Non-treated Condition Research Articles

Effect of Ultrasound Conditions on Germination and Drying Characteristics of Bengal Gram (Cicer arietinum L.) and Determination of Physicochemical and Functional Properties of Flours

ABSTRACTThis study aims to investigate the effect of ultrasound conditions on the germination kinetics and drying characteristics of a germinated Bengal gram at different drying temperatures. Ultrasound treatment was given to the Bengal gram seeds at two different conditions, that is, before (US) and after soaking (SU), which was then followed by germination. This study also determines mass transfer parameters at drying temperatures of 45°C, 55°C, and 65°C and assesses the influence on the physicofunctional characteristics of a germinated Bengal gram. The germination rate behavior was effectively predicted using a zero‐order kinetic model with the highest R2 value of 0.7974–0.8857 in each nontreated (S) and treated (SU, US) Bengal gram seed, respectively. This study showed that the ultrasound treatment effectively enhanced the germination rate in both conditions, and the highest germination rate was found in pretreated ultrasound Bengal gram samples. The logarithmic thin layer drying model, with the highest average R2 of 0.9954 and the lowest average RMSE value of 0.0160, is the best‐fitted model to predict the changes in moisture ratio in both treated and nontreated conditions. The moisture diffusivity values at drying temperatures ranging from 45°C to 65°C were found in treated (US, SU) and nontreated (S) germinated samples ranging from 3.34 × 10−8 to 4.03 × 10−8 m2/s, 1.30 × 10−8 to 2.01 × 10−8 m2/s, and 6.6 × 10−9 to 8.06 × 10−9 m2/s, respectively. The protein content increased in the ultrasound‐treated sample between 12.37% and 13.50%. The solubility ranged from 8% to 10.36% throughout the treated and nontreated germinated Bengal gram flour. This study provides a unified approach to utilizing ultrasound‐treated germinated Bengal gram seeds as an alternative option to develop a functional product with better nutritional and functional properties.

BUCKLING BEHAVIOUR OF HIGH-STRENGTH RETROFITTED STEEL SECTIONS MANUFACTURED BY POST HEAT-TREATMENT PROCESSES

High-strength steel is increasingly popular in construction for its strength-to-weight ratio, which lowers the self-weight of structures and reduces transportation, erection, and foundation costs. Induction hardening (IH) process which involves rapid heating and cooling of the material leads to microstructural changes which enhance the hardness and strength of conventional steel, elevating it to the level of High Strength (HS) steel. This study reports an extensive investigation on the buckling response and design of IH post-treated structural steel Circular Hollow Sections (CHS). It includes tensile coupon tests, microstructural analyses, initial geometric imperfection measurements, and residual stress evaluations to determine the effects of IH treatment on CHS. Column buckling tests were conducted, and a numerical model was developed and validated against the experimental results which was utilised to study systematically the effect of imperfections. The findings suggest that the magnitude of the imperfections in IH steel sections doubled compared to the non-treated condition, whilst there was a minimal impact on the residual stresses. A comprehensive parametric study was performed using finite element models to study the structural response of IH steel CHS columns over a large range of global slendernesses and allow the assessment of the buckling curves specified in EN 1993-1-1. It was concluded that the buckling curve ‘a’ (imperfection factor, α=0.21) specified in EN 1993-1-1 provides the best buckling load predictions for the IH steel CHS columns, the response of which is superior to that of their virgin counterparts, despite the increased imperfections caused by the heat-treating process.

Identification of Ru-based PDT resistance mechanisms by CRISPR/Cas9 screen in HNSCC

SignificanceThis project provides an in-depth knowledge of the mode of action of novel designed Ruthenium photodynamic therapy (PDT) complex, and provides information about how head and neck squamous cell carcinomas (HNSCC) cells resist to these treatments. ApproachTo obtain a comprehensive view of the molecular bases of Ru-based photocytotoxicity in HNSCC, we performed a genome-wide randomly knock-out clustered regularly interspaced short palindromic repeats (CRISPR)/Cas9 screen. The comparison of sequencing data from treated and non-treated conditions will identify deleted sequences in challenged SQ20B cells by next-generation sequencing (NGS). ResultsWe have identified HSPE1 gene is associated to resistance mechanisms induced by RuII-based PDT treatment. Further investigation of the candidate gene on apoptosis induction through gain- and loss- of function assays. ConclusionsIn this study, we employed a genome-wide CRISPR/Cas9 screen to decipher molecular response mechanisms of Ru-based PDT in HNSCC cells.

