Persistent neutrophil to lymphocyte ratio >3 during treatment with enzalutamide and clinical outcome in patients with castration-resistant prostate cancer

The baseline value of neutrophil to lymphocyte ratio (NLR) has been found to be prognostic in patients with metastatic castration resistant prostate cancer (CRPC). We evaluated the impact of baseline NLR and its change in patients receiving enzalutamide. We included consecutive metastatic CRPC patients treated with enzalutamide after docetaxel and studies the change of NLR (>3 vs ≤3) after week 4 and 12 weeks. Progression-free survival (PFS), overall survival (OS) and their 95% Confidence Intervals (95% CI) were estimated by the Kaplan-Meier method and compared with the log-rank test. The impact of NLR on PFS and OS was evaluated by Cox regression analyses and on prostate-specific antigen response rates (PSA RR; PSA decline >50%) were evaluated by binary logistic regression. Data collected on 193 patients from 9 centers were evaluated. Median age was 73.1 years (range, 42.8–90.7). The median baseline NLR was 3.2. The median PFS was 3.2 months (95% CI = 2.7–4.2) in patients with baseline NLR >3 and 7.4 months (95% CI = 5.5–9.7) in those with NLR ≤3, p < 0.0001. The median OS was 10.4 months (95% CI = 6.5–14.9) in patients with baseline NLR >3 and 16.9 months (95% CI = 11.2–20.9) in those with baseline NLR ≤3, p < 0.0001. In multivariate analysis, changes in NLR at 4 weeks were significant predictors of both PFS [hazard ratio (HR) 1.24, 95% confidence interval (95% CI) 1.07–1.42, p = 0.003, and OS (HR 1.29, 95% CI 1.10–1.51, p = 0.001. A persistent NLR >3 during treatment with enzalutamide seems to have both prognostic and predictive value in CRPC patients

Constraining the size of the narrow line region in distant quasars

We propose a proper method to measure the size of the narrow line region (NLR) in distant quasars. The apparent angular size of the NLR is, in general, too small to resolve technically. However, it is possible to map the NLR if with gravitational lensing. In our method, we directly compare the observed image of the NLR with the expected lensed images of the NLR for various source sizes and lens models. Seeking the best fit image via the comparison procedures, we can obtain the best-fit size and the best-fit lens model. We apply this method to the two-dimensional spectroscopic data of a famous lensed quasar, Q2237+0305. If the lens galaxy resembles the applied lens model, an upper limit to the NLR size can be set 750 pc. Further, we examine how the fitting results will be improved by future observations, taking into account the realistic observational effects, such as seeing. Future observations will provide us more stringent constraints on the size of the NLR and on the density profile of the lens galaxy.Comment: 17 pages including 4 figures, accepted to Ap

Comparative analysis of plant immune receptor architectures uncovers host proteins likely targeted by pathogens.

BACKGROUND: Plants deploy immune receptors to detect pathogen-derived molecules and initiate defense responses. Intracellular plant immune receptors called nucleotide-binding leucine-rich repeat (NLR) proteins contain a central nucleotide-binding (NB) domain followed by a series of leucine-rich repeats (LRRs), and are key initiators of plant defense responses. However, recent studies demonstrated that NLRs with non-canonical domain architectures play an important role in plant immunity. These composite immune receptors are thought to arise from fusions between NLRs and additional domains that serve as "baits" for the pathogen-derived effector proteins, thus enabling pathogen recognition. Several names have been proposed to describe these proteins, including "integrated decoys" and "integrated sensors". We adopt and argue for "integrated domains" or NLR-IDs, which describes the product of the fusion without assigning a universal mode of action. RESULTS: We have scanned available plant genome sequences for the full spectrum of NLR-IDs to evaluate the diversity of integrations of potential sensor/decoy domains across flowering plants, including 19 crop species. We manually curated wheat and brassicas and experimentally validated a subset of NLR-IDs in wild and cultivated wheat varieties. We have examined NLR fusions that occur in multiple plant families and identified that some domains show re-occurring integration across lineages. Domains fused to NLRs overlap with previously identified pathogen targets confirming that they act as baits for the pathogen. While some of the integrated domains have been previously implicated in disease resistance, others provide new targets for engineering durable resistance to plant pathogens. CONCLUSIONS: We have built a robust reproducible pipeline for detecting variable domain architectures in plant immune receptors across species. We hypothesize that NLR-IDs that we revealed provide clues to the host proteins targeted by pathogens, and that this information can be deployed to discover new sources of disease resistance

