Resistant Ones Research Articles

Strongly suppressed proximity effect and ferromagnetism in topological insulator/ferromagnet/superconductor thin film trilayers of Bi2Se3/SrRuO3/underdoped YBa2Cu3Ox: a possible new platform for Majorana nano-electronics

We report properties of a topological insulator–ferromagnet–superconductor trilayers comprised of thin films of 20 nm thick on 10 nm SrRuO3 on 30 nm . As deposited trilayers are underdoped and have a superconductive transition with onset at 75 K, zero resistance at 65 K, at 150 K and of about 200 K. Further reannealing under vacuum yields the 60 K phase of which still has zero resistance below about 40 K. Only when 10 × 100 microbridges were patterned in the trilayer, some of the bridges showed resistive behavior all the way down to low temperatures. Magnetoresistance versus temperature of the superconductive ones showed the typical peak due to flux flow against pinning below , while the resistive ones showed only the broad leading edge of such a peak. All this indicates clearly weak-link superconductivity in the resistive bridges between superconductive grains via the topological and ferromagnetic cap layers. Comparing our results to those of a reference trilayer (RTL) with the topological layer substituted by a non-superconducting highly overdoped , indicates that the superconductive proximity effect as well as ferromagnetism in the topological trilayer are actually strongly suppressed compared to the non-topological RTL. This strong suppression could originate in lattice and Fermi levels mismatch as well as in short coherence length and unfavorable effects of strong spin–orbit coupling in on the d-wave pairing of . Proximity induced edge currents in the SRO/YBCO layer could lead to Majorana bound states, a possible signature of which is observed in the present study as zero bias conductance peaks.

Apport De La Prospection Géoelectrique (Tomographie Et Trainé Éléctrique) À L’étude Des Tourmalinites Stanniferes d’Achmmache (Maroc Central)

The Achemmache region is located in the East of El Hammam district, in the Eastern part of the Northern Hercynian Central Morocco; Tin concentrations, economically exploitable, have been recognized in brecciated tourmaline structures of Late Visean, and generally oriented E-W. Therefore, they contrast with other tourmaline oriented NE-SW which proved barren. In order to keep the horizontal and vertical continuity as well as the dip and extension of mineralized structures in the sector, a geophysical survey by Horizontal Electrical resistivity (TE) prospecting and Electrical Tomography was performed in the region. The TE1 profile was performed in the West Zone where the mineralized structures outcrop; it allows highlighting four positive anomalies, while the TE2 profile was carried out in Eastern zone of the sector where the mineralized structures are largely hidden. It can also bring out only two rather distant positive anomalies. These anomalies correspond to mineralized structures of tourmaline. While a duplicate executing of TE1 and TE2, mineralized structures show that some resistant ones have different dips, while some others are subvertical. The TM1 profile was carried out at the same location of electrical TE1 profile in order to confirm the tourmaline structures. The TM1 shows from the NW to the SE an alternation of resistant levels with the relatively conductive levels. The resistive levels are correlated with tourmaline structures identified by the horizontal electrical resistivity. The structures dips show a good correlation between the electrical tomography results and these obtained by the horizontal electrical resistivity profiles with duplicate mode. The study of thin sections and polished sections of the SCA110 and SCA8 core drilling, carried out by BRPM, allowed to recognize, at the mineralized zones, a paragenesis composed of gangue minerals such as quartz, calcite, tourmaline metallic minerals, sulphides and oxides such as magnetite and cassiterite.

Agronomical, biochemical and histological response of resistant and susceptible wheat and barley under BYDV stress.

Barley yellow dwarf virus-PAV (BYDV-PAV) is one of the major viruses causing a widespread and serious viral disease affecting cereal crops. To gain a better understanding of plant defence mechanisms of BYDV resistance genes (Bdv2 and RYd2) against BYDV-PAV infection, the differences in agronomical, biochemical and histological changes between susceptible and resistant wheat and barley cultivars were investigated. We found that root growth and total dry matter of susceptible cultivars showed greater reduction than that of resistant ones after infection. BYDV infected leaves in susceptible wheat and barley cultivars showed a significant reduction in photosynthetic pigments, an increase in the concentration of reducing sugar. The protein levels were also low in infected leaves. There was a significant increase in total phenol contents in resistant cultivars, which might reflect a protective mechanism of plants against virus infection. In phloem tissue, sieve elements (SE) and companion cells (CC) were severely damaged in susceptible cultivars after infection. It is suggested that restriction of viral movement in the phloem tissue and increased production of phenolic compounds may play a role in the resistance and defensive mechanisms of both Bdv2 and RYd2 against virus infection.