A53 MOLECULAR MECHANISMS FOR A ROLE OF SHP-2 IN TLR4 SIGNALING IN INTESTINAL EPITHELIAL CELLS

Abstract Background Shp-2 gene polymorphisms are associated with greater susceptibility to ulcerative colitis. How Shp-2 contributes to disease susceptibility is however unclear. Intestinal epithelial cell (IEC)-specific deletion of Shp-2 results in severe colitis in mice (Shp-2IEC-KO). We found important alterations in microbiota composition, namely increased Enterobacteria of the Proteobacteria phylum and decreased Firmicutes levels, that preceded clinical signs of inflammation. Antibiotherapy or epithelial KO of Myd88 inhibits colitis in Shp-2IEC-KO mice. Notably, feces from Shp-2IEC-iKO mice display much more LPS-like bioactivity than do feces from controls (unpublished data). These observations support a role for TLR4/Myd88-bacterial recognition in initiation of colitis in Shp-2IEC-KO mice. Aims The aim of the present study was to identify the molecular mechanisms by which Shp-2 may regulate TLR4 signaling in IEC. Methods 1) The regulation of Shp-2 phosphorylation was analysed in IEC-6 cells stimulated or not with 10 ug/ml of LPS, a TLR4 ligand. 2) We mapped the Shp-2-dependent interactome in LPS-stimulated IEC-6 cells by an APEX2 proximity assay used in combination with mass spectrometry (MS) analysis. Cells stably expressing APEX2-tagged Shp-2 were generated. Addition of doxycycline results in expression of “physiological” levels of Shp-2;APEX2 construct. Proximity biotinylation labeling of Shp-2 by APEX2 was performed after 10 min stimulation with LPS and labeled candidates were analyzed by MS. Results 1) Upon stimulation of IEC-6 cells with LPS, Shp-2 protein is rapidly phosphorylated (Y542, Y580) and potentially activated. This increased phosphorylation is abolished by pretreatment with N-acetyl cystein, a commonly used antioxydant. 2) Using Prostar R package, the three replicates of MS data were filtered for the minimum quantification of 66,66% of each protein in at least one condition. They were normalized within conditions using VSN normalization, then the Partially Observed Values (POV) and the Missing in Entire Column (MEC) values were imputed respectively with SLSA and DetQuantile (Quantile 1%, Factor 0,2). A differential analysis between the LPS and non-treated conditions identified 334 proteins enriched with a FC of ± ≥2,5 with a p-value inferior then 0,05. Among the top Shp-2 interactors, we found Tak1 (ampersand:003E3,5X change) and Tab1 (ampersand:003E3,0X change), two proteins involved in NF-kB signaling. Decreased interaction with the TLR effectors Myd88 (ampersand:003C2,5X change) and Irak1 (ampersand:003C3,2X change) was also noted after LPS treatment. Conclusions These data suggest for the first time that Shp-2 may regulate NF-kB signaling downstream of TLR4 in IEC. Thus, SHP-2 may contribute to the maintenance of mucosal tolerance to microbiota in the colon. Funding Agencies CIHR

Exogenous Melatonin Enhances Moisture Stress Tolerance in Mango (Mangifera indica L.) through Alleviating Oxidative Damages.

