Soils as a factor in Pinyon Pine mortality due to Ips Beetle infestation in Garden Park, Colorado: a case study.

Abstract: Observations by European settlers indicate that the distribution of pinyon - juniper woodlands has been expanding in the southwestern United States over the last two centuries. Beginning in the late 1990s, drought conditions in the region, along with ips beetle infestations have led to destruction of entire viewsheds of pinyon pine trees. The reduced availability of moisture associated with drought stresses pinyon pines and reduces their ability to resist ips beetle infestation. They are unable to produce the sap necessary to pitch out the boring beetles. These woodlands exist on a marginal environment where slight variations in the moisture balance affect the survivability of such trees. Factors such as elevation, slope, aspect, tree density and soil properties affect the moisture availability of the trees. This study looks at the nature of soil as a possible factor in a tree's ability to resist ips beetle infestation. Trees situated on deeper, richer soils with greater water holding capacity and shallower slope were expected to show an increased resistance to ips beetle infestation. The results of this research, however, did not show any statistically significant difference between the soil conditions at infested and uninfected sites. This finding leads to speculation that after some as of yet unknown point in a drought cycle, even those trees on the best soils are susceptible to beetle infestation and cannot survive

The Bipartite Structure of the tRNA m\u3csup\u3e1\u3c/sup\u3eA58 Methyltransferase from \u3cem\u3eS. cerevisiae\u3c/em\u3e is Conserved in Humans

Among all types of RNA, tRNA is unique given that it possesses the largest assortment and abundance of modified nucleosides. The methylation at N1 of adenosine 58 is a conserved modification, occurring in bacterial, archaeal, and eukaryotic tRNAs. In the yeast Saccharomyces cerevisiae, the tRNA 1-methyladenosine 58 (m1A58) methyltransferase (Mtase) is a two-subunit enzyme encoded by the essential genes TRM6 (GCD10) and TRM61 (GCD14). While the significance of many tRNA modifications is poorly understood, methylation of A58 is known to be critical for maintaining the stability of initiator tRNAMet in yeast. Furthermore, all retroviruses utilize m1A58-containing tRNAs to prime reverse transcription, and it has been shown that the presence of m1A58 in human tRNA3 Lys is needed for accurate termination of plus-strand strong-stop DNA synthesis during HIV-1 replication. In this study we have identified the human homologs of the yeast m1A Mtase through amino acid sequence identity and complementation of trm6 and trm61 mutant phenotypes. When coexpressed in yeast, human Trm6p and Trm61p restored the formation of m1A in tRNA, modifying both yeast initiator tRNAMet and human tRNA3 Lys. Stable hTrm6p/hTrm61p complexes purified from yeast maintained tRNA m1A Mtase activity in vitro. The human m1A Mtase complex also exhibited substrate specificity—modifying wild-type yeast tRNAi Met but not an A58U mutant. Therefore, the human tRNA m1A Mtase shares both functional and structural homology with the yeast tRNA m1A Mtase, possessing similar enzymatic activity as well as a conserved binary composition

Nuclear Surveillance and Degradation of Hypomodified Initiator tRNA\u3csup\u3eMet\u3c/sup\u3e in \u3cem\u3eS. cerevisiae\u3c/em\u3e

The tRNA m1A58 methyltransferase is composed of two subunits encoded by the essential genes TRM6 and TRM61 (formerly GCD10 and GCD14). The trm6-504 mutation results in a defective m1A methyltransferase (Mtase) and a temperature-sensitive growth phenotype that is attributable to the absence of m1A58 and consequential tRNAiMet instability. We used a genetic approach to identify the genes responsible for tRNAiMet degradation in trm6 cells. Three recessive extragenic mutations that suppress trm6-504 mutant phenotypes and restore hypomodified tRNAiMet to near normal levels were identified. The wild-type allele of one suppressor, DIS3/RRP44, encodes a 3′-5′ exoribonuclease and a member of the multisubunit exosome complex. We provide evidence that a functional nuclear exosome is required for the degradation of tRNAiMet lacking m1A58. A second suppressor gene encodes Trf4p, a DNA polymerase (pol σ) with poly(A) polymerase activity. Whereas deletion of TRF4 leads to stabilization of tRNAiMet, overexpression of Trf4p destabilizes the hypomodified tRNAiMet in trm6 cells. The hypomodified, but not wild-type, pre-tRNAiMet accumulates as a polyadenylated species, whose abundance and length distribution both increase upon Trf4p overexpression. These data indicate that a tRNA surveillance pathway exists in yeast that requires Trf4p and the exosome for polyadenylation and degradation of hypomodified pre-tRNAiMet

