A New Approach toward Transition State Spectroscopy

Chirped-Pulse millimetre-Wave (CPmmW) rotational spectroscopy provides a new class of information about photolysis transition state(s). Measured intensities in rotational spectra determine species-isomer-vibrational populations, provided that rotational populations can be thermalized. The formation and detection of S0 vinylidene is discussed in the limits of low and high initial rotational excitation. CPmmW spectra of 193 nm photolysis of Vinyl Cyanide (Acrylonitrile) contain J=0-1 transitions in more than 20 vibrational levels of HCN, HNC, but no transitions in vinylidene or highly excited local-bender vibrational levels of acetylene. Reasons for the non-observation of the vinylidene co-product of HCN are discussed.Comment: Accepted by Faraday Discussion

Comparative genomics of Australian isolates of the wheat stem rust pathogen Puccinia graminis f. sp. tritici reveals extensive polymorphism in candidate effector genes

The wheat stem rust fungus Puccinia graminis f. sp. tritici (Pgt) is one of the most destructive pathogens of wheat. In this study, a draft genome was built for a founder Australian Pgt isolate of pathotype (pt.) 21-0 (collected in 1954) by next generation DNA sequencing. A combination of reference-based assembly using the genome of the previously sequenced American Pgt isolate CDL 75-36-700-3 (p7a) and de novo assembly were performed resulting in a 92 Mbp reference genome for Pgt isolate 21-0. Approximately 13 Mbp of de novo assembled sequence in this genome is not present in the p7a reference assembly. This novel sequence is not specific to 21-0 as it is also present in three other Pgt rust isolates of independent origin. The new reference genome was subsequently used to build a pan-genome based on five Australian Pgt isolates. Transcriptomes from germinated urediniospores and haustoria were separately assembled for pt. 21-0 and comparison of gene expression profiles showed differential expression in ∼10% of the genes each in germinated spores and haustoria. A total of 1,924 secreted proteins were predicted from the 21-0 transcriptome, of which 520 were classified as haustorial secreted proteins (HSPs). Comparison of 21-0 with two presumed clonal field derivatives of this lineage (collected in 1982 and 1984) that had evolved virulence on four additional resistance genes (Sr5, Sr11, Sr27, SrSatu) identified mutations in 25 HSP effector candidates. Some of these mutations could explain their novel virulence phenotypes.Authors wish to thank the Two Blades Foundation for financial support. Part of this work was supported through access to facilities managed by Bioplatforms Australia and funded by the Australian Government National Collaborative Research Infrastructure Strategy and Education Investment Fund Super Science Initiative

Attenuation of PTEN increases p21 stability and cytosolic localization in kidney cancer cells: a potential mechanism of apoptosis resistance

BACKGROUND: The PTEN (Phosphatase and Tensin homolog deleted on chromosome Ten) tumor suppressor gene is frequently mutated or deleted in a wide variety of solid tumors, and these cancers are generally more aggressive and difficult to treat than those possessing wild type PTEN. While PTEN lies upstream of the phosphoinositide-3 kinase signaling pathway, the mechanisms that mediate its effects on tumor survival remain incompletely understood. Renal cell carcinoma (RCC) is associated with frequent treatment failures (~90% in metastatic cases), and these tumors frequently contain PTEN abnormalities. RESULTS: Using the ACHN cell line containing wild type PTEN, we generated a stable PTEN knockdown RCC cell line using RNA interference. We then used this PTEN knockdown cell line to show that PTEN attenuation increases resistance to cisplatin-induced apoptosis, a finding associated with increased levels of the cyclin kinase inhibitor p21. Elevated levels of p21 result from stabilization of the protein, and they are dependent on the activities of phosphoinositide-3 kinase and Akt. More specifically, the accumulation of p21 occurs preferentially in the cytosolic compartment, which likely contributes to both cell cycle progression and resistance to apoptosis. CONCLUSION: Since p21 regulates a decision point between repair and apoptosis after DNA damage, our data suggest that p21 plays a key role in mechanisms used by PTEN-deficient tumors to escape chemotherapy. This in turn raises the possibility to use p21 attenuators as chemotherapy sensitizers, an area under active continuing investigation in our laboratories