In subtropical regions, April to June represents a temporary moisture stress for mango trees, leading to huge economic loss. Although water is available in the deep root zone, the upper soil surface, which has fibrous roots, is dry, and the tree transpiration rate is high. Moisture stress causes an increased oxidation state, which is detrimental to fruit growth and development. Finding substitutes for moisture stress management is important for sustainable mango production. To manage this moisture stress in mango, we tested if foliar application of 20, 50, 100 and 150 μM melatonin helped to maintain a reduced oxidation state in the cells. Applications were made at three phenological stages of fruit development (marble, egg and mature fruit stages) in 16-year-old trees and the same plants for each treatment were followed over three years. Melatonin application indeed improved the fruit yield of mango. Moisture stress decreased yield by 55.94% compared to irrigated trees but only by 7.5% in melatonin treatment. Also, more 'A' grade fruits were harvested in irrigated and melatonin-treated conditions than in non-irrigated and non-treated conditions. Indeed, the total chlorophyll content in the leaves of moisture-stressed melatonin-treated trees (12.58 mg.g-1 fresh weight) was well above non-treated trees (6.77 mg.g-1) and similar to irrigated trees (12.50 mg.g-1). A dose-dependent increase in the chlorophyll content of melatonin-treated plants was found. Similarly, the activities of catalase, peroxidase, superoxidase dismutase enzymes in leaves of irrigated and melatonin-treated trees were lower than in non-irrigated condition, and superoxide free radial formation was lower in moisture-stressed melatonin-treated trees (0.77 nmol H2O2.mg-1 protein) and irrigated trees (0.65) than moisture-stressed non-treated trees (4.27). Significant variations was found in antioxidants (total, reduced and oxidized glutathione and ascorbate) content and antioxidant enzymes' activities (i.e., glutathione reductase and ascorbate peroxidase) in irrigated, melatonin-treated and non-irrigated conditions. Overall, 150 μM exogenous melatonin applied three times at different fruit development stages may be a sustainable and useful approach to manage transient moisture stress in mango trees thanks to its positive action on the antioxidant system.

Nurse-supported care versus rheumatologist-led care in patients with rheumatoid arthritis at high disease activity: A retrospective study of two Chinese centers.

The European League Against Rheumatism recommendations for the management of rheumatoid arthritis advised the involvement of clinical nurses for the management of rheumatoid arthritis. However, The European League Against Rheumatism recommendations are difficult to apply to Chinese institutes. In China, the rheumatology nursing service is not widely adopted because the feasibility and quality of rheumatology nursing service have not been confirmed in the Chinese population by the Chinese authorities. The objectives of the study were to compare 2.5 years clinical outcomes of patients of rheumatoid arthritis (6 months history) with disease activity score 28-joint count with C-reactive protein (DAS28-CRP) > 5.1 who received nurse-supported care against those of patients who received rheumatologist-led care. Patients received 30 minutes/day and 6 times/week nurse-supported care (NC cohort, n = 127) or Patients had received 20 minutes session at every 3 months of conventional outpatient-based rheumatologist-led care (n = 131). Both types of care have involved the history of patients, care regarding effects and adverse effects of pharmacological treatments, patients education, overall well-being, everyday life, counseling, clarifications, and rehabilitation. Additionally, there were a cohort in which patients did not receive any nontreatment care (NN cohort, n = 141). All patients have definite depression and anxiety (hospital anxiety and depression scale Chinese version score ≥ 11) before nontreatment interventions. At 2.5 years of treatments with or without nontreatment interventions (EL) DAS28-CRP, depression, and anxiety scores of patients of the NC cohort were decreased as compared to their before any type of nontreatment interventions conditions and those of patients of the RC and NN cohorts at EL (P < .001 for all). At EL numbers of patients with moderate disease activity, (DAS28-CRP score: 3.2-5.1) and borderline depression and anxiety (hospital anxiety and depression scales Chinese version score: 8-10) were greater in the NC cohort than those of the RC and NN cohorts (P < .001 for all). Outpatient care satisfaction scores of patients of the NC cohort were higher than those of the RC [23 (27-17) vs 17 (21-14)] and NN [23 (7-17) vs 15 [18-12]) cohorts (P < .001 for both). Physiological and psychological conditions of patients with rheumatoid arthritis with DAS28-CRP > 5.1 are required to improve. Nurse-supported care is superior nontreatment compared to rheumatologist-led care in rheumatoid arthritis patients with high disease activity (Level of Evidence: IV; Technical Efficacy: Stage 5).

