Early Stages Of Initiation Research Articles

A novel murine wire injury based infectious endocarditis model aggravates aortic valve stenosis

Abstract Background With mortality rates up to 40% under optimal medical treatment, infectious endocarditis (IE) remains one of the deadliest infectious diseases worldwide. In the early stages of IE, diagnosis and treatment initiation are often difficult and research is limited due to unreliable models. Most murine IE models rely on permanent prosthetic wire placement and i.v. bacterial injection, thus making it inadequate to study IE pathophysiology with the aim to reflect the course of disease in humans. Purpose To develop a reproducible murine IE model, based on aortic valve injury preceding intravenous S. aureus bacterial challenge. Methods Using a wire-injury model we induced endothelial lesions. 72h after wire injury (WI), we performed intravenous bacterial challenge using S. aureus. Echocardiography was performed to confirm bacterial vegetations and assess valvular function. Cross sections of valvular leaflets were prepared for scanning electron microscopy (SEM). Macrophage, neutrophil and S. aureus-specific immunofluorescence staining was performed and visualized by immunofluorescence microscopy. Bacterial cultivation was performed from peripheral blood and valve tissue. Systemic immune response was analyzed using flow cytometry. Results WI induced endothelial damage in all mice verified using scanning electron microscopy imaging. The combination of wire injury and injection of 10^5 and 10^6 colonies-forming-units (CFU) S. aureus reliably caused IE validated via in vivo echocardiography as well as S.aureus immunofluorescence staining and SEM imaging. Mice undergoing bacterial challenge responded with significant neutrophilia in the blood. Using 10^6 CFU S. aureus was associated with an increased mortality, liver and kidney abscess formation due to systemic bacterial spreading compared to 10^5 CFU. Peak velocity across the aortic valve and aortic valve leaflet thickness as markers for aortic valve stenosis were increased in IE compared to WI only mice. Aortic regurgitation was more prevalent after bacterial challenge mediating increased left ventricular volumes, meanwhile ejection fraction was not altered. Immunofluorescence staining revealed a pro-inflammatory milieu including increased macrophage and neutrophil infiltration in IE compared to WI only mice. Conclusion In vivo echocardiography and ex vivo histological staining revealed reliable IE induction using our new model with S. aureus concentrations of 10^5 CFU. The additional bacterial challenge causes a more severe aortic valve stenosis compared to WI only mice, potentially due to an observed increase in valvular inflammation.Fig 1 Scanning electron microscopy after

A syngeneic spontaneous zebrafish model of tp53-deficient, EGFRvIII, and PI3KCAH1047R-driven glioblastoma reveals inhibitory roles for inflammation during tumor initiation and relapse in vivo.

High-throughput vertebrate animal model systems for the study of patient-specific biology and new therapeutic approaches for aggressive brain tumors are currently lacking, and new approaches are urgently needed. Therefore, to build a patient-relevant in vivo model of human glioblastoma, we expressed common oncogenic variants including activated human EGFRvIII and PI3KCAH1047R under the control of the radial glial-specific promoter her4.1 in syngeneic tp53 loss-of-function mutant zebrafish. Robust tumor formation was observed prior to 45 days of life, and tumors had a gene expression signature similar to human glioblastoma of the mesenchymal subtype, with a strong inflammatory component. Within early stage tumor lesions, and in an in vivo and endogenous tumor microenvironment, we visualized infiltration of phagocytic cells, as well as internalization of tumor cells by mpeg1.1:EGFP+ microglia/macrophages, suggesting negative regulatory pressure by pro-inflammatory cell types on tumor growth at early stages of glioblastoma initiation. Furthermore, CRISPR/Cas9-mediated gene targeting of master inflammatory transcription factors irf7 or irf8 led to increased tumor formation in the primary context, while suppression of phagocyte activity led to enhanced tumor cell engraftment following transplantation into otherwise immune-competent zebrafish hosts. Altogether, we developed a genetically relevant model of aggressive human glioblastoma and harnessed the unique advantages of zebrafish including live imaging, high-throughput genetic and chemical manipulations to highlight important tumor-suppressive roles for the innate immune system on glioblastoma initiation, with important future opportunities for therapeutic discovery and optimizations.

