Identification of diagnostic upper gastrointestinal cancer tissue type‑specific urinary biomarkers

Several potential urinary biomarkers exhibiting an association with upper gastrointestinal tumour growth have been previously identified, of which S100A6, S100A9, rabenosyn‑5 and programmed cell death 6‑interacting protein (PDCD6IP) were further validated and found to be upregulated in malignant tumours. The cancer cohort from our previous study was subclassified to assess whether distinct molecular markers can be identified for each individual cancer type using a similar approach. Urine samples from patients with cancers of the stomach, oesophagus, oesophagogastric junction or pancreas were analysed by surface‑enhanced laser desorption/ionization‑time‑of‑flight mass spectrometry using both CM10 and IMAC30 (Cu2+‑complexed) chip types and LC‑MS/MS‑based mass spectrometry after chromatographic enrichment. This was followed by protein identification, pattern matching and validation by western blotting. We found 8 m/z peaks with statistical significance for the four cancer types investigated, of which m/z 2447 and 2577 were identified by pattern matching as fragments of cathepsin‑B (CTSB) and cystatin‑B (CSTB); both molecules are indicative of pancreatic cancer. Additionally, we observed a potential association of upregulated α‑1‑antichymotrypsin with pancreatic and gastric cancers, of PDCD6IP, vitelline membrane outer layer protein 1 homolog (VMO1) and triosephosphate isomerase (TPI1) with oesophagogastric junctional cancers, and of complement C4‑A, prostatic acid phosphatase, azurocidin and histone‑H1 with oesophageal cancer. Furthermore, the potential pancreatic cancer biomarkers CSTB and CTSB were validated independently by western blotting. Therefore, the present study identified two new potential urinary biomarkers that appear to be associated with pancreatic cancer. This may provide a simple, non‑invasive screening test for use in the clinical setting.</p

Attosecond Time-Domain Measurement of Core-Level-Exciton Decay in Magnesium Oxide.

Excitation of ionic solids with extreme ultraviolet pulses creates localized core-level excitons, which in some cases couple strongly to the lattice. Here, core-level-exciton states of magnesium oxide are studied in the time domain at the Mg L_{2,3} edge with attosecond transient reflectivity spectroscopy. Attosecond pulses trigger the excitation of these short-lived quasiparticles, whose decay is perturbed by time-delayed near-infrared pulses. Combined with a few-state theoretical model, this reveals that the infrared pulse shifts the energy of bright (dipole-allowed) core-level-exciton states as well as induces features arising from dark core-level excitons. We report coherence lifetimes for the two lowest core-level excitons of 2.3±0.2 and 1.6±0.5  fs and show that these are primarily a consequence of strong exciton-phonon coupling, disclosing the drastic influence of structural effects in this ultrafast relaxation process

Direct Measurement of the Forbidden 23S1 → 33S1 Atomic Transition in Helium

We present the detection of the highly forbidden 2 3S1→ 3 3S1 atomic transition in helium, the weakest transition observed in any neutral atom. Our measurements of the transition frequency, upper state lifetime, and transition strength agree well with published theoretical values and can lead to tests of both QED contributions and different QED frameworks. To measure such a weak transition, we develop two methods using ultracold metastable (2 3S1) helium atoms: low background direct detection of excited then decayed atoms for sensitive measurement of the transition frequency and lifetime, and a pulsed atom laser heating measurement for determining the transition strength. These methods could possibly be applied to other atoms, providing new tools in the search for ultraweak transitions and precision metrology.This work was supported through Australian Research Council (ARC) Discovery Project Grants No. DP160102337 and DP180101093, as well as Linkage Project No. LE180100142. K. F. T. and D. K. S. are supported by Australian Government Research Training Program (RTP) scholarships. S. S. H. is supported by ARC Discovery Early Career Researcher Award No. DE150100315

Frequency measurements of transitions from the 2 P2 3 state to the 5 D2 1, 5 S1 3, and 5 D 3 states in ultracold helium

We perform laser absorption spectroscopy with ultracold 4 He atoms to measure the energy intervals between the 2 3 P2 level and five levels in the n = 5 manifold. The laser light perturbs the cold atomic cloud during the production of Bose-Einstein condensates and decreases the phase space density, causing a measurable decrease in the number of atoms in the final condensate. We improve on the precision of previous measurements by at least an order of magnitude, and report an observation of the spin-forbidden 2 3 P2 -5 1 D2 transition in helium. Theoretical transition energies agree with the observed values within our experimental uncertainty.The project was supported by Australian Research Council (ARC) Discovery Project Grants No. DP160102337 and No. DP180101093, and Linkage Project No. LE180100142. J.A.R. and K.F.T. were supported by the Australian Postgraduate Award (APA) and Australian Government Research Training Program (RTP) Scholarships, respectively

The Histone Deacetylase SIRT6 Restrains Transcription Elongation via Promoter-Proximal Pausing.