Foliar-applied nano-cerium dioxide differentially affect morpho-physiological traits and essential oil profile of Salvia mirzayanii Rech. f. & Esfand under drought stress and post-stress recovery conditions

Drought stress is known to diminish the growth and yield of plants by altering the physiological, biochemical and molecular processes, thus threatening food security worldwide. Nanoparticles (NPs) have emerged as an effective strategy to raise plant productivity under current rapid environmental challenges. However, there is little literature on mechanisms underlying the beneficial role of re-watering in drought-stressed plants treated with NPs. In this study, the effects of cerium dioxide nanoparticles [(CeO2 NPs), 0 (control), 125, 250, 500, and 1000 mL L−1] were investigated on morpho-physiological and phytochemical traits of Salvia mirzayanii plants under different drought stress intensities [(25%, 50%, 75%, and 100% (control) of field capacity (FC) moisture] and post-stress re-watering (recovery) in a three-way factorial arrangement based on randomized complete block design. Uptake and accumulation of CeO2 NPs in the leaf tissue of plant samples were confirmed using SEM and EDX techniques. The results of ANOVA demonstrated that growth and physio-phytochemical traits were significantly (p < 0.05) affected by individual treatment and/or their double and triple interactions. Exposure to various levels of CeO2 NPs during drought stress mitigated the adverse effects of stress on growth parameters (e.g., plant height, shoot and root dry weights, and root length) and photosynthetic pigments (chlorophyll a and b) content compared to the respective controls in varying degrees. However, proline and essential oil content were increased in drought-stressed plants, and tended to decrease during the period of recovery. Before re-watering, the antioxidant enzymes, CAT, POD, and SOD, activity in leaf tissues was increased with the increase of drought stress intensity upon both treated and non-treated CeO2 NPs conditions. However, the three-way interaction results demonstrated that recovery after drought stress following CeO2 NPs application particularly 1000 mL L−1 decreased the activity of antioxidant enzymes compared to the controls. Based on GC and GC-MS analysis, all essential oil samples predominantly composed of oxygenated monoterpenes and sesquiterpenes including Decane, Spathulenol, Octane, α-Terpinyl acetate, Hexyl isovalerate, Dodecane, Butanoic acid, Linalool, δ-Cadinene, Muurolol, α-Cadinol, Eudesm-7(11)-en-4-ol, which significantly (p < 0.05) changed under different experimental treatments. The recovery after stress, however, increased only the content of δ-Cadinene in plants from severe drought stress upon foliar application of 1000 mL L−1 CeO2 NPs compared to the non-recovery period. Conclusively, integrative use of CeO2 NPs and re-watering after drought stress could be an encouraging and eco-friendly strategy to improve both drought tolerance, growth and pyhtochemical contents in S. mirzayanii plants.

Transcriptome Analysis Revealed the Potential Molecular Mechanism of Anthocyanidins' Improved Salt Tolerance in Maize Seedlings.

Anthocyanin, a kind of flavonoid, plays a crucial role in plant resistance to abiotic stress. Salt stress is a kind of abiotic stress that can damage the growth and development of plant seedlings. However, limited research has been conducted on the involvement of maize seedlings in salt stress resistance via anthocyanin accumulation, and its potential molecular mechanism is still unclear. Therefore, it is of great significance for the normal growth and development of maize seedlings to explore the potential molecular mechanism of anthocyanin improving salt tolerance of seedlings via transcriptome analysis. In this study, we identified two W22 inbred lines (tolerant line pur-W22 and sensitive line bro-W22) exhibiting differential tolerance to salt stress during seedling growth and development but showing no significant differences in seedling characteristics under non-treatment conditions. In order to identify the specific genes involved in seedlings' salt stress response, we generated two recombinant inbred lines (RILpur-W22 and RILbro-W22) by crossing pur-W22 and bro-W22, and then performed transcriptome analysis on seedlings grown under both non-treatment and salt treatment conditions. A total of 6100 and 5710 differentially expressed genes (DEGs) were identified in RILpur-W22 and RILbro-W22 seedlings, respectively, under salt-stressed conditions when compared to the non-treated groups. Among these DEGs, 3160 were identified as being present in both RILpur-W22 and RILbro-W22, and these served as commonly stressed EDGs that were mainly enriched in the redox process, the monomer metabolic process, catalytic activity, the plasma membrane, and metabolic process regulation. Furthermore, we detected 1728 specific DEGs in the salt-tolerant RILpur-W22 line that were not detected in the salt-sensitive RILbro-W22 line, of which 887 were upregulated and 841 were downregulated. These DEGs are primarily associated with redox processes, biological regulation, and the plasma membrane. Notably, the anthocyanin synthesis related genes in RILpur-W22 were strongly induced under salt treatment conditions, which was consistented with the salt tolerance phenotype of its seedlings. In summary, the results of the transcriptome analysis not only expanded our understanding of the complex molecular mechanism of anthocyanin in improving the salt tolerance of maize seedlings, but also, the DEGs specifically expressed in the salt-tolerant line (RILpur-W22) provided candidate genes for further genetic analysis.