Abstract 1246: Erg-driven prostate cancer emerges from a basal subset of cells with luminal transcriptomic features

Abstract Translocations of the ETS family transcription factor ERG are found in nearly 150,000 newly diagnosed prostate cancers (PCas) each year in the United States underscoring the importance of defining the mechanism by which ERG promotes prostate epithelial transformation. A consequence of nearly all ERG translocations is the aberrant expression of ERG in prostate luminal cells under transcriptional control of TMPRSS2. Multiple lines of evidence implicate ERG translocations as an initiating event in prostate cancer. ERG expression is seen in prostatic intraepithelial neoplasia (PIN) and proliferative inflammatory atrophy; expression in cancers is typically uniform; and, in the context of PI3K pathway activation, ERG is sufficient to induce cancers in mice. Yet, despite extensive research the mechanism by which ERG initiates prostate cancer is unclear. To gain insight into how ERG translocations cause prostate cancer, we performed both transcriptional profiling (scRNA-seq) and chromatin accessibility via Assay for Transposase-Accessible Chromatin using sequencing (snATAC-seq) in single cells of an autochthonous mouse model at an early stage of disease initiation. Surprisingly, we observed in prostate epithelial cells broadly expressing ERG enhanced proliferation primarily in a hybrid subpopulation of cells having basal identity but with luminal morphology and cytokeratin expression. Through a series of lineage tracing and primary prostate epithelial transplantation experiments, we confirmed tumor initiating activity resided within a subpopulation of basal cells expressing luminal genes (e.g., Tmprss2 and Nkx3-1). A trajectory analysis from single-cell Chromatin accessibility indicated Erg+ cells began to lose basal (Trp63) accessibility and gained in STAT/NFAT TFs while retaining the ability to rapidly differentiate into luminal cells that reflect the lineage of ERG-positive cancers. These findings help resolve a preexisting debate about the cell of origin of ERG-driven prostate cancer and narrow the focus for future mechanistic studies to a basal-luminal subpopulation of tumor initiating cells. Citation Format: Erik Ladewig, Weiran Feng, Christina Leslie, Charles Sawyers. Erg-driven prostate cancer emerges from a basal subset of cells with luminal transcriptomic features [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2024; Part 1 (Regular Abstracts); 2024 Apr 5-10; San Diego, CA. Philadelphia (PA): AACR; Cancer Res 2024;84(6_Suppl):Abstract nr 1246.

Identification and Expression Analysis of Putative Sugar Transporter Gene Family during Bulb Formation in Lilies.

Sugar transporters play important roles in plant growth and development, flowering and fruiting, as well as responses to adverse abiotic and biotic environmental conditions. Lilies (Lilium spp.) are some of the most representative ornamental bulbous flowers. Sugar metabolism is critical for bulb formation in lilies; therefore, clarifying the amount and expression pattern of sugar transporters is essential for further analyzing their roles in bulb formation. In this study, based on the transcriptome data of the Lilium Oriental hybrid 'Sorbonne' and Lilium × formolongi, a total of 69 and 41 sugar transporters were identified in 'Sorbonne' and Lilium × formolongi, respectively, by performing bioinformatics analysis. Through phylogenetic analysis, monosaccharide transporters (MSTs) can be divided into seven subfamilies, sucrose transporters (SUTs) can be divided into three subgroups, and sugars will eventually be exported transporters (SWEETs) can be divided into four clades. According to an analysis of conserved motifs, 20, 14, and 12 conserved motifs were predicted in MSTs, SUTs, and SWEETs, respectively. A conserved domain analysis showed that MSTs and SUTs contained a single domain, whereas most of the SWEETs harbored two MtN3/saliva domains, also known as a PQ-loop repeat. The LohINT1, which was predicted to have a smaller number of transmembrane structural domains, was cloned and analyzed for subcellular localization. It was found that the LohINT1 protein is mainly localized in the cell membrane. In addition, the expression analysis indicated that 22 LohMSTs, 1 LohSUTs, and 5 LohSWEETs were upregulated in 'Sorbonne' 1 day after scale detachment treatment, suggesting that they may regulate the initiation of the bulblet. A total of 10 LflMSTs, 1 LflSUTs, and 6 LflSWEETs were upregulated 4~6 months after sowing, which corresponds to the juvenile-to-adult transition phase of Lilium × formolongi, suggesting that they may also play a role in the accompanying bulb swelling process. Combined with quantitative real-time PCR (qRT-PCR) analysis, LohSTP8 and LohSTP12 were significantly overexpressed during the extremely early stage of bulblet initiation, and LflERD6.3 was significantly overexpressed during the growth of the underground bulblet, suggesting that they may be key sugar transporters in the formation of lily bulbs, which needs further functional verification.