Nephrotic Syndrome Outcome in Children: An Epidemiological Study

Background: Nephrotic syndrome (NS) as a glomerular basal membrane disease has different outcomes. The current study aimed at evaluating epidemiologic status in NS and its correlation with the outcome in children. Methods: The current hospital based study evaluated the patients of pediatric clinic at Amir-Kabir hospital. Demographic information was obtained by interviewing both the physicians and patients. Also, to determine the sesitivityto steroid drugs, children were given prednisolone (2 mg/kg/day with maximum dose of 60 mg/day) for four weeks and syndromes were determined based on children responses to the drug. Patients were divided into four groups of 25. At the end, data were transfered to SPSS program and the correlations between epidemiological information and different types of NS were investigated Results: Results of the current study showed that steroid responded children with frequent relapse as well as steroid dependent children had better epidemiological and socioeconomic status compared with the steroid resistance ones (P < 0.05). Conclusions: Prognosis of NS or medication responses was related to epidemiological status of children.

Multidirectional Activities for Gene Pool Conservation in GCEARS-PSP

The Global Centre of Excellence for Advance Research in Sericulture and Promotion of Silk Production (GCEARS-PSP), recognised by ISC since 2014, was created with the main purposes: development of advanced research in sericulture and diagnostic services using modern techniques, achievement of a gene pool of different silkworms races and promotion of silk production. The objective of this study was to characterize the races from the GCEARS-PSP, in order to conserve the most valuable and resistant ones. This characterisation is a part of GCEARS-PSP’s strategy for the revival and development of sericulture and silk production in Romania. The GCEARS-PSP represents an important point of reference for Romanian sericulture. The experimental data described showed a good prospective for a proper functioning of the research centre and the obtained results are promising for the next lines of research.

Genetic diversity and virulence of Striga hermonthica from Kenya and Uganda on selected sorghum varieties

Joel KA, Runo S, Muchugi A. 2018. Genetic diversity and virulence study of Striga hermonthica from Kenya and Uganda on selected sorghum varieties. Nusantara Bioscience 10: 111-120. Parasitic weeds pose a severe problem in agricultural production, causing massive crop losses in many regions of the world and especially Africa. One example to be considered the most significant biological constraint to food production in sub-Saharan Africa (SSA) is Striga hermonthica, the most widespread among the Striga species in the semi-arid tropical African zones. The wide geographical distribution set conditions for genetically structured populations. The genetic variations among the weed populations allow for the quick breakdown of resistance in crops hence making control of the weed difficult. Efficient and effective control of S. hermonthica demands knowledge on inherent genetic variability within local and regional races of the weed. However, the genetic diversity and virulence of S. hermonthica ecotypes in Kenya and Uganda on selected sorghum varieties remain unknown. This study aimed at evaluating the genetic diversity among seven S. hermonthica populations from locations in Kenya and Uganda using 5 primer sets of Expressed Sequence Tags-Simple Sequence Repeats (EST-SSR). The genetic diversity was moderate as shown by the Nei’s genetic distance values. AMOVA measured low genetic differentiation among the populations. This study also investigated twelve sorghum varieties for their response to S. hermonthica infection. The result demonstrated that the varieties resistance responses to S. hermonthica varied widely. The phenotype of resistant interaction was characterized by the inability of the weeds haustoria to penetrate the sorghums root endodermis due to severe necrosis and in rare cases the parasites radicle growing away from the host root. The resistant sorghum varieties were the Asareca W2, Asareca AG3, N13 and the Wild-type which had low mean number of S. hermonthica plantlets growing on their roots, while the most susceptible varieties were Sap 027, Epurpur which had the highest mean number of S. hermonthica plantlets growing on their roots. There was a highly significant difference in the means of the number of Striga growing on the roots of sorghum varieties, Striga dry biomass and S. hermonthica length between the susceptible and resistant ones. This knowledge holds unique potentiality since resistant sorghum germplasm tested will be sourced and targeted to the seven specific geographical areas where virulence of the particular S. hermonthica populations was characterized.

