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Milking speed is an important trait influencing the udder health of dairy cows, as well as labor efficiency. However, it has received little attention in genomic association studies. The main objective of this study was to determine regions and genes on the genome with a potential effect on milking speed in Fleckvieh (dual-purpose Simmental) cattle. Genome-wide association studies were conducted using deregressed breeding values of bulls as phenotypes. We found 6 SNPs on 4 autosomes that were significantly associated with milking speed for additive effects. Significant regions on BTA4 and BTA19 correspond with findings for other dairy cattle breeds. Based on the observations of Fleckvieh breed managers, variation of milking speed in batches of daughters of some bulls is much higher than in daughter groups of other bulls. This difference in within-family variation may be caused by the transmission of alternative alleles from bulls being heterozygous for a gene affecting milking speed. To check on this, we considered the SD of yield deviations in milking speed of half-sib daughters as a new trait and performed GWAS for dominance effects. One signal on BTA5 passed the genome-wide Bonferroni threshold that corresponded to the significant signal from standard GWAS on deregressed breeding values. The key conclusion of this study is that several strong genomic signals were found for milking speed in Fleckvieh cattle, and that the strongest of them are supported by similar findings in Brown Swiss and Holstein Friesian cattle. Milking speed is a complex trait whose subprocesses have not yet been elucidated in detail. Hence, it remains a challenge to link the associated regions on the genome with causal genes and their functions. The list of standard abbreviations for JDS is available at adsa.org/jds-abbreviations-24. Nonstandard abbreviations are available in the Notes. [ABSTRACT FROM AUTHOR]

The purpose of this study was to determine whether two well-known risk factors for recidivism, criminal thinking and prior criminal arrests, were capable of achieving a combined effect, and if so, whether this effect was additive, interactive, or both. This hypothesis was tested in a group of 226 males incarcerated in a medium security federal prison who had participated in a criminal thinking intervention prior to their release from prison. The two main variables, criminal thinking (Exp(b) = 1.016 [1.007,1.024]) and prior arrests (Exp(b) = 1.062 [1.024, 1.102]), and their interaction (Exp(b) = 1.264 [1.002, 1.595]) were statistically significant according to the results of a Cox regression analysis. Moreover, the combined score displayed a small incremental increase in the area under the curve (AUC) of a receiver operating characteristic analysis (.660 [.583,.737]), whereas adding the interaction to the two-variable combination improved the AUC further (.668 [.592,.743]). These results suggest that risk factors for recidivism not only add predictive variance to a risk assessment they may also be capable of forming specific interactive effects with other risk factors, although the effects observed in the current study were small and in need of further evaluation. [ABSTRACT FROM AUTHOR]

Aims Methods and results Conclusion Long‐term fine particulate matter (PM2.5) exposure has been linked to incident heart failure (HF), but the impacts of its constituents remain unknown. We aimed to investigate the associations of PM2.5 constituents with incident HF, and further evaluate the modification effects of genetic susceptibility.PM2.5 and its constituents, including elemental carbon (EC), organic matter (OM), ammonium (NH4+), nitrate (NO3−), and sulfate (SO42−), were estimated using the European Monitoring and Evaluation Programme model applied to the UK (EMEP4UK) driven by Weather and Research Forecast model meteorology. A polygenic risk score (PRS) was calculated to represent genetic susceptibility to HF. We employed Cox models to evaluate the associations of PM2.5 constituents with incident HF. Quantile‐based g‐computation model was used to identify the main contributor of PM2.5 constituents. Among 411 807 individuals in the UK Biobank, 7554 participants developed HF during a median follow‐up of 12.05 years. The adjusted hazard ratios of HF for each interquartile range increase in PM2.5, EC, OM, NH4+, NO3−, and SO42− were 1.50 (1.46–1.54), 1.31 (1.27–1.34), 1.12 (1.09–1.15), 1.42 (1.41–1.44), 1.26 (1.23–1.29), and 1.25 (1.24–1.26), respectively. EC (43%) played the most important role, followed by NH4+ and SO42−. Moreover, synergistic additive interactions accounted for 9–16% of the HF events in individuals exposed to both PM2.5, NH4+, NO3−, and SO42− and PRS.Long‐term exposure to PM2.5 constituents may elevate HF risk, and EC was the major contributor. Additive effects of PM2.5 constituents and PRS on HF risk were revealed. [ABSTRACT FROM AUTHOR]

Selection is a fundamental part of the plant breeding process, enabling the identification and development of varieties with desirable traits. Thanks to advances in genetics and biotechnology, the selection process has become more precise and efficient, resulting in faster breeding progress and better adaptation of crops to environmental challenges. Genetic parameters related to gene additivity and epistasis play a key role and can influence decisions on the suitability of breeding material. In this study, 188 rapeseed doubled haploid lines were assessed in field conditions for resistance to Leptosphaeria spp. Through next-generation sequencing, a total of 133,764 molecular markers (96,121 SilicoDArT and 37,643 SNP) were obtained. The similarity of the DH lines at the phenotypic and genetic levels was calculated. The results indicate that the similarity at the phenotypic level was markedly different from the similarity at the genetic level. Genetic parameters related to additive gene action effects and epistasis (double and triple) were calculated using two methods: based on phenotypic observations only and using molecular marker observations. All evaluated genetic parameters (additive, additive-additive and additive-additive-additive) were statistically significant for both estimation methods. The parameters associated with the interaction (double and triple) had opposite signs depending on the estimation method. [ABSTRACT FROM AUTHOR]

A genome-wide association study of resistance to retained placenta (RETP) using 632,212 Holstein cows and 74,747 SNPs identified 200 additive effects with p-values < 10−8 on thirteen chromosomes but no dominance effect was statistically significant. The regions of 87.61–88.74 Mb of Chr09 about 1.13 Mb in size had the most significant effect in LOC112448080 and other highly significant effects in CCDC170 and ESR1, and in or near RMND1 and AKAP12. Four non-ESR1 genes in this region were reported to be involved in ESR1 fusions in humans. Chr23 had the largest number of significant effects that peaked in SLC17A1, which was involved in urate metabolism and transport that could contribute to kidney disease. The PKHD1 gene contained seven significant effects and was downstream of another six significant effects. The ACOT13 gene also had a highly significant effect. Both PKHD1 and ACOT13 were associated with kidney disease. Another highly significant effect was upstream of BOLA-DQA2. The KITLG gene of Chr05 that acts in utero in germ cell and neural cell development, and hematopoiesis was upstream of a highly significant effect, contained a significant effect, and was between another two significant effects. The results of this study provided a new understanding of genetic factors underlying RETP in U.S. Holstein cows. [ABSTRACT FROM AUTHOR]

The interactive effects of obesity and physical inactivity on lipid metabolism and prevalent dyslipidemia are scarcely reported in rural regions. 39029 subjects were obtained from the Henan Rural Cohort, and their metabolic equivalents (METs) of physical activity (PA) were computed. Independent associations of the obesity indices and PA with either lipid indices or prevalent dyslipidemia were analyzed by generalized linear models, and additive effects of obesity and PA on prevalent dyslipidemia were further quantified. Each obesity index was positively associated with total cholesterol, triglyceride, low-density lipoprotein or prevalent dyslipidemia but negatively associated with high-density lipoprotein, whereas the opposite association of PA with either each lipid index or prevalent dyslipidemia was observed. Joint association of PA and each obesity index with each lipid index and prevalent dyslipidemia was observed. Furthermore, the association of each obesity index in association with each lipid index was attenuated by increased PA levels. [ABSTRACT FROM AUTHOR]

In this article, we develop additive autoregressive models (Add‐ARM) for the time series data with matrix valued predictors. The proposed models assume separable row, column and lag effects of the matrix variables, attaining stronger interpretability when compared with existing bilinear matrix autoregressive models. We utilize the Gershgorin's circle theorem to impose some certain conditions on the parameter matrices, which make the underlying process strictly stationary. We also introduce the alternating least squares estimation method to solve the involved equality constrained optimization problems. Asymptotic distributions of the parameter estimators are derived. In addition, we employ hypothesis tests to run diagnostics on the parameter matrices. The performance of the proposed models and methods is further demonstrated through simulations and real data analysis. [ABSTRACT FROM AUTHOR]