Оценка перфузии и диастолической функции миокарда у больных с микрососудистой дисфункцией и гипертонической болезнью на ранней стадии по данным перфузионной С-ОФЭКТ-КТ с 99mTc-технетрилом

Objective: to study the correlation between quantitative perfusion parameters and the diastolic function in patients with microvascular dysfunction and arterial hypertension, stage 1, pain in the left half of the chest and intact coronary arteries (ICA), according to the single-photon emission computed tomography with 99mTc. Material and methods. The study included 29 patients with stage I arterial hypertension confirmed by 24-hour blood pressure monitoring, without left ventricular hypertrophy, with pain in the left half of the chest and ICA, each of whom underwent diagnostic invasive coronary angiography and SPECT/CT of the myocardium with 99mTc-technetrile at rest and in combination with stress. Results. In the examined patients with stage I arterial hypertension, without left ventricular hypertrophy with pain in the left half of the chest and ICA, according to S-SPECT/CT, disturbances in diastolic function (DF) of the LV, heterogeneity of perfusion at rest and stress-induced myocardial ischemia, corresponding to the initial manifestations of coronary insufficiency, were revealed, caused by a decrease in the perfusion reserve due to secondary microvascular dysfunction (vMSD), and is, apparently, the main factor in the occurrence of pain in the left half of the chest in this category of patients. A reliable inverse relationship has been established between speed and direct time indicators of LV DF and the prevalence and severity of stress-induced myocardial ischemia. Conclusion. In patients with stage I arterial hypertension, without left ventricular hypertrophy with pain in the left half of the chest and ICA perfusion deficiency and myocardial ischemia are associated with a significant increase in diastolic duration and a decrease in the velocity parameters of LV DF, which is revealed by SPECT/CT data already in the early stages and initial stage of the HD disease. The occurrence of left-sided heart failure in patients with hypertension and ICA is associated with coronary insufficiency caused by vMSD.

Intra−Neo-Tethyan subduction initiation inferred from the Indawgyi mafic rocks in the Central Ophiolite Belt, Myanmar

Geological evidence has demonstrated the presence of an intra−Neo-Tethyan subduction system during the Cretaceous. However, when and how this intra-oceanic subduction was initiated, especially for the eastern Neo-Tethys, are still not well constrained. Here we present geochemical and geochronological analyses of the Indawgyi mafic rocks from the Central Ophiolite Belt in the West Burma Block (Myanmar), which record early forearc spreading during the intra−Neo-Tethyan subduction initiation. Zircon U-Pb ages of gabbros indicate the ophiolitic crust formation at ca. 120 Ma. Gabbros show mid-oceanic-ridge basalt−like rare earth element patterns and depleted Sr-Nd-Pb isotopic compositions with negative anomalies of high field strength elements (e.g., Nb, Ta, Zr, and Hf), similar to forearc basalt characteristics. Basalts show more slab-derived component signatures than the gabbros and represent mantle wedge magmas most likely formed between forearc spreading and arc maturation. These data, together with regional geological records and geophysical observations, suggest that the Indawgyi gabbros were derived from an intra−Neo-Tethyan forearc setting during the early stage of subduction initiation. Considering the timing of supra-subduction zone ophiolites and metamorphic sole in the Indo-Burma Range, we propose that spontaneous subduction initiation and sinking of the eastern Neo-Tethyan lithosphere during the Early Cretaceous (ca. 120 Ma) led to formation of the Indawgyi forearc crust, whereas subsequent mature subduction resulted in the Middle Cretaceous (ca. 108‒90 Ma) arc magmatism in the West Burma Block. These findings confirm the double-subduction model of the Neo-Tethys Ocean and shed new light on the intra−Neo-Tethyan subduction initiation.

