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Purpose: To report acute and late genitourinary (GU) and gastrointestinal (GI) toxicities associated with post-prostatectomy proton therapy (PT). Methods: The first 100 consecutive patients from 2010 to 2016 were retrospectively assessed. Baseline characteristics, prospectively graded CTCAE v4.0 toxicities, and patient-reported outcomes were reported. Late outcomes were reported for 79 patients with 3 months minimum follow up. Toxicity-free survival Kaplan-Meier curves were estimated. Logistic regression assessed associations between toxicities and clinical and treatment characteristics (p Results: Median age, months after surgery, and months of follow-up were respectively 64 years (range 42–77), 25 (5–216), and 25 (0–47). PT received was 70.2 Gy (RBE) (89%), salvage (93%), prostate bed only (80%), pencil beam scanning (86%), with IMRT (31%), and with androgen deprivation (34%). Acute and late maximum toxicities, respectively were: GU grade 0 (14%; 18%), 1 (71%; 62%), 2 (15%; 20%), ≥3 (0), and GI: grade 0 (66%; 73%), 1 (34%; 27%), ≥2 (0). Toxicity-free survival at 24 months was GU grade 2 (83%) and GI grade 1 (74%). Mean (±std dev) baseline International Prostate Symptom Score (IPSS), International Index of Erectile Function, and Expanded Prostate Cancer Index Composite bowel function and bother were 6.6 ± 6.1, 10.5 ± 7.3, 90.9 ± 10.8, 93.3 ± 11.2, respectively, and largely unchanged at 2 years: 6.3 ± 3.6, 11.1 ± 6.3, 92.8 ± 5.8, and 90.9 ± 10.3. On multivariate analysis, baseline IPSS (p = .009) associated with GU grade 2 acute toxicity. Bladderless-CTV median dose, V30, and V40 associated with GU grade 2 acute toxicity and maximum dose with late (Ps p = .033) associated with acute grade 1 toxicity. Rectal minimum and median dose, V10, and V20, and anterior rectal wall median dose and V10 through V65 associated with acute grade 1 GI toxicity (Ps Conclusions: Post-prostatectomy PT for prostate cancer is feasible with a favorable GU and GI toxicity profile acutely and through early follow up.

Rice plants primed with beneficial microbes Bacillus amyloliquefaciens and Aspergillus spinulosporus with biocontrol potential against Xanthomonas oryzae pv. oryzae, provided protection from disease by reprogramming host defence response under pathogen challenge. Plant–beneficial microbe interactions taking place in the rhizosphere are widely used for growth promotion and mitigation of biotic stresses in plants. The present study aims to evaluate the defense network induced by beneficial microorganisms in the rice rhizosphere, and the three-way interaction involved upon inoculation with dreadful bacteria Xanthomonas oryzae pv. oryzae (Xoo). Differential expression of defense-related enzymes, proteins, and genes in rice variety Swarna primed with a microbial consortium of Bacillus amyloliquefaciens and Aspergillus spinulosporus were quantified in the presence and absence of Xoo. The time-based expression profile alterations in leaves under the five distinct treatments “(unprimed unchallenged, unprimed Xoo challenged, B. amyloliquefaciens primed and challenged, A. spinulosporus primed and challenged, B. amyloliquefaciens and A. spinulosporus consortium primed and challenged)” revealed differential early upregulation of SOD, PAL, PO, PPO activities and TPC content in beneficial microbes primed plants in comparison to unprimed challenged plants. The enhanced defense response in all the rice plants recruited with beneficial microbe was also reflected by reduced plant mortality and an increased plant dry biomass and chlorophyll content. Also, more than 550 protein spots were observed per gel by PD Quest software, a total of 55 differentially expressed protein spots were analysed used MALDI-TOF MS, out of which 48 spots were recognized with a significant score with direct or supporting roles in stress alleviation and disease resistance. qRT-PCR was carried out to compare the biochemical and proteomic data to mRNA levels. We conclude that protein biogenesis and alleviated resistance response may contribute to improved biotic stress adaptation. These results might accelerate the functional regulation of the Xoo-receptive proteins in the presence of beneficial rhizospheric microbes and their computation as promising molecular markers for superior disease management.