Brief Online Interventions to Improve 5K Running

Athletes and coaches strive to identify and learn to use interventions to enhance performance. The goal to be a competent user of psychological skills which aid performance is common among coaches and athletes. However, how frequently such skills are used and how they are learned is less well understood. Many athletes experience plateaus in performance despite efforts to improve, and as such are prime candidates to test interventions to enhance performance. To he present study investigate the effectiveness of learning brief psychological skills among athletes who competed in a weekly 5km time trial whose performances had plateaued. Participants (n = 7) volunteered to follow brief psychological skills training which involved watching brief videos on how to use one of self-talk, reappraisal, if-then plans, or a non-treatment condition, but in the context of the study represent receiving encouragement to mentally prepare. Data analysis compared intervention results with baseline data taken from 2 months of data before the intervention. Results Psychological skills usage associated with finishing 347.37m (p = .019) ahead of baseline. Post-race reflections indicated using psychological skills helped re-appraise fatigue. Findings offer encouraging data on encouraging runners to engage in mental preparation and that following brief psychological skills training is helpful, however, confirmatory research is needed with larger samples.

Effect of Shot Peening on Oxidation and Precipitation in Inconel 718

In this study, the effect of the surface state on the behaviour of Inconel 718 alloy exposed to 640 ^{circ }C and 700 ^{circ }C environments for times varying between one and one hundred hours was investigated. In particular, the focus was set on the evolution of oxidation and precipitation phenomena during thermal exposure. Three surface states were considered: two generated through shot peening treatments featuring different coverage levels, while the third condition is a non-peened one. Shot peening treatments modify the surface condition and introduce higher residual stresses and microhardness values than in the non-treated condition. The morphology of the oxides appears to be different depending on the condition observed. Regarding the kinetics, over time the oxidation process follows a parabolic trend and appears to be influenced by the surface state; in particular, severe shot peening treatment is characterized by the highest intensity of the phenomenon. However, the order of magnitude of the weight gains measured suggests that the observed variations can be neglected, and that the positive effect of shot peening can be exploited without introducing oxidation problems. From the point of view of the microstructural evolution, an increase in the coarsening kinetics of gamma” phase was observed in the shot peened layer.

Drug interference with biochemical laboratory tests.

Clinical laboratory practice represents an essential part of clinical decision-making, as it influences 60-70% of medical decisions at all levels of health care. Results of biochemical laboratory tests (BLTs) have a key role in establishment of adequate diagnosis as well as in evaluation of treatment progress and outcome. The prevalence of drug-laboratory test interactions (DLTIs) is up to 43% of patients who had laboratory results influenced by drugs. Unrecognized DLTIs may lead to misinterpreted BLTs results, incorrect or delayed diagnosis, extra costs for unnecessary additional tests or inadequate therapy, as all may cause false clinical decisions. The significance of timely and adequate recognition of DLTIs is to prevent common clinical consequences such as incorrectly interpreted test results, delayed or non-treated condition due to erroneous diagnosis or unnecessary extra tests or therapy. Medical professionals should be educated that it is essential to obtain patient data about medications especially for the drugs used in the last 10 days before biological material collection. Our mini-review aims to provide a comprehensive overview of the current state in this important domain of medical biochemistry with detailed analysis of the effect of drugs on BLTs and to give detailed information to medical specialists.

Evaluation of Short Chain Fatty Acids (SCFAs) intestinal absorption, following digestion and fermentation of a novel medical device containing partially-hydrolyzed Guar gum plus simethicone

