adaptation mechanisms employed by Bartonella during the transition between human host and arthropod vector. PMID:23554923

Activation of the unfolded protein response during anoxia exposure in the turtle Trachemys scripta elegans.

PubMed

Krivoruchko, Anastasia; Storey, Kenneth B

2013-02-01

Red-eared slider turtles, Trachemys scripta elegans, can survive for several weeks without oxygen when submerged in cold water. We hypothesized that anaerobiosis is aided by adaptive up-regulation of the unfolded protein response (UPR), a stress-responsive pathway that is activated by accumulation of unfolded proteins in the endoplasmic reticulum (ER) and functions to restore ER homeostasis. RT-PCR, western immunoblotting and DNA-binding assays were used to quantify the responses and/or activation status of UPR-responsive genes and proteins in turtle tissues after animal exposure to 5 or 20 h of anoxic submergence at 4 °C. The phosphorylation state of protein kinase-like ER kinase (PERK) (a UPR-regulated kinase) and eukaryotic initiation factor 2 (eIF2α) increased by 1.43-2.50 fold in response to anoxia in turtle heart, kidney, and liver. Activation of the PERK-regulated transcription factor, activating transcription factor 4 (ATF4), during anoxia was documented by elevated atf4 transcripts and total ATF4 protein (1.60-2.43 fold), increased nuclear ATF4 content, and increased DNA-binding activity (1.44-2.32 fold). ATF3 and GADD34 (downstream targets of ATF4) also increased by 1.38-3.32 fold in heart and liver under anoxia, and atf3 transcripts were also elevated in heart. Two characteristic chaperones of the UPR, GRP78, and GRP94, also responded positively to anoxia with strong increases in both the transcript and protein levels. The data demonstrate that the UPR is activated in turtle heart, kidney, and liver in response to anoxia, suggesting that this pathway mediates an integrated stress response to protect tissues during oxygen deprivation.

UV-B-Responsive Association of the Arabidopsis bZIP Transcription Factor ELONGATED HYPOCOTYL5 with Target Genes, Including Its Own Promoter[W][OPEN

PubMed Central

Binkert, Melanie; Kozma-Bognár, László; Terecskei, Kata; De Veylder, Lieven; Nagy, Ferenc; Ulm, Roman

2014-01-01

In plants subjected to UV-B radiation, responses are activated that minimize damage caused by UV-B. The bZIP transcription factor ELONGATED HYPOCOTYL5 (HY5) acts downstream of the UV-B photoreceptor UV RESISTANCE LOCUS8 (UVR8) and promotes UV-B-induced photomorphogenesis and acclimation. Expression of HY5 is induced by UV-B; however, the transcription factor(s) that regulate HY5 transcription in response to UV-B and the impact of UV-B on the association of HY5 with its target promoters are currently unclear. Here, we show that HY5 binding to the promoters of UV-B-responsive genes is enhanced by UV-B in a UVR8-dependent manner in Arabidopsis thaliana. In agreement, overexpression of REPRESSOR OF UV-B PHOTOMORPHOGENESIS2, a negative regulator of UVR8 function, blocks UV-B-responsive HY5 enrichment at target promoters. Moreover, we have identified a T/G-box in the HY5 promoter that is required for its UV-B responsiveness. We show that HY5 and its homolog HYH bind to the T/GHY5-box cis-acting element and that they act redundantly in the induction of HY5 expression upon UV-B exposure. Therefore, HY5 is enriched at target promoters in response to UV-B in a UVR8 photoreceptor-dependent manner, and HY5 and HYH interact directly with a T/G-box cis-acting element of the HY5 promoter, mediating the transcriptional activation of HY5 in response to UV-B. PMID:25351492

Superconductivity mediated by quantum critical antiferromagnetic fluctuations: The rise and fall of hot spots

NASA Astrophysics Data System (ADS)

Wang, Xiaoyu; Schattner, Yoni; Berg, Erez; Fernandes, Rafael M.

2017-05-01

In several unconventional superconductors, the highest superconducting transition temperature Tc is found in a region of the phase diagram where the antiferromagnetic transition temperature extrapolates to zero, signaling a putative quantum critical point. The elucidation of the interplay between these two phenomena—high-Tc superconductivity and magnetic quantum criticality—remains an important piece of the complex puzzle of unconventional superconductivity. In this paper, we combine sign-problem-free quantum Monte Carlo simulations and field-theoretical analytical calculations to unveil the microscopic mechanism responsible for the superconducting instability of a general low-energy model, called the spin-fermion model. In this approach, low-energy electronic states interact with each other via the exchange of quantum critical magnetic fluctuations. We find that even in the regime of moderately strong interactions, both the superconducting transition temperature and the pairing susceptibility are governed not by the properties of the entire Fermi surface, but instead by the properties of small portions of the Fermi surface called hot spots. Moreover, Tc increases with increasing interaction strength, until it starts to saturate at the crossover from hot-spots-dominated to Fermi-surface-dominated pairing. Our work provides not only invaluable insights into the system parameters that most strongly affect Tc, but also important benchmarks to assess the origin of superconductivity in both microscopic models and actual materials.

A survey of practice patterns in the use of laryngeal mask by pediatric anesthesiologists.

PubMed

Patel, Anuradha; Clark, Scott R; Schiffmiller, Moshe; Schoenberg, Catherine; Tewfik, George

2015-11-01

Laryngeal mask is frequently the airway device of choice in routine general anesthesia for many procedures in children. Several studies have described the use of laryngeal masks in unconventional situations. This survey was undertaken to assess how laryngeal masks are being used by pediatric anesthesiologists. The 40-question electronic survey using SurveyMonkey™ was sent to 2740 members of the Society for Pediatric Anesthesia (SPA). This survey assessed the age, work environment, types of practice, and training levels, as well as clinical situations in which the practitioners use laryngeal masks across different pediatric age groups. Seven hundred and forty-three (27.1%) responses were obtained. The use of laryngeal mask increased as the patient age increased in nearly every queried situation. The practitioners routinely utilize laryngeal masks in a variety of challenging scenarios, such as in patients with a recent upper respiratory infection, in the difficult airway, remote locations, and long-duration surgeries. A small percentage of pediatric anesthesiologists use laryngeal masks in laparoscopic surgery and prone position procedures. Pediatric anesthesiologists are using laryngeal masks in both routine and challenging/unconventional situations. Although many of the uses for laryngeal masks are not explicitly stated in the manufacturer guidelines, literature and current practice support the use of laryngeal masks in several of these scenarios. © 2015 John Wiley & Sons Ltd.

Public health implications of environmental noise associated with unconventional oil and gas development.

PubMed

Hays, Jake; McCawley, Michael; Shonkoff, Seth B C

2017-02-15

Modern oil and gas development frequently occurs in close proximity to human populations and increased levels of ambient noise have been documented throughout some phases of development. Numerous studies have evaluated air and water quality degradation and human exposure pathways, but few have evaluated potential health risks and impacts from environmental noise exposure. We reviewed the scientific literature on environmental noise exposure to determine the potential concerns, if any, that noise from oil and gas development activities present to public health. Data on noise levels associated with oil and gas development are limited, but measurements can be evaluated amidst the large body of epidemiology assessing the non-auditory effects of environmental noise exposure and established public health guidelines for community noise. There are a large number of noise dependent and subjective factors that make the determination of a dose response relationship between noise and health outcomes difficult. However, the literature indicates that oil and gas activities produce noise at levels that may increase the risk of adverse health outcomes, including annoyance, sleep disturbance, and cardiovascular disease. More studies that investigate the relationships between noise exposure and human health risks from unconventional oil and gas development are warranted. Finally, policies and mitigation techniques that limit human exposure to noise from oil and gas operations should be considered to reduce health risks. Copyright © 2016 Elsevier B.V. All rights reserved.

Hazard assessment of hydraulic fracturing chemicals using an indexing method.

