VCU Day of Service Toolkit (VCU-DST)

This team designed and developed a digital Day of Service Toolkit (VCU-DST) to help facilitate the planning and execution of community service projects by VCU students, faculty and staff. The VCU-DST includes guidance and relevant procedures for all the aspects of planning needed to execute both large-scale and small-scale projects, including resources for strategic partnerships, financial planning and event logistics and evaluation. The VCU-DST is designed to be utilized for day-of-service projects planned and initiated by VCU students, student leaders, and organizations at all levels (undergraduate, graduate, and professional). The VCU-DST is designed to be flexible and adaptable, assisting in the planning of events of all types and sizes for execution at future dates as the students and their leaders see fit. At the completion of this project, the digital VCU-DST will be delivered to our sponsor, Joyce Lloyd, the faculty advisor for the Graduate Student Government Association. It will also be made available to student leadership and service organizations to assist them in planning their community service project

TNF-α/TNFR1 Signaling Is Required for the Development and Function of Primary Nociceptors

SummaryPrimary nociceptors relay painful touch information from the periphery to the spinal cord. Although it is established that signals generated by receptor tyrosine kinases TrkA and Ret coordinate the development of distinct nociceptive circuits, mechanisms modulating TrkA or Ret pathways in developing nociceptors are unknown. We have identified tumor necrosis factor (TNF) receptor 1 (TNFR1) as a critical modifier of TrkA and Ret signaling in peptidergic and nonpeptidergic nociceptors. Specifically, TrkA+ peptidergic nociceptors require TNF-α-TNFR1 forward signaling to suppress nerve growth factor (NGF)-mediated neurite growth, survival, excitability, and differentiation. Conversely, TNFR1-TNF-α reverse signaling augments the neurite growth and excitability of Ret+ nonpeptidergic nociceptors. The developmental and functional nociceptive defects associated with loss of TNFR1 signaling manifest behaviorally as lower pain thresholds caused by increased sensitivity to NGF. Thus, TNFR1 exerts a dual role in nociceptor information processing by suppressing TrkA and enhancing Ret signaling in peptidergic and nonpeptidergic nociceptors, respectively

Heme oxygenase-1 induction by NRF2 requires inactivation of the transcriptional repressor BACH1

Oxidative stress activates the transcription factor NRF2, which in turn binds cis-acting antioxidant response element (ARE) enhancers and induces expression of protective antioxidant genes. In contrast, the transcriptional repressor BACH1 binds ARE-like enhancers in cells naïve to oxidative stress and antagonizes NRF2 binding until it becomes inactivated by pro-oxidants. Here, we describe the dynamic roles of BACH1 and NRF2 in the transcription of the heme oxygenase-1 (HMOX1) gene. HMOX1 induction, elicited by arsenite-mediated oxidative stress, follows inactivation of BACH1 and precedes activation of NRF2. BACH1 repression is dominant over NRF2-mediated HMOX1 transcription and inactivation of BACH1 is a prerequisite for HMOX1 induction. In contrast, thioredoxin reductase 1 (TXNRD1) is regulated by NRF2 but not by BACH1. By comparing the expression levels of HMOX1 with TXNRD1, we show that nuclear accumulation of NRF2 is not necessary for HMOX1 induction; rather, BACH1 inactivation permits NRF2 already present in the nucleus at low basal levels to bind the HMOX1 promoter and elicit HMOX1 induction. Thus, BACH1 confers an additional level of regulation to ARE-dependent genes that reveals a new dimension to the oxidative stress response

Motif grammar: The basis of the language of gene expression

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Molecular characterization of SMILE as a novel corepressor of nuclear receptors

SMILE (small heterodimer partner interacting leucine zipper protein) has been identified as a coregulator in ER signaling. In this study, we have examined the effects of SMILE on other NRs (nuclear receptors). SMILE inhibits GR, CAR and HNF4α-mediated transactivation. Knockdown of SMILE gene expression increases the transactivation of the NRs. SMILE interacts with GR, CAR and HNF4α in vitro and in vivo. SMILE and these NRs colocalize in the nucleus. SMILE binds to the ligand-binding domain or AF2 domain of the NRs. Competitions between SMILE and the coactivators GRIP1 or PGC-1α have been demonstrated in vitro and in vivo. Furthermore, an intrinsic repressive activity of SMILE is observed in Gal4-fusion system, and the intrinsic repressive domain is mapped to the C-terminus of SMILE, spanning residues 203–354. Moreover, SMILE interacts with specific HDACs (histone deacetylases) and SMILE-mediated repression is released by HDAC inhibitor trichostatin A, in a NR-specific manner. Finally, ChIP (chromatin immunoprecipitation) assays reveal that SMILE associates with the NRs on the target gene promoters. Adenoviral overexpression of SMILE represses GR-, CAR- and HNF4α-mediated target gene expression. Overall, these results suggest that SMILE functions as a novel corepressor of NRs via competition with coactivators and the recruitment of HDACs