Effect of salinity on Echinochloa crus-galli germination as affected by herbicide resistance

Salinity is one of the major abiotic stresses that may affect yield and quality of crops. Salinization, in combination with the presence of aggressive weeds, such as barnyard grass (Echinochloa spp.), can be considered one of the factors responsible for reducing yield in rice fields. The aims of the study were to evaluate the salt effect on germination and first seedling growth of six different Italian common barnyard grass (E. crus-galli) populations (three sensitive and three resistant to ALS-inhibitor herbicides) and to verify the presence of differences in salt response between populations sensitive and resistant to the ALS-inhibitor herbicides. Germination tests were conducted under nine different NaCl concentrations (from 0 mM to 400 mM). Significant differences in germination capacity were found between sensitive and resistant populations from 0 mM to 250 mM NaCl; in particular, germination capacity of the sensitive populations was higher (up to 90%) than that of the resistant ones (about 70%). The increase in salinity over 250 mM reduced progressively the germination capacity: from 300 mM onwards, no significant differences were found between sensitive and resistant populations and the germination resulted inhibited for two of them (one sensitive and one resistant). Speed of germination and root and shoot length of seedlings were also inversely related to salt concentration. Time required for achieving 50% of final germination capacity was extended from about three days at 0 mM NaCl up to about 10-12 days at 400 mM NaCl. Root length and shoot length ranged from 9.88 cm and 6.16 cm, at 0 mM NaCl, to 0.36 cm and 0.41 cm, at 400 mM NaCl. According to the results, there is no a clear evidence that response to saline conditions was related to resistance towards ALS-inhibitor herbicides, as in some cases significant differences were found between populations showing a similar herbicide sensitivity. Responses of barnyard grass to salinity are may play a role in the importance of this weed in future scenarios of salt intrusion: for example, a lower speed of germination at increasing salt levels could suggest a delayed emergence of this weed during crop establishment and first growth. To evaluate the real consequences in terms of competitions towards the crop, future studies are needed for assessing the response to salinity of the main rice varieties cultivated in the environment in which the E. crus-galli populations tested in this study were collected.

In vitro anti-leukemia activity of dual PI3K/mTOR inhibitor Voxtalisib on HL60 and K562 cells, as well as their multidrug resistance counterparts HL60/ADR and K562/A02 cells

Current treatment strategies for leukemia still have some limitations such as severe side effects and drug resistance. Less toxic and more effective drugs for leukemia patients are therefore expected. In the present study, the efficacy of a dual PI3K/mTOR inhibitor, Voxtalisib, on acute myeloid leukemia (AML) cell line HL60 and chronic myeloid leukemia (CML) cell line K562, as well as their Adriamycin (ADR)-selected multi drug resistance (MDR) counterparts HL60/ADR and K562/A02, was investigated. Voxtalisib exhibited potent anti-proliferative activity on these four cell lines dose-dependently, with IC50 values as 2.23 μM for HL60, 4.79 μM for HL60/ADR, 4.20 μM for K562 and 3.90 μM for K562/A02 cells. Voxtalisib arrested cell cycle progression at G1 phase in all cell lines by upregulating p27, downregulating cyclin D1 and p-pRb. When combined with ADR, Voxtalisib reversed the ADR-resistance of HL60/ADR and K562/A02 cells, possibly by reducing MDR1 and MRP1 expression. In conclusion, Voxtalisib showed anti-leukemia activity on AML and CML cell lines as well as their multidrug resistant ones, suggesting Voxtalisib might become a promising drug candidate for therapy of AML and CML in the future.

Vitamin D insufficiency is associated with insulin resistance independently of obesity in primary schoolchildren. The healthy growth study.

