Different Types Of Resistance Research Articles

Phytopathological screening of common winter wheat lines for resistance to Puccinia triticina

Abstract. Leaf rust on wheat caused by P. triticina is the most widespread fungal disease worldwide and in Bulgaria. The development of wheat genotypes resistant to leaf rust is related to the different types of resistance and ways of gene inheritance. The different varieties have different susceptibility during the different stages of their ontogenetic development. The study of the initial material is an important step in the breeding for resistance and it is an ongoing process. Two hundred and forty-six breeding lines were tested against the local population of P. triticina during 2015-2017, under conditions of infection field and in a greenhouse at Dobrudzha Agricultural Institute – General Toshevo, Bulgaria. Twenty lines were selected, which demonstrated different degrees of resistance under infection field conditions and which showed resistance to some of the seven pathotypes used in the study. The identification of the pathotypes was based on the type of reaction of 20 monogenic lines. The reaction of isogenic lines was compared with the reaction of the selection lines and the results showed that the reaction of line 165/05-46 corresponded to isogenic lines carrying genes Lr 9, Lr 19 and Lr 25. The response of the other 3 lines (245/03-72, 13/04-97, 14/06-110) partially coincided with the response of the above mentioned genes. The reaction of the other 3 lines (169/05-69, 14/06-81, 8/08-25) partially coincided with the reaction of isogenic lines carrying genes Lr 2a, Lr 28 and Lr 29. It was determined that seven of the lines were carriers of a race-specific gene and that it was necessary to subject these lines to further breeding and genetic studies to determine presence of race-specific resistance. Five of the lines (72/05-53, 61/03-75, 106/04-189, 268/03-151, 79/04-131) combined incomplete resistance at young stage with resistance at adult stage. Four of the tested lines (68/06-78, 29/02-133-38, 79/04-125-28, 197/05-33) exhibited typical race non-specific resistance or APR. Four lines (13/04-165, 14/05-119, 19/06-79 and 61/03-81) demonstrated “slow rusting” type of resistance. Twenty of the studied lines were carriers of effective resistance and can be included in the breeding programs as donors of resistance to P. triticina.

Resistance to technological innovation and brand equity in the banking sector

Abstract Consolidating strategies in the banking sector to reduce the impact of resistance barriers to technological innovation can bring brands closer to older people, thus reinforcing the brand value of banking institutions; therefore, the objective of this research was to identify the incidence of resistance barriers to technological innovation on the dimensions of brand equity in the banking sector by elderly people. For this purpose, a descriptive correlational study was developed with 502 elderly people living in the city of Bogotá, Colombia, aged between 60 and 80 years old. Data collection was carried out using a questionnaire applied in person, which was adjusted and validated based on the information obtained. The questionnaire assessed brand equity components of brand image and awareness, brand associations, perceived quality and performance, and brand loyalty, and included items to assess psychological and functional barriers. A confirmatory factor analysis and structural equation modelling were developed for the different barriers of resistance to technology and for the dimensions of brand equity, identifying that the different types of resistance to innovation affect only the dimensions of brand awareness and brand importance. The results lead to the conclusion that elderly people experience different barriers to using the technological applications of their banking products and that the design of these applications must consider them in order to achieve or maintain brand recognition in this segment, as well as to achieve true financial inclusion for elderly people.

Identification of a Locus for High-Temperature Adult-Plant Resistance to Stripe Rust in the Wheat Yr8 Near-Isogenic Line Through Mutagenesis and Molecular Mapping.

Aegilops species are wheat relatives that harbor valuable disease resistance genes for wheat breeding. The wheat Yr8 near-isogenic line AvSYr8NIL has long been believed to carry only Yr8 for race-specific all-stage resistance to stripe rust, caused by Puccinia striiformis f. sp. tritici, derived from Aegilops comosa. However, AvSYr8NIL has been found to have high-temperature adult-plant (HTAP) resistance in our field and greenhouse tests. To confirm both HTAP and Yr8 resistance, seeds from AvSYr8NIL were treated with ethyl methanesulfonate to generate mutant lines. The mutant lines with only Yr8 (M641) and only HTAP resistance (M488) were crossed with the susceptible recurrent parent Avocet S (AvS). The F1 and F4 lines of AvS/M641 were phenotyped with Yr8-avirulent races in the seedling stage at the low-temperature (4 to 20°C) profile, while the F1, F2, F4, and F5 lines of AvS/M488 were phenotyped with Yr8-virulent races in the adult-plant stage at the high-temperature (10 to 30°C) profile. Both Yr8 and the HTAP resistance gene (YrM488) were recessive. The F4 populations of AvS/M641 and AvS/M488 were genotyped using polymorphic Kompetitive allele-specific PCR markers converted from single-nucleotide polymorphisms. Yr8 was mapped to a 0.66-cM fragment, and YrM488 was mapped to a 1.22-cM interval on chromosome 2D. The physical distance between the two resistance genes was estimated to be more than 500 Mb, indicating their distinct loci. The mutant lines with separated resistance genes would be useful in enhancing our understanding of different types of resistance and in further studying the interactions between wheat and the stripe rust pathogen.