Transcriptional Regulation of T Helper 17 Cell Differentiation

The third lineage of T helper subsets, Th17, has recently been identified as an IL-17-producing CD4+ Th cell, and its functions and regulatory mechanisms have been extensively characterized in immune responses. Functional studies have provided evidence that Th17 cells are important for the modulation of autoimmune responses, such as chronic asthma, rheumatoid arthritis, inflammatory bowel diseases, and multiple sclerosis. Murine Th17 cell differentiation is enhanced by the coordinated functions of distinct cytokines including TGFβ, IL-6, IL-21, and IL-23, whereas IL-2, IL-4, IFNγ, and IL-27 inhibit its differentiation. In addition, Th17 cells are controlled by several transcription factors such as RORγ t, IRF4, BATF, FoxP3, T-bet, PPARγ, E-FABP, and SOCSs. This review focuses on the functions and regulatory mechanisms of several transcription factors in the control of Th17 cell differentiation

The Role of bZIP Transcription Factors in Green Plant Evolution: Adaptive Features Emerging from Four Founder Genes

BACKGROUND: Transcription factors of the basic leucine zipper (bZIP) family control important processes in all eukaryotes. In plants, bZIPs are regulators of many central developmental and physiological processes including photomorphogenesis, leaf and seed formation, energy homeostasis, and abiotic and biotic stress responses. Here we performed a comprehensive phylogenetic analysis of bZIP genes from algae, mosses, ferns, gymnosperms and angiosperms. METHODOLOGY/PRINCIPAL FINDINGS: We identified 13 groups of bZIP homologues in angiosperms, three more than known before, that represent 34 Possible Groups of Orthologues (PoGOs). The 34 PoGOs may correspond to the complete set of ancestral angiosperm bZIP genes that participated in the diversification of flowering plants. Homologous genes dedicated to seed-related processes and ABA-mediated stress responses originated in the common ancestor of seed plants, and three groups of homologues emerged in the angiosperm lineage, of which one group plays a role in optimizing the use of energy. CONCLUSIONS/SIGNIFICANCE: Our data suggest that the ancestor of green plants possessed four bZIP genes functionally involved in oxidative stress and unfolded protein responses that are bZIP-mediated processes in all eukaryotes, but also in light-dependent regulations. The four founder genes amplified and diverged significantly, generating traits that benefited the colonization of new environments

DETERMINATION OF MISCONCEPTIONS REGARDING "COMPOUNDS'' CHAPTER IN SECONDARY EDUCATION 9th GRADE BY TWO-TIER CONCEPTUAL UNDERSTANDING TEST

Bu çalışmada ortaöğretim 9. sınıf öğrencilerinin kimya dersi "Bileşikler" ünitesi ile ilgili kavram yanılgılarına sahip olup olmadıklarını ve sahip oldukları kavram yanılgıları varsa bu yanılgıların derecesini tespit edebilmek için iki aşamalı kavramsal anlama testini geliştirmek amaçlanmıştır. Çalışmada ayrıca geliştirilen bu test yoluyla öğrencilerin kavram yanılgılarının belirlenmesi hedeflenmiştir. Toplam 34 maddeden oluşan test İzmir ilinde bulunan ortaöğretim kurumlarında öğrenim görmekte olan ve konuyu bilen toplam 175 öğrenciye uygulanmıştır. Yapılan madde analizleri sonucunda testin güvenirliği, maddelerin güçlük ve ayırt edicilik indeksleri ve çeldirici fonksiyonları elde edilmiştir. Madde analizlerinin sonucunda iki aşamalı kavramsal anlama testinden 10 madde çıkarılmıştır. Testin güvenirlik katsayısı (Cronbach Alfa) 0.80 olarak bulunmuştur. Testin madde güçlük indeksleri 0.24-0.90 aralığında, ayırt edicilik indeksleri ise 0.22-0.50 aralığında bulunmuştur. Testte her bir maddeye verilen yanıtların incelenmesi sonucunda, ünite ile ilgili öğrencilerin bazı kavram yanılgılarına sahip oldukları belirlenmiştir. The aim of this study is to determine whether 9th grade students in secondary schools have misconceptions regarding ‘'compounds'' chapter and to develope a two-tier conceptual understanding test to be able to determine the degree of the misconceptions if there are any. Furthermore; this study aims determining the the misconceptions of the students by means of this test. The test, consisting of a total of 34 items, was carried out with 175 students familiar with the subject and receiving education in secondary schools in Izmir. As a result of item analyses made, the reliability of the test, the difficulty and distinctiveness indices and the distractor functions of the items were acquired. As a result of the analysis item two-tier conceptual understanding test 10 items were removed.The relaibility coefficient of the test (Cronbach Alfa) was found as 0.796. As a result of item analyses, the item difficulty indices were found to be between 0.24-0.90 and the item discrimination index were between 0.20-0.50. Some misconceptions about compounds chapter were determined after the analysis of the items in the tes