PubMed

Hu, Guangji; Liu, Tianyi; Hager, James; Hewage, Kasun; Sadiq, Rehan

2018-04-01

The rapid expansion of unconventional natural gas production has triggered considerable public concerns, particularly regarding environmental and human health (EHH) risks posed by various chemical additives used in hydraulic fracturing (HF) operations. There is a need to assess the potential EHH hazards of additives used in real-world HF operations. In this study, HF additive and fracturing fluid data was acquired, and EHH hazards were assessed using an indexing approach. The indexing system analyzed chemical toxicological data of different ingredients contained within additives and produced an aggregated EHH safety index for each additive, along with an indicator describing the completeness of the chemical toxicological data. The results show that commonly used additives are generally associated with medium-level EHH hazards. In each additive category, ingredients of high EHH concern were identified, and the high hazard designation was primarily attributed to ingredients' high aquatic toxicity and carcinogenic effects. Among all assessed additive categories, iron control agents were identified as the greatest EHH hazards. Lack of information, such as undisclosed ingredients and chemical toxicological data gaps, has resulted in different levels of assessment uncertainties. In particular, friction reducers show the highest data incompleteness with regards to EHH hazards. This study reveals the potential EHH hazards associated with chemicals used in current HF field operations and can provide decision makers with valuable information to facilitate sustainable and responsible unconventional gas production. Copyright © 2017 Elsevier B.V. All rights reserved.

Raman spectroscopy as a tool to understand Kerogen production potential

NASA Astrophysics Data System (ADS)

Khatibi, S.; Ostadhassan, M.; Mohammed, R. A.; Alexeyev, A.

2017-12-01

A lot attention has given to unconventional reservoirs specifically oil shale in North America during the last decades. Understanding Kerogen properties in terms of maturity and production potential are crucial for unconventional reservoir. Since, the amount of hydrocarbon generation is a function of kerogen type and content in the formation, and the magnitude and duration in which heat and pressure were applied. This study presents a non-destructive and fast method to determine Kerogen properties in terms of Rock-Eval parameters by means of Raman Spectroscopy. Samples were gathered from upper and lower Bakken formation, with different maturities at different depth. Raman spectroscopy as a powerful nondestructive analytical tool for molecular reconstruction was employed to find Raman spectra of different samples. In the next step, Rock-Eval was performed for each sample and different measurements were made. Then in an original approach, correlation between Rock-Eval parameters with Raman Spectroscopy results was established to fully understand how kerogen productivity potentials can be reflected on the Raman response. Results showed, maturity related parameters (RO, Tmax), S1 (already generated oil in the rock), S2 (potential hydrocarbon) and OSI (oil saturation index as indication of potential oil flow zones) can be correlated to band separation, D band intensity, G band intensity and G/D intensity, respectively. Proposed method provide a fast nondestructive method to evaluate Kerogen quality even at field without any special sample preparation.

Identification of mutations in the MYO9A gene in patients with congenital myasthenic syndrome

PubMed Central

O’Connor, Emily; Töpf, Ana; Müller, Juliane S.; Cox, Daniel; Evangelista, Teresinha; Colomer, Jaume; Abicht, Angela; Senderek, Jan; Hasselmann, Oswald; Yaramis, Ahmet; Laval, Steven H.

2016-01-01

Abstract Congenital myasthenic syndromes are a group of rare and genetically heterogenous disorders resulting from defects in the structure and function of the neuromuscular junction. Patients with congenital myasthenic syndrome exhibit fatigable muscle weakness with a variety of accompanying phenotypes depending on the protein affected. A cohort of patients with a clinical diagnosis of congenital myasthenic syndrome that lacked a genetic diagnosis underwent whole exome sequencing in order to identify genetic causation. Missense biallelic mutations in the MYO9A gene, encoding an unconventional myosin, were identified in two unrelated families. Depletion of MYO9A in NSC-34 cells revealed a direct effect of MYO9A on neuronal branching and axon guidance. Morpholino-mediated knockdown of the two MYO9A orthologues in zebrafish, myo9aa/ab, demonstrated a requirement for MYO9A in the formation of the neuromuscular junction during development. The morphants displayed shortened and abnormally branched motor axons, lack of movement within the chorion and abnormal swimming in response to tactile stimulation. We therefore conclude that MYO9A deficiency may affect the presynaptic motor axon, manifesting in congenital myasthenic syndrome. These results highlight the involvement of unconventional myosins in motor axon functionality, as well as the need to look outside traditional neuromuscular junction-specific proteins for further congenital myasthenic syndrome candidate genes. PMID:27259756

Duox, Flotillin-2, and Src42A Are Required to Activate or Delimit the Spread of the Transcriptional Response to Epidermal Wounds in Drosophila

PubMed Central

Juarez, Michelle T.; Patterson, Rachel A.; Sandoval-Guillen, Efren; McGinnis, William

2011-01-01

The epidermis is the largest organ of the body for most animals, and the first line of defense against invading pathogens. A breach in the epidermal cell layer triggers a variety of localized responses that in favorable circumstances result in the repair of the wound. Many cellular and genetic responses must be limited to epidermal cells that are close to wounds, but how this is regulated is still poorly understood. The order and hierarchy of epidermal wound signaling factors are also still obscure. The Drosophila embryonic epidermis provides an excellent system to study genes that regulate wound healing processes. We have developed a variety of fluorescent reporters that provide a visible readout of wound-dependent transcriptional activation near epidermal wound sites. A large screen for mutants that alter the activity of these wound reporters has identified seven new genes required to activate or delimit wound-induced transcriptional responses to a narrow zone of cells surrounding wound sites. Among the genes required to delimit the spread of wound responses are Drosophila Flotillin-2 and Src42A, both of which are transcriptionally activated around wound sites. Flotillin-2 and constitutively active Src42A are also sufficient, when overexpressed at high levels, to inhibit wound-induced transcription in epidermal cells. One gene required to activate epidermal wound reporters encodes Dual oxidase, an enzyme that produces hydrogen peroxide. We also find that four biochemical treatments (a serine protease, a Src kinase inhibitor, methyl-ß-cyclodextrin, and hydrogen peroxide) are sufficient to globally activate epidermal wound response genes in Drosophila embryos. We explore the epistatic relationships among the factors that induce or delimit the spread of epidermal wound signals. Our results define new genetic functions that interact to instruct only a limited number of cells around puncture wounds to mount a transcriptional response, mediating local repair and regeneration. PMID:22242003

Integration of transcriptomic and metabolic data reveals hub transcription factors involved in drought stress response in sunflower (Helianthus annuus L.).

PubMed

Moschen, Sebastián; Di Rienzo, Julio A; Higgins, Janet; Tohge, Takayuki; Watanabe, Mutsumi; González, Sergio; Rivarola, Máximo; García-García, Francisco; Dopazo, Joaquin; Hopp, H Esteban; Hoefgen, Rainer; Fernie, Alisdair R; Paniego, Norma; Fernández, Paula; Heinz, Ruth A

2017-07-01

By integration of transcriptional and metabolic profiles we identified pathways and hubs transcription factors regulated during drought conditions in sunflower, useful for applications in molecular and/or biotechnological breeding. Drought is one of the most important environmental stresses that effects crop productivity in many agricultural regions. Sunflower is tolerant to drought conditions but the mechanisms involved in this tolerance remain unclear at the molecular level. The aim of this study was to characterize and integrate transcriptional and metabolic pathways related to drought stress in sunflower plants, by using a system biology approach. Our results showed a delay in plant senescence with an increase in the expression level of photosynthesis related genes as well as higher levels of sugars, osmoprotectant amino acids and ionic nutrients under drought conditions. In addition, we identified transcription factors that were upregulated during drought conditions and that may act as hubs in the transcriptional network. Many of these transcription factors belong to families implicated in the drought response in model species. The integration of transcriptomic and metabolomic data in this study, together with physiological measurements, has improved our understanding of the biological responses during droughts and contributes to elucidate the molecular mechanisms involved under this environmental condition. These findings will provide useful biotechnological tools to improve stress tolerance while maintaining crop yield under restricted water availability.

