Eaf1p Is Required for Recruitment of NuA4 in Targeting TFIID to the Promoters of the Ribosomal Protein Genes for Transcriptional Initiation In Vivo.

NuA4 (nucleosome acetyltransferase of H4) promotes transcriptional initiation of TFIID (a complex of TBP and TBP-associated factors [TAFs])-dependent ribosomal protein genes involved in ribosome biogenesis. However, it is not clearly understood how NuA4 regulates the transcription of ribosomal protein genes. Here, we show that NuA4 is recruited to the promoters of ribosomal protein genes, such as RPS5, RPL2B, and RPS11B, for TFIID recruitment to initiate transcription, and the recruitment of NuA4 to these promoters is impaired in the absence of its Eaf1p component. Intriguingly, impaired NuA4 recruitment in a Δeaf1 strain depletes recruitment of TFIID (a TAF-dependent form of TBP) but not the TAF-independent form of TBP to the promoters of ribosomal protein genes. However, in the absence of NuA4, SAGA (Spt-Ada-Gcn5-acetyltransferase) is involved in targeting the TAF-independent form of TBP to the promoters of ribosomal protein genes for transcriptional initiation. Thus, NuA4 plays an important role in targeting TFIID to the promoters of ribosomal protein genes for transcriptional initiation in vivo. Such a function is mediated via its targeted histone acetyltransferase activity. In the absence of NuA4, ribosomal protein genes lose TFIID dependency and become SAGA dependent for transcriptional initiation. Collectively, these results provide significant insights into the regulation of ribosomal protein gene expression and, hence, ribosome biogenesis and functions

Curcumin supplementation in the rhesus monkey: effects on cognitive decline and neuroinflammation

Human and non-human primates (NHP) undergo age-related cognitive decline beginning as early as middle-age, even in the absence of an underlying pathology or disease. Growing evidence indicates that an increase in white mater pathology related to rising chronic levels of inflammation may be key contributors to age related cognitive decline. Curcumin (CUR), the active ingredient in turmeric, is a polyphenol nutraceutical with potent anti-inflammatory and antioxidative effects. Several ongoing research studies are underway to explore this potential anti-aging compound. For the first time in a rhesus monkey model of aging, we studied the effects of CUR supplementation on cognition and inflammation. Baseline MRI, blood, CSF and cognitive data were collected for all monkeys. Monkeys were fed daily doses of 500mg of CUR or a vehicle control over 18-months during which three rounds of a battery of cognitive testing was performed along with regular collection of blood, CSF and MRI. Following completion of this testing and specific to this thesis, monkeys were further tested on object discrimination, object and spatial reversal tasks. No significant differences were observed between groups in object discrimination task performance. CUR treatment improved performance on object reversal testing, with treated monkeys making fewer perseverative type errors. At the completion of behavioral testing, serum samples from two-year post treatment onset and brain tissue were harvested for post-mortem analysis of markers of inflammation. The density and morphology of microglia, the resident immune cells of the brain, were examined using immunohistochemistry on serial coronal sections through frontal cortical gray (A46, A25) and while matter (FWM, CC, and CngB) regions that are implicated in cognitive aging. We demonstrated that CUR treatment did not significantly alter the density of presumably immune-activated microglia expressing the MHC class II marker LN3. However, treatment did affect morphological features of microglia specifically within the while matter. Within the white matter, CUR treatment was associated with a significant increase in microglial ramification, evidenced by greater process length, number of nodes and convex-hull area and volume. Increased microglial ramification suggests greater likelihood of microglial surveillance within the white matter associated with CUR treatment. No significant group differences however were observed in the select serum cytokine levels quantified using multiplex ELISA, or in inflammatory gene expression in brain tissue measured with qRT-PCR. While our findings show the benefit of CUR supplementation on cognitive performance and its effects on microglial morphology, further study is needed to understand the precise changes that CUR supplementation may have on inflammation

Effects of 2015 earthquake on biological stability of water in Nepal

The April 2015 earthquake in Nepal resulted in the loss of 9000 lives, destroyed several infrastructures and displaced more than 2.3 million people. A study was conducted to analyze the perturbation in biological stability of the water sources compounded by poor sanitation practices in Kathmandu (severe earthquake damage) and Jhapa (no earthquake damage) using microbial source tracking and 16S rRNA sequencing. Samples from the same locations were taken before the earthquake in summer 2014, and then again in May to July, 2015 and in Dec. 2015, corresponding to one month and eight months after the 2015 earthquake. Microbial source tracking of human fecal contamination revealed the deteriorated sanitation practices in some specific sites in Kathmandu after the earthquake. The abundance of certain genera responsible for maintaining geobiochemical characteristics of water (Ammonia Oxidizing Archea and Bacteria, Nitrite Oxidizing Bacteria, Sulfate Reducing Bacteria), for example, Methylobacter, Nitrospira, Methylomonas, increased significantly right after the earthquake and decreased eight months later. This result indicated the disturbance in biostability of water right after the earthquake and also indicated the recovery of microbiomes with time. In addition, sudden spikes in some bacterial genera associated with opportunistic pathogens were observed after the earthquake, which associates with outbreaks observed after such event. This study highlighted the potential disruption of water microbiome after the earthquake and its restoration as a function of time and sanitation practices

Regulation of Antisense Transcription by NuA4 Histone Acetyltransferase and Other Chromatin Regulatory Factors.