Physical Conditions in the Narrow-Line Region of M51

We have investigated the physical conditions in the narrow-line region (NLR) of M51 using long-slit spectra obtained with the Space Telescope Imaging Spectrograph (STIS) aboard the Hubble Space Telescope (HST) and 3.6 cm radio continuum observations obtained with the Very Large Array (VLA). Emission-line diagnostics were employed for nine NLR clouds, which extend 2.5" (102 pc) from the nucleus, to examine the electron density, temperature, and ionization state of the NLR gas. The emission-line ratios are consistent with those typically found in Seyfert nuclei and indicate that within the inner near-nuclear region (r ~< 1") the ionization decreases with increasing radius. Upper-limits to the [O III] electron temperature (T ~< 11,000 K) for the inner NLR clouds indicate that photoionization is the dominant ionization mechanism close to the nucleus. The emission-line fluxes for most of the NLR clouds can be reproduced reasonably well by simple photoionization models using a central power-law continuum source and supersolar nitrogen abundances. Shock+precursor models, however, provide a better fit to the observed fluxes of an NLR cloud ~2.5" south of the nucleus that is identified with the extra-nuclear cloud (XNC). The large [O III] electron temperature of this cloud (T = 24,000 K) further suggests the presence of shocks. This cloud is straddled by two radio knots and lies near the location where a weak radio jet, ~2.5" (102pc) in extent, connects the near-nuclear radio emission with a diffuse lobe structure spanning \~4" (163 pc). It is plausible that this cloud represents the location where the radio jet impinges on the disk ISM.Comment: 25 pages, 26 figures (9 color), 7 tables. Accepted for publication in the Astrophysical Journa

Genomic evidence for genes encoding leucine-rich repeat receptors linked to resistance against the eukaryotic extra- and intracellular Brassica napus pathogens Leptosphaeria maculans and Plasmodiophora brassicae

© 2018 Stotz et al. This is an open access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.Genes coding for nucleotide-binding leucine-rich repeat (LRR) receptors (NLRs) control resistance against intracellular (cell-penetrating) pathogens. However, evidence for a role of genes coding for proteins with LRR domains in resistance against extracellular (apoplastic) fungal pathogens is limited. Here, the distribution of genes coding for proteins with eLRR domains but lacking kinase domains was determined for the Brassica napus genome. Predictions of signal peptide and transmembrane regions divided these genes into 184 coding for receptor-like proteins (RLPs) and 121 coding for secreted proteins (SPs). Together with previously annotated NLRs, a total of 720 LRR genes were found. Leptosphaeria maculans-induced expression during a compatible interaction with cultivar Topas differed between RLP, SP and NLR gene families; NLR genes were induced relatively late, during the necrotrophic phase of pathogen colonization. Seven RLP, one SP and two NLR genes were found in Rlm1 and Rlm3/Rlm4/Rlm7/Rlm9 loci for resistance against L. maculans on chromosome A07 of B. napus. One NLR gene at the Rlm9 locus was positively selected, as was the RLP gene on chromosome A10 with LepR3 and Rlm2 alleles conferring resistance against L. maculans races with corresponding effectors AvrLm1 and AvrLm2, respectively. Known loci for resistance against L. maculans (extracellular hemi-biotrophic fungus), Sclerotinia sclerotiorum (necrotrophic fungus) and Plasmodiophora brassicae (intracellular, obligate biotrophic protist) were examined for presence of RLPs, SPs and NLRs in these regions. Whereas loci for resistance against P. brassicae were enriched for NLRs, no such signature was observed for the other pathogens. These findings demonstrate involvement of (i) NLR genes in resistance against the intracellular pathogen P. brassicae and a putative NLR gene in Rlm9-mediated resistance against the extracellular pathogen L. maculans.Peer reviewe

Size and properties of the narrow-line region in Seyfert-2 galaxies from spatially-resolved optical spectroscopy