Background Suppression and activation of plant defense genes is comprehensively regulated by WRKY family transcription factors. Chickpea, the non-model crop legume suffers from wilt caused by Fusarium oxysporum f. sp. ciceri Race1 (Foc1), defense response mechanisms of which are poorly understood. Here, we attempted to show interaction between WRKY70 and several downstream signaling components involved in susceptibility/resistance response in chickpea upon challenge with Foc1. Results In the present study, we found Cicer arietinum L. WRKY70 (CaWRKY70) negatively governs multiple defense responsive pathways, including Systemic Acquired Resistance (SAR) activation in chickpea upon Foc1 infection. CaWRKY70 is found to be significantly accumulated at shoot tissues of susceptible (JG62) chickpea under Foc1 stress and salicylic acid (SA) application. CaWRKY70 overexpression promotes susceptibility in resistant chickpea (WR315) plants to Foc1 infection. Transgenic plants upon Foc1 inoculation demonstrated suppression of not only endogenous SA concentrations but expression of genes involved in SA signaling. CaWRKY70 overexpressing chickpea roots exhibited higher ion-leakage and Foc1 biomass accumulation compared to control transgenic (VC) plants. CaWRKY70 overexpression suppresses H2O2 production and resultant reactive oxygen species (ROS) induced cell death in Foc1 infected chickpea roots, stem and leaves. Being the nuclear targeted protein, CaWRKY70 suppresses CaMPK9-CaWRKY40 signaling in chickpea through its direct and indirect negative regulatory activities. Protein-protein interaction study revealed CaWRKY70 and CaRPP2-like CC-NB-ARC-LRR protein suppresses hyper-immune signaling in chickpea. Together, our study provides novel insights into mechanisms of suppression of the multiple defense signaling components in chickpea by CaWRKY70 under Foc1 stress. Conclusion CaWRKY70 mediated defense suppression unveils networking between several immune signaling events negatively affecting downstream resistance mechanisms in chickpea under Foc1 stress.

Proteomic approaches are being used to elucidate a better discretion of interactions occurring between host, pathogen, and/or beneficial microorganisms at the molecular level. Application of proteomic techniques, unravel pathogenicity, stress-related, and antioxidant proteins expressed amid plant-microbe interactions and good information have been generated. It is being perceived that a fine regulation of protein expression takes place for effective pathogen recognition, induction of resistance, and maintenance of host integrity. However, our knowledge of molecular plant-microbe interactions is still incomplete and inconsequential. This review aims to provide insight into numerous ways used for proteomic investigation including peptide/protein identification, separation, and quantification during host defense response. Here, we highlight the current progress in proteomics of defense responses elicited by bacterial, fungal, and viral pathogens in plants along with which the proteome level changes induced by beneficial microorganisms are also discussed.

The rhizosphere is the immediate area of soil encompassing plant roots that is inhabited by a large population of microorganisms and invertebrates, making its environment highly complex. Plants attract specific soil microorganisms using root exudates from large associations of soil microorganisms. The successful establishment of plant growth-promoting rhizospheric microorganisms is the first step in defending plants from soil-borne pathogenic organisms. Understanding rhizosphere’s unique and dynamic ecology will help in improving nutrient absorption, water use efficiency, modifying soil properties, thereby, enhancing plant growth, yield and integrating disease management strategies. In recent years, in the field of plant–microbe interaction, root exudates have received considerable importance in mediating interactions with nearby plants and microorganisms. Novel discernment of key factors framing the microbial community in rhizosphere will be very crucial in achieving sustainable agriculture. This review discusses on how root exudates play a crucial role in facilitating nutrient, signal exchange in rhizosphere and modulating changes in architecture of microbial community. We focus in particular on the influence of root exudates on positive and negative plant–microbe interactions occurring in rhizosphere and point out implicit avenues for further research.