To explore the associations of vitamin D status and obesity with insulin resistance (IR) in children. A sample of 2282 schoolchildren (9-13 years old) in Greece was examined. Sociodemographic, anthropometric (weight, height), biochemical (fasting plasma glucose, serum insulin and 25(OH)D), pubertal status and physical activity data were collected, using standard methods. The "Vitamin D Standardization Program" protocol was applied to standardize serum 25(OH)D values. The prevalence of vitamin D insufficiency (serum 25(OH)D < 50 nmol/L) was higher in obese children compared to their over- and normal-weight counterparts (60.5% vs 51.6% and 51%, P = .017). Furthermore, children with IR (both obese and non-obese) had higher prevalence of vitamin D insufficiency compared to non-obese, non-insulin resistant children (66% and 59.2% vs 49.8%, P < .05), possibly indicating that IR is associated with vitamin D insufficiency, independently of obesity. In line with the above, the results from logistic regression analyses controlled for several potential confounders, showed a 1.48 (95% C.I: 1.2-1.84) higher likelihood for vitamin D insufficiency for insulin resistant children compared to the non-insulin resistant ones, while no significant association was observed with obesity. The present study revealed a high prevalence of vitamin D insufficiency among schoolchildren in Greece, particularly among obese and insulin resistant ones. In addition, it highlighted that the significant association of vitamin D insufficiency with IR is possibly independent of obesity. Further clinical trials are needed to confirm this possible independent association but also explore the potential beneficial effect of vitamin D supplementation on IR and possibly on weight management too.

Yeast-insect associations: It takes guts.

Insects interact with microorganisms in several situations, ranging from the accidental interaction to locate attractive food or the acquisition of essential nutrients missing in the main food source. Despite a wealth of studies recently focused on bacteria, the interactions between insects and yeasts have relevant implications for both of the parties involved. The insect intestine shows several structural and physiological differences among species, but it is generally a hostile environment for many microorganisms, selecting against the most sensitive and at the same time guaranteeing a less competitive environment to resistant ones. An intensive characterization of the interactions between yeasts and insects has highlighted their relevance not only for attraction to food but also for the insect's development and behaviour. Conversely, some yeasts have been shown to benefit from interactions with insects, in some cases by being carried among different environments. In addition, the insect intestine may provide a place to reside for prolonged periods and possibly mate or generate sexual forms able to mate once back in the external environments.YEA‐May‐17‐0084.R3

Integrative transcriptome analysis identifies genes and pathways associated with enzalutamide resistance of prostate cancer

Background: Enzalutamide, a novel androgen receptor (AR) signaling inhibitor, has been widely used to increase survival in patients with castration-resistant prostate cancer. However, resistance to enzalutamide invariably develops.Methods: To understand the underlying mechanisms of resistance to enzalutamide, we performed integrative analysis on multiple transcriptome datasets to identify those genes constantly up- or down-regulated in response to enzalutamide treatment.Results: There were 703 and 581 differentially expressed genes derived from enzalutamide-sensitive and -resistant cell lines, respectively. Functional enrichment analysis on these genes demonstrated that biological processes of cell proliferation and ubiquitin mediated proteolysis pathway are specifically disturbed in sensitive cell lines but not resistant ones. Such divergence explained why enzalutamide ineffective for resistant prostate cancer.Conclusions: Taken together, the present study revealed a set of critical genes, which can provide etiologic clues as to enzalutamide-resistant prostate cancer and guide novel therapeutic approaches.

Tracking haplotype for QTLs associated with Fusarium head blight resistance in Japanese wheat (Triticum aestivum L.) lineage