Irritable Bowel Syndrome (IBS) is a common disease characterized by alternate symptoms (diarrhea and constipation) and intestinal gas overproduction. A new medical device (Fibergone®), containing Partially Hydrolyzed Guar Gum (PHGG) and Simethicone (SM) has been proposed for managing patients with bowel disorders. PHGG acts also as a prebiotic so increasing the Short-Chain Fatty Acid (SCFA) production, useful for intestinal physiology. This in vitro study investigated the effects exerted by PHGG+SM on SCFA production and their intestinal absorption following in vitro digestive process and fermentation model. An in vitro model evaluated the digestive process and fermentation using simulated digestive fluids and a human intestinal epithelium in vitro model derived from based on intestinal adenocarcinoma Caco-2 cells (ATCC, HTB-37TM) and organized as a functional monolayer on Transwell® inserts. PHGG+SM was added in experiments and compared with a control (non-treated). SCFA production and absorption were assessed. Viability and barrier integrity of the intestinal epithelium model were also evaluated. PHGG+SM significantly (p&lt;0.05) increased SCFAs content after fermentation, indicating that this medical device is effectively fermented at the large intestine level. However, in relation to SCFAs bioavailability, their absorption did not increase compared to the non-treated condition in the light of the physiological contribution of SCFAs resulting from the microflora. PHGG+SM did not affect intestinal epithelium apparent permeability (Papp) and viability. This in vitro study documented that partially hydrolyzed guar gum combined with simethicone significantly affects short-chain fatty acids production and consequently could be fruitfully employed in managing patients with intestinal disorders.

Mechanical properties studies on rubber composites reinforced with Acacia Caesia fibre

Acacia Caesias are inexpensive, have superior mechanical properties, high strength, are less abrasive, and are environmentally benign and biodegradable. The main objective of the present work is to study the mechanical properties of Acacia Caesia reinforced natural rubber composites at different weight fractions of Acacia Caesia under treated and non-treated conditions. At first, the fibre is treated with NaOH, and then a composite is manufactured for both untreated and treated fiber. After the synthesis of a Acacia Caesia reinforced natural rubber composite, the effects of surface treatment on its mechanical properties are studied. Natural reinforced natural rubber composites were manufactured according to ASTM standards using a compression moulding technique. The developed composites were then tested for their mechanical properties, tensile, tear, hardness, and properties. The standard test method used is ASTM D624 for tensile properties.

The Karrikin Receptor Karrikin Insensitive2 Positively Regulates Heat Stress Tolerance in Arabidopsis thaliana.

In this study, we investigated the potential role of the karrikin receptor KARRIKIN INSENSITIVE2 (KAI2) in the response of Arabidopsis seedlings to high-temperature stress. We performed phenotypic, physiological and transcriptome analyses of Arabidopsis kai2 mutants and wild-type (WT) plants under control (kai2_C and WT_C, respectively) and 6- and 24-h heat stress conditions (kai2_H6, kai2_H24, WT_H6 and WT_H24, respectively) to understand the basis for KAI2-regulated heat stress tolerance. We discovered that the kai2 mutants exhibited hypersensitivity to high-temperature stress relative to WT plants, which might be associated with a more highly increased leaf surface temperature and cell membrane damage in kai2 mutant plants. Next, we performed comparative transcriptome analysis of kai2_C, kai2_H6, kai2_H24, WT_C, WT_H6 and WT_H24 to identify transcriptome differences between WT and kai2 mutants in response to heat stress. K-mean clustering of normalized gene expression separated the investigated genotypes into three clusters based on heat-treated and non-treated control conditions. Within each cluster, the kai2 mutants were separated from WT plants, implying that kai2 mutants exhibited distinct transcriptome profiles relative to WT plants. Gene Ontology and Kyoto Encyclopedia of Genes and Genomes enrichment analyses showed a repression in 'misfolded protein binding', 'heat shock protein binding', 'unfolded protein binding' and 'protein processing in endoplasmic reticulum' pathways, which was consistent with the downregulation of several genes encoding heat shock proteins and heat shock transcription factors in the kai2 mutant versus WT plants under control and heat stress conditions. Our findings suggest that chemical or genetic manipulation of KAI2 signaling may provide a novel way to improve heat tolerance in plants.

