Promoter analysis of intestinal genes induced during iron-deprivation reveals enrichment of conserved SP1-like binding sites

<p>Abstract</p> <p>Background</p> <p>Iron-deficiency leads to the induction of genes related to intestinal iron absorption and homeostasis. By analyzing a large GeneChip^®dataset from the rat intestine, we identified a large cluster of 228 genes that was induced by iron-deprivation. Only 2 of these genes contained 3' iron-response elements, suggesting that other regulation including transcriptional may be involved. We therefore utilized computational methods to test the hypothesis that some of the genes within this large up-regulated cluster are co-ordinately regulated by common transcriptional mechanisms. We thus identified promoters from the up-regulated gene cluster from rat, mouse and human, and performed enrichment analyses with the Clover program and the TRANSFAC database.</p> <p>Results</p> <p>Surprisingly, we found a strong statistical enrichment for SP1 binding sites in our experimental promoters as compared to background sequences. As the TRANSFAC database cannot distinguish among SP/KLF family members, many of which bind similar GC-rich DNA sequences, we surmise that SP1 or an SP1-like factor could be involved in this response. In fact, we detected induction of SP6/KLF14 in the GeneChip^®studies, and confirmed it by real-time PCR. Additional computational analyses suggested that an SP1-like factor may function synergistically with a FOX TF to regulate a subset of these genes. Furthermore, analysis of promoter sequences identified many genes with multiple, conserved SP1 and FOX binding sites, the relative location of which within orthologous promoters was highly conserved.</p> <p>Conclusion</p> <p>SP1 or a closely related factor may play a primary role in the genetic response to iron-deficiency in the mammalian intestine.</p

Prediction of synergistic transcription factors by function conservation

A new strategy is proposed for identifying synergistic transcription factors by function conservation, leading to the identification of 51 homotypic transcription-factor combinations

Not Your Typical Administrator

Presenters will examine the trend of “wearing many hats” in higher education leadership. For example, being both a department chair and faculty member. In addition, the notion of successfully managing up, the importance of understanding each role you have, and understanding your situational role and the communication we use will be discussed. Lastly, participants will engage in case study scenarios challenging participants to consider various administrative situations and identifying reasonable approaches based on which “hat” you are wearing

So Much Change!

Presenters will examine change and change management in higher education leadership. For example, creating and managing fully remote faculty. Additionally, presenters will examine the importance of flexibility, as roles and demands change within administration. Lastly, participants will discuss strategies for navigating change

Intersection of Iron and Copper Metabolism in the Mammalian Intestine and Liver

Iron and copper have similar physiochemical properties; thus, physiologically relevant interactions seem likely. Indeed, points of intersection between these two essential trace minerals have been recognized for many decades, but mechanistic details have been lacking. Investigations in recent years have revealed that copper may positively influence iron homeostasis, and also that iron may antagonize copper metabolism. For example, when body iron stores are low, copper is apparently redistributed to tissues important for regulating iron balance, including enterocytes of upper small bowel, the liver, and blood. Copper in enterocytes may positively influence iron transport, and hepatic copper may enhance biosynthesis of a circulating ferroxidase, ceruloplasmin, which potentiates iron release from stores. Moreover, many intestinal genes related to iron absorption are transactivated by a hypoxia-inducible transcription factor, hypoxia- inducible factor-2 alpha (HIF2 alpha), during iron deficiency. Interestingly, copper influences the DNA-binding activity of the HIF factors, thus further exemplifying how copper may modulate intestinal iron homeostasis. Copper may also alter the activity of the iron-regulatory hormone hepcidin. Furthermore, copper depletion has been noted in iron-loading disorders, such as hereditary hemochromatosis. Copper depletion may also be caused by high-dose iron supplementation, raising concerns particularly in pregnancy when iron supplementation is widely recommended. This review will cover the basic physiology of intestinal iron and copper absorption as well as the metabolism of these minerals in the liver. Also considered in detail will be current experimental work in this field, with a focus on molecular aspects of intestinal and hepatic iron-copper interplay and how this relates to various disease states. (c) 2018 American Physiological Society.National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK)United States Department of Health & Human ServicesNational Institutes of Health (NIH) - USANIH National Institute of Diabetes & Digestive & Kidney Diseases (NIDDK) [R01 DK074867]; NIDDK and the Office of Dietary Supplements [R01 DK109717]; NATIONAL INSTITUTE OF DIABETES AND DIGESTIVE AND KIDNEY DISEASESUnited States Department of Health & Human ServicesNational Institutes of Health (NIH) - USANIH National Institute of Diabetes & Digestive & Kidney Diseases (NIDDK) [R01DK074867, R01DK109717] Funding Source: NIH RePORTERThe authors of this manuscript are supported by grants R01 DK074867 from the National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK) and R01 DK109717 from NIDDK and the Office of Dietary Supplements (J. F. Collins, PI)

Bare Below the Elbows: A comparative study of a tertiary and district general hospital.

A \u27Bare Below the Elbows\u27 (BBTE) dress code policy has been introduced by the majority of NHS trusts in the UK. The aim of this Irish study was to evaluate the impact of an educational intervention on perception of medical attire. The study was carried out in two centres: a tertiary referral centre (Beaumont Hospital) and a district hospital (MRH, Portlaoise). Two questionnaires, incorporating photographic evaluation of appropriate attire for consultants and junior doctors, were completed pre and post BBTE education. One hundred and five patients participated. Analysis pre BBTE education indicated patients considered formal attire and white coats most appropriate for consultants and junior doctors respectively. Post-intervention analysis revealed a significant reduction in the popularity of both (

Tuning and controlling gene expression noise in synthetic gene networks

Synthetic gene networks can be used to control gene expression and cellular phenotypes in a variety of applications. In many instances, however, such networks can behave unreliably due to gene expression noise. Accordingly, there is a need to develop systematic means to tune gene expression noise, so that it can be suppressed in some cases and harnessed in others, e.g. in cellular differentiation to create population-wide heterogeneity. Here, we present a method for controlling noise in synthetic eukaryotic gene expression systems, utilizing reduction of noise levels by TATA box mutations and noise propagation in transcriptional cascades. Specifically, we introduce TATA box mutations into promoters driving TetR expression and show that these mutations can be used to effectively tune the noise of a target gene while decoupling it from the mean, with negligible effects on the dynamic range and basal expression. We apply mathematical and computational modeling to explain the experimentally observed effects of TATA box mutations. This work, which highlights some important aspects of noise propagation in gene regulatory cascades, has practical implications for implementing gene expression control in synthetic gene networks

Mathematical modelling for the transmission dynamics of Rift Valley fever virus with human host

Rift Valley Fever (RVF) is a viral zoonosis spread primarily by mosquitos that primarily affects livestock but has the potential to affect humans. Because of its potential to spread quickly and become an epidemic, it has become a public concern. In this article, the transmission dynamics of RVF with mosquito, livestock and human host using a compartmental model is studied and analyzed. The basic reproduction number R0 is computed using next generation matrix and the disease-free equilibrium state is found to be locally asymptotically stable if R0 1 which implies that rift valley fever could be put under control in a population where the reproduction number is less than 1. The numerical simulations give insightful results to further explore the dynamics of the disease based on the effect of three interventions; efficacy of vaccination, culling of livestock and trapping of mosquitoes introduced in the model