The Pseudomonas aeruginosa Resistome: Permanent and Transient Antibiotic Resistance, an Overview.

One of the most concerning characteristics of Pseudomonas aeruginosa is its low susceptibility to several antibiotics of common use in clinics, as well as its facility to acquire increased resistance levels. Consequently, the study of the antibiotic resistance mechanisms of this bacterium is of relevance for human health. For such a study, different types of resistance should be distinguished. The intrinsic resistome is composed of a set of genes, present in the core genome of P. aeruginosa, which contributes to its characteristic, species-specific, phenotype of susceptibility to antibiotics. Acquired resistance refers to those genetic events, such as the acquisition of mutations or antibiotic resistance genes that reduce antibiotic susceptibility. Finally, antibiotic resistance can be transiently acquired in the presence of specific compounds or under some growing conditions. The current article provides information on methods currently used to analyze intrinsic, mutation-driven, and transient antibiotic resistance in P. aeruginosa.

From one to many: Hypertonia in schizophrenia spectrum psychosis an integrative review and adversarial collaboration report

Different types of resistance to passive movement, i.e. hypertonia, were described in schizophrenia spectrum disorders (SSD) long before the introduction of antipsychotics. While these have been rediscovered in antipsychotic-naïve patients and their non-affected relatives, the existence of intrinsic hypertonia vs drug-induced parkinsonism (DIP) in treated SSD remains controversial. This integrative review seeks to develop a commonly accepted framework to specify the putative clinical phenomena, highlight conflicting issues and discuss ways to challenge each hypothesis and model through adversarial collaboration.The authors agreed on a common framework inspired from systems neuroscience. Specification of DIP, locomotor paratonia (LMP) and psychomotor paratonia (PMP) identified points of disagreement. Some viewed parkinsonian rigidity to be sufficient for diagnosing DIP, while others viewed DIP as a syndrome that should include bradykinesia. Sensitivity of DIP to anticholinergic drugs and the nature of LPM and PMP were the most debated issues.It was agreed that treated SSD should be investigated first. Clinical features of the phenomena at issue could be confirmed by torque, EMG and joint angle measures that could help in challenging the selectivity of DIP to anticholinergics. LMP was modeled as the release of the reticular formation from the control of the supplementary motor area (SMA), which could be challenged by the tonic vibration reflex or acoustic startle. PMP was modeled as the release of primary motor cortex from the control of the SMA and may be informed by subclinical echopraxia. If these challenges are not met, this would put new constraints on the models and have clinical and therapeutic implications.

Characterization of Virulence Phenotypes of Heterodera glycines during 2020 in Indiana.

The soybean cyst nematode (SCN, Heterodera glycines) is the most yield-limiting pathogen of soybean in the US. This study was carried out in order to provide updated information on SCN virulence phenotypes in Indiana. A total of 124 soil samples were collected from soybean fields in 2020 and all of them tested positive for SCN. The virulence phenotypes of 42 representative SCN populations were determined with seven soybean indicator lines using the standard HG type test. The most predominant HG types were 2.5.7 and 1.2.5.7, which accounted for 64% and 14% of the SCN populations tested, respectively. None of the SCN populations tested were rated as HG type 0, compared with 28% of the populations in a previous survey in Indiana during 2006-2008. Nearly 88% of the SCN populations evaluated in this study overcame the resistance provided by PI 88788, which is the most common source of resistance in soybean, up from 56% in the 2006-2008 survey. Approximately 14% of SCN populations tested were virulent to PI 548402 (Peking), in contrast to 0% in the 2006-2008 survey. This study reveals a trend of increasing virulence of SCN populations to resistant sources of soybean in Indiana. The results highlighted the importance of rotating soybean varieties with different types of resistance and identifying new sources of resistance for sustainable management of SCN.

