scholarly journals Changes in DMI, SDHI, and QoI Fungicide Sensitivity in the Estonian Zymoseptoria tritici Population between 2019 and 2020

2021 ◽  
Vol 9 (4) ◽  
pp. 814
Author(s):  
Riinu Kiiker ◽  
Marite Juurik ◽  
Thies Marten Heick ◽  
Andres Mäe
Keyword(s):  
Selection Pressure ◽  
Gene Mutations ◽  
Primary Objective ◽  
Cytb Gene ◽  
Zymoseptoria Tritici ◽  
Fungicide Sensitivity ◽  
Resistance Strategies ◽  
Knowledge Based ◽  
Gene Alterations ◽  
Succinate Dehydrogenase Inhibitors

Zymoseptoria tritici (Zt) populations adapt under the selection pressure of fungicides applied for disease control. The primary objective of this study was to assess fungicide sensitivity in the Estonian Zt population. A total of 282 Zt isolates from 2019 and 2020 were tested for sensitivity to azoles (DMIs; prothioconazole-desthio, epoxiconazole, mefentrifluconazole) and succinate dehydrogenase inhibitors (SDHIs; boscalid, fluxapyroxad). The efficacy of the tested fungicides varied considerably between the Estonian counties, but the Zt population is mainly sensitive to DMIs. Additionally, the frequencies of CYP51 gene alterations varied; D134G, V136C, A379G, and S524T had increased, but V136A and I381V showed a moderate decrease in 2020 in comparison to 2019. Sensitivity to SDHIs was stable, but boscalid was less effective than fluxapyroxad. SdhC gene mutations C-T33N, C-T34N, and C-N86S were common, but not linked with SDHI fungicide sensitivity assay results. Otherwise, mutation B-N225I in the SdhB subunit occurred in isolates with reduced sensitivity to SDHIs. Sensitivity to strobilurins was evaluated by the mutation G143A in the CytB gene, which was present in nearly half of the population. The data presented confirm the ongoing evolution of fungicide sensitivity in the Zt population in Estonia and highlight the importance of knowledge-based decisions for optimizing anti-resistance strategies in the field.

scholarly journals Fungicide strategies and resistance of Ramularia collo-cygni to demethylation and succinate dehydrogenase inhibitors in Austrian winter barley (Hordeum vulgare)

2021 ◽  
Author(s):  
Thomas Assinger ◽  
Stefano F. F. Torriani ◽  
Salvatore Accardo ◽  
James Fountaine ◽  
Siegrid Steinkellner
Keyword(s):  
Succinate Dehydrogenase ◽  
Fungicide Resistance ◽  
Growth Parameters ◽  
Field Trials ◽  
Low Frequencies ◽  
Resistance Strategies ◽  
Growing Seasons ◽  
Ramularia Leaf Spot ◽  
Application Frequency ◽  
Succinate Dehydrogenase Inhibitors

AbstractRamularia collo-cygni B. Sutton and J.M. Waller is a major disease in Austrian barley-growing regions. To date, fungicide application is the most effective method to manage the disease; however, fungicide resistance to demethylation and succinate dehydrogenase inhibitors has developed over the last few years. In the growing seasons 2016/2017 and 2017/2018, field trials were carried out to analyze the efficiency of fungicide strategies based on different fungicide classes. Disease development, growth parameters and monitoring of CYP51 and sdh mutations were determined. Fungicide treatments resulted in higher disease control, green leaf area and grain yield. In Austrian R. collo-cygni field populations, the frequency of the mutations CYP51-I325T and CYP51-I328L was low to moderate. Frequency of mutations sdhC-H146R and sdhC-H153R was low. Frequencies of CYP51-I325T and -I328L were similar and increased following DMI application. Frequency of sdhC-H146R was higher compared to sdhC-H153R. The SDHI benzovindiflupyr showed a higher selection rate for sdh mutations compared to bixafen. These sdh mutations were not selected if chlorothalonil was used as mixing partner, leading to a stable composition of sdh resistance alleles over the last two years. Chlorothalonil was proven to be an effective tool for anti-resistance strategies. Currently, SDHIs and DMIs are the backbone of Ramularia leaf spot control in Austria; however, the level of resistance is likely to increase in absence of suitable anti-resistance strategies and following the ban of chlorothalonil.