Phosphorylation of Trihelix Transcriptional Repressor ASR3 by MAP KINASE4 Negatively Regulates Arabidopsis Immunity

PubMed Central

Li, Bo; Jiang, Shan; Yu, Xiao; Cheng, Cheng; Chen, Sixue; Cheng, Yanbing; Yuan, Joshua S.; Jiang, Daohong; He, Ping; Shan, Libo

2015-01-01

Proper control of immune-related gene expression is crucial for the host to launch an effective defense response. Perception of microbe-associated molecular patterns (MAMPs) induces rapid and profound transcriptional reprogramming via unclear mechanisms. Here, we show that ASR3 (ARABIDOPSIS SH4-RELATED3) functions as a transcriptional repressor and plays a negative role in regulating pattern-triggered immunity (PTI) in Arabidopsis thaliana. ASR3 belongs to a plant-specific trihelix transcription factor family for which functional studies are lacking. MAMP treatments induce rapid phosphorylation of ASR3 at threonine 189 via MPK4, a mitogen-activated protein kinase that negatively regulates PTI responses downstream of multiple MAMP receptors. ASR3 possesses transcriptional repressor activity via its ERF-associated amphiphilic repression motifs and negatively regulates a large subset of flg22-induced genes. Phosphorylation of ASR3 by MPK4 enhances its DNA binding activity to suppress gene expression. Importantly, the asr3 mutant shows enhanced disease resistance to virulent bacterial pathogen infection, whereas transgenic plants overexpressing the wild-type or phospho-mimetic form of ASR3 exhibit compromised PTI responses. Our studies reveal a function of the trihelix transcription factors in plant innate immunity and provide evidence that ASR3 functions as a transcriptional repressor regulated by MAMP-activated MPK4 to fine-tune plant immune gene expression. PMID:25770109

Role of the inflammasome in defense against venoms

PubMed Central

Palm, Noah W.; Medzhitov, Ruslan

2013-01-01

Venoms consist of a complex mixture of toxic components that are used by a variety of animal species for defense and predation. Envenomation of mammalian species leads to an acute inflammatory response and can lead to the development of IgE-dependent venom allergy. However, the mechanisms by which the innate immune system detects envenomation and initiates inflammatory and allergic responses to venoms remain largely unknown. Here we show that bee venom is detected by the NOD-like receptor family, pyrin domain-containing 3 inflammasome and can trigger activation of caspase-1 and the subsequent processing and unconventional secretion of the leaderless proinflammatory cytokine IL-1β in macrophages. Whereas activation of the inflammasome by bee venom induces a caspase-1–dependent inflammatory response, characterized by recruitment of neutrophils to the site or envenomation, the inflammasome is dispensable for the allergic response to bee venom. Finally, we find that caspase-1–deficient mice are more susceptible to the noxious effects of bee and snake venoms, suggesting that a caspase-1–dependent immune response can protect against the damaging effects of envenomation. PMID:23297192

Sex-related differences in murine hepatic transcriptional and proteomic responses to TCDD

DOE Office of Scientific and Technical Information (OSTI.GOV)

Prokopec, Stephenie D.; Watson, John D.; Lee, Jamie

2,3,7,8-Tetrachlorodibenzo-p-dioxin (TCDD) is an environmental contaminant that produces myriad toxicities in most mammals. In rodents alone, there is a huge divergence in the toxicological response across species, as well as among different strains within a species. But there are also significant differences between males and females animals of a single strain. These differences are inconsistent across model systems: the severity of toxicity is greater in female rats than males, while male mice and guinea pigs are more sensitive than females. Because the specific events that underlie this difference remain unclear, we characterized the hepatic transcriptional response of adult male andmore » female C57BL/6 mice to 500 μg/kg TCDD at multiple time-points. The transcriptional profile diverged significantly between the sexes. Female mice demonstrated a large number of altered transcripts as early as 6 h following treatment, suggesting a large primary response. Conversely, male animals showed the greatest TCDD-mediated response 144 h following exposure, potentially implicating significant secondary responses. Nr1i3 was statistically significantly induced at all time-points in the sensitive male animals. This mRNA encodes the constitutive androstane receptor (CAR), a transcription factor involved in the regulation of xenobiotic metabolism, lipid metabolism, cell cycle and apoptosis. Surprisingly though, changes at the protein level (aside from the positive control, CYP1A1) were modest, with only FMO3 showing clear induction, and no genes with sex-differences. Thus, while male and female mice show transcriptional differences in their response to TCDD, their association with TCDD-induced toxicities remains unclear. - Highlights: • Differences exist between the toxicity phenotypes to TCDD in male and female mice. • TCDD-mediated transcriptomic differences were identified between the sexes. • Resistant female mice displayed a large, early-onset, transcriptomic response. • Sensitive male mice displayed a large, late-onset, transcriptomic response. • Fmo2, Fmo3 and Nr1i3 were induced across the time-course in only male mice.« less

A Global Genomic and Genetic Strategy to Predict Pathway Activation of Xenobiotic Responsive Transcription Factors in the Mouse Liver

EPA Science Inventory

Many drugs and environmentally-relevant chemicals activate xenobiotic-responsive transcription factors(TF). Identification of target genes of these factors would be useful in predicting pathway activation in in vitro chemical screening. Starting with a large compendium of Affymet...

Design of a Temperature-Responsive Transcription Terminator.

PubMed

Roßmanith, Johanna; Weskamp, Mareen; Narberhaus, Franz

2018-02-16

RNA structures regulate various steps in gene expression. Transcription in bacteria is typically terminated by stable hairpin structures. Translation initiation can be modulated by metabolite- or temperature-sensitive RNA structures, called riboswitches or RNA thermometers (RNATs), respectively. RNATs control translation initiation by occlusion of the ribosome binding site at low temperatures. Increasing temperatures destabilize the RNA structure and facilitate ribosome access. In this study, we exploited temperature-responsive RNAT structures to design regulatory elements that control transcription termination instead of translation initiation in Escherichia coli. In order to mimic the structure of factor-independent intrinsic terminators, naturally occurring RNAT hairpins were genetically engineered to be followed by a U-stretch. Functional temperature-responsive terminators (thermoterms) prevented mRNA synthesis at low temperatures but resumed transcription after a temperature upshift. The successful design of temperature-controlled terminators highlights the potential of RNA structures as versatile gene expression control elements.

Inositol polyphosphate multikinase is a coactivator for serum response factor-dependent induction of immediate early genes

PubMed Central

Kim, Eunha; Tyagi, Richa; Lee, Joo-Young; Park, Jina; Kim, Young-ran; Beon, Jiyoon; Chen, Po Yu; Cha, Jiyoung Y.; Snyder, Solomon H.; Kim, Seyun

2013-01-01

Inositol polyphosphate multikinase (IPMK) is a notably pleiotropic protein. It displays both inositol phosphate kinase and phosphatidylinositol kinase catalytic activities. Noncatalytically, IPMK stabilizes the mammalian target of rapamycin complex 1 and acts as a transcriptional coactivator for CREB-binding protein/E1A binding protein p300 and tumor suppressor protein p53. Serum response factor (SRF) is a major transcription factor for a wide range of immediate early genes. We report that IPMK, in a noncatalytic role, is a transcriptional coactivator for SRF mediating the transcription of immediate early genes. Stimulation by serum of many immediate early genes is greatly reduced by IPMK deletion. IPMK stimulates expression of these genes, an influence also displayed by catalytically inactive IPMK. IPMK acts by binding directly to SRF and thereby enhancing interactions of SRF with the serum response element of diverse genes. PMID:24248338

Genome-Wide Identification of Binding Sites Defines Distinct Functions for Caenorhabditis elegans PHA-4/FOXA in Development and Environmental Response

PubMed Central

Zhong, Mei; Niu, Wei; Lu, Zhi John; Sarov, Mihail; Murray, John I.; Janette, Judith; Raha, Debasish; Sheaffer, Karyn L.; Lam, Hugo Y. K.; Preston, Elicia; Slightham, Cindie; Hillier, LaDeana W.; Brock, Trisha; Agarwal, Ashish; Auerbach, Raymond; Hyman, Anthony A.; Gerstein, Mark; Mango, Susan E.; Kim, Stuart K.; Waterston, Robert H.; Reinke, Valerie; Snyder, Michael

2010-01-01

Transcription factors are key components of regulatory networks that control development, as well as the response to environmental stimuli. We have established an experimental pipeline in Caenorhabditis elegans that permits global identification of the binding sites for transcription factors using chromatin immunoprecipitation and deep sequencing. We describe and validate this strategy, and apply it to the transcription factor PHA-4, which plays critical roles in organ development and other cellular processes. We identified thousands of binding sites for PHA-4 during formation of the embryonic pharynx, and also found a role for this factor during the starvation response. Many binding sites were found to shift dramatically between embryos and starved larvae, from developmentally regulated genes to genes involved in metabolism. These results indicate distinct roles for this regulator in two different biological processes and demonstrate the versatility of transcription factors in mediating diverse biological roles. PMID:20174564

Transcription Factors Involved in Plant Resistance to Pathogens.