Synthetic Molecular Clouds from Supersonic MHD and Non-LTE Radiative Transfer Calculations

The dynamics of molecular clouds is characterized by supersonic random motions in the presence of a magnetic field. We study this situation using numerical solutions of the three-dimensional compressible magneto-hydrodynamic (MHD) equations in a regime of highly supersonic random motions. The non-LTE radiative transfer calculations are performed through the complex density and velocity fields obtained as solutions of the MHD equations, and more than 5x10^5 synthetic molecular spectra are obtained. We use a numerical flow without gravity or external forcing. The flow is super-Alfvenic and corresponds to model A of Padoan and Nordlund (1997). Synthetic data consist of sets of 90x90 synthetic spectra with 60 velocity channels, in five molecular transitions: J=1-0 and J=2-1 for 12CO and 13CO, and J=1-0 for CS. Though we do not consider the effects of stellar radiation, gravity, or mechanical energy input from discrete sources, our models do contain the basic physics of magneto-fluid dynamics and non-LTE radiation transfer and are therefore more realistic than previous calculations. As a result, these synthetic maps and spectra bear a remarkable resemblance to the corresponding observations of real clouds.Comment: 33 pages, 12 figures included, 5 jpeg figures not included (fig1a, fig1b, fig3, fig4 fig5), submitted to Ap

A high-throughput \u3ci\u3ede novo\u3c/i\u3e sequencing approach for shotgun proteomics using high-resolution tandem mass spectrometry

Abstract Background High-resolution tandem mass spectra can now be readily acquired with hybrid instruments, such as LTQ-Orbitrap and LTQ-FT, in high-throughput shotgun proteomics workflows. The improved spectral quality enables more accurate de novo sequencing for identification of post-translational modifications and amino acid polymorphisms. Results In this study, a new de novo sequencing algorithm, called Vonode, has been developed specifically for analysis of such high-resolution tandem mass spectra. To fully exploit the high mass accuracy of these spectra, a unique scoring system is proposed to evaluate sequence tags based primarily on mass accuracy information of fragment ions. Consensus sequence tags were inferred for 11,422 spectra with an average peptide length of 5.5 residues from a total of 40,297 input spectra acquired in a 24-hour proteomics measurement of Rhodopseudomonas palustris. The accuracy of inferred consensus sequence tags was 84%. According to our comparison, the performance of Vonode was shown to be superior to the PepNovo v2.0 algorithm, in terms of the number of de novo sequenced spectra and the sequencing accuracy. Conclusions Here, we improved de novo sequencing performance by developing a new algorithm specifically for high-resolution tandem mass spectral data. The Vonode algorithm is freely available for download at http://compbio.ornl.gov/Vonode webcite

Common peroneal nerve palsy following total knee arthroplasty: prognostic factors and course of recovery.

Common peroneal nerve palsy (CPNP) is a serious complication following total knee arthroplasty (TKA). There is little information regarding the clinical course and prognostic factors for recovery. Between January 2000 and December 2008, 44 patients (0.53%) developed CPNP following TKA and were matched to 100 control patients based on year of surgery, type of surgery and surgeon. Regression analysis was performed to identify prognostic factors for recovery. A significant difference was seen in CPNP patients who were on average younger (62.1 years) and had higher BMI (34.5 kg/m(2)) than those who did not have nerve palsy (67.5 years and 31.8 kg/m(2), respectively). Only 37 patients with palsies could be followed, 32 (62.2%) had incomplete nerve palsy, twenty four (75%) of them fully recovered, while only 1 of patients with complete nerve palsy fully recovered. More severe initial injury was a negative prognostic factor for recovery of palsy (P\u3c0.03)

Circadian patterns of Wikipedia editorial activity: A demographic analysis

Wikipedia (WP) as a collaborative, dynamical system of humans is an appropriate subject of social studies. Each single action of the members of this society, i.e. editors, is well recorded and accessible. Using the cumulative data of 34 Wikipedias in different languages, we try to characterize and find the universalities and differences in temporal activity patterns of editors. Based on this data, we estimate the geographical distribution of editors for each WP in the globe. Furthermore we also clarify the differences among different groups of WPs, which originate in the variance of cultural and social features of the communities of editors