The Effect of Water during the Compaction Process on Surface Characteristics of HMA Pavement.

During the compaction process of HMA pavement, it is common to spray cold water on the wheel of a road roller to prevent the mixture from sticking to the wheel, which might deteriorate the bonding strength between the asphalt binder and aggregate, and consequently lead to surface polishing of the pavement. This paper aims to demonstrate whether the water used during the compaction process affects the surface performance of HMA pavement. In this study, the black pixel ratio and mass loss ratio were used to evaluate the water effect on the surface performance of asphalt pavement, considering the water consumption, molding temperature and long-term ageing process. The test results indicated that the water used during the compaction process would increase the risk of surface polishing of HMA pavement. This adverse effect became more significant if the HMA samples were prepared using greater water consumption, a greater molding temperature and a long-term ageing process. Moreover, there exists a certain correlation between the black pixel ratio and mass loss ratio, and their relationships were demonstrated by the experimental results in this study. It is recommended that further research concentrates on the influencing mechanism and the treatment strategy for the adverse effect caused by the water used during the compaction process. The use of more types of asphalt binders, aggregate and methodologies is also recommended in further studies.

Utilisation of Waste Sludge from Drinking Water Treatment as a Filler Material in Hot Mix Asphalt.

This research investigated the suitability of using sludge from the treatment of drinking water in hot mix asphalt (HMA) as a filler material. The storage and environmental impact of sludge is an enormous problem, especially for countries with large populations. Two different types of sludges, ferric chloride (FC) and aluminium sulphate (AS), were used as a filler material in HMA. The Hamburg Wheel Tracking (HWT) test, which correlates with rutting, and the Indirect Tensile Strength (ITS) test, which indicates the moisture sensitivity of HMA, were carried out at the optimum bitumen content of the mixes to investigate the usability of sludge in HMA. The test results indicate the usability of FC and AS in HMA compared to the reference mixes. However, the AS type of sludge has better rutting resistance than the FC type. Although the results support the usability of both sludges in HMA, it should be noted that the increased cost of the mix containing sludges due to the combustion process and the increased bitumen content during application should be considered.

Cadmium and zinc accumulation and tolerance in two Egyptian cultivars (S53 and V120) of Helianthus annuus L. as potential phytoremediator.

One of the most important oil crops in the world, sunflower (Helianthus annuus L.), is recognized to help in soil phytoremediation. Heavy metal (HM) contamination is one of the most abiotic challenges that may affect the growth and productivity of such an important crop plant. We studied the influence of HM-contaminated soils on metal homeostasis and the potential hypertolerance mechanisms in two sunflower Egyptian cultivars (V120 and S53). Both cultivars accumulated significantly higher cadmium concentrations in their roots compared to their shoots during Cd and Zn/Cd treatments. Higher root concentrations of 121 mg g-1 dry weight (DW) and 125 mg g-1 DW were measured in V120 plants compared to relatively lower values of 111 mg g-1 DW and 105 mg g-1 DW in the roots of S53 plants, respectively. Cadmium contamination significantly upregulated the expression of heavy metal ATPases (HaHMA4) in the shoots of V120 plants. On the other hand, their roots displayed a notable expression of HaHMA3. This study indicates that V120 plants accumulated and sequestered Cd in their roots. Therefore, it is advised to cultivate the V120 cultivar in areas contaminated with heavy metals as it is a promising Cd phytoremediator.

The current study confirms and provides new insights into the low Cd and Zn concentration responses of two cultivars of Helianthus annuus as potential HM phytoremediators. HMA3 and HMA4 mediated both root sequestration and reduced root-to-shoot translocation rates. Moreover, high CAT and POX activities may reduce oxidative damage and enhance plant tolerance. The V120 showed higher levels of Cd accumulation in its roots and could be a promising cultivar for the phytoremediation of this heavy metal. This work recalls that Cd tolerance is a trait that may vary among cultivars of the same species and should be taken into consideration in the phytomanagement of heavy metals in contaminated soils.

Enhancing Fatigue Resistance in Asphalt Mixtures with a Novel Additive Derived from Recycled Polymeric Fibers from End-of-Life Tyres (ELTs).