PubMed

Amorim, Lidiane L B; da Fonseca Dos Santos, Romulo; Neto, Joao Pacífico Bezerra; Guida-Santos, Mauro; Crovella, Sergio; Benko-Iseppon, Ana Maria

2017-01-01

Phytopathogenic microorganisms have a significant influence on survival and productivity of several crop plants. Transcription factors (TFs) are important players in the response to biotic stresses, as insect attack and pathogen infection. In face of such adversities many TFs families have been previously reported as differentially expressed in plants as a reaction to bacterial, fungal and viral infection. This review highlights recent progresses in understanding the structure, function, signal regulation and interaction of transcription factors with other proteins in response to pathogens. Hence, we focus on three families of transcription factors: ERF, bZIP and WRKY, due to their abundance, importance and the availability of functionally well-characterized members in response to pathogen attack. Their roles and the possibilities related to the use of this knowledge for engineering pathogen resistance in crop plants are also discussed. Copyright© Bentham Science Publishers; For any queries, please email at epub@benthamscience.org.

Transcriptional specialization of human dendritic cell subsets in response to microbial vaccines

PubMed Central

Banchereau, Romain; Baldwin, Nicole; Cepika, Alma-Martina; Athale, Shruti; Xue, Yaming; Yu, Chun I; Metang, Patrick; Cheruku, Abhilasha; Berthier, Isabelle; Gayet, Ingrid; Wang, Yuanyuan; Ohouo, Marina; Snipes, LuAnn; Xu, Hui; Obermoser, Gerlinde; Blankenship, Derek; Oh, Sangkon; Ramilo, Octavio; Chaussabel, Damien; Banchereau, Jacques; Palucka, Karolina; Pascual, Virginia

2014-01-01

The mechanisms by which microbial vaccines interact with human APCs remain elusive. Herein, we describe the transcriptional programs induced in human DCs by pathogens, innate receptor ligands and vaccines. Exposure of DCs to influenza, Salmonella enterica and Staphylococcus aureus allows us to build a modular framework containing 204 transcript clusters. We use this framework to characterize the responses of human monocytes, monocyte-derived DCs and blood DC subsets to 13 vaccines. Different vaccines induce distinct transcriptional programs based on pathogen type, adjuvant formulation and APC targeted. Fluzone, Pneumovax and Gardasil, respectively, activate monocyte-derived DCs, monocytes and CD1c+ blood DCs, highlighting APC specialization in response to vaccines. Finally, the blood signatures from individuals vaccinated with Fluzone or infected with influenza reveal a signature of adaptive immunity activation following vaccination and symptomatic infections, but not asymptomatic infections. These data, offered with a web interface, may guide the development of improved vaccines. PMID:25335753

A Conserved Structural Module Regulates Transcriptional Responses to Diverse Stress Signals in Bacteria

PubMed Central

Campbell, Elizabeth A.; Greenwell, Roger; Anthony, Jennifer R.; Wang, Sheng; Lim, Lionel; Das, Kalyan; Sofia, Heidi J.; Donohue, Timothy J.; Darst, Seth A.

2008-01-01

SUMMARY A transcriptional response to singlet oxygen in Rhodobacter sphaeroides is controlled by the group IV σ factor σE and its cognate anti-σ ChrR. Crystal structures of the σE/ChrR complex reveal a modular, two-domain architecture for ChrR. The ChrR N-terminal anti-σ domain (ASD) binds a Zn2+ ion, contacts σE, and is sufficient to inhibit σE-dependent transcription. The ChrR C-terminal domain adopts a cupin fold, can coordinate an additional Zn2+, and is required for the transcriptional response to singlet oxygen. Structure-based sequence analyses predict that the ASD defines a common structural fold among predicted group IV antiσs. These ASDs are fused to diverse C-terminal domains that are likely involved in responding to specific environmental signals that control the activity of their cognate σ factor. PMID:17803943

Mechanistic Insights in Ethylene Perception and Signal Transduction1

PubMed Central

Ju, Chuanli; Chang, Caren

2015-01-01

The gaseous hormone ethylene profoundly affects plant growth, development, and stress responses. Ethylene perception occurs at the endoplasmic reticulum membrane, and signal transduction leads to a transcriptional cascade that initiates diverse responses, often in conjunction with other signals. Recent findings provide a more complete picture of the components and mechanisms in ethylene signaling, now rendering a more dynamic view of this conserved pathway. This includes newly identified protein-protein interactions at the endoplasmic reticulum membrane, as well as the major discoveries that the central regulator ETHYLENE INSENSITIVE2 (EIN2) is the long-sought phosphorylation substrate for the CONSTITUTIVE RESPONSE1 protein kinase, and that cleavage of EIN2 transmits the signal to the nucleus. In the nucleus, hundreds of potential gene targets of the EIN3 master transcription factor have been identified and found to be induced in transcriptional waves, and transcriptional coregulation has been shown to be a mechanism of ethylene cross talk. PMID:26246449

Anomalous stress response of ultrahard WB n compounds

DOE PAGES

Li, Quan; Zhou, Dan; Zheng, Weitao; ...

2015-10-29

Boron-rich tungsten borides are premier prototypes of a new class of ultrahard compounds. Here, we show by first-principles calculations that their stress-strain relations display surprisingly diverse and anomalous behavior under a variety of loading conditions. Most remarkable is the dramatically changing bonding configurations and deformation modes with rising boron concentration in WB n (n=2, 3, 4), resulting in significantly different stress responses and unexpected indentation strength variations. This novel phenomenon stems from the peculiar structural arrangements in tungsten borides driven by boron’s ability to form unusually versatile bonding states. Our results elucidate the intriguing deformation mechanisms that define a distinctmore » type of ultrahard material. Here, these new insights underscore the need to explore unconventional structure-property relations in a broad range of transition-metal light-element compounds.« less

Transcriptional 'memory' of a stress: transient chromatin and memory (epigenetic) marks at stress-response genes.

PubMed

Avramova, Zoya

2015-07-01

Drought, salinity, extreme temperature variations, pathogen and herbivory attacks are recurring environmental stresses experienced by plants throughout their life. To survive repeated stresses, plants provide responses that may be different from their response during the first encounter with the stress. A different response to a similar stress represents the concept of 'stress memory'. A coordinated reaction at the organismal, cellular and gene/genome levels is thought to increase survival chances by improving the plant's tolerance/avoidance abilities. Ultimately, stress memory may provide a mechanism for acclimation and adaptation. At the molecular level, the concept of stress memory indicates that the mechanisms responsible for memory-type transcription during repeated stresses are not based on repetitive activation of the same response pathways activated by the first stress. Some recent advances in the search for transcription 'memory factors' are discussed with an emphasis on super-induced dehydration stress memory response genes in Arabidopsis. © 2015 The Author The Plant Journal © 2015 John Wiley & Sons Ltd.

Water deficit-induced changes in transcription factor expression in maize seedlings

USDA-ARS?s Scientific Manuscript database

Plants tolerate water deficits by regulating gene networks controlling cellular and physiological traits to modify growth and development. Transcription factor (TFs) directed regulation of transcription within these gene networks is key to eliciting appropriate responses. In this study, reverse tran...

Hippo, TGF-β, and Src-MAPK pathways regulate transcription of the upd3 cytokine in Drosophila enterocytes upon bacterial infection.

PubMed

Houtz, Philip; Bonfini, Alessandro; Liu, Xi; Revah, Jonathan; Guillou, Aurélien; Poidevin, Mickael; Hens, Korneel; Huang, Hsin-Yi; Deplancke, Bart; Tsai, Yu-Chen; Buchon, Nicolas

2017-11-01

Cytokine signaling is responsible for coordinating conserved epithelial regeneration and immune responses in the digestive tract. In the Drosophila midgut, Upd3 is a major cytokine, which is induced in enterocytes (EC) and enteroblasts (EB) upon oral infection, and initiates intestinal stem cell (ISC) dependent tissue repair. To date, the genetic network directing upd3 transcription remains largely uncharacterized. Here, we have identified the key infection-responsive enhancers of the upd3 gene and show that distinct enhancers respond to various stresses. Furthermore, through functional genetic screening, bioinformatic analyses and yeast one-hybrid screening, we determined that the transcription factors Scalloped (Sd), Mothers against dpp (Mad), and D-Fos are principal regulators of upd3 expression. Our study demonstrates that upd3 transcription in the gut is regulated by the activation of multiple pathways, including the Hippo, TGF-β/Dpp, and Src, as well as p38-dependent MAPK pathways. Thus, these essential pathways, which are known to control ISC proliferation cell-autonomously, are also activated in ECs to promote tissue turnover the regulation of upd3 transcription.