TOP-UP OPERATIONAL EXPERIENCE AT ELETTRA

Abstract Since May 2010 Elettra, operates in top-up at both 2 and 2.4 GeV user energies. In this paper the experience during more than a year of operation in top-up is discussed and the machine up time statistics are presented and compared with the before top up period

BEAM ORBIT STABILITY AT ELETTRA

Abstract The top-up operation established since 2010 at the Elettra third-generation synchrotron light source has solved the problems related to thermal drifts and beam current dependence, and a series of feedback loops acting on the machine optics and radio-frequency systems made easier to setup and operate the ring. Those systems together with the fast orbit feedback in operation since 2007, contributed to very high electron beam orbit stability. A description of the active systems and their performance, future perspectives as well as some still open issues will be presented and discussed

Common operation metrics for storage ring light sources

Storage ring light sources aim for high operational reliability. Very often beam availability is used as an operation metric to measure the reliability. A survey of several light sources reveals that the calculation of availability varies significantly between facilities. This complicates useful comparisons of reliability. Furthermore the beam availability does not provide insight regarding reliability of beam characteristics such as orbit and beam size stability. The authors propose specific metrics to evaluate the reliability of storage ring light sources; these metrics allow a detailed and meaningful comparison across facilities. Such comparisons are useful to further optimize the reliability of storage ring light source facilities

Assessment of ifosfamide pharmacokinetics, toxicity, and relation to CYP3A4 activity as measured by the erythromycin breath test in patients with sarcoma

BACKGROUND. Ifosfamide is a chemotherapeutic agent that requires cytochrome P450 3A (CYP3A) for bioactivation and metabolism. To the authors' knowledge, the correlation between dose, pharmacokinetics, CYP3A, and toxicity has not been fully evaluated. A randomized Phase II trial was performed on 22 soft tissue sarcoma patients treated with doxorubicin (60 mg/m 2 /cycle) and either high-dose ifosfamide (12 g/m 2 /cycle) or standard-dose ifosfamide (6 g/m 2 /cycle). The pharmacokinetics of ifosfamide and CYP3A measurements observed are reported. METHODS. Pharmacokinetic parameters for ifosfamide, 2-dichloroethylifosfamide (2-DCE), and 3-dichloroethylifosfamide (3-DCE) were collected after the first ifosfamide infusion in 13 patients. Bayesian designed limited pharmacokinetic data were collected from an additional 41 patients. The erythromycin breath test (ERMBT) was performed on 81 patients as an in vivo phenotypic assessment of CYP3A activity. RESULTS. Fourteen-hour (peak) plasma levels of ifosfamide, 2-DCE, and 3-DCE were found to correlate strongly with the respective area under the curve (AUC) 0–24 values ( r = 0.97, 0.94, and 0.95; P < .0001). Patients who experienced a grade 3–4 absolute neutrophil count (ANC), platelet, or creatinine toxicity (using the National Cancer Institute Common Toxicity Criteria [version 2]) were found to have statistically significantly higher median 14-hour plasma levels of ifosfamide, 2-DCE, and 3-DCE compared with patients with grade 0–2 toxicity. ERMBT was not found to correlate with pharmacokinetic parameters of ifosfamide and metabolites or toxicity. CONCLUSIONS. The 14-hour plasma level of ifosfamide, 2-DCE, and 3-DCE is a simple and appropriate substitute for describing the AUC of ifosfamide after 1 day of a 1-hour to 2-hour infusion of drug. Fourteen-hour plasma levels of ifosfamide and metabolites are useful predictors of neutropenia, thrombocytopenia, and creatinine toxicity. ERMBT was not found to accurately correlate with ifosfamide pharmacokinetics or clinical toxicity. Cancer 2007. © 2007 American Cancer Society.Peer Reviewedhttp://deepblue.lib.umich.edu/bitstream/2027.42/56045/1/22669_ftp.pd