Characterization and Molecular Mapping of a Gene Conferring High-Temperature Adult-Plant Resistance to Stripe Rust Originally from Aegilops ventricosa.

Wheat near-isogenic line AvSYr17NIL carrying Yr17, originally from Aegilops ventricosa for all-stage resistance to Puccinia striiformis f. sp. tritici, also shows nonrace-specific, high-temperature adult-plant (HTAP) resistance to the stripe rust pathogen. To separate and identify the HTAP resistance gene, seeds of AvSYr17NIL were treated with ethyl methanesulfonate. Mutant lines with only HTAP resistance were obtained, and one of the lines, M1225, was crossed with the susceptible recurrent parent Avocet S (AvS). Field responses of the F2 plants and F3 lines, together with the parents, were recorded at the adult-plant stage in Pullman and Mount Vernon, WA under natural P. striiformis f. sp. tritici infection. The parents and the F4 population were phenotyped with a Yr17-virulent P. striiformis f. sp. tritici race in the adult-plant stage under the high-temperature profile in the greenhouse. The phenotypic results were confirmed by testing the F5 population in the field under natural P. striiformis f. sp. tritici infection. The F2 data indicated a single recessive gene, temporarily named YrM1225, for HTAP resistance. The F4 lines were genotyped with Kompetitive allele-specific PCR markers converted from single-nucleotide polymorphism markers polymorphic between M1225 and AvS. The HTAP resistance gene was mapped on the short arm of chromosome 2A in an interval of 7.5 centimorgans using both linkage and quantitative trait locus mapping approaches. The separation of the HTAP resistance gene from Yr17 should improve the understanding and utilization of the different types of resistance.

Direct GDP-KRASG12C inhibitors and mechanisms of resistance: the tip of the iceberg.

Kirsten rat sarcoma viral oncogene homolog mutations are observed in 25% of lung adenocarcinoma and 40% of these are G12C mutations. Historically, no approved targeted agents were available for patients with any KRAS mutation, and response rates to standard-of-care therapies were suboptimal. Newly developed inhibitors directed toward KRASG12C have been successful in clinical trials with overall response rates ranging between 32% and 46%, and two FDA approvals were granted in May 2021 and December 2022 as second-line or later monotherapies. However, rapid tumor resistance complicates their use as a monotherapy. With the rapid development of this novel class of inhibitors, it is important to discern the different types of tumor resistance that may arise and how each can differently contribute to tumor growth and survival. G12C inhibitor resistance is under investigation and combinations of therapies with G12C inhibitors have been proposed. Much of this insight is gleaned from preclinical investigations, as our knowledge of clinical resistance is in its infancy. In this review, we summarize the preclinical development of KRASG12C inhibitors, their clinical evaluations, different types of resistance mechanisms to these compounds, and ways of overcoming them. Finally, we underscore the importance of basic and translational investigations of these molecules in a landscape where their clinical evaluations garner the most attention, and we set the stage for what is to come.

Wheat Genes Associated with Different Types of Resistance against Stem Rust (Puccinia graminis Pers.).

Stem rust is one wheat’s most dangerous fungal diseases. Yield losses caused by stem rust have been significant enough to cause famine in the past. Some races of stem rust are considered to be a threat to food security even nowadays. Resistance genes are considered to be the most rational environment-friendly and widely used way to control the spread of stem rust and prevent yield losses. More than 60 genes conferring resistance against stem rust have been discovered so far (so-called Sr genes). The majority of the Sr genes discovered have lost their effectiveness due to the emergence of new races of stem rust. There are some known resistance genes that have been used for over 50 years and are still effective against most known races of stem rust. The goal of this article is to outline the different types of resistance against stem rust as well as the effective and noneffective genes, conferring each type of resistance with a brief overview of their origin and usage.

Linking Multi-Omics to Wheat Resistance Types to Fusarium Head Blight to Reveal the Underlying Mechanisms.

Fusarium head blight (FHB) caused by Fusarium graminearum is a worldwide disease which has destructive effects on wheat production, resulting in severe yield reduction and quality deterioration, while FHB-infected wheat grains are toxic to people and animals due to accumulation of fungal toxins. Although impressive progress towards understanding host resistance has been achieved, our knowledge of the mechanism underlying host resistance is still quite limited due to the complexity of wheat–pathogen interactions. In recent years, disease epidemics, the resistance germplasms and components, the genetic mechanism of FHB, and disease management and control, etc., have been well reviewed. However, the resistance mechanism of FHB is quite complex with Type I, II to V resistances. In this review, we focus on the potential resistance mechanisms by linking different resistance types to multi-omics and emphasize the pathways or genes that may play significant roles in the different types of resistance. Deciphering the complicated mechanism of FHB resistance types in wheat at the integral levels based on multi-omics may help discover the genes or pathways that are critical for different FHB resistance, which could then be utilized and manipulated to improve FHB resistance in wheat breeding programs by using transgenic approaches, gene editing, or marker assisted selection strategies.