NuA4 histone lysine (K) acetyltransferase (KAT) promotes transcriptional initiation of TATA-binding protein (TBP)-associated factor (TAF)-dependent ribosomal protein genes. TAFs have also been recently found to enhance antisense transcription from the 3\u27 end of the GAL10 coding sequence. However, it remains unknown whether, like sense transcription of the ribosomal protein genes, TAF-dependent antisense transcription of GAL10 also requires NuA4 KAT. Here, we show that NuA4 KAT associates with the GAL10 antisense transcription initiation site at the 3\u27 end of the coding sequence. Such association of NuA4 KAT depends on the Reb1p-binding site that recruits Reb1p activator to the GAL10 antisense transcription initiation site. Targeted recruitment of NuA4 KAT to the GAL10 antisense transcription initiation site promotes GAL10 antisense transcription. Like NuA4 KAT, histone H3 K4/36 methyltransferases and histone H2B ubiquitin conjugase facilitate GAL10 antisense transcription, while the Swi/Snf and SAGA chromatin remodeling/modification factors are dispensable for antisense, but not sense, transcription of GAL10. Taken together, our results demonstrate for the first time the roles of NuA4 KAT and other chromatin regulatory factors in controlling antisense transcription, thus illuminating chromatin regulation of antisense transcription

Rrd1p, an RNA polymerase II-specific prolyl isomerase and activator of phosphoprotein phosphatase, promotes transcription independently of rapamycin response.

Rrd1p (resistance to rapamycin deletion 1) has been previously implicated in controlling transcription of rapamycin-regulated genes in response to rapamycin treatment. Intriguingly, we show here that Rrd1p associates with the coding sequence of a galactose-inducible and rapamycin non-responsive GAL1 gene, and promotes the association of RNA polymerase II with GAL1 in the absence of rapamycin treatment following transcriptional induction. Consistently, nucleosomal disassembly at GAL1 is impaired in the absence of Rrd1p, and GAL1 transcription is reduced in the Δrrd1 strain. Likewise, Rrd1p associates with the coding sequences of other rapamycin non-responsive and inducible GAL genes to promote their transcription in the absence of rapamycin treatment. Similarly, inducible, but rapamycin-responsive, non-GAL genes such as CTT1, STL1 and CUP1 are also regulated by Rrd1p. However, transcription of these inducible GAL and non-GAL genes is not altered in the absence of Rrd1p when the steady-state is reached after long transcriptional induction. Consistently, transcription of the constitutively active genes is not changed in the Δrrd1 strain. Taken together, our results demonstrate a new function of Rrd1p in stimulation of initial rounds of transcription, but not steady-state/constitutive transcription, of both rapamycin-responsive and non-responsive genes independently of rapamycin treatment

Controlling opioid receptor functional selectivity by targeting distinct subpockets of the orthosteric site

Controlling receptor functional selectivity profiles for opioid receptors is a promising approach for discovering safer analgesics; however, the structural determinants conferring functional selectivity are not well understood. Here, we used crystal structures of opioid receptors, including the recently solved active state kappa opioid complex wit

Session 2 -Mapping and Soil Micronutrient Status Mapping Spatial Zinc Distribution in Rupandehi District, Nepal

Abstrac

DXL: a sounding rocket mission for the study of solar wind charge exchange and local hot bubble X-ray emission

The Diffuse X-rays from the Local galaxy (DXL) mission is an approved sounding rocket project with a first launch scheduled around December 2012. Its goal is to identify and separate the X-ray emission generated by solar wind charge exchange from that of the local hot bubble to improve our understanding of both. With 1,000 cm2 proportional counters and grasp of about 10 cm2 sr both in the 1/4 and 3/4 keV bands, DXL will achieve in a 5-minute flight what cannot be achieved by current and future X-ray satellites.Comment: 15 Pages, 5 figures. Accepted for publication on Experimental Astronom

THE STRUCTURE OF THE LOCAL HOT BUBBLE

Diffuse X-rays from the Local Galaxy (DXL) is a sounding rocket mission designed to quantify and characterize the contribution of Solar Wind Charge eXchange (SWCX) to the Diffuse X-ray Background and study the properties of the Local Hot Bubble (LHB). Based on the results from the DXL mission, we quantified and removed the contribution of SWCX to the diffuse X-ray background measured by the ROSAT All Sky Survey. The "cleaned" maps were used to investigate the physical properties of the LHB. Assuming thermal ionization equilibrium, we measured a highly uniform temperature distributed around kT = 0.097 keV ± 0.013 keV (FWHM) ± 0.006 keV (systematic). We also generated a thermal emission measure map and used it to characterize the three-dimensional (3D) structure of the LHB, which we found to be in good agreement with the structure of the local cavity measured from dust and gas