Translocation and Distribution of Carbon-Nitrogen in Relation to Rice Yield and Grain Quality as Affected by High Temperature at Early Panicle Initiation Stage

Translocation and Distribution of Carbon-Nitrogen in Relation to Rice Yield and Grain Quality as Affected by High Temperature at Early Panicle Initiation Stage

Effect of hydrogen on the dislocation evolution in an aluminum alloy under cyclic loading by two-dimensional discrete dislocation dynamics

The aim of this research is to reveal the effect of hydrogen on fatigue crack initiation in an aluminum alloy. First, the effect of hydrogen on the dislocation movement, that is, the hydrogen-enhanced localized plasticity (HELP), was modeled. Two mechanisms of HELP were modeled: reduction of the dislocation interaction stress and an increase of the dislocation velocity by hydrogen. Next, simulations of the early stage of crack initiation were performed by discrete dislocation dynamics with the HELP model. The simulation results indicated that HELP accelerates fatigue crack initiation and the increase of the dislocation velocity by hydrogen is the main mechanism of HELP.

The Utilization of Sodium Concentration in Human Milk from Pump-Dependent Mothers of Preterm Infants as a Measure of Milk Production.

Objective: This study investigated changes in sodium concentrations in human milk from mothers of premature infants using different breast pumps for 14 days postpartum, and the correlation between the sodium concentration in mother's own milk (MOM) and the volume pumped. Study Design: This randomized controlled study recruited 66 mothers of premature infants delivered in our hospital from February to December 2018, and we assigned them to three groups using an envelope method. In intervention group 1, a hospital-grade electric breast pump was used from postpartum day 1 to 14; in intervention group 2, a hospital-grade electric breast pump was used on postpartum days 1 to 5 and a normal personal electric breast pump on postpartum days 6 to 14; in the control group, a personal normal electric breast pump was used from postpartum day 1 to 14. Data recorded included the breast milk volume pumped and milk sodium concentration. Results: The average daily volume of MOM pumped differed statistically (p < 0.05) between the intervention and control groups at postpartum days 7 and 14. The average daily volume pumped did not differ between intervention groups 1 and 2 by postpartum day 14 (p > 0.05). However, the time taken for the sodium concentrations to normalize differed significantly (p < 0.01). At postpartum day 5, the sodium concentrations of 73% of intervention group 1 and 2 mothers were within normal limits, and they were maintained until day 14. In comparison, only 41% of the controls had normal MOM sodium levels on day 5, and they were still high on day 7 in 27.3% of controls. Conclusions: In the early stage of lactation initiation (within 5 days postpartum), using a hospital-grade electric breast pump promotes lactation in mothers who deliver prematurely and the sodium concentrations normalize more quickly. Sodium can be used as an objective biomarker of MOM to evaluate the possibility of delayed lactation in mothers of premature infants, and it could assist interventions in the early postpartum period. Trial Registration: Chinese Clinical Trial Registry, ChiCTR2200061384.

Abstract PR007: ERG-driven luminal prostate cancers emerge from Ck5+/Nkx3.1+ basal cells

Abstract TMPRSS2-ERG translocations are initiating lesions in nearly 50% of human prostate adenocarcinomas, often in conjunction with PTEN loss. In mice, prostate-specific expression of ERG using a Probasin-Cre driver (Pb-Cre4) is sufficient to induce invasive Ck8+ luminal adenocarcinoma with high penetrance in the context of Pten loss. Because TMPRSS2 expression in the human prostate is androgen-regulated and thereby largely restricted to luminal epithelial cells, it has been assumed that luminal cells are the likely cell of origin for TMPRSS2-ERG positive prostate cancers. To gain further support for this hypothesis, we examined the early stages of luminal adenocarcinoma initiation in the Pb-Cre ERG/Pten model at a single cell level. To our surprise, we found a highly proliferative population of ERG+ Ck5+ (a putative basal marker) cells that are enriched at the invasive front in a background of more canonical ERG+/Ck8+/Ck5- luminal tumor cells. We next performed lineage tracing experiments using Ck5-, Ck8- as well as Nkx3.1-Cre drivers, introduced via viral injection or tamoxifen induction, which collectively support the hypothesis that ERG-driven tumors originate in a subset of basal cells defined by Ck5+/Nkx3.1+. This conclusion is further supported by orthotopic transplantation of freshly isolated primary mouse prostate basal (Cd49f high) or luminal (Cd24 high) cells showing that ERG+/Ck8+ tumors arise preferentially from basal cells following ex vivo ERG/Pten activation. Time course experiments in organoids and in vivo show that ERG promotes Ck8+ luminal differentiation from highly proliferative Ck5+ cells, progressing through a Ck5+/Ck8+ intermediate cell state. Collectively, these data implicate a tumor initiating cell population defined by a mix of basal (Ck5) and luminal (Nkx3.1) markers that, under the influence of ERG expression, can expand and invade while retaining full luminal differentiation potential. Our results also suggest that widely held assumptions regarding luminal-specific expression of canonical markers such as Nkx3.1 and Probasin may need revision. Citation Format: Weiran Feng, Erik Ladewig, Nazifa Salsabeel, Huiyong Zhao, Young Sun Lee, Anuradha Gopalan, Hanzhi Luo, Wenfei Kang, Ning Fan, Eric Rosiek, Ignas Masilionis, Katia Manova-Todorova, Ronan Chaligné, Elisa de Stanchina, Brett S. Carver, Yu Chen, Dong Gao, Christina S. Leslie, Charles L. Sawyers. ERG-driven luminal prostate cancers emerge from Ck5+/Nkx3.1+ basal cells [abstract]. In: Proceedings of the AACR Special Conference: Advances in Prostate Cancer Research; 2023 Mar 15-18; Denver, Colorado. Philadelphia (PA): AACR; Cancer Res 2023;83(11 Suppl):Abstract nr PR007.