Transglutaminase-2 mediates acquisition of neratinib resistance in metastatic breast cancer

Acquisition of resistance to targeted therapies remains a major clinical obstacle for the HER2+ subtype of breast cancer. Using an isogeneic progression series of HER2+ breast cancer metastasis we demonstrate that metastatic cells have an increased capacity to acquire resistance to the covalent, pan-ErbB inhibitor, neratinib. RNA sequencing analyses comparing parental and metastatic cells identified upregulation of transglutaminase 2 (TG2). Genetic depletion and overexpression approaches established that TG2 is both necessary and sufficient for acquisition of neratinib resistance. Mechanistically, we describe a pathway in which TG2-mediates activation of NF-κB signaling leading to upregulation of IL-6 in metastatic cells. This autocrine expression of IL-6 functions to maintain enhanced levels of TG2 via JAK:STAT3 signaling. This drug persistence feedback loop can be interrupted through the use of the JAK1/2 inhibitor ruxolitinib. In vivo application of ruxolitinib had no effect on tumor growth under non-treated conditions, but effectively prevented acquisition of resistance, leading to tumor regression upon coadministration with neratinib. Overall, our studies reveal a mechanism in metastatic breast cancer cells that predisposes them to acquisition of resistance to ErbB-targeted therapeutics. Clinically, immediate application of ruxolitinib could prevent acquisition of resistance and improve patient responses to HER2-targeted therapies.

Lysine acetylation during oxidative stress response in the halophilic archaeon Haloferax volcanii

Stress adaptation strategies have been a central topic of research in halophilic organisms due to biotechnological and astrobiological applications. This study is focused on how the halophilic archaeon Haloferax volcaniimay use lysine acetylation to regulate the oxidative stress response. Previous studies have shown that a) HOCl stress causes the lysine acetyltransferases Pat2:Pat1 ratios to increase and b) mutation of the lysine deacetylase sir2 gene renders cells hypertolerant to oxidative stress, suggesting this post translational modification system has a role during oxidative stress response. Immunoblotting experiments carried out in this study show an increase in lysine acetylation when glycerol‐grown cells are exposed to sodium hypochlorite. Mass spectrometry analysis of the lysine acetylome shows central metabolism pathways are modified under non‐treatment conditions. Of note during oxidative stress, a 2Fe‐2S ferredoxin (HVO_2995) was shown to be reduced in lysine acetylation levels suggesting an important role during oxidative stress response in the organism. These results now pave the way for a comprehensive quantitative mass spectrometry study to assess the global role of lysine acetylation during this oxidative stress response in the organism. Understanding this system can give us new answers into mechanisms of stress response in halophilic archaea. Expansion of this knowledge can provide a balanced evolutionary perspective of post translational modifications in living organisms.

Priming of defense-related genes in Brassica oleracea var. capitata using concentrated metabolites produced by Rhizobium tropici CIAT 899.

To verify the potential of metabolites extracted from Rhizobium tropici to trigger the priming of defense responses in cruciferous plants, we analyzed the expression of defense-related genes by qRT-PCR. Brassica oleracea var. capitata, susceptible to Xanthomonas campestris pv. campestris, were grown in greenhouse conditions. At 18days after sowing, plants were inoculated with 1mL of 1% concentrated metabolites produced by R. tropici (CM-RT) in the root. In a second experiment, leaves were sprayed with 1mL of a solution containing 1% CM-RT. Aerial and root tissue were collected separately at 0 (non-treated control condition), 24, and 48h after application, submitted to RNA extraction and gene expression analysis by qRT-PCR. The results showed that, after root treatment with CM-RT, most evaluated genes were upregulated at 24h after application and downregulated at 48h after application in roots, while in leaves, genes were downregulated both at 24 and 48h after application. On the other hand, leaf treatment with CM-RT showed that most evaluated genes in leaves and roots were upregulated at 24 and 48h after application. These results indicate that the effect of CM-RT applied in roots seems restricted to the applied region and is not sustained, while the application in leaves results in a more systemic response and maintenance of the effect of CM-RT for a longer period. The results obtained in this study emphasize the biotechnological potential of using metabolites of R. tropici as an elicitor of active defense responses in plants.