Purpose: Despite increasing use, proton therapy (PT) remains a relatively limited resource. The purpose of this study was to assess clinical and demographic differences in PT use for prostate cancer compared to intensity modulated radiation therapy (IMRT) at a single institution. Methods and materials: All patients with low- and intermediate-risk prostate cancer (N = 633) who underwent definitive radiation therapy between 2010 and 2015 were divided into PT (n = 508) and IMRT (n = 125) comparison groups and compared using χ2 and independent sample t tests. Univariable and multivariable logistic regression analyses were conducted to assess the associations between PT use and demographic, clinical, and treatment characteristics. Results: The PT and IMRT cohorts varied by age, race, poverty, distance, treatment year, and treating physician. Patients who underwent IMRT were more likely to be older (mean age, 66 vs. 68 years), black (51% vs. 75%), and living in poverty or close to the facility (mean distance between residence and facility, 90 vs. 21 miles; P < .05). Prostate-specific antigen, prostate volume, and International Index of Erectile Function were significantly higher in the IMRT cohort (P < .05), but insurance type, risk group, tumor stage, Gleason score, and patient-reported urinary and bowel scores did not differ significantly (P > .05). Patients who underwent PT were more likely to receive hypofractionated therapy and less likely to receive androgen deprivation therapy (P < .01). On multivariable analysis, black (odds ratio [OR], 0.29; 95% confidence interval [CI], 0.15-0.57) and other race (OR, 0.42; 95% CI, 0.20-0.90); distance (OR, 1.14; 95% CI, 1.06-1.24); treatment years 2011 (OR, 4.87; 95% CI, 2.23-10.6), 2012 (OR, 8.27; 95% CI, 3.43-19.9), and 2014 (OR, 4.44; 95% CI, 1.94-10.2) relative to 2010; and a single treating physician (OR, 0.38; 95% CI, 0.18-0.81) relative to the reference physician with the highest rate of use were associated with PT use, whereas clinical factors such as prostate-specific antigen, prostate volume, International Index of Erectile Function, and androgen deprivation therapy were not. Conclusion: Sociodemographic disparities exist in PT use for prostate cancer at an urban academic institution. Further investigation of potential barriers to access is warranted to ensure equitable distribution across all demographic groups.

All nicotinic acetylcholine receptors (nAChRs) evolved from homomeric nAChRs in which all five subunits are involved in forming acetylcholine (ACh) binding sites at their interfaces. Heteromeric α4β2* nAChRs typically have two ACh binding sites at α4/β2 interfaces and a fifth accessory subunit surrounding the central cation channel. β2 accessory subunits do not form ACh binding sites, but α4 accessory subunits do at the α4/α4 interface in (α4β2)2α4 nAChRs. α5 and β3 are closely related subunits that had been thought to act only as accessory subunits and not take part in forming ACh binding sites. The effect of agonists at various subunit interfaces was determined by blocking homologous sites at these interfaces using the thioreactive agent 2-((trimethylammonium)ethyl) methanethiosulfonate (MTSET). We found that α5/α4 and β3/α4 interfaces formed ACh binding sites in (α4β2)2α5 and (α4β2)2β3 nAChRs. The α4/α5 interface in (β2α4)2α5 nAChRs also formed an ACh binding site. Blocking of these sites with MTSET reduced the maximal ACh evoked responses of these nAChRs by 30–50%. However, site-selective agonists NS9283 (for the α4/α4 site) and sazetidine-A (for the α4/β2 site) did not act on the ACh sites formed by the α5/α4 or β3/α4 interfaces. This suggests that unorthodox sites formed by α5 and β3 subunits have unique ligand selectivity. Agonists or antagonists for these unorthodox sites might be selective and effective drugs for modulating nAChR function to treat nicotine addiction and other disorders.

In due course of evolution many pathogens alter their effector molecules to modulate the host plants' metabolism and immune responses triggered upon proper recognition by the intracellular nucleotide-binding oligomerization domain containing leucine-rich repeat (NLR) proteins. Likewise, host plants have also evolved with diversified NLR proteins as a survival strategy to win the battle against pathogen invasion. NLR protein indeed detects pathogen derived effector proteins leading to the activation of defense responses associated with programmed cell death (PCD). In this interactive process, genome structure and plasticity play pivotal role in the development of innate immunity. Despite being quite conserved with similar biological functions in all eukaryotes, the intracellular NLR immune receptor proteins happen to be structurally distinct. Recent studies have made progress in identifying transcriptional regulatory complexes activated by NLR proteins. In this review, we attempt to decipher the intracellular NLR proteins mediated surveillance across the evolutionarily diverse taxa, highlighting some of the recent updates on NLR protein compartmentalization, molecular interactions before and after activation along with insights into the finer role of these receptor proteins to combat invading pathogens upon their recognition. Latest information on NLR sensors, helpers and NLR proteins with integrated domains in the context of plant pathogen interactions are also discussed.