BackgroundFusarium head blight (FHB) resistance in wheat (Triticum aestivum L.) has been enhanced by combining resistant alleles with transgressive segregation. In Japan, intensive FHB resistance breeding was initiated in 1970s in Kyushu and in 1990s in Hokkaido. The breeding objectives for climatic adaptation are different between Kyushu and Hokkaido. The objective of this study is to determine how and what type of alleles should be introduced into current cultivars by characterizing the track of allelic selection in both breeding lineages.ResultsHerein, we traced haplotype of SSR markers for allelic selection of FHB resistance-related quantitative trait loci (QTLs) in the Japanese breeding lineages of Kyushu and Hokkaido where the climatic adaptations of wheat are dissimilar. In Kyushu, resistant haplotypes on chromosomes 3BS, 5AS, and 6BS were frequently found in old cultivars, and those on 3BS and 5AS were transmitted to modern cultivars with incorporating the resistant allele on 2DL. The winter cultivars of Hokkaido lacked the resistant allele set of the markers at 3BS, but the resistant haplotypes at 2DL and 5AS were predominantly retained. The resistant allele combinations at 6BS and 2DS were mostly excluded from Kyushu and the winter cultivars of Hokkaido. The susceptible haplotype on 2DS was co-inherited with the semi-dwarfing allele at Xgwm261 which is diagnostic for the presence of the dwarfing gene Rht8 and the allele of the photoperiod insensitive at Ppd-D1 in Kyushu, indicating a linkage drag between a FHB resistance allele and ones underling agronomic characters. In Hokkaido, six cultivars were found to have the resistant haplotype on 2DS with the semi-dwarfing allele of Xgwm261.ConclusionsOur results suggest that a trade-off between FHB resistance and quality or agronomic traits has contributed to the history of Japanese FHB resistance breeding. To enhance FHB resistance in current cultivars, introducing the resistant allele of QTL on 2DS should be a promising option. The six winter cultivars found in the Hokkaido lineage can be used as new donors for introducing FHB resistance alleles of QTL on 2DS into modern cultivars together with the semi-dwarfing allele at Xgwm261.

Study of the Right Heart of High-Level African Adult Athletes: Electrocardiographic and Echocardiographic Aspects

Despite the growing interest in athlete’s right ventricle and various work carried out, many uncertainties are remaining. The interest of this work resides in the determination of the particularity in right heart of the black athlete subject. We conducted a prospective study from August to October 2016 in the cardiology department of Aristide Le Dantec University Hospital in Dakar. The included patients were divided according to the sporting practice as enduring, resistant and non-athletes. The parameters studied were electrocardiographic (atrial or ventricular hypertrophies), echocardiographic: dimensions of the right cavities, systolic and diastolic functions of the right ventricle. We included 58 subjects: 38 athletes including 28 endurance and 10 resistance and 20 non-athletes. The average age of the endurance athletes was 21.9 ± 3, 75 years, 26.30 ± 4.64 in resistance ones and 24.10 ± 1.89 in the non-athletic group. Two cases of first-degree atrioventricular block were recorded in athletes. On the echocardiographic point, the atrium surfaces, as well as the transverse diameter, were greater in athletes, especially in the endurance group. The mean diameters of the admission chamber and those of the right ventricular flush chamber were larger in the group of endurance athletes. It was the same for the annular and sagittal basal mean diameters of the RV as well as the RV/LV ratio. The anterior wall of the right ventricle was larger in athletes compared to non-athletes. The vena cava was greater in athletes, the pulmonary arterial pressure higher in resistance ones.

Identifying an Elite Panel of Apple Rootstock Germplasm with Contrasting Root Resistance to Pythium ultimum

Apple replants disease (ARD), incited by a soil borne pathogen complex, is a major obstacle to establishing an economically viable apple orchard at replant sites. The predominant control method is pre-plant chemical fumigation of orchard soil, which is expensive and comes with environmental and regulatory concerns. To maximize the exploitation of host resistance for ARD management, high quality resistance phenotypes in apple roots to ARD pathogen infection are required for elucidating the underlying resistance mechanisms. In this study, root resistance responses to Pythium ultimum infection were systematically evaluated among the ‘Ottawa 3’ × ‘Robusta 5’ (O3R5) F1 progeny. Tissue culture-based micro propagation was employed to generate genetically-defined and age-equivalent apple plants for repeated infection assays. A wide range of plant survival rates were observed, with fewer than 30% for the susceptible genotypes and over 80% for the resistant ones. The levels of root and shoot biomass reduction among the surviving plants varied substantially between the most resistant genotypes and the most susceptible genotypes. Contrasting necrosis patterns were demonstrated along the infected roots between resistant and susceptible genotypes using a novel glass-box pot for continuous microscopic observation. Swift necrosis occurred across the entire root system within 24 hours for the susceptible genotypes; in sharp contrast, evidently deterred root necrosis was observed for the resistant genotypes. A well-defined boundary separating healthy and necrotic root tissues were often accompanied with the infected roots of resistant genotypes, while the profuse growth of P. ultimum hyphae was specifically associated with the infected roots of susceptible genotypes. The results from this study represented the first comprehensive and detailed effort undertaken to define the genotype-specific resistance responses in apple roots as they are challenged by a soil-borne pathogen.