Transcriptional regulation in eukaryotes occurs at promoter-proximal regions wherein transcriptionally engaged RNA polymerase II (Pol II) pauses before proceeding toward productive elongation. The role of chromatin in pausing remains poorly understood. Here, we demonstrate that the histone deacetylase SIRT6 binds to Pol II and prevents the release of the negative elongation factor (NELF), thus stabilizing Pol II promoter-proximal pausing. Genetic depletion of SIRT6 or its chromatin deficiency upon glucose deprivation causes intragenic enrichment of acetylated histone H3 at lysines 9 (H3K9ac) and 56 (H3K56ac), activation of cyclin-dependent kinase 9 (CDK9)-that phosphorylates NELF and the carboxyl terminal domain of Pol II-and enrichment of the positive transcription elongation factors MYC, BRD4, PAF1, and the super elongation factors AFF4 and ELL2. These events lead to increased expression of genes involved in metabolism, protein synthesis, and embryonic development. Our results identified SIRT6 as a Pol II promoter-proximal pausing-dedicated histone deacetylase

Effects of Transitioning From Conventional Methods to Liquid Based Methods on Unsatisfactory Pap Tests: Results from a Multicenter U.S. Study (poster)

Background: Pap testing has transitioned from conventional preparations (CP) to liquid based preparations (LBP) due to perceived superiority of LBPs. Many studies conclude LBPs reduce unsatisfactory (UNSAT) tests however some believe the evidence to substantiate this claim is weak. We studied the effect of the transition from CPs to LBPs on the proportion of UNSAT Pap tests (PT) in four health care systems in the United States participating in the NIH-funded SEARCH project. Methods: Our study cohort consisted of 548,174 women with 1,443,725 total PTs, ages 21-65 years, between 2000 and 2010. We used segmented regression analysis to estimate the effect of adopting LBPs on the proportion of UNSAT PTs after adjusting for age. Results: Three sites implementing SurePath LBP experienced significant reductions in UNSAT PTs (Site 1 estimated effect: -2.46% [95% CI: -1.47%, -3.45%], Site 2: -1.78% [95% CI: -1.54%, -2.02%], Site 3: -8.25% [95% CI: -7.33%, -9.17%]. The fourth site implementing ThinPrep LBP did not experience a reduction in UNSAT studies. The relative risk of an UNSAT PT in women \u3e 50 increased after the transition to LBPs (SurePath: RR 2.1 [95% CI: 1.9, 2.2] and ThinPrep: RR 1.7 [95% CI: 1.5, 2.0]). Conclusions: The observed changes in the proportion of UNSAT PTs varied across the participating sites and it was dependent on the type of LBP technology, age of women and the rates prior to the implementation of this technology

Demersal fishes associated with Lophelia pertusa coral and hard-substrate biotopes on the continental slope, northern Gulf of Mexico

The demersal fish fauna of Lophelia pertusa (Linnaeus, 1758) coral reefs and associated hard-bottom biotopes was investigated at two depth horizons in the northern Gulf of Mexico using a manned submersible and remote sampling. The Viosca Knoll fauna consisted of at least 53 demersal fish species, 37 of which were documented by submersible video. On the 325 m horizon, dominant taxa determined from frame-by-frame video analysis included Stromateidae, Serranidae, Trachichthyidae, Congridae, Scorpaenidae, and Gadiformes. On the 500 m horizon, large mobile visual macrocarnivores of families Stromateidae and Serranidae dropped out, while a zeiform microcarnivore assumed importance on reef “Thicket” biotope, and the open-slope taxa Macrouridae and Squalidae gained in importance. The most consistent faunal groups at both depths included sit-and-wait and hover-and-wait strategists (Scorpaenidae, Congridae, Trachichthyidae), along with generalized mesocarnivores (Gadiformes). The specialized microcarnivore, Grammicolepis brachiusculus Poey, 1873, appears to be highly associated with Lophelia reefs. The coral “Thicket” biotope was extensively developed on the 500 m site, but fish abundance was low with only 95 fish per hectare. In contrast to Lophelia reefs from the eastern the North Atlantic, the coral “Rubble” biotope was essentially absent. This study represents the first quantitative analysis of fishes associated with Lophelia reefs in the Gulf of Mexico, and generally in the western North Atlantic