A hybrid CNN-LSTM model for diagnosing rice nutrient levels at the rice panicle initiation stage

Nitrogen (N) and potassium (K) are two key mineral nutrient elements involved in rice growth. Accurate diagnosis of N and K status is very important for the rational application of fertilizers at a specific rice growth stage. Therefore, we propose a hybrid model for diagnosing rice nutrient levels at the early panicle initiation stage (EPIS), which combines a convolutional neural network (CNN) with an attention mechanism and a long short-term memory network (LSTM). The model was validated on a large set of sequential images collected by an unmanned aerial vehicle (UAV) from rice canopies at different growth stages during a two-year experiment. Compared with VGG16, AlexNet, GoogleNet, DenseNet, and inceptionV3, ResNet101 combined with LSTM obtained the highest average accuracy of 83.81% on the dataset of Huanghuazhan (HHZ, an indica cultivar). When tested on the datasets of HHZ and Xiushui 134 (XS134, a japonica rice variety) in 2021, the ResNet101-LSTM model enhanced with the squeeze-and-excitation (SE) block achieved the highest accuracies of 85.38 and 88.38%, respectively. Through the cross-dataset method, the average accuracies on the HHZ and XS134 datasets tested in 2022 were 81.25 and 82.50%, respectively, showing a good generalization. Our proposed model works with the dynamic information of different rice growth stages and can efficiently diagnose different rice nutrient status levels at EPIS, which are helpful for making practical decisions regarding rational fertilization treatments at the panicle initiation stage.

Loss of the MLL3 tumor suppressor accelerates breast tumor onset via HIF1a-induced CCL2-mediated recruitment of CCR2 +regulatory T cells

Abstract Understanding how specific cancer mutations modulate the tumor microenvironment is essential for developing new precision cancer therapies. The histone methyltransferase MLL3 is a tumor suppressor that is frequently mutated together with p53 and PI3-kinase in breast cancer. Herein, using a mouse mammary-stem-cell-based tumor model and CRISPR gene editing, we recapitulated this genetic setting and revealed that Mll3 loss promotes tumorigenesis through enhancing tumor-intrinsic aggressiveness and establishing an immunosuppressive microenvironment. Specifically, HIF1a was upregulated in Mll3-mutant tumors and controlled proliferation and stem cell activity of the tumor cells. HIF1a also transcriptionally upregulated expression of the chemokine CCL2 by tumor cells. CCL2 further contributed to rapid CCR2-dependent accumulation of activated, proliferative KLRG1 +Foxp3 +regulatory T (T reg) cells at very early stages of tumor initiation, promoting faster tumor onset. These results link MLL3 loss to HIF signaling, CCL2 and Treg cells, and the establishment of an early immune-suppressive microenvironment, a finding that may open new therapeutic opportunities for MLL3-mutant cancers. Department of Defense Breakthrough awards BC161696 and BC200410

Coordination of floral and fiber development in cotton (Gossypium) by hormone- and flavonoid-signalling associated regulatory miRNAs.