Agricultural land use alters nitrate (NO3–) uptake dynamics in streams, but the specific mechanisms linking individual agricultural stressors to benthic and hyporheic uptake remain unclear. Using stream-side mesocosms and 15N-nitrate additions, we examined the individual and combined effects of fine sediment (FS) and augmented light and phosphorus levels (L&P) on benthic and hyporheic NO3– uptake rates. In absence of FS, L&P stimulated uptake of autotrophic and heterotrophic biofilms, leading to a 12- and 7-fold increase in the benthic and hyporheic compartments, respectively. Under ambient light and nutrient conditions, FS reduced by 3-fold benthic uptake, but effects were not significant. Conversely, in the hyporheic compartment, FS induced anoxic conditions, likely stimulating denitrification and causing a 14-fold increase in hyporheic uptake. When these stressors were combined, they did not interact in the benthic compartment. Conversely, in the hyporheic compartment they interacted antagonistically, with L&P diminishing the increase in uptake induced by FS. Our results indicate that the previously observed increase of whole-stream NO3– uptake in agricultural streams is attributable to nutrients and light stimulating benthic uptake, while fine sediment effects and the role of the hyporheic compartment to total uptake are modest. Moreover, the finding that stressor interactions vary with ecosystem compartments calls for a consideration of all compartments and their contribution to whole-system functioning in multiple stressor studies. We are beginning to understand how multiple interacting stressors affect stream functioning, but more mechanistic evidence is needed to disentangle whether additive or non-additive effects prevail in human-altered ecosystems. [ABSTRACT FROM AUTHOR]

IntroductionWheat performance is always affected by climate change and environmental stresses such as drought stress. Development of high-yielding cultivars requires genetic diversity. Awareness about heritability of traits can be helpful in determining the appropriate breeding strategy for any environmental conditions. By progeny trial after a diallel crossing, the function of genes and inheritance of quantitative traits can be estimated. This increases the ability to select parental lines, to participate in crosses, and determines the management of generations in the segregating populations. Materials and methodsIn order to understand the genetic structure of grain yield and some morphological traits of bread wheat under normal and drought stress conditions, eight bread wheat cultivars including Star; Tirgan; Ehsan; Shirodi; Bam; Tajan, Yang and Akbari were planted in the crossing block and direct crosses were performed among the eight cultivars to produce F1 generation. This research carries out in Gorgan agricultural research station in 2020-2021 cropping season, under normal and drought stress conditions. The progenies of the crosses with their parents were evaluated based on a randomized complete block design (RCBD) with three replications. Imposing stress by terminating irrigation was initiated at the Zadoks 60 (full heading emergence) stage. Results and discussionCombined analysis of variance under normal and drought stress conditions showed that the simple effects of genotype and environment were statistically significant in all traits. Also, the interaction effects of genotype×environment was statistically significant for grain yield, biological yield and 100-kernel weight. In fact, for these traits the response of genotypes was different under normal and stress conditions. Analysis of variance of Griffing's diallel method showed a statistically significant difference between genotypes in all studied traits. Therefore, among the progenies of the crosses it is possible to select superior genotypes. In biological yield and grain yield under both normal and drought stress conditions, Tirgan cultivar had the highest general combining ability, while Star cultivar showed the lowest general combining ability. Tirgan cultivar can be used to increase grain yield and biological yield under both conditions. In plant height, peduncle length and harvest index, Tajan×Yang, Ehsan×Shirodi and Bam×Yang crosses had the maximum specific combining ability, respectively. In other traits, in each condition, an individual cross had the highest specific combining ability. Under normal conditions, Tajan×Akbari cross had the highest specific combining ability in grain yield. Under drought stress conditions, Bam×Akbari cross had the highest specific combining ability in biological yield and grain yield, it simultaneously had a high specific combinability in 100-grain weight, harvest index and number of grains per spike. Therefore, Bam×Akbari cross was determined as the best cross in genetic improvement of desirable agronomic traits with high specific combining ability in yield and yield components, under drought stress conditions. The ratio of additive variance from genetic variance for plant height and peduncle length was greater than dominance variance. Subsequently, the highest narrow-sense heritability in both normal and drought stress conditions was related to plant height and peduncle length. In both normal and drought stress conditions, the highest degree of dominance was related to harvest index traits and number of grains per spike, respectively. Therefore, in these traits the lowest narrow-sense heritability, the lowest Baker's genetic ratio and the highest ratio of dominance variance from genetic variance were observed in both normal and drought stress conditions. In grain yield, a high ratio of dominance variance from genetic variance was assigned under normal (84%) and drought stress (88%) conditions, hence low narrow-sense heritability was observed under normal (8%) and drought stress (5%) conditions. In general, in grain yield, biological yield and 100-kernel weight, narrow-sense heritability was lower under drought stress conditions, compared to normal conditions, which indicates a greater ratio of non-additive effects under drought stress conditions. ConclusionThe results of this study showed that under both conditions, Tirgan cultivar had the highest general combining ability in grain yield and biological yield. Tajan×Akbari and Bam×Akbari crosses were determined as the best cross in genetic improvement of desirable agronomic traits with high specific combining ability in yield and yield components, under normal and drought stress conditions, respectively. In grain yield, biological yield and 100-kernel weight, narrow-sense heritability was lower under drought stress conditions, compared to normal conditions. Based our results under both conditions in the progenies of the crosses, genetic improvement can be done in plant height and peduncle length in the initial generations, but for other traits including grain yield and its components, selection should be postponed to more advanced generations.

Co-application of fertilisers and biofertilisers increases solubility and concentration of nutrient elements in the soil. However, information on the effect of P fertiliser and rhizobium inoculation on the concentration of mineral elements in the rhizosphere of field-grown chickpea in contrasting soil types is lacking. We assessed the effect of phosphorus fertiliser, rhizobium inoculation, and rhizobium inoculation plus P fertilizer on the concentration of nutrients in the rhizosphere of 2 chickpea genotypes (ACC#1 & ACC#5) at clay and sandy soil sites in two consecutive years. ACC#5 accumulated higher amounts of rhizospheric nutrients than ACC#1 in both soil types despite the variable response to fertiliser treatment. Rhizobium inoculation plus P fertiliser resulted in higher accumulations of rhizosphere N (7-219%), P (20-348%), K (9-365%), Ca (2-155%) and Zn (15-259%) compared to the other fertiliser treatments suggesting an additive effect of P fertiliser and rhizobium inoculation. Moreover, the effect of fertiliser treatments was more pronounced in the clay than the sandy soil. Our investigation is the first to document the effects of fertiliser treatment, genotype, and soil type on the accumulation of rhizosphere nutrients in field-grown chickpea. However, we propose further studies, incorporating more cultivars and environments, before making practical recommendations.

Selection is a fundamental part of the plant breeding process, enabling the identification and development of varieties with desirable traits. Thanks to advances in genetics and biotechnology, the selection process has become more precise and efficient, resulting in faster breeding progress and better adaptation of crops to environmental challenges. Genetic parameters related to gene additivity and epistasis play a key role and can influence decisions on the suitability of breeding material. In this study, 188 rapeseed doubled haploid lines were assessed in field conditions for resistance to Leptosphaeria spp. Through next-generation sequencing, a total of 133,764 molecular markers (96,121 SilicoDArT and 37,643 SNP) were obtained. The similarity of the DH lines at the phenotypic and genetic levels was calculated. The results indicate that the similarity at the phenotypic level was markedly different from the similarity at the genetic level. Genetic parameters related to additive gene action effects and epistasis (double and triple) were calculated using two methods: based on phenotypic observations only and using molecular marker observations. All evaluated genetic parameters (additive, additive-additive and additive-additive-additive) were statistically significant for both estimation methods. The parameters associated with the interaction (double and triple) had opposite signs depending on the estimation method.

Cadmium (Cd) contamination is a widespread environmental issue. There is a lack of knowledge about the impacts of applying arbuscular mycorrhizal fungi (AMF) and biochar, either alone or in their combination, on alleviating Cd phytotoxicity in Ligustrum lucidum. Therefore, a pot experiment was conducted in a greenhouse, where L. lucidum seedlings were randomly subjected to four regimes of AMF treatments (inoculation with sterilized AMF, with Rhizophagus irregularis, Diversispora versiformis, alone or a mixture of these two fungi), and two regimes of biochar treatments (with or without rice-husk biochar), as well as three regimes of Cd treatments (0, 15, and 150 mg kg−1), to examine the responses of growth, photosynthetic capabilities, soil enzymatic activities, nutritional concentrations, and Cd absorption of L. lucidum plants to the interactive effects of AMF, biochar, and Cd. The results demonstrated that under Cd contaminations, AMF alone significantly increased plant total dry weight, soil pH, and plant nitrogen (N) concentration by 84%, 3.2%, and 13.2%, respectively, and inhibited soil Cd transferring to plant shoot by 42.2%; biochar alone significantly enhanced net photosynthetic rate, soil pH, and soil catalase of non-mycorrhizal plants by 16.4%, 9%, and 11.9%, respectively, and reduced the soil Cd transferring to plant shoot by 44.7%; the additive effect between AMF and biochar greatly enhanced plant total dry weight by 101.9%, and reduced the soil Cd transferring to plant shoot by 51.6%. Furthermore, dual inoculation with D. versiformis and R. irregularis conferred more benefits on plants than the single fungal species did. Accordingly, amending Cd-contaminated soil with the combination of mixed-fungi inoculation and biochar application performed the best than either AMF or biochar alone. These responses may have been attributed to higher mycorrhizal colonization, soil pH, biomass accumulation, and biomass allocation to the roots, as well as photosynthetic capabilities. In conclusion, the combined use of mixed-fungi involving D. versiformis and R. irregularis and biochar addition had significant synergistic effects on enhancing plant performance and reducing Cd uptake of L. lucidum plants in Cd-contaminated soil. [ABSTRACT FROM AUTHOR]