ПОИСК ШТАММОВ ЛИПОПЕПТИД-ПРОДУЦИРУЮЩИХ ЭНДОФИТНЫХ БАКТЕРИЙ РОДА BACILLUS С РОСТ-СТИМУЛИРУЮЩИМИ И ИММУНОСТИМУЛИРУЮЩИМИ СВОЙСТВАМИ, СПОСОБНЫХ МОДУЛИРОВАТЬ УСТОЙЧИВОСТЬ РАСТЕНИЙ ПШЕНИЦЫ К ЗЛАКОВОЙ ТЛЕ SCHIZAPHIS GRAMINUM

For experiments, endophytic strains B. subtilis 26D, B. subtilis 11VM, B. thuringiensis B-6066 and two isolates of Bacillus sp. isolated from wheat leaves growing on the territory of the Republic of Bashkortostan Bacillus sp. Tas1 and Tas8.2 were selected. These strains and isolates produced lipopeptides of three families: surfactins, fengycins, and iturins. We obtained lipopeptide-rich fractions (LRF) from the cultivation medium of all strains and isolates. The aim of the work was to select growth-promoting and immunostimulating concentrations of bacterial strains and isolates and their LRFs, which are capable of modulating different types of resistance (antibiosis and endurance) of wheat plants against Greenbug aphid Schizaphis graminum Rond. Growth-promoting concentrations for bacterial suspensions were selected in the range of 1.0–2.0 μl of suspension per 1 g of seeds, and for LRF within 1.5–2.5 μg/ml. Treatment of seeds with bacterial suspensions and their LRF increased germination and elevated the growth of wet and dry biomass in test for effectiveness of biocontrol agents (GOST 12038-84). Bacteria and their LRF at growth-promoting concentrations indirectly increased plant endurance, which was expressed in leaf growth, and enhanced mortality of the pest that fed on plants treated with bacteria or LRF. All studied bacterial strains and isolates are promising for protection of wheat plants from cereal aphids.

Investigation of the antioxidant activity of the peroxidase system of cell nuclei during germination of wheat embryos with different types of resistance to temperature stress

The yield of agricultural crops directly depends on their ability to adapt to a constantly changing environment, the unfavorable climatic conditions of which cause oxidative stress, accompanied by the generation of reactive oxygen species in plant cells, which can cause damage to heteropolymer cell structures, thereby leading to suppression of plant growth and a decrease in productivity grains. It has been shown that the profile of the antioxidant activity of the peroxidase system in histone and non-histone blocks of structures (nucleoplasm, chromatin) of cell nuclei during germination is more pronounced in the cold-resistant variety Mironovskaya 808 (winter) compared to Mironovskaya yarovaya (spring), which correlates with the intensity of growth processes and can be associated with participation in the realization of proliferation and differentiation programs. A direct relationship between the scavenging of ROS and plant resistance to temperature stress, which is often associated with the increased activity of antioxidant enzymes that impart stress resistance to both high and low temperature stress, apparently also exists at the level of the plant cell nucleus.

Investigation of the antioxidant activity of the peroxidase system of cell nuclei during germination of wheat embryos with different types of resistance to temperature stress

The yield of agricultural crops directly depends on their ability to adapt to a constantly changing environment, the unfavorable climatic conditions of which cause oxidative stress, accompanied by the generation of reactive oxygen species in plant cells, which can cause damage to heteropolymer cell structures, thereby leading to suppression of plant growth and a decrease in productivity grains. It has been shown that the profile of the antioxidant activity of the peroxidase system in histone and non-histone blocks of structures (nucleoplasm, chromatin) of cell nuclei during germination is more pronounced in the cold-resistant variety Mironovskaya 808 (winter) compared to Mironovskaya yarovaya (spring), which correlates with the intensity of growth processes and can be associated with participation in the realization of proliferation and differentiation programs. A direct relationship between the scavenging of ROS and plant resistance to temperature stress, which is often associated with the increased activity of antioxidant enzymes that impart stress resistance to both high and low temperature stress, apparently also exists at the level of the plant cell nucleus.