On the Minimization of Fluctuations in the Response Times of Autoregulatory Gene Networks

PubMed Central

Murugan, Rajamanickam; Kreiman, Gabriel

2011-01-01

The temporal dynamics of the concentrations of several proteins are tightly regulated, particularly for critical nodes in biological networks such as transcription factors. An important mechanism to control transcription factor levels is through autoregulatory feedback loops where the protein can bind its own promoter. Here we use theoretical tools and computational simulations to further our understanding of transcription-factor autoregulatory loops. We show that the stochastic dynamics of feedback and mRNA synthesis can significantly influence the speed of response of autoregulatory genetic networks toward external stimuli. The fluctuations in the response-times associated with the accumulation of the transcription factor in the presence of negative or positive autoregulation can be minimized by confining the ratio of mRNA/protein lifetimes within 1:10. This predicted range of mRNA/protein lifetime agrees with ranges observed empirically in prokaryotes and eukaryotes. The theory can quantitatively and systematically account for the influence of regulatory element binding and unbinding dynamics on the transcription-factor concentration rise-times. The simulation results are robust against changes in several system parameters of the gene expression machinery. PMID:21943410

Opposing PKA and Hog1 signals control the post-transcriptional response to glucose availability in Cryptococcus neoformans.

PubMed

Banerjee, Dithi; Bloom, Amanda L M; Panepinto, John C

2016-10-01

The pathogenic fungus Cryptococcus neoformans must adapt to glucose-limited conditions in the lung and glucose replete conditions upon dissemination to the brain. We report that glucose controls ribosome biogenesis and translation by modulating mRNA decay through a balance of PKA and Hog1 signalling. Glucose signalling through PKA stabilized ribosomal protein (RP) mRNAs whereas glucose starvation destabilized RP transcripts through Hog1. Glucose starvation-induced oxidative stress response genes, and treatment of glucose-fed cells with reactive oxygen species (ROS) generating compounds repressed RP transcripts, both of which were dependent on Hog1. Stabilization of RP transcripts led to retention of polysomes in a hog1Δ mutant, whereas stabilization of RP transcripts by cyclic AMP did not affect translation repression, suggesting that Hog1 alone signals translation repression. In sum, this work describes a novel antagonism between PKA and Hog1 controlling ribosome biogenesis via mRNA stability in response to glucose availability in this important human pathogen. © 2016 John Wiley & Sons Ltd.

CacyBP/SIP as a regulator of transcriptional responses in brain cells

PubMed Central

Kilanczyk, Ewa; Filipek, Anna; Hetman, Michal

2014-01-01

Summary The Calcyclin-Binding Protein/Siah-1-Interacting Protein (CacyBP/SIP) is highly expressed in the brain and was shown to regulate the β-catenin-driven transcription in thymocytes. Therefore, it was investigated whether in brain cells CacyBP/SIP might play a role as a transcriptional regulator. In BDNF- or forskolin-stimulated rat primary cortical neurons, overexpression of CacyBP/SIP enhanced transcriptional activity of the cAMP-response element (CRE). In addition, overexpressed CacyBP/SIP enhanced BDNF-mediated activation of the Nuclear Factor of Activated T-cells (NFAT) but not the Serum Response Element (SRE). These stimulatory effects required an intact C-terminal domain of CacyBP/SIP. Moreover, in C6 rat glioma cells, the overexpressed CacyBP/SIP enhanced activation of CRE- or NFAT- following forskolin- or serum stimulation, respectively. Conversely, knockdown of endogenous CacyBP/SIP reduced activation of CRE- and NFAT but not SRE. Taken together, these results indicate that CacyBP/SIP is a novel regulator of CRE- and NFAT-driven transcription. PMID:25163685

Aptazyme-embedded guide RNAs enable ligand-responsive genome editing and transcriptional activation

PubMed Central

Tang, Weixin; Hu, Johnny H.; Liu, David R.

2017-01-01

Programmable sequence-specific genome editing agents such as CRISPR-Cas9 have greatly advanced our ability to manipulate the human genome. Although canonical forms of genome-editing agents and programmable transcriptional regulators are constitutively active, precise temporal and spatial control over genome editing and transcriptional regulation activities would enable the more selective and potentially safer use of these powerful technologies. Here, by incorporating ligand-responsive self-cleaving catalytic RNAs (aptazymes) into guide RNAs, we developed a set of aptazyme-embedded guide RNAs that enable small molecule-controlled nuclease-mediated genome editing and small molecule-controlled base editing, as well as small molecule-dependent transcriptional activation in mammalian cells. PMID:28656978

Uncovering the Role of RNA-Binding Proteins in Gene Expression in the Immune System

PubMed Central

Díaz-Muñoz, Manuel D.; Turner, Martin

2018-01-01

Fighting external pathogens requires an ever-changing immune system that relies on tight regulation of gene expression. Transcriptional control is the first step to build efficient responses while preventing immunodeficiencies and autoimmunity. Post-transcriptional regulation of RNA editing, location, stability, and translation are the other key steps for final gene expression, and they are all controlled by RNA-binding proteins (RBPs). Nowadays we have a deep understanding of how transcription factors control the immune system but recent evidences suggest that post-transcriptional regulation by RBPs is equally important for both development and activation of immune responses. Here, we review current knowledge about how post-transcriptional control by RBPs shapes our immune system and discuss the perspective of RBPs being the key players of a hidden immune cell epitranscriptome. PMID:29875770

HSP70 and heat shock factor 1 cooperate to repress Ras-induced transcriptional activation of the c-fos gene

PubMed Central

He, Haiying; Chen, Changmin; Xie, Yue; Asea, Alexzander; Calderwood, Stuart K.

2000-01-01

Heat shock protein 70 (HSP70) is a molecular chaperone involved in protein folding and resistance to the deleterious effects of stress. Here we show that HSP70 suppresses transcription of c-fos, an early response gene that is a key component of the ubiquitous AP-1 transcription factor complex. HSP70 repressed Ras-induced c-fos transcription only in the presence of functional heat shock factor1 (HSF1). This suggests that HSP70 functions as a corepressor with HSF1 to inhibit c-fos gene transcription. Therefore, besides its known function in the stress response, HSP70 also has the property of a corepressor and combines with HSF1 to antagonize Fos expression and may thus impact multiple aspects of cell regulation. PMID:11189444

Translational Upregulation of an Individual p21Cip1 Transcript Variant by GCN2 Regulates Cell Proliferation and Survival under Nutrient Stress

PubMed Central

Lehman, Stacey L.; Cerniglia, George J.; Johannes, Gregg J.; Ye, Jiangbin; Ryeom, Sandra; Koumenis, Constantinos

2015-01-01

Multiple transcripts encode for the cell cycle inhibitor p21Cip1. These transcripts produce identical proteins but differ in their 5’ untranslated regions (UTRs). Although several stresses that induce p21 have been characterized, the mechanisms regulating the individual transcript variants and their functional significance are unknown. Here we demonstrate through 35S labeling, luciferase reporter assays, and polysome transcript profiling that activation of the Integrated Stress Response (ISR) kinase GCN2 selectively upregulates the translation of a p21 transcript variant containing 5’ upstream open reading frames (uORFs) through phosphorylation of the eukaryotic translation initiation factor eIF2α. Mutational analysis reveals that the uORFs suppress translation under basal conditions, but promote translation under stress. Functionally, ablation of p21 ameliorates G1/S arrest and reduces cell survival in response to GCN2 activation. These findings uncover a novel mechanism of p21 post-transcriptional regulation, offer functional significance for the existence of multiple p21 transcripts, and support a key role for GCN2 in regulating the cell cycle under stress. PMID:26102367

Health concerns associated with unconventional gas mining in rural Australia.

