Root uptake of lipophilic zinc-rhamnolipid complexes

This study investigated the formation and plant uptake of lipophilic metal-rhamnolipid complexes. Monorhamnosyl and dirhamnosyl rhamnolipids formed lipophilic complexes with copper (Cu), manganese (Mn), and zinc (Zn). Rhamnolipids significantly increased Zn absorption by Brassica napus var. Pinnacle roots in 65Zn-spiked ice-cold solutions, compared with ZnSO4 alone. Therefore, rhamnolipid appeared to facilitate Zn absorption via a nonmetabolically mediated pathway. Synchrotron XRF and XAS showed that Zn was present in roots as Zn-phytate-like compounds when roots were treated with Zn-free solutions, ZnSO4, or Zn-EDTA. With rhamnolipid application, Zn was predominantly found in roots as the Zn-rhamnolipid complex. When applied to a calcareous soil, rhamnolipids increased dry matter production and Zn concentrations in durum (Triticum durum L. cv. Balcali-2000) and bread wheat (Triticum aestivum L. cv. BDME-10) shoots. Rhamnolipids either increased total plant uptake of Zn from the soil or increased Zn translocation by reducing the prevalence of insoluble Zn-phytate-like compounds in roots

HDAC inhibitors increase NRF2-signaling in tumour cells and blunt the efficacy of co-adminstered cytotoxic agents

The NRF2 signalling cascade provides a primary response against electrophilic chemicals and oxidative stress. The activation of NRF2-signaling is anticipated to have adverse clinical consequences; NRF2 is activated in a number of cancers and, additionally, its pharmacological activation by one compound can reduce the toxicity or efficiency of a second agent administered concomitantly. In this work, we have analysed systematically the ability of 152 research, pre-clinical or clinically used drugs to induce an NRF2 response using the MCF7-AREc32 NRF2 reporter. Ten percent of the tested drugs induced an NRF2 response. The NRF2 activators were not restricted to classical cytotoxic alkylating agents but also included a number of emerging anticancer drugs, including an IGF1-R inhibitor (NVP-AEW541), a PIM-1 kinase inhibitor (Pim1 inhibitor 2), a PLK1 inhibitor (BI 2536) and most strikingly seven of nine tested HDAC inhibitors. These findings were further confirmed by demonstrating NRF2-dependent induction of endogenous AKR genes, biomarkers of NRF2 activity. The ability of HDAC inhibitors to stimulate NRF2-signalling did not diminish their own potency as antitumour agents. However, when used to pre-treat cells, they did reduce the efficacy of acrolein. Taken together, our data suggest that the ability of drugs to stimulate NRF2 activity is common and should be investigated as part of the drug-development process

Inhibition of DNA polymerase reactions by pyrimidine nucleotide analogues lacking the 2-keto group

To investigate the influence of the pyrimidine 2-keto group on selection of nucleotides for incorporation into DNA by polymerases, we have prepared two C nucleoside triphosphates that are analogues of dCTP and dTTP, namely 2-amino-5-(2′-deoxy-β-d-ribofuranosyl) pyridine-5′-triphosphate (d*CTP) and 5-(2′-deoxy-β-d-ribofuranosyl)-3-methyl-2-pyridone-5′-triphosphate (d*TTP) respectively. Both proved strongly inhibitory to PCR catalysed by Taq polymerase; d*TTP rather more so than d*CTP. In primer extension experiments conducted with either Taq polymerase or the Klenow fragment of Escherichia coli DNA polymerase I, both nucleotides failed to substitute for their natural pyrimidine counterparts. Neither derivative was incorporated as a chain terminator. Their capacity to inhibit DNA polymerase activity may well result from incompatibility with the correctly folded form of the polymerase enzyme needed to stabilize the transition state and catalyse phosphodiester bond formatio

The RRAT Trap: Interferometric Localization of Radio Pulses from J0628+0909

We present the first blind interferometric detection and imaging of a millisecond radio transient with an observation of transient pulsar J0628+0909. We developed a special observing mode of the Karl G. Jansky Very Large Array (VLA) to produce correlated data products (i.e., visibilities and images) on a time scale of 10 ms. Correlated data effectively produce thousands of beams on the sky that can localize sources anywhere over a wide field of view. We used this new observing mode to find and image pulses from the rotating radio transient (RRAT) J0628+0909, improving its localization by two orders of magnitude. Since the location of the RRAT was only approximately known when first observed, we searched for transients using a wide-field detection algorithm based on the bispectrum, an interferometric closure quantity. Over 16 minutes of observing, this algorithm detected one transient offset roughly 1' from its nominal location; this allowed us to image the RRAT to localize it with an accuracy of 1.6". With a priori knowledge of the RRAT location, a traditional beamforming search of the same data found two, lower significance pulses. The refined RRAT position excludes all potential multiwavelength counterparts, limiting its optical luminosity to L_i'<1.1x10^31 erg/s and excluding its association with a young, luminous neutron star.Comment: Submitted to ApJ, 7 pages, 5 figure

The OGF-OGFr axis utilizes the p21 pathway to restrict progression of human pancreatic cancer

<p>Abstract</p> <p>Background</p> <p>Pancreatic cancer is the 4th leading cause of death from cancer in the U.S. The opioid growth factor (OGF; [Met⁵]-enkephalin) and the OGF receptor form an inhibitory growth regulatory system involved in the pathogenesis and treatment of pancreatic cancer. The OGF-OGFr axis influences the G₀/G₁phase of the cell cycle. In this investigation, we elucidate the pathway of OGF in the cell cycle.</p> <p>Results</p> <p>Using BxPC-3 cells, OGF decreased phosphorylation of retinoblastoma (Rb) protein without changing total Rb. This change was correlated with reduced cyclin-dependent kinase protein (Cdk) 2 kinase activity, but not total Cdk2. OGF treatment increased cyclin-dependent kinase inhibitor (CKI) p21 protein expression in comparison to controls, as well levels of p21 complexed with Cdk2. Naloxone abolished the increased expression of p21 protein by OGF, suggesting a receptor-mediated activity. p21 specific siRNAs blocked OGF's repressive action on proliferation in BxPC-3, PANC-1, and Capan-2 cells; cells transfected with negative control siRNA had no alteration in p21 expression, and therefore were inhibited by OGF.</p> <p>Conclusion</p> <p>These data are the first to reveal that the target of cell proliferative inhibitory action of OGF in human pancreatic cancer is a p21 CKI pathway, expanding strategies for diagnosis and treatment of these neoplasias.</p

Retinometra albeolae n.sp. (Cestoda: Hymenolepididae) from the bufflehead duck, Bucephala albeola L.

Retinometra albeolae n.sp. is described from bufflehead ducks (Bucephala albeola L.) from Manitoba, Canada. It is armed with eight skrjabinoid rostellar hooks 69–75 μm long, and has a cirrus sac 240–480 μm long that extends to approximately the midline of mature proglottids, a trilobed ovary, and a lobed vitelline gland. Staphylepis indica and Staphylepis meggitti, currently included in the genus Retinometra, are returned to Staphylepis on the basis of proglottid morphology and the apparent lack of a cirrus stylet in both species

Imaging of ischemia, obstruction and infection in the abdomen

Intestinal ischemia is a serious condition that continues to be associated with mortalities in excess of 70%. Intestinal obstruction and gastrointestinal tract sepsis are common conditions, accounting for a large proportion of patients admitted to emergency departments with acute abdominal symptoms. This article discusses the imaging methods and key findings of these entities in the emergency radiology department. The article includes imaging examples, diagnostic options, protocol selections, diagnostic criteria, and differential diagnoses