“The law is the law”: The Malaysian police readiness for the implementation of restorative policing

In Malaysia, restorative justice is a relatively new concept in its criminal justice system and assessing the readiness of police officers in accepting the implementation of restorative justice in the police departments (i.e., restorative policing) is crucial. In this qualitative study, 28 police officers were interviewed regarding their readiness to accept the roles to implement restorative justice through the exploration of three key themes: ownership of crime, police culture, and acceptance of new roles. Our findings indicated that their readiness on the implementation of restorative justice appeared to have patterns which are categorized into cautious, in-the-box, and balanced. The different patterns of readiness provide illumination into implementing restorative policing in Malaysia through the different types of resistance shown. The findings indicate that top-down and bottom-up implementation policies are useful as they can foster shared valued among the police within their departments and the police and the communities.

Modeling of cable-stayed bridge and research of frequency characteristics

The frequency characteristics of the cablestayed bridge according to several of its schemes are considered. The analysis of the influence on the frequency characteristics of the type of resistance according to different sets is carried out. Among the types of resistance were taken complete whitening, hinge and lack of resistance. Goal. The purpose of the study is to determine the causes of emergencies, including those recorded as road accidents. For this purpose it is offered to carry out the analysis of natural frequencies of the cablestayed bridge on its different types of contact (resistance) with columns. The object of this study is a cablestayed bridge, which has been in operation for 45 years. The bridge is a system of three types of elements: pylon, span and columns. The subject of the study is the spectrum of natural frequencies of the bridge according to its various models. Methodology. The research was performed using the methods of oscillations and finite elements, as well as the methods developed by the author for building models of complex machine-building systems. Results. According to the results of the performed researches, mathematical threedimensional finiteelement models of parts and the whole system of the bridge were made for different types of resistance, natural frequencies for each system were obtained. The conducted research provided grounds for conclusions on concretization of the causes of emergency situations and directions for their avoidance. Originality. Regarding the type of developed models of the cablestayed bridge, we note their uniqueness. Due to the existing personalities of the models used, it is possible to model three states of interaction of parts of the system. To conduct a study with a high degree of reliability of the real model, you need to have available data on the types of connections of its elements. This is possible with the help of unique author’s methods of model construction and use of universal possibilities of the finite element method. Research of the bridge by other methods did not allow to solve the set tasks on emergence of emergency situations. Practical value. The results of the work have a direct practical application. Based on the results of the work, a conclusion was made on measures to increase the troublefree operation of the system and measures to avoid the occurrence of an emergency situation.

SEARCH FOR BIOLOGICALLY ACTUVE SUBSTANCES WITH ANTIMICROBIAL AND ANTIBIOTIC POTENTIATING PROPERTIES AMOUNG MEMBERS OF THE GENUS ARTEMISIA AGAINTS THE MAIN PATHOGENS OF INFECTIOUS SKIN LESIONS