Propofol and fentanyl have broadly used alone or in combination to induce sedation or anesthesia. The current study aims to assess the additive impact and economic benefit of using combination of propofol and fentanyl in elective curettage cases in Iraq. A total of 75 women were recruited to perform clinical trial between 1st January and 10th March 2023 at the department of gynecology and obstetrics in the Baghdad teaching hospital, Iraq. The sample was subdivided equally into three groups and received different doses of propofol alone (GI), Fentanyl alone (GII), and combination of propofol and fentanyl (GIII) respectively. The dose required for propofol to induce general anesthesia declined to 1.4 mg/kg -1.5 mg/kg instead of 2.5mg/kg, and 2 µg/kg instead of 8 µg/kg for fentanyl in the combination. Out of 25 cases, 19 (76%) patients being unconscious in a time of two minutes as a result of additive effect. Moreover, the cost evaluation showed a cost saving of USD 0.09/minute for every operated curettage weighing 65kg and average surgical time of 21.57+11.06 minutes. The combination of propofol and fentanyl is effective for sedation and anesthesia and cost saving. [ABSTRACT FROM AUTHOR]

Single segment substitution line (SSSL) libraries are an ideal platform for breeding by design. To develop SSSLs-Xihui18 covering the whole genome, a novel rice chromosome segment substitution line (CSSL), Z783, carrying two substitution segments (average length of 6.55 Mb) on Chr.4 and Chr.9 was identified, which was a gap in the library previously. Z783 was developed from the progeny of recipient "Xihui18" (an indica restorer line) and donor "Huhan3" (a japonica cultivar) by advanced backcross combined molecular marker-assisted selection (MAS). It displayed multiple panicles and less spikelets and wide grains. Then, a F2 population derived from Xihui18/Z783 was used to map quantitative trait loci (QTLs) for yield-related traits by the mixed linear model method. Nine QTLs were detected (p < 0.05). Furthermore, three SSSLs were constructed by MAS, and all 9 QTLs could be validated, and 15 novel QTLs could be detected by these SSSLs by a one-way ANOVA analysis. The genetic analysis showed that qSSP4 for less spikelets and qGW9 for wide grain all displayed dominant gene action in their SSSLs. Finally, qSSP4 and qGW9 were fine-mapped to intervals of 2.75 Mb and 1.84 Mb, on Chromosomes 4 and 9, respectively. The results lay a solid foundation for their map cloning and molecular breeding by design. [ABSTRACT FROM AUTHOR]

The main aim of this study is antimicrobial screening of the n-hexane, ethyl acetate and aqueous extracts obtained from aerial parts of Achillea setacea Waldst. amp; Kit. and Achillea coarctata Poir. against the bacterial strains Escherichia coli ATCC 8739, Staphylococcus aureus ATCC 14028 and the yeast Candida albicans ATCC 6633 by the microdilution method. In addition, the effect of the aqueous extract of A. coarctata combined with fluconazole againts C. albicans ATCC 6633, C. parapsilosis ATCC 22019, C. tropicalis ATCC 750 and C. glabrata ATCC 90030 was tested with the checkerboard method. The chemical components of the volatiles and fatty acid methyl esters were identified using the Gas Chromatography (GC) and Gas Chromatography/Mass Spectrometry (GC/MS) techniques. The main components of the volatile oil were found to be 1,8-cineole (16.1%) and β-pinene (14.5%) for A. setacea and camphor (35.4%) and borneol (12.9%) for A. coarctata. The ethyl acetate extracts of A. setacea (MIC=156.25 µg/mL) and A. coarctata (MIC=312.5 µg/mL) were found more active against the tested Candida Berkh. species. The combination of aqueous extract of A. coarctata with fluconazole showed additive effect for the tested Candida species with FIC values within the range of 0.53-0.625 µg/mL.

Heterosis has been extensively used for pig genetic breeding and production, but the genetic basis of heterosis remains largely elusive. Crossbreeding between commercial and native breeds provides a good model to parse the genetic basis of heterosis. This study uses Duhua hybrid pigs, a crossbreed of Duroc and Liangguang small spotted pigs, as materials to explore the genetic basis underlying heterosis related to growth traits at the genomic level. The mid-parent heterosis (MPH) analysis showed heterosis of this Duhua offspring on growth traits. In this study, we examined the impact of additive and dominance effects on 100 AGE (age adjusted to 100 kg) and 100 BF (backfat thickness adjusted to 100 kg) of Duhua hybrid pigs. Meanwhile, we successfully identified SNPs associated with growth traits through both additive and dominance GWASs (genome-wide association studies). These findings will facilitate the subsequent in-depth studies of heterosis in the growth traits of Duhua pigs.

Peanut pod shape is a heritable trait which affects the market acceptance of in-shell peanut products. In order to determine the genetic control of pod shape, six component traits of pod shape (pod length, pod width, pod length/width ratio, pod roundness, beak degree and constriction degree) were measured using an image-based phenotyping method. A recombinant inbred line (RIL) population consisting of 181 lines was phenotyped across three environments. Continuous distributions and transgressive segregations were demonstrated in all measured traits and environments. Significant correlations were found among most component traits with broad-sense heritability ranging from 0.87 to 0.95. Quantitative trait locus (QTL) analysis yielded 26 additive QTLs explaining 3.79 to 52.37% phenotypic variations. A novel, stable and major QTL region conditioning multiple shape features was detected on chromosome 2, which spans a 10.81-Mb genomic region with 543 putative genes. Bioinformatics analysis revealed several candidate genes in this region. In addition, 73 pairs of epistatic interactions involving 92 loci were identified for six component traits explaining 0.94–6.45% phenotypic variations. These results provide new genetic loci to facilitate genomics-assisted breeding of peanut pod shape.

ABSTRACT The emergence of antibiotic resistance in Mycobacterium tuberculosis has been the culprit behind the inefficient treatment of tuberculosis (TB). Mycobacteriophages being rapid and specific in their activity against mycobacteria including M. tuberculosis are an emerging alternative solution to the antibiotic resistance problem. D29 mycobacteriophage is known as an efficient lytic phage. Its lytic cassette encodes for two lytic proteins, Lysin A (LysA) and Lysin B (LysB), and a holin protein responsible for the translocation of the former two. LysB is a mycolyl-arabinogalactan esterase, which has shown a promising lytic effect on M. tuberculosis. In this study, we explored the lytic efficiency of D29 mycobacteriophage LysB protein on drug-resistant strains of M. tuberculosis. We demonstrate that LysB effectively lyses multi-drug-resistant M. tuberculosis both alone and along with anti-TB drugs. We also report that the surfactant Tween-80, although not vital, potentiates LysB activity. We are able to demonstrate that LysB can eliminate M. tuberculosis residing in mouse macrophages. Thus, by combining our in vitro and ex vivo data, we are able to claim that LysB is a potential phage-derived therapeutic which should undergo pre-clinical and clinical trials. IMPORTANCE To combat the rapidly emerging drug-resistant M. tuberculosis, it is now essential to look for alternative therapeutics. Mycobacteriophages can be considered as efficient therapeutics due to their natural ability to infect and kill mycobacteria including M. tuberculosis. Here, we have exploited the mycolyl-arabinogalactan esterase property of LysB encoded from mycobacteriophage D29. This study is novel in terms of targeting a multi-drug-resistant pathogenic strain of M. tuberculosis with LysB and also examining the combination of anti-TB drugs and LysB. All the experiments include external administration of LysB. Therefore, the remarkable lytic activity of LysB overcomes the difficulty to enter the complex cell envelope of mycobacteria. Targeting the intracellularly located M. tuberculosis by LysB and non-toxicity to macrophages take the process of the development of LysB as a drug one step ahead, and also, the interaction studies with rifampicin and isoniazid will help to form a new treatment regimen against tuberculosis.