Performance Analysis of a Boost Converter with Components Losses

A theoretical study of a conventional boost converter is presented. Based on the real behavior of the components, two models of the boost converter are introduced: one dealing only with losses through inductor and capacitor and another taking into account switching losses in addition to resistive ones. From these two models, the detailed analytical expressions of both voltage gain factor and conversion efficiency are established taking into account the losses through parasitic resistances and switching losses. The behavior of the converter is then analyzed for each model by simulation for the voltage gain factor and the conversion efficiency.

Prevalence and molecular characteristics of multi-resistant Escherichia coli in wild birds

Humans and animals share the same bacterial species including the resistant ones. For that reason, epidemiological studies in domestic and wild animals should be performed on a regular basis. Wild, particularly migratory birds, should be investigated as potential carriers of antimicrobial resistant bacteria that can be spread globally in a short time. The aim of this study was to investigate the prevalence and to characterize multi-resistant Escherichia coli in wild birds. Three hundred and ninety two samples were obtained from different bird species including gulls (Larus spp.), mallards (Anas platyrhynchos), mute swans (Cygnus olor), as well as other species of birds. Phenotypical and genotypical resistance of E. coli was investigated. In total 60 isolates from 179 tested were resistant to three or more antimicrobial classes and treated as multi-resistant (33.5%; 95% CI 21.56–45.44); the isolates were obtained from gulls, mallards, swans, and rooks. All of the strains demonstrated resistance to aztreonam and cefpodoxime. The most frequent resistance prevalence of the above-mentioned isolates in vitro was also demonstrated to ampicillin (82%), ampicillin/sulbactam (68%), cefazolin (66%), ceftriaxone (55%), and ciprofloxacin (47%). All E. coli isolates were susceptible to amikacin. The results of polymerase chain reaction confirmed the presence of the genes encoding resistance to beta-lactams, aminoglycosides, tetracycline, amphenicols, trimethoprim, and sulphonamides. Consequently, wild birds might constitute a potential hazard to human and animal health by transmitting multi-resistant E. coli strains to waterways and other environmental sources via bird faeces.

Генетическое разнообразие мягкой яровой пшеницы по устойчивости к ранней засухе

Soft spring wheat has a wide range of genetic diversity in water deficiency response at juvenile stage of plant development. Fifty-nine collection samples were studied under laboratory conditions. In control variant distilled water was used, in experiment - sucrose solution (9 atm). The relative index of seed roots number is the most information-bearing criterion for estimation of potential drought-resistance level. Based on this criterion 16.9% samples of the studied set are estimated as highly resistant, 50.8% - as resistant ones. Low level of resistance is characteristic for only 5.1% of studied genotypes. The following species were recognized as having high drought-resistance level: ANK-4 (Novosibirsk region, Russia), Vetluzhanka (Krasnoyarsk territory, Russia), Vishivanka (Ukraine), E-737 (Kazakhstan), Cahuide (Peru), Klein Vencedor (Argentina), Musket (Great Britain), NOS Norko (Germany), Ta 3332 (Finland). Cluster analysis divided the whole set of variety samples into 5 groups having different combinations of such parameters as seed germination ability, number of seed roots, the intensity of root development and germ growth both under control and in conditions of physiological drought. To raise the level of potential drought resistance it is possible to use genotypes from remote clusters for crossing.

Screening of green gram (Vigna radiata) Cultivars against pulse beetle (Callosobruchus Spp.)