Strategic Orientation and Performance of Istanbul Stock Market Businesses

2019 ◽  
pp. 94-114 ◽  
Author(s):  
Yakup Akgül ◽  
Mustafa Zihni Tunca
Keyword(s):  
Information Systems ◽  
Firm Performance ◽  
Stock Market ◽  
Middle Managers ◽  
Primary Objective ◽  
Strategic Orientation ◽  
Knowledge Based ◽  
Strategic Orientations ◽  
Inferential Analysis ◽  
And Performance

The primary objective of this chapter is to critically examine the effect of strategic orientations on the innovation and the performance of İstanbul stock market businesses in Turkey. The three most comprehensive constructs, namely strategic orientation of business enterprises (STROBE), strategic orientation of information systems (STROIS), and strategic orientation of knowledge-based enterprises (STROKE) instruments, were adopted to present a holistic picture of the effect of strategic orientation on innovation and firm performance. A survey was administered and a sample of 203 middle managers was analyzed using SmartPLS version 3.2.7 for inferential analysis and SPSS version 24 for descriptive insights.

Anti-resistance strategies for fungicides against wheat pathogen Zymoseptoria tritici with focus on DMI fungicides

2017 ◽  
Vol 99 ◽  
pp. 108-117 ◽  
Author(s):  
Thies Marten Heick ◽  
Annemarie Fejer Justesen ◽  
Lise Nistrup Jørgensen
Keyword(s):  
Zymoseptoria Tritici ◽  
Resistance Strategies ◽  
Dmi Fungicides

Expression (Exp) of FIP200 and Rb in breast cancer (BreastCA) metastasis (met) to the brain.

2011 ◽  
Vol 29 (27_suppl) ◽  
pp. 222-222
Author(s):  
N. Hashemi Sadraei ◽  
M. Burgett ◽  
M. S. Ahluwalia ◽  
R. Tipps ◽  
D. Khosla ◽  
...  
Keyword(s):  
Cellular Localization ◽  
Dna Analysis ◽  
Gene Mutations ◽  
Genetic Alterations ◽  
Copy Number Variations ◽  
Deletion Mutations ◽  
The Us ◽  
Her 2 ◽  
The Brain ◽  
Gene Alterations

222 Background: BreastCA is the 2nd leading cause of cancer deaths in women in the US. Although the outcome for BreastCA with brain met remains poor, there is significant variation in overall survival (OS). Yet, there are no markers or models to predict OS. FIP200 regulates several pathways. In the nucleus, it inhibits cell proliferation by promoting Rb-1 and p21, and in the cytoplasm it promotes cell survival by inhibiting Pyk2 and regulating autophagy. It has been reported that FIP200 gene is deleted or mutated in 20% of primary BreastCAs, and its Exp is correlated with Rb1 levels. FIP200 Exp, its cellular localization, and gene alterations have not been examined in brain met of any cancer. Methods: Brain met tissues of 21 BreastCA patients (pts) biopsied in our institution between 8/2000 and 3/2010 were obtained and Exp of FIP200 and Rb1 were analyzed. Biopsies were selected based on tissue adequacy and prior diagnosis (Dx) of invasive intra-ductal BreastCA. Immunohistochemistry (IHC) was used to evaluate the localization and Exp levels of FIP200 and Rb1 which in turn were tested as predictors of OS. Genetic alterations in FIP200 and Rb1 were examined after DNA extraction. Results: Median time from Dx to met was 23 (range 0-245) months (mos), and median OS from Dx was 43 (range 6-264) mos. Nuclear Exp of Rb1 in < 30% vs. ≥ 30% of cells were seen in 11 vs. 10 pts. Median OS was 39 (range 6-264) mos for Rb1 Exp < 30% and 47 (range 20-190) mo for Rb1 Exp ≥ 30%. Nuclear Exp of FIP200 in <20% vs. ≥ 20% of cells were seen in 13 vs. 8 pts. Median OS was 39 (range 6-264) mo for FIP200 nuclear Exp <20% and 45 (range 43-122) mo for FIP200 Exp ≥ 20%. DNA analysis of 11 pts for copy number variations and loss of heterozygocity (LOH) showed no deletion mutations in FIP200 or Rb1, loss of p53 in 4 of 11, ErbB2 (Her-2) amplification in 4 of 11, and no EGFR gene mutations. Conclusions: The nuclear Exp of Rb1 in brain met from invasive intra-ductal BreastCA may be linked OS. An expanded study is underway to define whether nuclear FIP200 in >20% of cells correlates with nuclear Rb and OS in BreastCA.

