Herschel observations of water vapour in Markarian 231

The Ultra Luminous InfraRed Galaxy Mrk 231 reveals up to seven rotational lines of water (H2O) in emission, including a very high-lying (E_{upper}=640 K) line detected at a 4sigma level, within the Herschel/SPIRE wavelength range, whereas PACS observations show one H2O line at 78 microns in absorption, as found for other H2O lines previously detected by ISO. The absorption/emission dichotomy is caused by the pumping of the rotational levels by far-infrared radiation emitted by dust, and subsequent relaxation through lines at longer wavelengths, which allows us to estimate both the column density of H2O and the general characteristics of the underlying far-infrared continuum source. Radiative transfer models including excitation through both absorption of far-infrared radiation emitted by dust and collisions are used to calculate the equilibrium level populations of H2O and the corresponding line fluxes. The highest-lying H2O lines detected in emission, with levels at 300-640 K above the ground state, indicate that the source of far-infrared radiation responsible for the pumping is compact (radius=110-180 pc) and warm (T_{dust}=85-95 K), accounting for at least 45% of the bolometric luminosity. The high column density, N(H2O)~5x10^{17} cm^{-2}, found in this nuclear component, is most probably the consequence of shocks/cosmic rays, an XDR chemistry, and/or an "undepleted chemistry" where grain mantles are evaporated. A more extended region, presumably the inner region of the 1-kpc disk observed in other molecular species, could contribute to the flux observed in low-lying H2O lines through dense hot cores, and/or shocks. The H2O 78 micron line observed with PACS shows hints of a blue-shifted wing seen in absorption, possibly indicating the occurrence of H2O in the prominent outflow detected in OH (Fischer et al., this volume).Comment: 5 pages, 3 figure

Black hole accretion and star formation as drivers of gas excitation and chemistry in Mrk231

We present a full high resolution SPIRE FTS spectrum of the nearby ultraluminous infrared galaxy Mrk231. In total 25 lines are detected, including CO J=5-4 through J=13-12, 7 rotational lines of H2O, 3 of OH+ and one line each of H2O+, CH+, and HF. We find that the excitation of the CO rotational levels up to J=8 can be accounted for by UV radiation from star formation. However, the approximately flat luminosity distribution of the CO lines over the rotational ladder above J=8 requires the presence of a separate source of excitation for the highest CO lines. We explore X-ray heating by the accreting supermassive black hole in Mrk231 as a source of excitation for these lines, and find that it can reproduce the observed luminosities. We also consider a model with dense gas in a strong UV radiation field to produce the highest CO lines, but find that this model strongly overpredicts the hot dust mass in Mrk231. Our favoured model consists of a star forming disk of radius 560 pc, containing clumps of dense gas exposed to strong UV radiation, dominating the emission of CO lines up to J=8. X-rays from the accreting supermassive black hole in Mrk231 dominate the excitation and chemistry of the inner disk out to a radius of 160 pc, consistent with the X-ray power of the AGN in Mrk231. The extraordinary luminosity of the OH+ and H2O+ lines reveals the signature of X-ray driven excitation and chemistry in this region.Comment: 5 pages, 2 figures, accepted for publication in Astronomy & Astrophysics Special Issue on Herschel first result

Transduction of SIV-Specific TCR Genes into Rhesus Macaque CD8+ T Cells Conveys the Ability to Suppress SIV Replication

The SIV/rhesus macaque model for HIV/AIDS is a powerful system for examining the contribution of T cells in the control of AIDS viruses. To better our understanding of CD8(+) T-cell control of SIV replication in CD4(+) T cells, we asked whether TCRs isolated from rhesus macaque CD8(+) T-cell clones that exhibited varying abilities to suppress SIV replication could convey their suppressive properties to CD8(+) T cells obtained from an uninfected/unvaccinated animal.We transferred SIV-specific TCR genes isolated from rhesus macaque CD8(+) T-cell clones with varying abilities to suppress SIV replication in vitro into CD8(+) T cells obtained from an uninfected animal by retroviral transduction. After sorting and expansion, transduced CD8(+) T-cell lines were obtained that specifically bound their cognate SIV tetramer. These cell lines displayed appropriate effector function and specificity, expressing intracellular IFNγ upon peptide stimulation. Importantly, the SIV suppression properties of the transduced cell lines mirrored those of the original TCR donor clones: cell lines expressing TCRs transferred from highly suppressive clones effectively reduced wild-type SIV replication, while expression of a non-suppressing TCR failed to reduce the spread of virus. However, all TCRs were able to suppress the replication of an SIV mutant that did not downregulate MHC-I, recapitulating the properties of their donor clones.Our results show that antigen-specific SIV suppression can be transferred between allogenic T cells simply by TCR gene transfer. This advance provides a platform for examining the contributions of TCRs versus the intrinsic effector characteristics of T-cell clones in virus suppression. Additionally, this approach can be applied to develop non-human primate models to evaluate adoptive T-cell transfer therapy for AIDS and other diseases

A Systems Biology Approach Reveals the Role of a Novel Methyltransferase in Response to Chemical Stress and Lipid Homeostasis