Abstract. Active components of the genus Artemisia show a wide range of antimicrobial effect against most bacterial pathogens. In addition, artemisin isolated from wormwood is used to treat chloroquine-resistant malaria. Antimicrobial and antibiotic-potentiating effects of eight aqueous ethanolic extracts (40 %, 70 % and 90 %) aerial part of the genus Artemisia aqueous against S. aureus and S. epidermidis strains with various types of resistance to macrolides, lincosamides, tetracyclines and fluoroquinolones isolated from outpatients with different forms of pyoderma have been researched with agar diffusion micromethod. Determination of effective antimicrobial concentrations of antimicrobials and test extracts against staphylococci have been performed with serial dilutions micromethod. The statistical program "Statistica", computer programs UTHSCSA Image Tool 3.0 and Microsoft Office Excel 2016 have been used for statistical processing of microbiological research results. The pronounced antimicrobial effect of the wormwood extract Artemisia dracunculus L. (MIC 125.0 - 250.0 μg/ml) against all S. aureus and S. epidermidis test strains has been established. Other studied extracts showed much weaker antimicrobial effect (MIC 1000.0 - 1500.0 μg/ml). It was found that the species of staphylococci and the phenotype of resistance of test strains do not affect antimicrobial activity of the studied extracts. We have found that there is no clear сorrelation between antimicrobial properties of the studied extracts and the phenotype of resistance of staphylococci test-strains. Extracts were equally effective against staphylococcal strains with low level of resistance by efflux of antimicrobial drug and skin isolates with chromosomal resistance. The greatest resistance to BAC of the studied extracts was showed by test strains with a high level of resistance to antibiotics of MLS-group and tetracycline, exhibiting sensitivity only to tarragon wormwood.
 Active components of 70, 90 % common mugwort extract Artemisia vulgaris L. (increase of the inhibition zone up to 117 – 142 %, p<0.05) and southern wormwood extract (increase of the inhibition zone up to 50 – 59 % and 74 – 122 %, respectively, p<0.05) showed dose-dependent synergistic interaction with erythromycin. Common mugwort extract (70 %) showed synergistic interaction with ¼ MIC of tetracycline (increase of the inhibition zone up to 100 %) against strains with combined resistance to all studied antimicrobials. For the study we used crude total extracts of medicinal plants (40 %, 70 % and 90 % ethanol), so we expect their significantly higher antimicrobial effect against staphylococcal strains while optimizing the extraction process and subsequent purification. It should be noted that 90 % aqueous ethanol extracts showed significantly better antimicrobial properties compared to 40 % and 70 % extracts. Active compounds of tarragon wormwood Artemisia dracunculus L. extract show pronounced antimicrobial effect against S. aureus and S. epidermidis strains, the main causative agents of infectious skin lesions, with different types of resistance to macrolides, lincosamides, tetracyclines and fluoroquinolones. Dose-dependent synergistic interaction with macrolides of common mugwort Artemisia vulgaris L. extracts and southern wormwood Artemisia abrotanum L. extract with macrolides (erythromycin) and tetracycline has been revealed.

Efficacy of Peptone Glycerol Broth in Long-term Storage of the Bacterial and Yeast Cultures

Introduction: Bacterial isolates and control strains stocking is an integral part of clinical microbiology laboratories. This is an essential step in maintaining quality. Preserving the strains without altering the character is an essentiality. There are different stock culture preparations studied in past showing varied level of performance. Aim: To evaluate the performance in terms of longevity and phenotypic character preservation of Peptone Glycerol Broth (PGB) in comparison to Brucella Glycerol Broth (BGB) and Skim Milk (SKM). Materials and Methods: The present study was a prospective analytical study. Three quality control strains and seven clinical isolates with different types of resistance were stocked in triplicates with cryobead based peptone broth with 15% glycerol, Brucella Broth (BB) with 15% glycerol and 10% SKM and stored at -80°C. Isolates were revived in monthly pattern, quarterly pattern and once after 10 months to assess the variations in viability and loss of phenotypic properties arising out of repeated freeze thaw and contaminations. Viability was assessed by time taken to produce observable confluent growth on revival. Metabolic characters and antibiotic susceptibility testing were compared before and after stock revival at intervals. Results: The phenotypic characters like metabolic features and antibiotic susceptibility were preserved with all three preparations both with repeated freeze thaw and single freeze thaw at the end of 10 months. PGB and BGB had a 100% revival rate of stored isolates with a confluent growth at 24 hours in comparison to 93.56% with SKM. Conclusion: Cryobead preparation of peptone broth-15% glycerol can be used as an effective preparation for stock culture maintenance of non-fastidious bacteria and yeast.

Targeting ROR1 Using the Antibody Drug Conjugate Vls-101 in Aggressive Mantle Cell Lymphoma