PubMed

Haswell, Melissa R; Bethmont, Anna

2016-01-01

Many governments globally are investigating the benefits and risks associated with unconventional gas mining for shale, tight and coal seam gas (coalbed methane) to determine whether the industry should proceed in their jurisdiction. Most locations likely to be developed are in rural areas, with potential impact on farmers and small communities. Despite significant health concerns, public health knowledge and growing evidence are often overlooked in decision-making. It is difficult to gain a broad but accurate understanding of the health concerns for rural communities because the evidence has grown very recently and rapidly, is complex and largely based in the USA, where the industry is advanced. In 2016, a concerned South Australian beef and lamb farmer in an area targeted for potential unconventional gas development organised visits to homes in developed unconventional gas areas of Pennsylvania and forums with leading researchers and lawyers in Pennsylvania and New York. Guided by priorities identified during this trip, this communication concisely distils the research evidence on these key concerns, highlighting the Australian situation where evidence exists. It summarises key information of particular concern to rural regions, using Australia as an example, to assist rural health professionals to be better prepared to engage in decision-making and address the challenges associated with this new industry. Discussions with communities and experts, supported by the expanding research from the USA and Australia, revealed increasing health concerns in six key areas. These are absence of a safe solution to the toxic wastewater management problems, air pollution, land and water competition, mental health and psychosocial wellbeing risks, fugitive methane emissions and lack of proven regulatory regimes. Emerging epidemiological studies suggesting interference with foetal development and birth outcomes, and exacerbation of asthma conditions, are particularly concerning to rural families and livestock. Rural residents in potentially affected areas should be supported to access and interpret the best current evidence regarding the multiple health concerns associated with unconventional gas mining. This knowledge should be part of wider discourse and decision-making processes driving local economic development and national and global energy choices.

Analysis of an acyl-CoA binding protein in Aspergillus oryzae that undergoes unconventional secretion.

PubMed

Kwon, Hee Su; Kawaguchi, Kouhei; Kikuma, Takashi; Takegawa, Kaoru; Kitamoto, Katsuhiko; Higuchi, Yujiro

2017-11-04

Acyl-CoA binding protein (ACBP) plays important roles in the metabolism of lipids in eukaryotic cells. In the industrially important filamentous fungus Aspergillus oryzae, although we have previously demonstrated that the A. oryzae ACBP (AoACBP) localizes to punctate structures and exhibits long-range motility, which is dependent on autophagy-related proteins, the physiological role of AoACBP remains elusive. Here, we describe identification and characterization of another ACBP from A. oryzae; we named this ACBP as AoAcb2 and accordingly renamed AoACBP as AoAcb1. The deduced amino acid sequence of AoAcb2 lacked a signal peptide. Phylogenetic analysis classified AoAcb2 into a clade that was same as the ACBP Acb1 of the model yeast Saccharomyces cerevisiae, but was different from that of AoAcb1. In contrast to punctate localization of AoAcb1, AoAcb2 was found to be dispersedly distributed in the cytoplasm, as was previously observed for the S. cerevisiae Acb1. Since we could not generate an Aoacb2 disruptant, we created an Aoacb2 conditional mutant that exhibited less growth under Aoacb2-repressed condition, suggesting that Aoacb2 is an essential gene for growth. Moreover, we observed that A. oryzae AoAcb2, but not A. oryzae AoAcb1, was secreted under carbon-starved condition, suggesting that AoAcb2 might be secreted via the unconventional protein secretion (UPS) pathway, just like S. cerevisiae Acb1. We also demonstrated that the unconventional secretion of AoAcb2 was dependent on the t-SNARE AoSso1, but was independent of the autophagy-related protein AoAtg1, suggesting that the unconventional secretion of AoAcb2, unlike that of S. cerevisiae Acb1, via the UPS pathway, is not regulated by the autophagy machinery. Thus, the filamentous fungus A. oryzae harbors two types of ACBPs, one of which appears to be essential for growth and undergoes unconventional secretion. Copyright © 2017 Elsevier Inc. All rights reserved.

Unconventional politics of unconventional gas: Environmental reframing and policy change

NASA Astrophysics Data System (ADS)

Kear, Andrew Robert

The present Rocky Mountain West natural gas boom, enabled by historic pro-resource-development political, institutional, economic, and cultural structures, is a politically contested battle over values. Volatile political action, unconventional coalitions, and unconventional politics engulf this unconventional gas boom -- especially at the state level. In this comparative case study of natural gas policy in Wyoming, Colorado, and New Mexico, I measure and compare these values, expressed as frames, through textual analysis of interest group public documents and state legislative bills and statutes from 1999-2008. By developing a new measure of state legislative framing, I test the relationship between interest group and institutional framing and also provide a viable measure of policy change useful to Narrative Policy Analysis theory. Results show that competing interest group and state legislative framing efforts are dynamic, measurably different, and periodically correlative. Competing interest groups rarely engage each other, except as the conflict matures when status-quo-supporters break their silence and engage the challengers' frames that have gained legislative traction. Environmental and land-use counter-framing ensues, but status-quo-supporters remain vigilant in their economic framing. Economic frames retain their institutional privilege within Wyoming and New Mexico, but natural gas policy undergoes a complete environmental reframe in the Colorado state legislature. Although the historically dominant economy frame based on "Old West" values remains largely intact, the respective state legislatures partially reframe policy (within 4 years) using environment, alternative land-uses, and democracy frames based on "New West" and long-extant but previously marginalized status-quo-challenger definitions. This reframing is not a strictly partisan issue, but rather it is influenced by political context, policy diffusion, and long-term interest group advocacy and framing efforts. A policy punctuation is observed in state legislative reframing and by the passage of three status-quo-challenging statutes in Wyoming (2005), four in Colorado (2007), and one in New Mexico (2007). Policy reframing, although rare in most policy areas, is common during this natural gas policy punctuation. The politics of successful reframing is the politics of punctuation.

bZIP17 regulates the expression of genes related to seed storage and germination, reducing seed susceptibility to osmotic stress.

PubMed

Cifuentes-Esquivel, Nicolás; Celiz-Balboa, Jonathan; Henriquez-Valencia, Carlos; Mitina, Irina; Arraño-Salinas, Paulina; Moreno, Adrián A; Meneses, Claudio; Blanco-Herrera, Francisca; Orellana, Ariel

2018-04-25

Low temperatures, salinity, and drought cause significant crop losses. These conditions involve osmotic stress, triggering transcriptional remodeling, and consequently, the restitution of cellular homeostasis and growth recovery. Protein transcription factors regulate target genes, thereby mediating plant responses to stress. bZIP17 is a transcription factor involved in cellular responses to salinity and the unfolded protein response. Because salinity can also produce osmotic stress, the role of bZIP17 in response to osmotic stress was assessed. Mannitol treatments induced the transcript accumulation and protein processing of bZIP17. Transcriptomic analyses showed that several genes associated with seed storage and germination showed lower expression in bzip17 mutants than in wild-type plants. Interestingly, bZIP17 transcript was more abundant in seeds, and germination analyses revealed that wild-type plants germinated later than bzip17 mutants in the presence of mannitol, but no effects were observed when the seeds were exposed to ABA. Finally, the transcript levels of bZIP17 target genes that control seed storage and germination were assessed in seeds exposed to mannitol treatments, which showed lower expression levels in bzip17 mutants compared to the wild-type seeds. These results suggest that bZIP17 plays a role in osmotic stress, acting as a negative regulator of germination through the regulation of genes involved in seed storage and germination. © 2018 Wiley Periodicals, Inc.

The Arabidopsis NAC Transcription Factor ANAC096 Cooperates with bZIP-Type Transcription Factors in Dehydration and Osmotic Stress Responses[W

PubMed Central

Xu, Zheng-Yi; Kim, Soo Youn; Hyeon, Do Young; Kim, Dae Heon; Dong, Ting; Park, Youngmin; Jin, Jing Bo; Joo, Se-Hwan; Kim, Seong-Ki; Hong, Jong Chan; Hwang, Daehee; Hwang, Inhwan

2013-01-01

Multiple transcription factors (TFs) play essential roles in plants under abiotic stress, but how these multiple TFs cooperate in abiotic stress responses remains largely unknown. In this study, we provide evidence that the NAC (for NAM, ATAF1/2, and CUC2) TF ANAC096 cooperates with the bZIP-type TFs ABRE binding factor and ABRE binding protein (ABF/AREB) to help plants survive under dehydration and osmotic stress conditions. ANAC096 directly interacts with ABF2 and ABF4, but not with ABF3, both in vitro and in vivo. ANAC096 and ABF2 synergistically activate RD29A transcription. Our genome-wide gene expression analysis revealed that a major proportion of abscisic acid (ABA)–responsive genes are under the transcriptional regulation of ANAC096. We found that the Arabidopsis thaliana anac096 mutant is hyposensitive to exogenous ABA and shows impaired ABA-induced stomatal closure and increased water loss under dehydration stress conditions. Furthermore, we found the anac096 abf2 abf4 triple mutant is much more sensitive to dehydration and osmotic stresses than the anac096 single mutant or the abf2 abf4 double mutant. Based on these results, we propose that ANAC096 is involved in a synergistic relationship with a subset of ABFs for the transcriptional activation of ABA-inducible genes in response to dehydration and osmotic stresses. PMID:24285786