An Acute Permethrin Exposure Causes Significant Microbial Shifts in Montastraea cavernosa

Insecticide use is common in developed tropical regions where it may enter coastal reef ecosystems through land-based sources. This local introduction of contaminants could affect ecosystem health as corals can better withstand global stressors more readily if local pressures are reduced. The present study investigated the microbial community and photochemical efficiency of the reef building coral, Montastraea cavernosa, when exposed to the commercially applied insecticide, permethrin. Montastraea cavernosa was exposed to an acute concentration of permethrin for 24 h in a controlled laboratory setting. Fourteen fragments were integrated across four treatments (2 or 0.325 μg/l of permethrin, acetone control, and saltwater control) with three to four replicates per treatment. Photosynthetic efficiency was measured by quantifying the maximum photochemical yield and maximum electron transport rate (ETR), which were recorded for each fragment before exposure and 24 h after exposure to permethrin. The microbial communities of M. cavernosa tissue was measured using 16S rRNA sequencing for each fragment. Permethrin exposure at the tested concentrations suggested no significant effect on the M. cavernosa’s photochemical parameters measured during the 24-h permethrin exposure. Microbial communities were significantly different between permethrin treated (2 and 0.325 μg/l) and non-treated conditions (acetone and saltwater controls). In permethrin treated coral, this study documented a significant increase in Burkholderia pyroccinnia and Bacillus sp., bacteria groups known to bioremediate insecticides. Exposure of permethrin also decreased the relative abundance of Mesorhizobium sp., Sediminibacterium sp., Sphingorhabdus sp., and Chondromyces sp., which are known to inhibit pathogen colonization and provide essential macromolecules. Therefore, although the symbiotic relationship between the host and the intracellular algae remained intact after the corals were exposed to permethrin, the significant shift in the microbiome indicate permethrin may destabilize the microbial composition of the holobiont.

Vitamin E Decreases Cytotoxicity and Mitigates Inflammatory and Oxidative Stress Responses in a Ferret Organotypic Brain Slice Model of Neonatal Hypoxia-Ischemia

The gyrencephalic ferret brain is an excellent model in which to study hypoxia-ischemia (HI), a significant contributor to neurological injury in neonates. Vitamin E, an essential fat-soluble antioxidant, reduces oxidative stress and inflammation in both animal models and human infants. The aim of this study was to assess the effects of vitamin E after oxygen-glucose deprivation (OGD) in an organotypic ferret brain slice model of neonatal HI. We hypothesized that vitamin E would decrease cytotoxicity, inflammation, and oxidative stress in OGD-exposed brain slices. Term-equivalent ferrets were sacrificed at postnatal (P) day 21–23 and 300 µM whole-hemisphere brain slices were obtained. During a 24-h rest period, slices were cultured in either nontreated control conditions or with erastin, a promotor of oxidative stress. Slices were then exposed to 2 h of OGD followed by vitamin E (25–100 IU/kg), erastin (10 µM), or ferrostatin (1 µM), an inhibitor of ferroptosis. Relative cytotoxicity was determined using a lactate dehydrogenase assay, cell death was quantified via nuclear propidium iodide staining, oxidative stress was quantified via cellular glutathione (GSH) levels, and target genes responsive to oxidative stress and inflammation were evaluated by qRT-PCR. OGD increased cytotoxicity, which was significantly reduced by treatment with vitamin E. Vitamin E also preserved GSH after OGD and decreased amplification of certain markers of oxidative stress (CHAC1, SLC7A11) and inflammation (TNF-alpha, IL-8). Vitamin E remained protective after pretreatment with erastin and was more protective than ferrostatin, presumably due to its added anti-inflammatory properties. Results from the ferret whole-hemisphere OGD model support the premise that vitamin E neuroprotection is mediated by restoring GSH and acutely decreasing inflammation and oxidative stress after neonatal HI.

LAUGHTER AND EMPATHY

At a biological level, laughter was found to help in dealing with pain and suffering. From a psychological perspective, its effects have been studied both at intrapersonal and interpersonal levels. At an intrapersonal level, laughter contributes to self-regulating emotions (especially lowering the trait anxiety), diminishing the expression of anger, internally or externally, the same time with increasing self-acceptance. At interpersonal level, laughing together builds trust, while being laughed at may be traumatic. In the present study, the objective was to investigate the effects of laughter on empathy, awareness, and acceptance of personal experience. The participants in the study, all women, watched a situational comedy for 1.5 hours, with different life situations which may seem negative, but presented in an amusing manner, and, very important, with a happy end. At the end, they completed the empathy and awareness questionnaires. Statistical analysis, comparing their scores with those in a non-treatment condition, showed that laughing at the situational comedy significantly influenced almost all aspects of empathy, significantly decreasing the personal distress from empathizing with others, but also sensitivity and emotional interest towards them, without significant influence on awareness and acceptance of personal experience.