ROR1 is a transmembrane receptor with tightly controlled expression during embryonic development. While it is expressed on multiple tumor types it is not expressed in normal adult tissues. ROR1-positive B cell non-Hodgkin's lymphomas (B-NHL) include mantle cell lymphoma (MCL), and diffuse large B cell lymphoma. Given its unique expression pattern, ROR1 represents a tumor-specific therapeutic target with little or no normal tissue toxicity. VLS-101, utilizes the UC-961 anti-ROR1 antibody which is conjugated to monomethyl auristatin E (MMAE) via a cleavable linker. VLS-101/ROR1 complex induce internalization facilitates the release of a cytotoxic agent resulting in killing of ROR1-expressing cancer cells. With the rise of novel targeted therapies, resistance has been a major challenge among MCL patients. MCL is one of the most therapeutically resistant and aggressive forms of NHL-B, making it a challenging cancer to treat. The advancement of ibrutinib, a Bruton's tyrosine kinase (BTK) inhibitor, has been a beneficial change; however, ibrutinib-resistant MCL remains an urgent unmet clinical need. Furthermore, MCLs are either intrinsically resistant to ibrutinib, as well as to venetoclax (Bcl-2 inhibitor) and CAR T-cell therapy, or they may acquire resistance after a short response to these therapies. While many studies have looked into overcoming each of these different types of resistance, no studies have been conducted to overcome a multiple-resistance phenotype simultaneously. Therefore, identifying effective therapies that target these resistance mechanisms is crucial. In this study, we assessed the efficacy of VLS-101 in preclinical models of MCL with intrinsic or aquired resistance to ibrutinib, venetoclax, and CD19 CAR T therapies. By using MCL cell lines, primary patient samples and our established MCL patient-derived xenografts, we explored the expression of ROR1 in MCL and investigated the effects of in vitro and in vivo effects ROR1 targeting using VLS-101. To assess total and cell surface ROR1 expression we used flow cytometry (FACS), western blot analysis, and reverse-transcriptase-polymerase chain reaction (RT-PCR). Cell viability and apoptosis assays were performed to evaluate the in vitro efficacy of VLS-101 in MCL cell lines and primary patient MCL samples. To assess the apoptosis and cell cycle arrest in cells treated with VLS-101, we used annexin V/propidium iodide-staining followed by flow cytometry analyses. In vivo efficacy was tested using various PDX models with various multiple resistances. All 5 cell lines and all 9 PDX models of MCL tested showed high ROR1 mRNA and protein expression levels, whereas 3 out of 4 primary human samples expressed cell surface ROR1. VLS-101 treatment showed anti-MCL activity at the concentrations of 0.3-9 μg/ml in most of cell models tested, which correlated with a significant G2/M cell cycle arrest. Furthermore, VLS-101 induced a time- and dose-dependent apoptosis, as shown by increases in annexin V/propidium iodide-staining. VLS-101 treatment of ibrutinib-venetoclax dual-resistant ROR1+ PDX model resulted in significant regressions of the tumor bearing spleens and livers when compared to vehicle controls (p=0.0001 and p=0.002 respectively). In the ibrutinib-CD19 CAR T dual-resistant ROR1+ model, vehicle-treated animals showed s.c. tumor masses with a mean volume of 1440 mm3, whereas tumor masses were barely palpable (mean = 160 mm3) or had completely regressed in animals treated with VLS-101 at 1.0 mg/kg or 2.0 mg/kg, respectively. VLS-101 showed no adverse effects as monitored by animal clinical observations and weekly body weight measurements. Collectively, these results indicate that ROR1 expression on MCL cells can be utilized for selective targeting. These preclinical data document that the MMAE-containing ADC, VLS-101, can cause cell cycle arrest and induce apoptosis in vitro and safely induce tumor regressions in highly resistant in vivo PDX models of MCL derived from patient tumors. Importantly, our study revealed that even the heavyly pretreated tumors in the clinical setting may express targetable levels of ROR1 and that targeting ROR1 using ADC is a promising approach for the treatment of MCL. Building on these types of results, a Phase 1 clinical trial on VLS-101 (NCT03833180) is ongoing in patients with lymphoid cancers. Disclosures Jessen: VelosBio: Current Employment, Current equity holder in private company; eFFECTOR: Current equity holder in private company. Lannutti:VelosBio: Current Employment, Current equity holder in private company; Gilead Sciences: Current equity holder in publicly-traded company. Wang:Dava Oncology: Honoraria; AstraZeneca: Consultancy, Honoraria, Other: Travel, accommodation, expenses, Research Funding; MoreHealth: Consultancy; BioInvent: Research Funding; VelosBio: Research Funding; Acerta Pharma: Research Funding; Lu Daopei Medical Group: Honoraria; Molecular Templates: Research Funding; Oncternal: Consultancy, Research Funding; OMI: Honoraria, Other: Travel, accommodation, expenses; Janssen: Consultancy, Honoraria, Other: Travel, accommodation, expenses, Research Funding; Pharmacyclics: Consultancy, Honoraria, Other: Travel, accommodation, expenses, Research Funding; Celgene: Consultancy, Other: Travel, accommodation, expenses, Research Funding; InnoCare: Consultancy; Pulse Biosciences: Consultancy; Juno: Consultancy, Research Funding; Beijing Medical Award Foundation: Honoraria; Nobel Insights: Consultancy; Verastem: Research Funding; Kite Pharma: Consultancy, Other: Travel, accommodation, expenses, Research Funding; OncLive: Honoraria; Guidepoint Global: Consultancy; Loxo Oncology: Consultancy, Research Funding; Targeted Oncology: Honoraria.