Aim of the present study was to test whether ionizing radiation (IR) treatment along with 3,3′‐diselenodipropionic acid (DSePA), a redox active organodiselenide achieved better tumor control by suppressing the growth and migration of lung cancer cells. The results indicated that post‐IR (2 Gy) treatment of DSePA (5 μM) led to a significantly higher cell death as compared to that of DSePA and IR treatments separately. Importantly, combinatorial treatment also showed reduction in the proportion of cancer stem cells and the clonogenic survival of A549 cells. The mechanistic studies indicated that combinatorial treatment although exhibited reductive environment (marked by decrease in ROS and increase of GSH/GSSG) at early time points (2–6 h postradiation), slowed DNA repair, inhibited epithelial–mesenchymal transition (EMT)/cell migration and induced significant level of apoptosis. DSePA mediated suppression of ATM/DNAPKs/p53 (DNA damage response signaling) and Akt/G‐CSF (EMT) pathways appeared to be the major mechanism responsible for its radio‐modulating activity. Finally, the combined treatment of IR (2 Gy × 4) and DSePA (0.1–0.25 mg/kg body weight daily through oral gavage) showed a significantly higher tumor suppression of the A549 xenograft as compared to that of DSePA and IR treatments separately in the mouse model. In conclusion, post‐IR treatment of DSePA augmented cell kill by inhibiting DNA repair and cell migration in A549 cells. [ABSTRACT FROM AUTHOR]

The main aim of this study is antimicrobial screening of the n-hexane, ethyl acetate and aqueous extracts obtained from aerial parts of Achillea setacea Waldst. & Kit. and Achillea coarctata Poir. against the bacterial strains Escherichia coli ATCC 8739, Staphylococcus aureus ATCC 14028 and the yeast Candida albicans ATCC 6633 by the microdilution method. In addition, the effect of the aqueous extract of A. coarctata combined with fluconazole againts C. albicans ATCC 6633, C. parapsilosis ATCC 22019, C. tropicalis ATCC 750 and C. glabrata ATCC 90030 was tested with the checkerboard method. The chemical components of the volatiles and fatty acid methyl esters were identified using the Gas Chromatography (GC) and Gas Chromatography/Mass Spectrometry (GC/MS) techniques. The main components of the volatile oil were found to be 1,8-cineole (16.1%) and β-pinene (14.5%) for A. setacea and camphor (35.4%) and borneol (12.9%) for A. coarctata. The ethyl acetate extracts of A. setacea (MIC=156.25 µg/mL) and A. coarctata (MIC=312.5 µg/mL) were found more active against the tested Candida Berkh. species. The combination of aqueous extract of A. coarctata with fluconazole showed additive effect for the tested Candida species with FIC values within the range of 0.53-0.625 µg/mL [ABSTRACT FROM AUTHOR]

The assessment of 1000-kernel weight holds significant importance in determining maize grain yield, and elucidating its underlying genetic mechanisms is imperative for enhancing its overall performance. The material for the study consisted of 26 doubled-haploid (DH) maize lines obtained from crossing two cultivars with flint kernels. Lines were planted in the northern part of the Lower Silesia voivodship in Poland over ten years (2013–2022). The 1000-kernel weight was assessed. The purposes of the research were as follows: (1) to assess genotype by environment interaction (GEI by the additive main effects and multiplicative interaction (AMMI) model; (2) the selection of stable DH lines and environment-specific lines; and (3) the estimation of parameters related to additive and additive–additive gene interaction (epistasis). The results indicate the significant effects of genotype and environment, as well as the GEI, on the 1000-kernel weight. Estimates of additive gene action effects were statistically significant in every year of the study, except 2022. Estimates of epistasis (total additive-by-additive interaction) effects for 1000-kernel weight were statistically significant in 2013, 2015, and 2017 (positive effects), as well as in 2018 and 2020 (negative effects). The lines KN07 and KN10 are recommended for further inclusion in the breeding program due to their stability and highest average of 1000-kernel weight. [ABSTRACT FROM AUTHOR]

Baculoviruses are insect-specific DNA viruses that have been exploited as bioinsecticides for the control of agricultural and forest pests around the world. Mixed infections with two different baculoviruses have been found in nature, infecting the same host. They have been studied to understand the biology of virus interactions, their effects on susceptible insects, and their insecticidal implications. In this work, we summarize and analyze the in vivo baculovirus co-infections reported in the literature, mainly focusing on pest biocontrol applications. We discuss the most common terms used to describe the effects of mixed infections, such as synergism, neutralism, and antagonism, and how to determine them based on host mortality. Frequently, baculovirus co-infections found in nature are caused by a combination of a nucleopolyhedrovirus and a granulovirus. Studies performed with mixed infections indicated that viral dose, larval stage, or the presence of synergistic factors in baculovirus occlusion bodies are important for the type of virus interaction. We also enumerate and discuss technical aspects to take into account in studies on mixed infections, such as statistical procedures, quantification of viral inocula, the selection of instars, and molecular methodologies for an appropriate analysis of baculovirus interaction. Several experimental infections using two different baculoviruses demonstrated increased viral mortality or a synergistic effect on the target larvae compared to single infections. This can be exploited to improve the baculovirus-killing properties of commercial formulations. In this work, we offer a current overview of baculovirus interactions in vivo and discuss their potential applications in pest control strategies. [ABSTRACT FROM AUTHOR]

High temperatures present a formidable challenge to the cultivation of hot pepper, profoundly impacting not only vegetative growth but also leading to flower and fruit abscission, thereby causing a significant reduction in yield. To unravel the intricate genetic mechanisms governing heat tolerance in hot pepper, an F2 population was developed through the crossing of two distinct genotypes exhibiting contrasting heat tolerance characteristics: DLS-161-1 (heat tolerant) and DChBL-240 (heat susceptible). The F2 population, along with the parental lines, was subjected to comprehensive phenotyping encompassing diverse morphological, physiological, and biochemical heat-related traits under high temperature conditions (with maximum temperature ranging from 31 to 46.5°C and minimum temperature from 15.4 to 30.5°C). Leveraging the Illumina Nova Seq-6000 platform, Double digest restriction-site associated DNA sequencing (ddRAD-seq) was employed to generate 67.215 Gb data, with subsequent alignment of 218.93 million processed reads against the reference genome of Capsicum annuum. Subsequent variant calling and ordering resulted in 5806 polymorphic SNP markers grouped into 12 LGs. Further QTL analysis identified 64 QTLs with LOD values ranging from 2.517 to 11.170 and explained phenotypic variance ranging from 4.05 to 19.39%. Among them, 21 QTLs, explaining more than 10% phenotypic variance, were identified as major QTLs controlling 9 morphological, 3 physiological, and 2 biochemical traits. Interestingly, several QTLs governing distinct parameters were found to be colocalized, suggesting either a profound correlation between the QTLs regulating these traits or their significant genomic proximity. In addition to the QTLs, we also identified 368380 SSR loci within the identified QTL regions, dinucleotides being the most abundant type (211,381). These findings provide valuable insights into the genetics of heat tolerance in hot peppers. The identified QTLs and SSR markers offer opportunities to develop heat-tolerant varieties, ensuring better crop performance under high-temperature conditions. [ABSTRACT FROM AUTHOR]

Understanding how plants adapt to specific environmental changes and identifying genetic markers associated with phenotypic plasticity can help breeders develop plant varieties adapted to a rapidly changing climate. Here, we propose the use of marker effect networks as a novel method to identify markers associated with environmental adaptability. These marker effect networks are built by adapting commonly used software for building gene coexpression networks with marker effects across growth environments as the input data into the networks. To demonstrate the utility of these networks, we built networks from the marker effects of ~2,000 nonredundant markers from 400 maize hybrids across 9 environments. We demonstrate that networks can be generated using this approach, and that the markers that are covarying are rarely in linkage disequilibrium, thus representing higher biological relevance. Multiple covarying marker modules associated with different weather factors throughout the growing season were identified within the marker effect networks. Finally, a factorial test of analysis parameters demonstrated that marker effect networks are relatively robust to these options, with high overlap in modules associated with the same weather factors across analysis parameters. This novel application of network analysis provides unique insights into phenotypic plasticity and specific environmental factors that modulate the genome. [ABSTRACT FROM AUTHOR]

High-precision radiotherapy with proton beams is frequently used in the management of aggressive soft tissue sarcoma (STS) and is often combined with doxorubicin (Dox), the first-line chemotherapy for STS. However, current treatment approaches continue to result in high local recurrence rates often occurring within the treatment field. This strongly indicates the need of optimized treatment protocols taking the vast heterogeneity of STS into account, thereby fostering personalized treatment approaches. Here, we used preclinical STS models to investigate the radiation response following photon (X) or proton (H) irradiation alone and in combination with different treatment schedules of Dox. As preclinical models, fibrosarcoma (HT-1080), undifferentiated pleiomorphic sarcoma (GCT), and embryonal rhabdomyosarcoma (RD) cell lines were used; the latter two are mutated for TP53. The cellular response regarding clonogenic survival, apoptosis, cell-cycle distribution, proliferation, viability, morphology, and motility was investigated. The different STS cell types revealed a dose-dependent radiation response with reduced survival, proliferation, viability, and motility whereas G2/M phase arrest as well as apoptosis were induced. RD cells showed the most radiosensitive phenotype; the linear quadratic model fit could not be applied. In combined treatment schedules, Dox showed the highest efficiency when applied after or before and after radiation; Dox treatment only before radiation was less efficient. GCT cells were the most chemoresistant cell line in this study most probably due to their TP53 mutation status. Interestingly, similar additive effects could be observed for X or H irradiation in combination with Dox treatment. However, the additive effects were determined more frequently for X than for H irradiation. Thus, further investigations are needed to specify alternative drug therapies that display superior efficacy when combined with H therapy. [ABSTRACT FROM AUTHOR]