Cross-species transcriptional network analysis reveals conservation and variation in response to metal stress in cyanobacteria

PubMed Central

2013-01-01

Background As one of the most dominant bacterial groups on Earth, cyanobacteria play a pivotal role in the global carbon cycling and the Earth atmosphere composition. Understanding their molecular responses to environmental perturbations has important scientific and environmental values. Since important biological processes or networks are often evolutionarily conserved, the cross-species transcriptional network analysis offers a useful strategy to decipher conserved and species-specific transcriptional mechanisms that cells utilize to deal with various biotic and abiotic disturbances, and it will eventually lead to a better understanding of associated adaptation and regulatory networks. Results In this study, the Weighted Gene Co-expression Network Analysis (WGCNA) approach was used to establish transcriptional networks for four important cyanobacteria species under metal stress, including iron depletion and high copper conditions. Cross-species network comparison led to discovery of several core response modules and genes possibly essential to metal stress, as well as species-specific hub genes for metal stresses in different cyanobacteria species, shedding light on survival strategies of cyanobacteria responding to different environmental perturbations. Conclusions The WGCNA analysis demonstrated that the application of cross-species transcriptional network analysis will lead to novel insights to molecular response to environmental changes which will otherwise not be achieved by analyzing data from a single species. PMID:23421563

Transcriptional Profiling Identifies Functional Interactions of TGFβ and PPARβ/δ Signaling

PubMed Central

Kaddatz, Kerstin; Adhikary, Till; Finkernagel, Florian; Meissner, Wolfgang; Müller-Brüsselbach, Sabine; Müller, Rolf

2010-01-01

Peroxisome proliferator-activated receptors (PPARs) not only play a key role in regulating metabolic pathways but also modulate inflammatory processes, pointing to a functional interaction between PPAR and cytokine signaling pathways. In this study, we show by genome-wide transcriptional profiling that PPARβ/δ and transforming growth factor-β (TGFβ) pathways functionally interact in human myofibroblasts and that a subset of these genes is cooperatively activated by TGFβ and PPARβ/δ. Using the angiopoietin-like 4 (ANGPTL4) gene as a model, we demonstrate that two enhancer regions cooperate to mediate the observed synergistic response. A TGFβ-responsive enhancer located ∼8 kb upstream of the transcriptional start site is regulated by a mechanism involving SMAD3, ETS1, RUNX, and AP-1 transcription factors that interact with multiple contiguous binding sites. A second enhancer (PPAR-E) consisting of three juxtaposed PPAR response elements is located in the third intron ∼3.5 kb downstream of the transcriptional start site. The PPAR-E is strongly activated by all three PPAR subtypes, with a novel type of PPAR response element motif playing a central role. Although the PPAR-E is not regulated by TGFβ, it interacts with SMAD3, ETS1, RUNX2, and AP-1 in vivo, providing a possible mechanistic explanation for the observed synergism. PMID:20595396

A single-molecule view of gene regulation in cancer

NASA Astrophysics Data System (ADS)

Larson, Daniel

2013-03-01

Single-cell analysis has revealed that transcription is dynamic and stochastic, but tools are lacking that can determine the mechanism operating at a single gene. Here we utilize single-molecule observations of RNA in fixed and living cells to develop a single-cell model of steroid-receptor mediated gene activation. Steroid receptors coordinate a diverse range of responses in higher eukaryotes and are involved in a wide range of human diseases, including cancer. Steroid receptor response elements are present throughout the human genome and modulate chromatin remodeling and transcription in both a local and long-range fashion. As such, steroid receptor-mediated transcription is a paradigm of genetic control in the metazoan nucleus. Moreover, the ligand-dependent nature of these transcription factors makes them appealing targets for therapeutic intervention, necessitating a quantitative understanding of how receptors control output from target genes. We determine that steroids drive mRNA synthesis by frequency modulation of transcription. This digital behavior in single cells gives rise to the well-known analog dose response across the population. To test this model, we developed a light-activation technology to turn on a single gene and follow dynamic synthesis of RNA from the activated locus. The response delay is a measure of time required for chromatin remodeling at a single gene.

A Spatio-Temporal Understanding of Growth Regulation during the Salt Stress Response in Arabidopsis[W

PubMed Central

Geng, Yu; Wu, Rui; Wee, Choon Wei; Xie, Fei; Wei, Xueliang; Chan, Penny Mei Yeen; Tham, Cliff; Duan, Lina; Dinneny, José R.

2013-01-01

Plant environmental responses involve dynamic changes in growth and signaling, yet little is understood as to how progress through these events is regulated. Here, we explored the phenotypic and transcriptional events involved in the acclimation of the Arabidopsis thaliana seedling root to a rapid change in salinity. Using live-imaging analysis, we show that growth is dynamically regulated with a period of quiescence followed by recovery then homeostasis. Through the use of a new high-resolution spatio-temporal transcriptional map, we identify the key hormone signaling pathways that regulate specific transcriptional programs, predict their spatial domain of action, and link the activity of these pathways to the regulation of specific phases of growth. We use tissue-specific approaches to suppress the abscisic acid (ABA) signaling pathway and demonstrate that ABA likely acts in select tissue layers to regulate spatially localized transcriptional programs and promote growth recovery. Finally, we show that salt also regulates many tissue-specific and time point–specific transcriptional responses that are expected to modify water transport, Casparian strip formation, and protein translation. Together, our data reveal a sophisticated assortment of regulatory programs acting together to coordinate spatially patterned biological changes involved in the immediate and long-term response to a stressful shift in environment. PMID:23898029

Comparative Transcriptomic Analysis of the Response to Cold Acclimation in Eucalyptus dunnii

PubMed Central

Liu, Yiqing; Jiang, Yusong; Lan, Jianbin; Zou, Yong; Gao, Junping

2014-01-01

Eucalyptus dunnii is an important macrophanerophyte with high economic value. However, low temperature stress limits its productivity and distribution. To study the cold response mechanisms of E. dunnii, 5 cDNA libraries were constructed from mRNA extracted from leaves exposed to cold stress for varying lengths of time and were evaluated by RNA-Seq analysis. The assembly of the Illumina datasets was optimized using various assembly programs and parameters. The final optimized assembly generated 205,325 transcripts with an average length of 1,701 bp and N50 of 2,627 bp, representing 349.38 Mb of the E. dunnii transcriptome. Among these transcripts, 134,358 transcripts (65.4%) were annotated in the Nr database. According to the differential analysis results, most transcripts were up-regulated as the cold stress prolonging, suggesting that these transcripts may be involved in the response to cold stress. In addition, the cold-relevant GO categories, such as ‘response to stress’ and ‘translational initiation’, were the markedly enriched GO terms. The assembly of the E. dunnii gene index and the GO classification performed in this study will serve as useful genomic resources for the genetic improvement of E. dunnii and also provide insights into the molecular mechanisms of cold acclimation in E. dunnii. PMID:25412179

Protein Kinases and Transcription Factors Activation in Response to UV-Radiation of Skin: Implications for Carcinogenesis

PubMed Central

López-Camarillo, César; Ocampo, Elena Aréchaga; Casamichana, Mavil López; Pérez-Plasencia, Carlos; Álvarez-Sánchez, Elizbeth; Marchat, Laurence A.

2012-01-01

Solar ultraviolet (UV) radiation is an important environmental factor that leads to immune suppression, inflammation, photoaging, and skin carcinogenesis. Here, we reviewed the specific signal transduction pathways and transcription factors involved in the cellular response to UV-irradiation. Increasing experimental data supporting a role for p38, MAPK, JNK, ERK1/2, and ATM kinases in the response network to UV exposure is discussed. We also reviewed the participation of NF-κB, AP-1, and NRF2 transcription factors in the control of gene expression after UV-irradiation. In addition, we discussed the promising chemotherapeutic intervention of transcription factors signaling by natural compounds. Finally, we focused on the review of data emerging from the use of DNA microarray technology to determine changes in global gene expression in keratinocytes and melanocytes in response to UV treatment. Efforts to obtain a comprehensive portrait of the transcriptional events regulating photodamage of intact human epidermis after UV exposure reveals the existence of novel factors participating in UV-induced cell death. Progress in understanding the multitude of mechanisms induced by UV-irradiation could lead to the potential use of protein kinases and novel proteins as specific targets for the prevention and control of skin cancer. PMID:22312244

Transcriptional regulation of xenobiotic detoxification in Drosophila

PubMed Central

Misra, Jyoti R.; Horner, Michael A.; Lam, Geanette; Thummel, Carl S.