A phase I/II study of ABT-888 in combination with 5-fluorouracil (5-FU) and oxaliplatin (Ox) in patients with metastatic pancreatic cancer (MPC).

2013 ◽  
Vol 31 (4_suppl) ◽  
pp. 147-147 ◽  
Author(s):  
Michael J. Pishvaian ◽  
Hongkun Wang ◽  
Tingting Zhuang ◽  
Aiwu Ruth He ◽  
Jimmy J. Hwang ◽  
...  
Keyword(s):  
Phase I ◽  
Parp Inhibitor ◽  
Gene Mutations ◽  
Brca2 Gene ◽  
Progression Free Survival ◽  
Final Analysis ◽  
Primary Objective ◽  
Repair Mechanisms ◽  
Recommended Phase Ii Dose ◽  
Ecog Ps

147 Background: The PARP inhibitor, ABT-888 is a potent sensitizing agent for, and has been safely combined with DNA-damaging chemotherapies. The sensitizing effects of ABT-888 are magnified when cancer cells harbor underlying defects in DNA repair mechanisms, such as BRCA2 mutations. Methods: We have initiated a Phase I/II trial, and we present here the data from the Phase I portion. Patients (pts) with MPC who had any number of prior therapies were eligible. A standard 3+3 dose escalation of ABT-888 was employed, in cohorts of 40, 60, 80, 100, 150, 200, 250, and 300mg orally twice a day, days 1-7 of a 14 day cycle. Pts also received 85mg/m2 of Ox, 400mg/m2 of 5-FU, and 400mg/m2 of leucovorin on Day 1, and 2400mg/m2 of 5-FU continuous infusion Days 1-3. Restaging studies were performed every 4 cycles. The primary objective was to determine the Recommended Phase II Dose (RP2D) of ABT-888 combined with 5-FU and Ox. Secondary clinical objectives included an assessment of the pharmacokinetics (PKs) of ABT-888 metabolism, as well as response rate (RR), progression-free survival (PFS), and overall survival (OS). Results: Between 01-2011 and 09-2012, 22 pts received treatment. 55% were male; median age = 64, most with an ECOG PS of 1. 55% were previously untreated. The first 6 pts experienced persistent ≤Grade 2 myelosuppression, primarily thrombocytopenia, prompting an amendment to drop the 5-FU bolus. In the latter 16 pts, the combination of ABT-888 plus 5-FU and Ox was well tolerated, with no DLTs. The RP2D is expected to be 300mg BID of ABT-888, with the final analysis including ABT-888 PKs to be presented. For the 22 pts, the RR was 14%, and the PFS and OS were 2.9 and 5.4 months, respectively. Of the 11 previously untreated pts, the RR was 18%, and the PFS and OS were 4.3 and 7.7 months, respectively. 2 pts with deleterious mutations in BRCA2 were included: Pt 6 had a PR and remains on study after 17 months; Pt 14 had a CR and a normalization of CA 19-9, and is still on treatment after 10 months. Conclusions: The combination of ABT-888, 5-FU, and Ox is safe and well tolerated. The combination has demonstrated promising efficacy in MPC, particularly in pts with BRCA2 gene mutations. Clinical trial information: NCT01489865.