Introduction The methods used to analyze genotype-environment interaction and determine the stability and adaptability of genotypes are continuously evolving to improve the accuracy of evaluating genotypes and studying environmental interaction components. Using a combination of several methods provides a more comprehensive understanding of the genotype-environment interaction from multiple dimensions. In this study, the genotype-environment interaction was investigated using the AMMI method, along with the development of appropriate statistical techniques. Materials and Methods For this purpose, 25 sugar beet genotypes, consisting of 18 new hybrids and seven controls, were cultivated in seven environments: Karaj, Mashhad, Shiraz, Miandoab, Kermanshah, Hamadan, and Khoi. The experiment followed a randomized complete block design with four replications during the year 2020. After checking the uniformity of the variance of the experimental errors using Bartlett's test, the stability of the genotypes was analyzed based on the AMMI model. In this study, 12 statistics obtained from the AMMI model, including ASTAB, ASI, ASV, AVAMGE, DA, DZ, EV, FA, MASI, MASV, SIPC, and Za, were used to identify stable. genotypes. To further investigate the stability of the experimental genotypes, the SIIG index was also estimated, taking into account the criteria provided by each index based on the AMMI model. Resultsand Discussion The results obtained from Bartlett's test confirmed the homogeneity of the variance of experimental errors in experiments from different regions. Therefore, a combined variance analysis was performed based on the AMMI model. The combined analysis of variance, based on the AMMI model, indicated the significance of the additive effects of the environment and genotype, as well as the multiplicative effect of genotype environment interaction at the 1% probability level. Analyzing the interaction effects into principal components showed that the first four components were significant at the 1% probability level and explained 93.50% of the variations related to genotype-environment interaction. According to the AMMII biplot, hybrids 3 and 9 were recognized as the most stable genotypes due to having a sugar yield higher than the overall average and a low value of the first interaction component. According to the AMMI2 biplot, hybrid 3 and BTS 335 with the Miandoab environment, Lexia and 4 with the Mashhad environment, Lexia with the Hamedan environment, 14 and 15 with the Kermanshah environment, 13 and 17 with the Shiraz environment, 11 with the Karaj environment, and Baloo with the Khoi environment have considerable specific adaptability. Hybrid 9, followed by 6, 2, and 8, had general adaptability. The SIIG index, calculated based on AMMI model statistics, identified 2, 9, 10, and 8 as the most stable genotypes with optimal yield. Conclusion Based on the obtained results, the environment and its interaction with the genetic structure of different genotypes have played a significant role in the phenotypic expression of white sugar yield and have caused the genotypes to provide different responses in terms of white sugar yield according to the conditions of different environments. In general, based on the results of the present study, hybrid 9 and then hybrids 6, 2, 8, 7, and 10 had high white sugar yield and yield stability. Generally, real progress in sugar beet breeding will be obtained if the genetic factors controlling the sensitivity of sugar beet genotypes to a variable environment are identified. [ABSTRACT FROM AUTHOR]

OBJECTIVE: The human papilloma virus (HPV) is the etiological agent of cervical cancer in more than 95% of cases worldwide. Although most HPV infections clear up on their own and most pre-cancerous lesions spontaneously resolve, in some cases, they can persist, leading to lesions which may progress towards invasive cervical cancer. MATERIALS AND METHODS: We evaluated the effects of the association of epigallocatechin gallate (EGCG) + folic acid (FA) + vitamin B12 (B12) + hyaluronic acid (HA) on HPV-positive cervical cancer cells (HeLa). RESULTS: The association of EGCG + FA + B12 + HA induced a significant increase of apoptosis and p53 gene expression with a concomitant decrease of E6/E7 gene expression, a marker of HPV infection. CONCLUSIONS: This study provides for the first-time evidence on the potential additive activity of EGCG + FA + B12 + HA in counteracting HPV infection, by increasing apoptosis and p53 expression in HPV-infected cervical HeLa cells [ABSTRACT FROM AUTHOR]

Urbanization affects various biotic and abiotic conditions through the disturbance and modification of the environment by human activity. Anthropogenic noise and artificial light at night (ALAN) associated with urbanization have negative impacts on wildlife. However, few studies have focused on the combined effects of noise and ALAN, and the counter‐adaptation of urban individuals to environmental pollution. We examined the single and combined effects of ALAN and noise on life history traits, including developmental period, survival rate, egg diapause, the number of progeny, and body size, of the cricket Dianemobius nigrofasciatus. We examined whether urban individuals are adapted to these factors by a common garden experiment using the crickets of both urban and rural origin. Our findings revealed no combined effect of ALAN and noise on the life‐history traits of D. nigrofasciatus except on that of survival and progeny production. Both ALAN and noise alone delayed development and prevented egg diapause. Neither noise nor ALAN had a significant effect on body size. The survival rate of rural crickets was not affected by noise and ALAN, but there was a negative synergetic effect. However, there were no significant effects of ALAN, noise, or their combined effect on the survival rate of urban crickets. These results suggest that urban individuals exhibit adaptive evolution to these factors. The number of progeny was positively affected by noise and not affected by ALAN, while the combined effect negatively affected the progeny production. The results suggest that a combined effect of noise and ALAN on important factors for the cricket such as survival and reproduction. [ABSTRACT FROM AUTHOR]

Pyramiding multiple resistant genes has been proposed as the most effective way to control wheat rust diseases globally. Identifying the most effective pyramids is challenged by the large pool of rust resistance genes and limited information about their mechanisms of resistance and interactions. Here. using a high-density genetic map, a double haploid population, and multi -rust field testing. we aimed to systematically characterize the most effective gene pyramids for rust resistance from highthe durable multi-rust resistant CIMMYT cultivar Parula. We revealed that the Parula resistance gene pyramid contains L)·34/Yr] 8/Sr57 (L, 34), Lr46/Yr29/S,·58 (L,·46). Li-27/Yr30/S,-2 (Srl). and L,-68. The efficacy. magnitude of effect. and interactions varied for the three I-lIst diseases. A subpopulation mapping approach was applied to characterize the complex interactions of the resistance genes by controlling for the effect of Li·34. Using this approach. we found that Lr34 and L}·68 have a strong additive effect for leaf rust. whereas no additive effects were observed for any rusts between L,·34 and Lr46. Lr34 combined synergistically with Sr\1 from Thatcher for stem rust. whereas the additive effect of Li·34 and Sr2 was dependent on the type of rust and environment. Two novel leaf rust quantitative trait loci (QTLE) from Parula were identified in this study. a stable QTL QLr-7BS and QL,·-5AS. which showed Lr34 dependent expression. With these findings. we propose combining two to three highthe value genes from Canadian wheat (e. g ., Srj2 from Thatcher) with a foundational multi -adult plant resistance cassette for desirable and durable resistance to ai] three rusts in Canadian wheat. [ABSTRACT FROM AUTHOR]

A genome-wide association study (GWAS) of age at first calving (AFC) using 813,114 first lactation Holstein cows and 75,524 SNPs identified 2063 additive effects and 29 dominance effects with p-values < 10−8. Three chromosomes had highly significant additive effects in the regions of 7.86–8.12 Mb of Chr15, 27.07–27.48 Mb and 31.25–32.11 Mb of Chr19, and 26.92–32.60 Mb of Chr23. Two of the genes in those regions were reproductive hormone genes with known biological functions that should be relevant to AFC, the sex hormone binding globulin (SHBG) gene, and the progesterone receptor (PGR) gene. The most significant dominance effects were near or in EIF4B and AAAS of Chr05 and AFF1 and KLHL8 of Chr06. All dominance effects were positive overdominance effects where the heterozygous genotype had an advantage, and the homozygous recessive genotype of each SNP had a very negative dominance value. Results from this study provided new evidence and understanding about the genetic variants and genome regions affecting AFC in U.S. Holstein cows. [ABSTRACT FROM AUTHOR]