Влияние сортов озимой пшеницы с разными типами устойчивости к возбудителю бурой ржавчины на изменение структуры популяции по признаку вирулентности

Abstract. A change in the varietal composition of wheat causes response changes in the population of the fungus, which evolves conjugately. Population studies of the causative agent of leaf rust of wheat are carried out in many countries. Comparison of populations of P. triticina is mainly carried out geographically. The purpose of the study was to analyze the dynamics of the virulence of North Caucasus Puccinia triticina populations under the influence of winter wheat varieties with different types of leaf rust resistance. Methods. The study was carried out in 2018 in the experimental field and greenhouses All-Russian Research Institute of Biological Plant Protection. Two varieties of winter wheat: Kralya and Vershina with different types of resistance to leaf rust, were used for the experiment. Cultivar Kralya had race-specific resistance; cultivar a Vershina had race-nonspecific resistance to leaf rust. Virulence analysis of the impact of each cultivar on the structure of the pathogen population based on the results of differentiation of P. triticina populations, collected from each cultivar and compared to the mixed pathogens population. As a result, it was found that the genotype of a winter wheat variety with race-specific resistance significantly affects the virulence of the P. triticina population. The frequency of virulent pathogen isolates to most lines with Lr genes has changed under the influence of driving selection. Therefore, the wide regionalization of varieties with race-specific resistance will contribute to selective pressure on the P. triticina population and the accumulation of virulent phenotypes in it. The genotype of a wheat variety with nonspecific resistance did not cause significant changes in the gene pool of the virulence of the leaf rust pathogen population. In accordance with the obtained values of the Nei index, the pathogen population collected from a variety with race-specific resistance has significant differences with the combined population (N = 0.68), in contrast to the population of P. triticina collected from the Vershina variety (N = 0.41). The results obtained confirm the importance of screening varieties by resistance types for further decision making on their placement. Varieties with race-specific resistance are best used for mosaic placement with subsequent mandatory rotation in time and space. And varieties with nonspecific resistance, which are weakly affected by all races of the pathogen and cannot be carriers of infection, can be used over large areas for a longer time, combined with varieties from various groups, including their own. Scientific novelty. There have been practically no studies on the effect of wheat varieties with different types of resistance on the virulence of rust fungi populations, although this direction is of great practical interest for both selection and varietal placement.

Students’ Resistance Behaviors: What Do Turkish Primary Teachers Face?

Abstract Introduction: Students could react to the learning activities, teachers, or administrators knowingly and willfully, many times intentionally by resisting in various ways. A detailed analysis of this definition indicates that unlike naughty behaviors, resistance behaviors do not develop suddenly, they are often planned beforehand by the student, and they contain some messages to the person or institution they are directed at. These kinds of behaviors could have negative effects not only on students’ academic, social, and psychological development but also on teachers’ professional satisfaction. Therefore, these issues should be elaborated carefully. However, despite the importance indicated in the literature, students’ resistance behaviors are one of the neglected issues that are not investigated adequately. With reference to this need, the presented study aims to identify perceptions of primary school teachers about students’ resistance behaviors. Methods: The participants were 152 primary school teachers. Data were collected through the Student Resistance Behaviors Scale for Teachers (SRBS-T) and Teacher Interview Form. In addition to descriptive statistics, data were analyzed using t-test and one-way ANOVA. Also, a qualitative descriptive analysis was conducted regarding qualitative data of the study. Results: Results show that the mean scores for SRBS were “medium” on a 5-point Likert scale. While teachers’ perceptions about resistance behaviors showed no significant differences according to gender and the type of school they graduated from, scores showed significant differences in terms of teachers’ years of seniority. According to the teachers, the most encountered resistant behaviors were gathered under the themes of resistance to teacher authority and hostile attitudes towards the teacher/peers. Discussion: Through discussion, the results obtained by the scale and interviews were discussed. All the findings showed that teachers are important receivers of resistance behaviors and they are facing with different types of resistance in the classroom. Limitations: It is obvious that these results were limited to the reached primary school teachers. Another limitation was that the data within the study collected via SRBS-T and interviews. Conclusions: The study showed that teachers and students are the key components of the educational process and students could show resistance to both the process and teachers in different ways. As this study only focused on primary teachers’ experiences, more studies could be organized through understanding the resistance middle and high school teachers face with as well. Further research could be conducted with students to see how they feel and behave when they feel resistance as well as with other teachers working at various levels of education and in various institutions.