The potential biomarkers of checkpoint inhibitor immunotherapy in solid malignancies.

2020 ◽  
Vol 38 (15_suppl) ◽  
pp. e15226-e15226
Author(s):  
Nausheen Hakim ◽  
Jeffrey Chi ◽  
Rajvi Patel ◽  
Ryann Quinn ◽  
Xinhua Zhu
Keyword(s):  
Single Agent ◽  
Gene Mutations ◽  
Complete Response ◽  
Common Gene ◽  
Tumor Mutational Burden ◽  
Progression Of Disease ◽  
Line Setting ◽  
Tumor Types ◽  
Gene Alterations ◽  
Potential Biomarkers

e15226 Background: Tumor mutational burden (TMB), PDL1 status, microsatellite status (MS), tumor infiltrating lymphocyte, and the microbiome profile are commonly used biomarkers to predict which patients (pts) may benefit from immunotherapy (IO). However, they are imperfect and cannot be used to predict complete response (CR). Next Generation Sequencing (NGS) from Foundation Medicine has identified many gene mutations. We aim to identify potential biomarkers in pts who achieved CR with immunotherapies as opposed to in those who had upfront progression of disease (PD). Methods: We conducted a retrospective analysis of pts with metastatic solid tumors at our institution that received IO after NGS testing. Pts who achieved CR or PD per imaging studies and clinical settings were included. Gene alterations through NGS were identified in each group. Results: Eighty-one pts received IO who had NGS sent prior to treatment. Pembrolizumab, ipilimumab, nivolumab, durvalumab and atezolizumab were used as single agent or in combination with another IO or chemotherapy. 19 pts achieved CR, 18 pts had PD. In the CR group, melanoma and lung adenocarcinoma were most common tumor types (Table). 15 pts (78.9%) received IO as 1st line treatment. Most common gene mutations in CR group were ROS1 (52.6%), LRP1B (52.6%), GRIN2A (47.4%), and EPHA7 (42.1%) in 19 patients. 18 pts with various tumor types (Table) had PD. Most of IOs were given as 2nd or 3rd line setting in NR group. Most common gene alterations were MLL2 (33.3%), CDKN2A/B (27.8%), NTRK1 (27.8%), ARID1B (22.2%) in 18 patients. Conclusions: The cohort of patients who achieved CR with IO had the most common gene mutations of ROS1, LRP1B, GRIN2A, and EPHA7 which can potentially serve as a biomarker to predict response to IO. Increased frequencies of MLL2, CDKN2A/ B, NTRK1, ARID1B mutations were found in patients with PD. The gene mutations in CR and PD groups are mutually exclusive. Further explorations at tumor environment, RNA and proteins levels are needed to identify combined potential biomarkers to predict IO response, followed by validation in the prospective study. The limitation is that the study is retrospective. [Table: see text]

scholarly journals Status of Knowledge Based Economy in the Kingdom of Saudi Arabia: An Analysis

2013 ◽  
Vol 4 (6) ◽  
pp. 268-277
Author(s):  
Omar Salem Bashehab
Keyword(s):  
Saudi Arabia ◽  
Human Resource Development ◽  
Secondary Data ◽  
Primary Objective ◽  
Kingdom Of Saudi Arabia ◽  
Knowledge Based ◽  
Knowledge Based Economy ◽  
The Status ◽  
Emerging Issues ◽  
The Government