Simple Summary: Theoretically, the joint use of augmentative biological control (ABC) and sterile insects (SIT) can generate an additive or synergistic effect on the control of fruit fly pests. Field cage evaluations demonstrated that the sequential use of both techniques on a confined population of Anastrepha ludens lead to greater suppression than each technique acting alone. This was observed with the use of the larval parasitoid Diachasmimorpha longicaudata (parasitism ~70%), as well as the pupal parasitoid Coptera haywardi (~35% parasitism), although the high parasitism percentages by D. longicaudata contributed a greater suppressive effect on the fly population. The joint use of ABC and SIT induced ~70% sterility in the A. ludens population; however, the impact on the reproduction parameters of the fly population suggest that the joint action of both techniques was synergistic. Decreases in the fertility rate and hatching percentage of A. ludens eggs resulted in a lower intrinsic rate of increase (up to 50%) in the fly population. Pest control models integrating the use of the sterile insect technique (SIT) and augmentative biological control (ABC) have postulated that it is possible to obtain a synergistic effect from the joint use of these technologies. This synergistic effect is attributed to the simultaneous attack on two different biological stages of the pest (immature and adult flies), which would produce higher suppression on the pest populations. Here we evaluated the effect of the joint application of sterile males of A. ludens of the genetic sexing strain Tap-7 along with two parasitoid species at the field cage level. The parasitoids D. longicaudata and C. haywardi were used separately to determine their effect on the suppression of the fly populations. Our results showed that egg hatching percentage was different between treatments, with the highest percentage in the control treatment and a gradual reduction in the treatments with only parasitoids or only sterile males. The greatest induction of sterility (i.e., the lowest egg hatching percentage) occurred with the joint use of ABC and SIT, demonstrating that the earlier parasitism caused by each parasitoid species was important reaching high levels of sterility. Gross fertility rate decreased up to 15 and 6 times when sterile flies were combined with D. longicaudata and C. haywardi, respectively. The higher parasitism by D. longicaudata was determinant in the decrease of this parameter and had a stronger effect when combined with the SIT. We conclude that the joint use of ABC and SIT on the A. ludens population had a direct additive effect, but a synergistic effect was observed in the parameters of population dynamics throughout the periodic releases of both types of insects. This effect can be of crucial importance in the suppression or eradication of fruit fly populations, with the added advantage of the low ecological impact that characterizes both techniques. [ABSTRACT FROM AUTHOR]

Background: Individuals with the 2p15p16.1 microdeletion syndrome share a complex phenotype including neurodevelopmental delay, brain malformations, microcephaly, and autistic behavior. The analysis of the shortest region of overlap (SRO) between deletions in ~ 40 patients has led to the identification of two critical regions and four strongly candidate genes (BCL11A, REL, USP34 and XPO1). However, the delineation of their role in the occurrence of specific traits is hampered by their incomplete penetrance. Objective: To better delineate the role of hemizygosity of specific regions in selected traits by leveraging information both from penetrant and non − penetrant deletions. Methods: Deletions in patients that do not present a specific trait cannot contribute to delineate the SROs. We recently developed a probabilistic model that, by considering also the non − penetrant deletions, allows a more reliable assignment of peculiar traits to specific genomic segments. We apply this method adding two new patients to the published cases. Results: Our results delineate an intricate pattern of genotype − phenotype correlation where BCL11A emerges as the main gene for autistic behavior while USP34 and/or XPO1 haploinsufficiency are mainly associated with microcephaly, hearing loss and IUGR. BCL11A, USP34 and XPO1 genes are broadly related with brain malformations albeit with distinct patterns of brain damage. Conclusions: The observed penetrance of deletions encompassing different SROs and that predicted when considering each single SRO as acting independently, may reflect a more complex model than the additive one. Our approach may improve the genotype/phenotype correlation and may help to identify specific pathogenic mechanisms in contiguous gene syndromes. [ABSTRACT FROM AUTHOR]

Rice grain size is a complex agronomic trait, controlled by multiple genes. Chromosome segment substitution lines are an effective method for creating natural occurring variations and are as the ideal materials for exploring the complex traits. In this study, a novel rice long-large grain chromosome segment substitution line Z66 was developed. Z66 contained 12 substitution segments from R225 (average substitution length was 3.32 Mb) based on the genetic backgrounds of Nipponbare. Then, 12 QTLs for rice grain size were identified by the secondary F2 population from Nipponbare/Z66, and 5 novel single-segment substitution lines (SSSLs, S1-S5), and 4 novel double-segment substitution lines (DSSLs, D1-D4) harboring target QTL were developed. Among them, 9 QTLs (qGL3, qGL7, qGL10, qGW6, qGW10, qRLW3, qRLW10, qGWT3, and qGWT10) could be verified by the SSSLs, indicating that these QTLs were genetically stable. In addition, 6 novel QTLs (qGL9-2, qGW9-2, qRLW6, qRLW7, qRLW9-2, and qGWT7) were detected by the SSSLs. Among 18 QTLs, 5 QTLs (qGL9-2, qRLW9-1, qRLW9-2, qGW9-2, and qGWT9-2) might be novel. Target QTLs pyramiding showed that the pyramid of different QTLs had various epistasis effects. For example, the pyramids of qRLW3 (a=0.21) and qRLW9-2 (a=0.08) produced an epistasis effect of 0.10, which made the ratio of grain length to width in D2 significantly larger than that in Nipponbare, S1 (qRLW3), and S4 (qRLW9-2). The pyramid of qGWT3 (a=3.99) and qGWT10 (a=3.98) yielded an epistasis effect of -5.35, and its genetic effects in D3 (2.62 g) significantly increased 1000-grain weight of D3 than in Nipponbare, but significantly decreased than that in S1 (qGWT3) and S5 (qGWT10). Understanding the interaction effects between target QTLs can predict the phenotype of futural QTL pyramid genotypes, which is important for intelligent design breeding in rice. [ABSTRACT FROM AUTHOR]

High-precision radiotherapy with proton beams is frequently used in the management of aggressive soft tissue sarcoma (STS) and is often combined with doxorubicin (Dox), the first-line chemotherapy for STS. However, current treatment approaches continue to result in high local recurrence rates often occurring within the treatment field. This strongly indicates the need of optimized treatment protocols taking the vast heterogeneity of STS into account, thereby fostering personalized treatment approaches. Here, we used preclinical STS models to investigate the radiation response following photon (X) or proton (H) irradiation alone and in combination with different treatment schedules of Dox. As preclinical models, fibrosarcoma (HT-1080), undifferentiated pleiomorphic sarcoma (GCT), and embryonal rhabdomyosarcoma (RD) cell lines were used; the latter two are mutated for TP53. The cellular response regarding clonogenic survival, apoptosis, cell-cycle distribution, proliferation, viability, morphology, and motility was investigated. The different STS cell types revealed a dose-dependent radiation response with reduced survival, proliferation, viability, and motility whereas G2/M phase arrest as well as apoptosis were induced. RD cells showed the most radiosensitive phenotype; the linear quadratic model fit could not be applied. In combined treatment schedules, Dox showed the highest efficiency when applied after or before and after radiation; Dox treatment only before radiation was less efficient. GCT cells were the most chemoresistant cell line in this study most probably due to their TP53 mutation status. Interestingly, similar additive effects could be observed for X or H irradiation in combination with Dox treatment. However, the additive effects were determined more frequently for X than for H irradiation. Thus, further investigations are needed to specify alternative drug therapies that display superior efficacy when combined with H therapy.

Electronic word of mouth (eWoM) messages are increasingly consequential for consumers' decisions regarding products/services. This has led to a large body of scholarly research on factors affecting eWoM message adoption. Adoption of an eWoM message refers to accepting the information and recommendations contained in an eWoM message, which consequently influence consumers' cognitive and behavioral tendencies toward pertinent products/services. Notwithstanding the contributions of prior eWoM studies, we observe inconsistent findings across these studies that make a consensus difficult to reach. Lack of consistency is also evident among eWoM service providers in the selection and presentation order of the pertinent factors on their sites. To address this gap, we draw on the heuristic-systematic model in a meta-analytic structural equation modeling study to test a nomological eWoM adoption model that assesses the factors affecting the adoption of an eWoM message. Our meta-analysis of 87 eWoM studies, comprising 105,318 observations, sheds light on eight factors toward eWoM message adoption. Our findings unravel the multitude of ways in which these factors can influence eWoM message adoption and show the relative importance of these factors based on their total effects on eWoM message adoption. This enables the eWoM service providers to enhance the inconsistencies in the selection and presentation order of important factors toward eWoM message adoption on their sites. [ABSTRACT FROM AUTHOR]