Using small molecule probes to understand gene function is an attractive approach that allows functional characterization of genes that are dispensable in standard laboratory conditions and provides insight into the mode of action of these compounds. Using chemogenomic assays we previously identified yeast Crg1, an uncharacterized SAM-dependent methyltransferase, as a novel interactor of the protein phosphatase inhibitor cantharidin. In this study we used a combinatorial approach that exploits contemporary high-throughput techniques available in Saccharomyces cerevisiae combined with rigorous biological follow-up to characterize the interaction of Crg1 with cantharidin. Biochemical analysis of this enzyme followed by a systematic analysis of the interactome and lipidome of CRG1 mutants revealed that Crg1, a stress-responsive SAM-dependent methyltransferase, methylates cantharidin in vitro. Chemogenomic assays uncovered that lipid-related processes are essential for cantharidin resistance in cells sensitized by deletion of the CRG1 gene. Lipidome-wide analysis of mutants further showed that cantharidin induces alterations in glycerophospholipid and sphingolipid abundance in a Crg1-dependent manner. We propose that Crg1 is a small molecule methyltransferase important for maintaining lipid homeostasis in response to drug perturbation. This approach demonstrates the value of combining chemical genomics with other systems-based methods for characterizing proteins and elucidating previously unknown mechanisms of action of small molecule inhibitors

Genomic organization, sequence analysis and expression of all five genes encoding the small subunit of ribulose-1,5-bisphosphate carboxylase/oxygenase from tomato

We have cloned and sequenced all five members of the gene family for the small subunit (rbcS) of ribulose-1,5-bisphosphate carboxylase/oxygenase from tomato, Lycopersicon esculentum cv. VFNT LA 1221 cherry line. Two of the five genes, designated Rbcs-1 and Rbcs-2 , are present as single genes at individual loci. Three genes, designated Rbcs-3A, Rbcs-3B and Rbcs-3C , are organized in a tandem array within 10 kb at a third independent locus. The Rbcs-2 gene contains three introns; all the other members of the tomato gene family contain two introns. The coding sequence of Rbcs-1 differs by 14.0% from that of Rbcs-2 and by 13.3% from that of Rbcs-3 genes. Rbcs-2 shows 10.4% divergence from Rbcs-3 . The exon and intron sequences of Rbcs-3A are identical to those of Rbcs-3C , and differ by 1.9% from those of Rbcs-3B . Nucleotide sequence analysis suggests that the five rbcS genes encode four different precursors, and three different mature polypeptides. S 1 nuclease mapping of the 5′ end of rbcS mRNAs revealed that the mRNA leader sequences vary in length from 8 to 75 nucleotides. Northern analysis using gene-specific oligonucleotide probes from the 3′ non-coding region of each gene reveals a four to five-fold difference among the five genes in maximal steady-state mRNA levels in leaves.Peer Reviewedhttp://deepblue.lib.umich.edu/bitstream/2027.42/47566/1/438_2004_Article_BF00329650.pd

Low temperature-short duration steaming of soil kills soil-borne pathogens, nematode pests and weeds

Agricultural soil samples containing survival structures of the fungal crop pathogens Verticillium dahliae, Sclerotinia sclerotiorum, Sclerotium cepivorum, Pythium ultimum, potato cyst nematodes Globodera rostochiensis and G. pallida and weeds Chenopodium album and Agropyron repens [Elymus repens] were treated in the laboratory with aerated steam at temperatures ranging from 40 to 80degreesC in a specially constructed apparatus. Steaming at 50 or 60degreesC for 3 min, followed by an 8-min resting period in the steamed soil and immediate removal from the soil thereafter, resulted in 100% kill of all weeds, diseases and nematodes. When steamed at 45degreesC, there was a small but significant reduction in the survival of V. dahliae microsclerotia but no reduction in survival of S. cepivorum

Implementation of a semiautomatic method to design patient-specific instruments for corrective osteotomy of the radius

PURPOSE: 3D-printed patient-specific instruments (PSIs), such as surgical guides and implants, show great promise for accurate navigation in surgical correction of post-traumatic deformities of the distal radius. However, existing costs of computer-aided design and manufacturing process prevent everyday surgical use. In this paper, we propose an innovative semiautomatic methodology to streamline the PSIs design. METHODS: The new method was implemented as an extension of our existing 3D planning software. It facilitates the design of a regular and smooth implant and a companion guide starting from a user-selected surface on the affected bone. We evaluated the software by designing PSIs starting from preoperative virtual 3D plans of five patients previously treated at our institute for corrective osteotomy. We repeated the design for the same cases also with commercially available software, with and without dedicated customization. We measured design time and tracked user activity during the design process of implants, guides and subsequent modifications. RESULTS: All the designed shapes were considered valid. Median design times ([Formula: see text]) were reduced for implants (([Formula: see text]) = 2.2 min) and guides (([Formula: see text]) = 1.0 min) compared to the standard (([Formula: see text]) = 13 min and ([Formula: see text]) = 8 min) and the partially customized (([Formula: see text]) = 6.5 min and ([Formula: see text]) = 6.0 min) commercially available alternatives. Mouse and keyboard activities were reduced (median count of strokes and clicks during implant design (([Formula: see text]) = 53, and guide design (([Formula: see text]) = 27) compared to using standard software (([Formula: see text]) = 559 and ([Formula: see text]) = 380) and customized commercial software (([Formula: see text]) = 217 and ([Formula: see text]) = 180). CONCLUSION: Our software solution efficiently streamlines the design of PSIs for distal radius malunion. It represents a first step in making 3D-printed PSIs technology more accessible