2011-01-01

Living organisms, from bacteria to humans, display a coordinated transcriptional response to xenobiotic exposure, inducing enzymes and transporters that facilitate detoxification. Several transcription factors have been identified in vertebrates that contribute to this regulatory response. In contrast, little is known about this pathway in insects. Here we show that the Drosophila Nrf2 (NF-E2-related factor 2) ortholog CncC (cap ‘n’ collar isoform-C) is a central regulator of xenobiotic detoxification responses. A binding site for CncC and its heterodimer partner Maf (muscle aponeurosis fibromatosis) is sufficient and necessary for robust transcriptional responses to three xenobiotic compounds: phenobarbital (PB), chlorpromazine, and caffeine. Genetic manipulations that alter the levels of CncC or its negative regulator, Keap1 (Kelch-like ECH-associated protein 1), lead to predictable changes in xenobiotic-inducible gene expression. Transcriptional profiling studies reveal that more than half of the genes regulated by PB are also controlled by CncC. Consistent with these effects on detoxification gene expression, activation of the CncC/Keap1 pathway in Drosophila is sufficient to confer resistance to the lethal effects of the pesticide malathion. These studies establish a molecular mechanism for the regulation of xenobiotic detoxification in Drosophila and have implications for controlling insect populations and the spread of insect-borne human diseases. PMID:21896655

Transcriptional regulation of gene expression clusters in motor neurons following spinal cord injury.

PubMed

Ryge, Jesper; Winther, Ole; Wienecke, Jacob; Sandelin, Albin; Westerdahl, Ann-Charlotte; Hultborn, Hans; Kiehn, Ole

2010-06-09

Spinal cord injury leads to neurological dysfunctions affecting the motor, sensory as well as the autonomic systems. Increased excitability of motor neurons has been implicated in injury-induced spasticity, where the reappearance of self-sustained plateau potentials in the absence of modulatory inputs from the brain correlates with the development of spasticity. Here we examine the dynamic transcriptional response of motor neurons to spinal cord injury as it evolves over time to unravel common gene expression patterns and their underlying regulatory mechanisms. For this we use a rat-tail-model with complete spinal cord transection causing injury-induced spasticity, where gene expression profiles are obtained from labeled motor neurons extracted with laser microdissection 0, 2, 7, 21 and 60 days post injury. Consensus clustering identifies 12 gene clusters with distinct time expression profiles. Analysis of these gene clusters identifies early immunological/inflammatory and late developmental responses as well as a regulation of genes relating to neuron excitability that support the development of motor neuron hyper-excitability and the reappearance of plateau potentials in the late phase of the injury response. Transcription factor motif analysis identifies differentially expressed transcription factors involved in the regulation of each gene cluster, shaping the expression of the identified biological processes and their associated genes underlying the changes in motor neuron excitability. This analysis provides important clues to the underlying mechanisms of transcriptional regulation responsible for the increased excitability observed in motor neurons in the late chronic phase of spinal cord injury suggesting alternative targets for treatment of spinal cord injury. Several transcription factors were identified as potential regulators of gene clusters containing elements related to motor neuron hyper-excitability, the manipulation of which potentially could be used to alter the transcriptional response to prevent the motor neurons from entering a state of hyper-excitability.

Transcriptional regulation of gene expression clusters in motor neurons following spinal cord injury

PubMed Central

2010-01-01

Background Spinal cord injury leads to neurological dysfunctions affecting the motor, sensory as well as the autonomic systems. Increased excitability of motor neurons has been implicated in injury-induced spasticity, where the reappearance of self-sustained plateau potentials in the absence of modulatory inputs from the brain correlates with the development of spasticity. Results Here we examine the dynamic transcriptional response of motor neurons to spinal cord injury as it evolves over time to unravel common gene expression patterns and their underlying regulatory mechanisms. For this we use a rat-tail-model with complete spinal cord transection causing injury-induced spasticity, where gene expression profiles are obtained from labeled motor neurons extracted with laser microdissection 0, 2, 7, 21 and 60 days post injury. Consensus clustering identifies 12 gene clusters with distinct time expression profiles. Analysis of these gene clusters identifies early immunological/inflammatory and late developmental responses as well as a regulation of genes relating to neuron excitability that support the development of motor neuron hyper-excitability and the reappearance of plateau potentials in the late phase of the injury response. Transcription factor motif analysis identifies differentially expressed transcription factors involved in the regulation of each gene cluster, shaping the expression of the identified biological processes and their associated genes underlying the changes in motor neuron excitability. Conclusions This analysis provides important clues to the underlying mechanisms of transcriptional regulation responsible for the increased excitability observed in motor neurons in the late chronic phase of spinal cord injury suggesting alternative targets for treatment of spinal cord injury. Several transcription factors were identified as potential regulators of gene clusters containing elements related to motor neuron hyper-excitability, the manipulation of which potentially could be used to alter the transcriptional response to prevent the motor neurons from entering a state of hyper-excitability. PMID:20534130

Sec16 in conventional and unconventional exocytosis: Working at the interface of membrane traffic and secretory autophagy?

PubMed

Tang, Bor Luen

2017-12-01

Sec16 is classically perceived to be a scaffolding protein localized to the transitional endoplasmic reticulum (tER) or the ER exit sites (ERES), and has a conserved function in facilitating coat protein II (COPII) complex-mediated ER exit. Recent findings have, however, pointed toward a role for Sec16 in unconventional exocytosis of certain membrane proteins, such as the Cystic fibrosis transmembrane conductance regulator (CFTR) in mammalian cells, and possibly also α-integrin in certain contexts of Drosophila development. In this regard, Sec16 interacts with components of a recently deciphered pathway of stress-induced unconventional exocytosis, which is dependent on the tether protein Golgi reassembly stacking proteins (GRASPs) and the autophagy pathway. Intriguingly, Sec16 also appears to be post-translationally modified by autophagy-related signaling processes. Sec16 is known to be phosphorylated by the atypical extracellular signal regulated kinase 7 (Erk7) upon serum and amino acid starvation, both represent conditions that trigger autophagy. Recent work has also shown that Sec16 is phosphorylated, and thus regulated by the prominent autophagy-initiating Unc-51-like autophagy activating kinase 1 (Ulk1), as well as another autophagy modulator Leucine-rich repeat kinase 2 (Lrrk2). The picture emerging from Sec16's network of physical and functional interactors allows the speculation that Sec16 is situated (and may in yet undefined ways function) at the interface between COPII-mediated exocytosis of conventional vesicular traffic and the GRASP/autophagy-dependent mode of unconventional exocytosis. © 2017 Wiley Periodicals, Inc.

Cigarette Smokers’ Use of Unconventional Tobacco Products and Associations With Quitting Activity: Findings From the ITC-4 U.S. Cohort

PubMed Central

2014-01-01

Introduction: The purpose of this study was to evaluate the prevalence and correlates of use of nicotine-containing tobacco products such as cigars, pipe tobacco, and cigarettes that promise less exposure to toxins; e-cigarettes; and smokeless tobacco products among a cohort of conventional cigarette smokers followed over the past decade. We also evaluated associations between use of such products and cigarette quitting. Methods: Participants were 6,110 adult smokers in the United States, who were interviewed as part of the International Tobacco Control Four Country Survey between 2002 and 2011. Respondents reported their concurrent use of other smoked tobacco products (including cigars, pipe tobacco, and cigarillos), smokeless tobacco products (including chewing tobacco, snus, and snuff), unconventional cigarettes (including Omni, Accord, and Eclipse), and electronic cigarettes. Prevalence and correlates of use and associations between use and cigarette quitting were assessed using regression analyses via generalized estimating equations. Results: Most cigarette smokers did not use unconventional tobacco products, although use of any of these products started to rise at the end of the study period (2011). For each type of tobacco product evaluated, use was most prevalent among those aged 18–24 years. Smokers who did use unconventional tobacco products did not experience a clear cessation advantage. Conclusions: During the past decade, relatively few cigarette smokers reported also using other tobacco products. Those that did use such products were no more likely to stop using conventional cigarettes compared with those who did not use such products. PMID:24376276