Noonan syndrome (NS) is an autosomal dominant multisystem disorder, characterized by variable expressivity and locus heterogeneity, being caused by mutations in one of a subset of RAS pathway genes. Nevertheless, for 20–30% of patients it is not possible to provide molecular diagnosis, suggesting that further unknown genes or mechanisms are involved in NS pathogenesis. Recently, we proposed a digenic inheritance of subclinical variants as an alternative NS pathogenic model in two NS patients negative for molecular diagnosis. They showed hypomorphic variants of RAS pathway genes co-inherited from both their healthy parents that we hypothesized to generate an additive effect. Here, we report on the phosphoproteome and proteome analysis by liquid chromatography tandem mass spectrometry (LC-MS/MS) performed on the immortalized peripheral blood mononuclear cells (PBMCs) from the two above trios. Our results indicate that the two unrelated patients show overlapped profiles in both protein abundances and their phosphorylation levels not reached by their parents. IPA software predicted RAS-related pathways as significantly activated in the two patients. Interestingly, they remained unchanged or only slightly activated in both patients' parents. These findings suggest that the presence of one subclinical variant can activate the RAS pathway below the pathological threshold, which can instead be exceeded by the additive effect due to the co-presence of two subclinical variants causing NS, supporting our digenic inheritance hypothesis. [ABSTRACT FROM AUTHOR]

[Introduction] Emicizumab, a bispecific antibody mimicking activated factor VIII (FVIII), is increasingly used in prophylaxis against bleeding in hemophilia A. Human factor-based chromogenic substrate assay (hCSA) shows concentration-dependency between emicizumab and reported FVIII activity. However, the assay measurement settings have not been optimized for emicizumab, and the reported FVIII activity cannot be directly referred as surrogate FVIII activity. [Materials and Methods] For in vitro validation of hCSA-reported surrogate FVIII activity, we compared the equation curves for emicizumab concentration with surrogate FVIII activity using spiked plasma in the thrombin generation assay (TGA), hCSA, and clot waveform analysis (CWA). Then, we generated conversion equations for hCSA-reported surrogate FVIII value to that of TGA. We also assessed the additive effect of rFVIII onto 340 nM (i.e., 50 μg/mL) emicizumab using the same assays. [Results] With 1:20 diluted plasma, halving hCSA-reported surrogate FVIII activity can be approximated to that in TGA triggered by the extrinsic pathway reagent (27.3 IU/dL vs. 13.9 IU/dL) under therapeutic emicizumab concentration. Both in TGA and hCSA, the additive effect of added FVIII on therapeutic emicizumab concentration (340 nM) was maintained at low levels of FVIII but gradually decreased at higher levels. [Conclusions] Surrogate FVIII activity can be estimated simply by halving hCSA-reported FVIII value, and the additive effect of FVIII on emicizumab diminishes at high concentrations. Based on our in vitro study, a clinical study is currently being conducted to compare individual variation of surrogate FVIII activity in hCSA and TGA. [ABSTRACT FROM AUTHOR]

Active and passive exposure to tobacco smoke may increase risk of cognitive decline. However, effects of enhanced the aging process on the association of urinary nicotine metabolites with cognitive impairment remain unclear. In this study, 6657 Chinese older adults completed the physical examinations and cognitive tests. We measured urinary nicotine metabolite levels, mitochondrial DNA copy number (mtDNA-CN), and relative telomere length (RTL) and analyzed effects of urinary nicotine metabolites and their interaction with mtDNA-CN or RTL on cognitive impairment by generalized linear models and qg-computation, respectively. Each 1-unit increase in urinary 3-OHCot, 3-OHCotGluc, CotGluc, or NicGluc levels corresponded to a 1.05-, 1.09-, 1.04-, and 0.90-fold increased risk of cognitive impairment. Each 1-quantile increment in the mixture level of 8 nicotine metabolites corresponded to an increment of 1.40- and 1.34-fold risk of cognitive impairment in individuals with longer RTL or low mtDNA-CN. Urinary 3-OHCotGluc and RTL or mtDNA-CN exhibited an additive effect on cognitive impairment in addition to the mixture of 8 nicotine metabolites and mtDNA-CN. The findings suggested that aging process may increase the risk of tobacco-related cognitive impairment. [ABSTRACT FROM AUTHOR]

A major concern voiced by motor behavior scientists is to find useful practice techniques that can be effective in improving motor learning and performance. Neurofeedback and self-controlled practice are among the techniques that have recently drawn attention from specialists in this area. The present study examined the additive and individual effects of sensorimotor rhythm (SMR) neurofeedback as well as self-controlled practice on motor learning and performance in novice golfers. In this semi-empirical study, forty adults (20 females, Meanage = 26.10, SD = 5.56 years) were conveniently selected and randomly assigned to four groups: (1) neurofeedback/self-controlled practice, (2) neurofeedback/yoked practice, (3) sham/self-controlled practice, and (4) sham/yoked practice. The participants performed golf putting task in four stages, namely pretest (12 trials), intervention (one day after pretest; 6 sessions, 36 trails each), post-test (one day after intervention; 12 trials), and follow-up (two weeks after interventions; 12 trials). In addition, the participants had their EEG (SMR wave in Cz point) recorded during pretest, post-test, and follow-up. The results indicated that, although no additive effect was observed for the two practices during different stages of the experiment (p > 0.05), in acquisition and post-test stages, SMR neurofeedback and self-controlled practice independently facilitated golf putting (p ≤ 0.05). However, in the follow-up test, only the neurofeedback practice maintained its positive effects (p ≤ 0.05). The results also showed that participation in SMR neurofeedback practice can enhance the power of the SMR wave (p ≤ 0.05), regardless of the type of the self-controlled practice used. In sum, the two practice techniques seem to be independently effective in facilitating motor learning in instructional settings, particularly for golfers. [ABSTRACT FROM AUTHOR]

Co-application of fertilisers and biofertilisers increases solubility and concentration of nutrient elements in the soil. However, information on the effect of P fertiliser and rhizobium inoculation on the concentration of mineral elements in the rhizosphere of field-grown chickpea in contrasting soil types is lacking. We assessed the effect of phosphorus fertiliser, rhizobium inoculation, and rhizobium inoculation plus P fertilizer on the concentration of nutrients in the rhizosphere of 2 chickpea genotypes (ACC#1 & ACC#5) at clay and sandy soil sites in two consecutive years. ACC#5 accumulated higher amounts of rhizospheric nutrients than ACC#1 in both soil types despite the variable response to fertiliser treatment. Rhizobium inoculation plus P fertiliser resulted in higher accumulations of rhizosphere N (7-219%), P (20-348%), K (9-365%), Ca (2-155%) and Zn (15-259%) compared to the other fertiliser treatments suggesting an additive effect of P fertiliser and rhizobium inoculation. Moreover, the effect of fertiliser treatments was more pronounced in the clay than the sandy soil. Our investigation is the first to document the effects of fertiliser treatment, genotype, and soil type on the accumulation of rhizosphere nutrients in field-grown chickpea. However, we propose further studies, incorporating more cultivars and environments, before making practical recommendations. [ABSTRACT FROM AUTHOR]

The use of biocontrol agents based on endophytic bacteria against phloem-feeding insects is limited by a lack of knowledge and understanding of the mechanism of action of the endophyte community that makes up the plant microbiome. In this work, the mechanisms of the additive action of endophytic strains B. subtilis 26D and B. subtilis 11VM on the resistance of bread spring wheat against greenbug aphid Schizaphis graminum, was studied. It was shown that B. subtilis 26D secreted lipopeptide surfactin and phytohormones cytokinins, and B. subtilis 11VM produced iturin and auxins into the cultivation medium. Both strains and their lipopeptide-rich fractions showed direct aphicidal activity against greenbug aphid. For the first time, it was shown that B. subtilis 26D and B. subtilis 11VM in the same manner, as well as their lipopeptide-rich fractions, activated the expression of salicylate- and ethylene-dependent PR genes, and influenced plant redox metabolism, which led to an increase in plant endurance against aphids. The composition of endophytic strains B. subtilis 26D + B. subtilis 11VM had an additive effect on plant resistance to aphids due to an increase in the number of endophytic bacterial cells, and, as well as due to the synergistic effect of their mixture of lipopeptides − surfactin + iturin, both on the aphid mortality and on the expression of PR1 and PR3 genes. All these factors can be the reason for the observed increase in the growth of plants affected by aphids under the influence of B. subtilis 26D and B. subtilis 11VM, individually and in composition. The study demonstrates the possibility of creating in the future an artificial composition to enhance plant microbiome with endophytic bacteria, which combines growth-promoting and plant immunity stimulating properties against phloem-feeding insects. This direction is one of the most promising approaches to green pesticide discovery in the future. [ABSTRACT FROM AUTHOR]