While [OIII] narrow-band imaging is commonly used to measure the size of the narrow-line regions (NLRs) in active galactic nuclei (AGNs), it can be contaminated by emission from surrounding starbursts. Recently, we have shown that long-slit spectroscopy provides a valuable alternative approach to probe the size in terms of AGN photoionisation. Moreover, several parameters of the NLR can be directly accessed. We here apply the same methods developed and described for the Seyfert-2 galaxy NGC1386 to study the NLR of five other Seyfert-2 galaxies by using high-sensitivity spatially-resolved optical spectroscopy obtained at the VLT and the NTT. We probe the AGN-photoionisation of the NLR and thus, its ``real'' size using diagnostic line-ratio diagrams.We derive physical properties of the NLR such as reddening, ionisation parameter, electron density, and velocity as a function of distance from the nucleus. For NGC5643, the diagnostic diagrams unveil a similar transition between line ratios falling in the AGN regime and those typical for HII regions as found for NGC1386, thus determining the size of the NLR. For the other four objects, all measured line ratios fall in the AGN regime. In almost all cases, both electron density and ionisation parameter decrease with radius. Deviations from this general behaviour (such as a secondary peak) seen in both the ionisation parameter and electron density can be interpreted as signs of shocks from the interaction of a radio jet and the NLR gas. In several objects, the gaseous velocity distribution is characteristic for rotational motion in an (inclined) emission-line disk in the centre. We compare our results to those of NGC1386 and show that the latter can be considered as prototypical also for this larger sample. We discuss our findings in detail for each object.Comment: 23 pages, 41 figures, accepted for publication in A&

ISO-SWS spectroscopy of NGC 1068

We present ISO-SWS spectroscopy of NGC 1068 for the wavelength range 2.4 to 45um, detecting a total of 36 emission lines. Most of the observed transitions are fine structure and recombination lines originating in the narrow line region. We compare the line profiles of optical lines and reddening-insensitive infrared lines to constrain the dynamical structure and extinction properties of the NLR. The considerable differences found are most likely explained by two effects. (1) The spatial structure of the NLR is a combination of a highly ionized outflow cone and lower excitation extended emission. (2) Parts of the NLR, mainly in the receding part at velocities above systemic, are subject to extinction that is significantly suppressing optical emission. Line asymmetries and net blueshifts remain, however, even for infrared fine structure lines suffering very little obscuration. This may be either due to an intrinsic asymmetry of the NLR, or due to a very high column density obscuring component which is hiding part of the NLR even from infrared view. Mid-infrared emission of molecular hydrogen in NGC 1068 arises in a dense molecular medium at temperatures of a few hundred Kelvin that is most likely closely related to the warm and dense components seen in the near-infrared H2 transitions, and in millimeter wave tracers of molecular gas. Any emission of the putative pc-scale molecular torus is likely overwhelmed by this larger scale emission.Comment: aastex (V4), 9 eps figures. Accepted by Ap

Evidence for a Physically Compact Narrow-Line Region in the Seyfert 1 Galaxy NGC 5548

We have combined HST/FOS and ground-based spectra of the Seyfert 1 galaxy NGC 5548 to study the narrow emission lines over the 1200 -- 10,000 angstrom region. All of the spectra were obtained when the broad emission line and continuum fluxes were at an historic low level, allowing us to accurately determine the contribution of the narrow-line region (NLR) to the emission lines. We have generated multicomponent photoionization models to investigate the relative strength of the high ionization lines compared to those in Seyfert 2 galaxies, and the weakness of the narrow Mg II 2800 line. We present evidence for a high ionization component of NLR gas that is very close to the nucleus (~1 pc). This component must be optically thin to ionizing radiation at the Lyman edge (tau = 2.5) to avoid producing [O I] and Mg II in a partially ionized zone. The very high ionization lines (N V, [Ne V], [Fe VII], [Fe X]) are stronger than the predictions of our standard model, and we show that this may be due to supersolar abundances and/or a ``blue bump'' in the extreme ultraviolet (although recent observations do not support the latter). An outer component of NLR gas (at only ~70 pc from the continuum source) is needed to produce the low ionization lines. We show that the outer component may contain dust, which further reduces the Mg II flux by depletion and by absorption of the resonance photons after multiple scatterings. We show that the majority of the emission in the NLR of NGC 5548 must arise within about ~70 pc from the nucleus. Thus, the NLR in this Seyfert 1 galaxy is very physically compact, compared to the typical NLR in Seyfert 2 galaxies.Comment: 38 pages, Latex, includes 2 figures (postscript), to appear in Ap