Evaluation of 100 cultivars of green gram Vigna radiata (L.) Wilczeck under no choice condition against three species of pulse beetle viz. Callosobruchus maculatus F., C. analis F., and C. chinensis L. was undertaken. Observations on the number of eggs laid on grain surface, emergence and mean development period (MDP) under storage conditions at 27 + 1.5°C and 60% RH were made. On the basis of growth index value, out of 100 cultivars, 15 cultivars were selected for each species of bruchid. The results led to selection of five cultivars each as resistant, least susceptible and most susceptible ones.

Pharmacological treatment with inhibitors of nuclear export enhances the antitumor activity of docetaxel in human prostate cancer.

Background and aimsDocetaxel (DTX) modestly increases patient survival of metastatic castration-resistant prostate cancer (mCRPC) due to insurgence of pharmacological resistance. Deregulation of Chromosome Region Maintenance (CRM-1)/ exportin-1 (XPO-1)-mediated nuclear export may play a crucial role in this phenomenon.Material and methodsHere, we evaluated the effects of two Selective Inhibitor of Nuclear Export (SINE) compounds, selinexor (KPT-330) and KPT-251, in association with DTX by using 22rv1, PC3 and DU145 cell lines with their. DTX resistant derivatives.Results and conclusionsWe show that DTX resistance may involve overexpression of β-III tubulin (TUBB3) and P-glycoprotein as well as increased cytoplasmic accumulation of Foxo3a. Increased levels of XPO-1 were also observed in DTX resistant cells suggesting that SINE compounds may modulate DTX effectiveness in sensitive cells as well as restore the sensitivity to DTX in resistant ones. Pretreatment with SINE compounds, indeed, sensitized to DTX through increased tumor shrinkage and apoptosis by preventing DTX-induced cell cycle arrest. Basally SINE compounds induce FOXO3a activation and nuclear accumulation increasing the expression of FOXO-responsive genes including p21, p27 and Bim causing cell cycle arrest. SINE compounds-catenin and survivin supporting apoptosis. βdown-regulated Cyclin D1, c-myc, Nuclear sequestration of p-Foxo3a was able to reduce ABCB1 and TUBB3 H2AX levels, prolonged γ expression. Selinexor treatment increased DTX-mediated double strand breaks (DSB), and reduced the levels of DNA repairing proteins including DNA PKc and Topo2A. Our results provide supportive evidence for the therapeutic use of SINE compounds in combination with DTX suggesting their clinical use in mCRPC patients.

A New Ala-122-Asn Amino Acid Change Confers Decreased Fitness to ALS-Resistant Echinochloa crus-galli

Gene mutations conferring herbicide resistance may cause pleiotropic effects on plant fitness. Knowledge of these effects is important for managing the evolution of herbicide-resistant weeds. An Echinochloa crus-galli population resistant to acetolactate synthase (ALS) herbicides was collected in a maize field in north-eastern Italy and the cross-resistance pattern, resistance mechanism and fitness costs associated to mutant-resistant plants under field conditions in the presence or absence of intra-specific competition were determined. The study reports for the first time the Ala-122-Asn amino-acid change in the ALS gene that confers high levels of cross-resistance to all ALS inhibitors tested. Results of 3-year growth analysis showed that mutant resistant E. crus-galli plants had a delayed development in comparison with susceptible plants and this was registered in both competitive (3, 7, and 20 plants m-2) and non-competitive (spaced plants) situations. The number of panicles produced by resistant plants was also lower (about 40% fewer panicles) than susceptible plants under no-intraspecific competition. Instead, with the increasing competition level, the difference in panicle production at harvest time decreased until it became negligible at 20 plants m-2. Evaluation of total dry biomass as well as biomass allocation in vegetative parts did not highlight any difference between resistant and susceptible plants. Instead, panicle dry weight was higher in susceptible plants indicating that they allocated more biomass than resistant ones to the reproductive organs, especially in no-competition and in competition situations at lower plant densities. The different fitness between resistant and susceptible phenotypes suggests that keeping the infestation density as low as possible can increase the reproduction success of the susceptible phenotype and therefore contribute to lowering the ratio between resistant and susceptible alleles. If adequately embedded in a medium or long-term integrated weed management strategy, the presence of R plants with a fitness penalty provides an opportunity to minimize or reverse herbicide resistance evolution through the implementation of integrated weed management, i.e., all possible control tools available.