This paper highlights on the emerging issues that compelled Saudi Arabia in transforming its economy to a knowledge-based one. It discusses the pillars of a knowledge-based economy i.e. the institutional model; education; research and development (R&D); and information and communication technology (ICT) adopted by the World Bank Institute framework to analyze the status of a knowledge-based economy in Saudi Arabia. The primary objective of this article is to understand the status of the knowledgebased economy in the Kingdom of Saudi Arabia. Secondary data was collected for writing the paper. The nine developmental plans of Saudi Arabia (Ministry of Economy and Planning), Ministry of Education reports, Ministry of Communications and Information Technology reports, and Saudi Arabian Monetary Agency (SAMA) reports are some of the important sources of data. The government of Saudi Arabia has laid the foundation for transforming its economy to a knowledge-based one but more is required especially in the field of human resource development and innovation to expedite the easiness of the transforming process.

scholarly journals Targeted Therapy for Non-Small Cell Lung Cancer

2020 ◽  
Vol 95 (2) ◽  
pp. 78-88
Author(s):  
Jung Sun Kim ◽  
Eun Joo Kang
Keyword(s):  
Lung Cancer ◽  
Small Cell Lung Cancer ◽  
Cell Lung Cancer ◽  
Survival Benefit ◽  
Target Genes ◽  
Gene Mutations ◽  
Therapeutic Agents ◽  
Small Cell ◽  
Small Cell Lung ◽  
Gene Alterations

Treatment of progressive non-small cell lung cancer (NSCLC) has advanced remarkably, due in part to the development of targeted therapies. Several gene alterations, including EGFR, ALK, ROS1, and BRAF, play important roles in carcinogenesis. Therefore, many targeted agents focusing these gene alterations have been developed and proving their therapeutic efficacies in many clinical trials. Now we should test these gene mutations and should apply treatments individually and properly to ensure the maximal survival benefit of each patient. In this review, we summarize the target genes and respective therapeutic agents in NSCLC.

scholarly journals Clinical Determinants of Disease Progression in Patients With Beta-Sarcoglycan Gene Mutations

2021 ◽  
Vol 12 ◽  
Author(s):  
Giulia Bruna Marchetti ◽  
Luca Valenti ◽  
Yvan Torrente
Keyword(s):  
Muscular Dystrophy ◽  
Disease Progression ◽  
Current Knowledge ◽  
Gene Mutations ◽  
Left Ventricular ◽  
Primary Objective ◽  
Limb Girdle Muscular Dystrophy ◽  
Lv Function ◽  
Respiratory Impairment ◽  
Rate Of Decline

Background: Limb-girdle muscular dystrophy 2E (LGMD 2E), recently renamed as autosomal recessive limb-girdle muscular dystrophy-4 (LGMDR4), is characterized by the lack of beta-sarcoglycan, normally expressed in skeletal muscles and cardiomyocytes. We hypothesized that progressive respiratory and left ventricular (LV) failure in LGMDR4 could be associated with the age and interrelated phenomena of the disease's natural history.Methods: We conducted a retrospective review of the records of 26 patients with LGMDR4. Our primary objective was to compare the rates of decline among creatine phosphokinase (CPK) values, pulmonary function test (PFT) measures, and echocardiographic estimates and to relate them to patients' age.Results: The rates of decline/year of CPK, PFTs, and LV function estimates are significatively bound to age, with the LV ejection fraction (EF) being the strongest independent variable describing disease progression. Moreover, the rate of decline of CPK, PFTs, and LV differed in patients grouped according to their genetic mutations, demonstrating a possible genotype–phenotype correlation. The parallel trend of decline in CPK, PFT, and EF values demonstrates the presence in LGMDR4 of a simultaneous and progressive deterioration in muscular, respiratory, and cardiac function.Conclusions: This study expands the current knowledge regarding the trend of CPK values and cardiac and respiratory impairment in patients with LGMDR4, to optimize the monitoring of these patients, to improve their quality of life, and to provide clinical indices capable of quantifying the effects of any new gene or drug therapy.

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