Electron Tomography Reveals Posttranscriptional Binding of Pre-Mrnps to Specific Fibers in the Nucleoplasm

Using electron tomography, we have analyzed whether the Balbiani ring (BR) pre-mRNP particles in transit from the gene to the nuclear pore complex (NPC) are bound to any structure that could impair free diffusion through the nucleoplasm. We show that one-third of the BR particles are in contact with thin connecting fibers (CFs), which in some cases merge into large fibrogranular clusters. The CFs have a specific protein composition different from that of BR particles, as shown by immuno-EM. Moreover, we have identified hrp65 as one of the protein components of the CFs. The sequencing of hrp65 cDNA reveals similarities with hnRNP proteins and splicing factors. However, hrp65 is likely to have a different function because it does not bind to nascent pre-mRNA and is not part of the pre-mRNP itself. Taken together, our observations indicate that pre-mRNPs are not always freely diffusible in the nucleoplasm but interact with fibers of specific structure and composition, which implies that some of the posttranscriptional events that the pre-mRNPs undergo before reaching the NPC occur in a bound state

Soluble egg antigen of Schistosoma Haematobium induces HCV replication in PBMC from patients with chronic HCV infection

BACKGROUND: This study was conducted to examine, in vitro , the effect of soluble egg antigen (SEA) of S. haematobium on intracellular HCV RNA load in peripheral mononuclear cells (PBMC) as well as on cell proliferation in patients with chronic HCV infection. METHODS: PBMC from 26 patients with chronic HCV infection were cultured for 72 hours in presence and absence of 50 μg SEA/ml medium. Intracellular HCV RNA quantification of plus and minus strands was assessed before and after stimulation. PBMC from five healthy subjects were cultured for 7 days, flow cytometric analysis of DNA content was used to assess the mitogenic effect of SEA on PBMC proliferation compared to phytoheamaglutinine (PHA). RESULTS: Quantification of the intracellular viral load showed increased copy number/cell of both or either viral strands after induction with SEA in 18 of 26 patients (69.2%) thus indicating stimulation of viral replication. Flow cytometric analysis showed that mean ± S.D. of percent values of cell proliferation was induced from 3.2 ± 1.5% in un-stimulated cells to 16.7 ± 2.5 % and 16.84 ± 1.7 % in cells stimulated with PHA and SEA respectively. CONCLUSION: the present study supports earlier reports on SEA proliferative activity on PBMC and provides a strong evidence that the higher morbidity observed in patients co-infected with schistosomiasis and HCV is related, at least in part, to direct stimulation of viral replication by SEA

Deregulated expression of hnRNP A/B proteins in human non-small cell lung cancer: parallel assessment of protein and mRNA levels in paired tumour/non-tumour tissues

<p>Abstract</p> <p>Background</p> <p>Heterogeneous nuclear ribonucleoproteins (hnRNPs) of the A/B type (hnRNP A1, A2/B1, A3) are highly related multifunctional proteins participating in alternative splicing by antagonising other splicing factors, notably ASF/SF2. The altered expression pattern of hnRNP A2/B1 and/or splicing variant B1 alone in human lung cancer and their potential to serve as molecular markers for early diagnosis remain issues of intense investigation. The main objective of the present study was to use paired tumour/non-tumour biopsies from patients with non-small cell lung cancer (NSCLC) to investigate the expression profiles of hnRNP A1, A2/B1 and A3 in conjunction with ASF/SF2.</p> <p>Methods</p> <p>We combined western blotting of tissue homogenates with immunohistochemical examination of fixed tissue sections and quantification of mRNA expression levels in tumour versus adjacent normal-looking areas of the lung in the same patient.</p> <p>Results</p> <p>Our study, in addition to clear evidence of mostly uncoupled deregulation of hnRNPs A/B, has revealed hnRNP A1 to be the most deregulated protein with a high frequency of over-expression (76%), followed by A3 (52%) and A2/B1 (43%). Moreover, direct comparison of protein/mRNA levels showed a lack of correlation in the case of hnRNP A1 (as well as of ASF/SF2), but not of A2/B1, suggesting that different mechanisms underlie their deregulation.</p> <p>Conclusion</p> <p>Our results provide strong evidence for the up-regulation of hnRNP A/B in NSCLC, and they support the existence of distinct mechanisms responsible for their deregulated expression.</p