Various plant development activities and stress responses are tightly regulated by various microRNAs (miRNA) and their target genes, or transcription factors in a spatiotemporal manner. Here, to exemplify how flowering-associated regulatory miRNAs synchronize their expression dynamics during floral and fiber development in cotton, constitutive expression diminution transgenic lines of auxin-signaling regulatory Gh-miR167 (35S-MIM167) were developed through target mimicry approach. 'Moderate' (58% to 80%)- and 'high' (> 80%)-Gh-miR167 diminution mimic lines showed dosage-dependent developmental deformities in anther development, pollen maturation, and fruit (= boll) formation. Cross pollination of 'moderate'35S-MIM167 mimiclines with wild type (WT) plant partially restored boll formation and emergence of fiber initials on the ovule surface. Gh-miR167 diminution favored organ-specific transcription biases in miR159, miR166 as well as miR160, miR164, and miR172 alongwith their target genes during anther and petal development, respectively. Similarly, accumulative effect of percent Gh-miR167 diminution, cross regulation of its target ARF6/8 genes, and temporal mis-expression of hormone signaling- and flavonoid biosynthesis-associated regulatory miRNAs at early fiber initiation stage caused irregular fiber formation. Spatial and temporal transcription proportions of regulatory miRNAs were also found crucial for the execution of hormone- and flavonoid-dependent progression of floral and fiber development. These observations discover how assorted regulatory genetic circuits get organized in response to Gh-miR167 diminution and converge upon ensuing episodes of floral and fiber development in cotton.

Crack Initiation Mechanism of AISI 4340 Steel for High‐Cycle Torsional Fatigue Loading

The nucleation of microstructural fatigue cracks in AISI 4340 steel is investigated. The pre‐electropolished specimen is employed for the observation of the very early stage of fatigue crack initiation correlated with the microstructure. It is found that there are precipitate‐free zones (PFZs) around the lath and packet boundary, and the strength of PFZ is lower than that of the lath due to the lack of second‐phase strengthening. Therefore, the fatigue crack would first initiate within the PFZ. Besides, the initiated crack plane usually is the maximum shear stress plane. However, the MnS inclusions would cause stress concentration so that the lath boundary (LB) deviating from the maximum shear stress plane could also have sufficient driving force to crack. In contrast, when the LB is vertical to the cracked MnS inclusion, it would prevent the crack from propagating into the matrix because of the anisotropy of lath martensite. The effects of the stress concentration caused by the MnS inclusion on the maximum deviation angle and the S‐N curve are discussed.

Species-specific transcriptional reprogramming during adventitious root initiation.

Adventitious roots or shoot-borne roots transdifferentiate from cells close to vascular tissues after cell reprogramming, which is associated with increased transcriptional activity. Recently, Garg et al. provided a genome-wide landscape of transcriptional signatures during the early stages of adventitious root initiation in rice and showed that conserved transcription factors acquire species-specific function.

Mechanisms of intergranular fatigue crack initiation in polycrystalline materials

Fatigue failure in polycrystalline materials occurs by initiation and propagation of fatigue cracks. Fatigue cracks can initiate transgranularly or intergranularly. While considerable progress has been achieved in the explanation of the mechanism of transgranular fatigue crack initiation intergranular initiation is still the subject of controversy. A recent study of the crack initiation in superaustenitic Sanicro 25 steel [1] revealed the important role of persistent slip markings (PSMs) in the grains adjoining the grain boundary. A novel mechanism of intergranular fatigue crack initiation has been proposed. Provided the cyclic slip cannot proceed from one grain to the neighbour one, extrusions and intrusions arise not only on the surface but also on the grain boundary. Growing intrusions represent void-like defects and growing intrusions push neighbour grain apart. A systematic study of intergranular cracking has been performed on polycrystalline copper cycled with high and low strain amplitudes. SEM observations of the early stages of fatigue crack initiation on the grain boundaries, EBSD study of grains orientation, FIB cutting of the grain boundaries and simultaneous documentation of the effect of extrusions and intrusions on the grain boundary cohesion are reported simultaneously with the conditions favourable for the initiation of the fatigue cracks.

Early Stages of Fatigue Crack Initiation in Relation With Twin Boundaries in Polycrystalline Ni-Based Superalloy AD730™

Early Stages of Fatigue Crack Initiation in Relation With Twin Boundaries in Polycrystalline Ni-Based Superalloy AD730™

Phenolic signals for prehaustorium formation in Striga hermonthica.