Tomato is an interesting vegetable crop and numerous genetic studies have been conducted to increase the efficiency of tomato breeding strategies. Yield is an economically important trait and therefore improving yield is the main focus in breeding projects. The selecting efficient breeding strategy needs comprehensive information about the genetic controlling of interested traits. The aim of this study was to determine genetic parameters for yield and yield component tomato through generation mean analysis. Generation mean analysis was conducted using six basic generations (P1, P2, F1, F2, BC1, BC2) derived from a cross between two lines (M110 and P110) of tomato. M110 and P110 have a determinate and indeterminate growth habit respectively. Results showed that a simple additive dominance model was adequate to explain variability among traits of interest. Non-additive gene effects were predominant for all characters in this study. Broad sense heritability was calculated at over 50% for all traits while narrow sense heritability was less than 50%. Therefore, direct selection for these traits might not be useful, and recurrent selection procedures could increase the frequency of favorable alleles in breeding populations to enable the selection and development of genotypes with superior plants. [ABSTRACT FROM AUTHOR]

General and specific combining abilities of three cytoplasmic male sterile and four restorer lines of sunflower were studied in a randomized complete block design with three replications under normal irrigation and drought stress conditions in Eslamabad-e-Gharb, Iran during two growing season (2019 and 2020). Drought stress reduced seed yield, oil yield, thousand seeds weight and head diameter by 21.9%, 18.1%, 14.3% and 11.5%, respectively. Line × tester analysis indicated that the effect of lines was significant for the number of days to flowering, plant height, grain yield and seed oil percentage under both normal and drought stress conditions. The effect of lines was significant for number of days to maturity and number of seeds per head under normal condition and for thousand seeds weight under drought stress condition. Contribution of lines × testers were higher than the variances of lines or testers for of most of all the studied traits indicating the major role of non-additive effects on expression of theses traits. R131 was differentiated with the highest positive general combining ability for grain and oil yield in both normal and drought stress conditions. Among the testers, AGK32 and AF81-222 had the highest general combining ability for grain yield under normal and stressed conditions, respectively. R131×AGK38, with grain yields of 4414 and 3457 kg ha-1 under normal and drought stress conditions respectively, had the highest specific combining ability for grain and oil yield under both conditions. The results of this study showed that the genetic materials and environmental conditions can affect the nature of gene effect and combining ability of sunflower parent lines and crosses. [ABSTRACT FROM AUTHOR]

Generation mean analysis of brinjal lines, GL 401 × BR 104 (CROSS I), GL 401 × W 230 (CROSS II) and W 230 × RMO 1142 (CROSS III) six generation of three crosses viz. highlighted the involvement of epistatic interactions (duplicate) for most of the qualitative traits. However, the number of fruits per plant in CROSS I & III and fruit girth, calyx length, and yield per plant in CROSS II confirmed the occurrence of complementary epistasis. Mainly, additive effect for fruit girth, non-additive effect for calyx length, calyx width, peduncle girth, fruit weight, and fruit length, and both types for peduncle length, number of fruits /cluster, number of fruits/ plant, and yield/ plant were experienced. Additive × dominance or dominance × dominance type of interactions were more prevalent than additive × additive type of interactions for different traits. Cluster bearing was monogenic dominant and green color of calyx as well as peduncle was dominant over purple with the duplicate type of epistasis. Fruit shape was digenic with incomplete dominance. Fruit color displayed digenic control in CROSS I & II and tri-genic ratio in CROSS III with incomplete dominance of purple and green pigmentations producing variable color intensity in homozygous or heterozygous conditions. [ABSTRACT FROM AUTHOR]

The assessment of 1000-kernel weight holds significant importance in determining maize grain yield, and elucidating its underlying genetic mechanisms is imperative for enhancing its overall performance. The material for the study consisted of 26 doubled-haploid (DH) maize lines obtained from crossing two cultivars with flint kernels. Lines were planted in the northern part of the Lower Silesia voivodship in Poland over ten years (2013–2022). The 1000-kernel weight was assessed. The purposes of the research were as follows: (1) to assess genotype by environment interaction (GEI by the additive main effects and multiplicative interaction (AMMI) model; (2) the selection of stable DH lines and environment-specific lines; and (3) the estimation of parameters related to additive and additive–additive gene interaction (epistasis). The results indicate the significant effects of genotype and environment, as well as the GEI, on the 1000-kernel weight. Estimates of additive gene action effects were statistically significant in every year of the study, except 2022. Estimates of epistasis (total additive-by-additive interaction) effects for 1000-kernel weight were statistically significant in 2013, 2015, and 2017 (positive effects), as well as in 2018 and 2020 (negative effects). The lines KN07 and KN10 are recommended for further inclusion in the breeding program due to their stability and highest average of 1000-kernel weight.

Changes in temperature and nitrogen (N) deposition determine the growth and competitive dominance of both invasive and native plants. However, a paucity of experimental evidence limits understanding of how these changes influence plant invasion. Therefore, we conducted a greenhouse experiment in which invasive Solidago canadensis L. was planted in mixed culture with native Artemisia argyi Levl. et Van under combined conditions of warming and N addition. Our results show that due to the strong positive effect of nitrogen addition, the temperature increases and nitrogen deposition interaction resulted in greatly enhanced species performance. Most of the relative change ratios (RCR) of phenotypic traits differences between S. canadensis and A. argyi occur in the low invasion stage, and six of eight traits had higher RCR in response to N addition and/or warming in native A. argyi than in invasive S. canadensis. Our results also demonstrate that the effects of the warming and nitrogen interaction on growth-related traits and competitiveness of S. canadensis and A. argyi were usually additive rather than synergistic or antagonistic. This conclusion suggests that the impact of warming and nitrogen deposition on S. canadensis can be inferred from single factor studies. Further, environmental changes did not modify the competitive relationship between invasive S. canadensis and native A. argyi but the relative yield of S. canadensis was significantly greater than A. argyi. This finding indicated that we can rule out the influence of environmental changes such as N addition and warming which makes S. canadensis successfully invade new habitats through competition. Correlation analysis showed that invasive S. canadensis may be more inclined to mobilize various characteristics to strengthen competition during the invasion process, which will facilitate S. canadensis becoming the superior competitor in S. canadensis-A. argyi interactions. These findings contribute to our understanding of the spreading of invasive plants such as S. canadensis under climate change and help identify potential precautionary measures that could prevent biological invasions. [ABSTRACT FROM AUTHOR]

Background and Objectives: Gynociouce hybrids have the advantage of high yield; therefore, gynocioucy should always be considered in the production of cucumber hybrid cultivars. There are at least five genes that affect the expression of gynocioucy in cucumber. In order to improve cucumber for production new cultivars with higher yield and better quality, using of genetic diversity and cucumber germplasm is extremely essential. Knowing the importance and extent of controller genetic effects the inheritance of traits can lead to the selection of appropriate corrective methods. Therefore, the present study took with this goal how inheritance of the gynoeciouce trait and, to investigate the effects of controller genes on this trait and, other performance components in crossing between a commercial hybrid and a selected line. Finally a proper amendatory plan is adopted. Materials and Methods: In order to evaluate genetic and determinate heritability of gynoecioucy in cucumber seven generation including P1, P2, F1, F2, BC1, BC2 and F3 from a cross between two gynoeciouce (N10) and androciouce (A11) cucumber lines were supplied. Number of female and, male flowers, number of fruits per plant, length of plant and length of internode were evaluated in a randomized complete blocks design with three replications. Cause on create populations, experiments were carried out in the spring and autumn of 2017 to 2018 in three stages in the greenhouse of the college of Agricultural Sciences, University of Guilan and population assessment was performed in 2019 in the research farm of the faculty of agricultural sciences, university of Guilan. First year, in order to produce hybrid seeds, a cross was made between gynoeciouce N10 and androeciouce A11 lines. After producing and cultivating hybrid seeds in the second stage, self-pollination and hybrid cross-breeding with parents were carried out and F2 populations and backcrosses were created. In the second year, samples of second-generation seeds were planted in greenhouses for creating self-pollination and third-generation populations. In the greenhouse, hydroponic cultivation system was used and fertilization and irrigation of plants were done at regular intervals. In the field plant were cultivated using drip irrigation system and, cover mulch and all necessary agricultural care were done. Data normality was tested by SPSS software and data analysis was performed by SAS software. Generation mean comparison was also performed using LSD test at 5% and 1% probability levels. Results: About the gynoecioucy there was a significant difference among case study generations. Examination of scale tests for this trait also showed that there are allele interactions among the genes controlling this trait. Examination of genetical parameter and scale tests showed that for all of study traits there are epistasis effects. The results showed about number of female flowers all of the genetic parameters was significant and for number of male flowers, number of fruit per plant and length of internode traits all of the genetic parameters was significant except dominance-dominance epistasis, whereas for length of plant trait all of the genetic parameters was significant except additive-additive epistasis. Discussion: Evaluation of narrow sense heritability and dominance degree showed that additive variance was more important in genetically controlling of number of female flower and number of fruits per plant. Therefore superior genotypes can be improved by selecting in the study population. [ABSTRACT FROM AUTHOR]