Striga hermonthica is a root parasitic plant that causes considerable crop yield losses. To parasitize host plants, parasitic plants develop a specialized organ called the haustorium that functions in host invasion and nutrient absorption. The initiation of a prehaustorium, the primitive haustorium structure before host invasion, requires the perception of host-derived compounds, collectively called haustorium-inducing factors (HIFs). HIFs comprise quinones, phenolics, flavonoids and cytokinins for S. hermonthica; however, the signaling pathways from various HIFs leading to prehaustorium formation remain largely uncharacterized. It has been proposed that quinones serve as direct signaling molecules for prehaustorium induction and phenolic compounds originating from the host cell wall are the oxidative precursors, but the overlap and distinction of their downstream signaling remain unknown. Here we show that quinone and phenolic-triggered prehaustorium induction in S. hermonthica occurs through partially divergent signaling pathways. We found that ASBr, an inhibitor of acetosyringone in virulence gene induction in the soil bacterium Agrobacterium, compromised prehaustorium formation in S. hermonthica. In addition, LGR-991, a competitive inhibitor of cytokinin receptors, inhibited phenolic-triggered but not quinone-triggered prehaustorium formation, demonstrating divergent signaling pathways of phenolics and quinones for prehaustorium formation. Comparisons of genome-wide transcriptional activation in response to either phenolic or quinone-type HIFs revealed markedly distinct gene expression patterns specifically at the early initiation stage. While quinone DMBQ triggered rapid and massive transcriptional changes in genes at early stages, only limited numbers of genes were induced by phenolic syringic acid. The number of genes that are commonly upregulated by DMBQ and syringic acid is gradually increased, and many genes involved in oxidoreduction and cell wall modification are upregulated at the later stages by both HIFs. Our results show kinetic and signaling differences in quinone and phenolic HIFs, providing useful insights for understanding how parasitic plants interpret different host signals for successful parasitism.

Investigation of subsurface microcracks causing premature failure in wind turbine gearbox bearings

One of the reasons behind the low rate of expansion of power production driven by wind turbines is the premature failure of their gearbox bearings, which fail within the first quarter of their designed life. The leading causes of fatigue damage in wind turbine gearbox bearings (WTGBs) are not well recognized despite the massive studies in this field. The damage initiates as subsurface microcracks, propagating to a macro scale and reaching the contact surface. For that, studying the microcracks in the early initiation stage (1–15 μm) significantly impacts the bearing damage trigger. This study is based on evaluating the role of non-metallic inclusions and voids on crack initiation, revealing the varying parts of (maximum shear stress, Von-Mises stress, and traction force) in crack initiation. The results indicated that the effect of inclusion is relatively limited on cracking initiation regardless of their sizes, other than voids, which probably have a considerable role in crack initiation and propagation. The three factors (Von-Mises stress, maximum shear stress, and traction force) played significant roles in the initiation of cracks. However, there is an urgent need to improve the design and manufacturing of WTGBs to decrease the formation of voids and carbides and revise the design standards for both (bearing life and contact stress) to consider the actual relative effects of the severe operating events.

Methane and Nitrous Oxide Emissions from Lowland Rice as Affected by Farmers’ Adopted Fertilizer Applications under Two Crop Establishment Methods in Myanmar

Identifying the optimal rice establishment option combined with specific fertilizer application can lower the global warming potential (GWP) and greenhouse gases intensity (GHGI) of rice production. In this study, methane (CH4) and nitric oxide (N2O) emissions and rice yields under different fertilizer application methods and two different planting methods, transplanted rice (TPR) and wet bed direct seeded rice (WDSR), was measured. Field experiments using a split plot design and closed chamber-GC method for gas flux measurements were conducted. CH4 and N2O emissions ranged from 1.83-4.68 mg/m2/h and 0.073-0.135 mg/m2/h, respectively. Minimum CH4 and N2O emissions were observed at 48-69 days after seedling (DAS) (tiller stage), while maximum emissions were generally found at 90 DAS or early primordial initiation (EPI) stage. It was found that TPR produced more CH4 and N2O than WDSR across fertilizers methods almost each growth stage throughout the growing period. Regarding GHGs emission factors, CH4 emissions were negatively correlated with soil pH (-0.35*, N=18). At higher soil pH, lower CH4 emissions were found in early growth stages. The N2O emissions did not correlate with soil pH (-0.04 ns, N=18). The highest average CH4 emission was reached in 90 days after seedling and EPI when the soil temperature was maximal at 34.8ºC. The correlation coefficient (r) between CH4 emission and soil temperature was 0.48*, N=18, indicating a positive correlation.