Waste-tire textile fibers (WTTF) represent a challenge for the recycling industry since there are currently very few alternatives for their use. In this study, an evaluation of the effect of a new additive developed in two granular formats from WTTF on the fatigue behavior of asphalt mixtures was performed. For the first format of the WTTF-based additive, its effect was evaluated on hot-mix asphalt (HMA), while for the second format of the additive, the effects were evaluated on stone mastic asphalt (SMA). This second format represents an alternative that allows for the total replacement of the cellulose stabilizing additive used in the reference mix. The evaluation of fatigue damage in the mixes was performed using the four-point bending beam (4PB) test specified in European standard EN 12697-24. The test results show that the asphalt mixtures manufactured with WTTF-based additives exhibited a higher capacity to resist load cycles before failure compared to the reference mixtures. Likewise, once the asphalt mixtures were evaluated in a pavement structure by means of an empirical mechanistic analysis, the pavement structures composed of asphalt mixtures with WTTF-based additives showed significant improvements in their durability for the different load axes evaluated. For an average thickness of 15 cm of asphalt mix of a pavement-type structure, the use of the WTTF additive increases the durability of the structures by up to 129% and 112% compared to the HMA and SMA reference mixtures, respectively. These results show that both formats of the WTTF-based admixture improve the fatigue damage resistance of the HMA and SMA asphalt mixtures.

Increased expression of CD70 in relapsed acute myeloid leukemia after hypomethylating agents.

Acute myeloid leukemia (AML) is the most common acute leukemia in adults. While induction chemotherapy leads to remission in most patients, a significant number will experience relapse. Therefore, there is a need for novel therapies that can improve remission rates in patients with relapsed and refractory AML. CD70 is the natural ligand for CD27 (a member of the TNF superfamily) and appears to be a promising therapeutic target. Consequently, there is considerable interest in developing chimeric antigen receptor (CAR) T-cell therapy products that can specifically target CD70 in various neoplasms, including AML. In this study, we employed routine diagnostic techniques, such as immunohistochemistry and flow cytometry, to investigate the expression of CD70 in bone marrow samples from treatment-naïve and relapsed AML patients after hypomethylating agents (HMA). Also, we evaluated the impact of HMA on CD70 expression and examined CD70 expression in various leukemic cell subsets and normal hematopoietic progenitors.

Predictive value of DNA methylation patterns in AML patients treated with an azacytidine containing induction regimen.

BACKGROUND: Acute myeloid leukemia (AML) is a heterogeneous disease with a poor prognosis. Dysregulation of the epigenetic machinery is a significant contributor to disease development. Some AML patients benefit from treatment with hypomethylating agents (HMAs), but no predictive biomarkers for therapy response exist. Here, we investigated whether unbiased genome-wide assessment of pre-treatment DNA-methylation profiles in AML bone marrow blasts can help to identify patients who will achieve a remission after an azacytidine-containing induction regimen. RESULTS: A total of n = 155 patients with newly diagnosed AML treated in the AMLSG 12-09 trial were randomly assigned to a screening and a refinement and validation cohort. The cohorts were divided according to azacytidine-containing induction regimens and response status. Methylation status was assessed for 664,227 500-bp-regions using methyl-CpG immunoprecipitation-seq, resulting in 1755 differentially methylated regions (DMRs). Top regions were distilled and included genes such as WNT10A and GATA3. 80% of regions identified as a hit were represented on HumanMethlyation 450k Bead Chips. Quantitative methylation analysis confirmed 90% of these regions (36 of 40 DMRs). A classifier was trained using penalized logistic regression and fivefold cross validation containing 17 CpGs. Validation based on mass spectra generated by MALDI-TOF failed (AUC 0.59). However, discriminative ability was maintained by adding neighboring CpGs. A recomposed classifier with 12 CpGs resulted in an AUC of 0.77. When evaluated in the non-azacytidine containing group, the AUC was 0.76. CONCLUSIONS: Our analysis evaluated the value of a whole genome methyl-CpG screening assay for the identification of informative methylation changes. We also compared the informative content and discriminatory power of regions and single CpGs for predicting response to therapy. The relevance of the identified DMRs is supported by their association with key regulatory processes of oncogenic transformation and support the idea of relevant DMRs being enriched at distinct loci rather than evenly distribution across the genome. Predictive response to therapy could be established but lacked specificity for treatment with azacytidine. Our results suggest that a predictive epigenotype carries its methylation information at a complex, genome-wide level, that is confined to regions, rather than to single CpGs. With increasing application of combinatorial regimens, response prediction may become even more complicated.

The Molecular Docking of MAX Fungal Effectors with Plant HMA Domain-Binding Proteins.

Fungal effector proteins are important in mediating disease infections in agriculturally important crops. These secreted small proteins are known to interact with their respective host receptor binding partners in the host, either inside the cells or in the apoplastic space, depending on the localisation of the effector proteins. Consequently, it is important to understand the interactions between fungal effector proteins and their target host receptor binding partners, particularly since this can be used for the selection of potential plant resistance or susceptibility-related proteins that can be applied to the breeding of new cultivars with disease resistance. In this study, molecular docking simulations were used to characterise protein-protein interactions between effector and plant receptors. Benchmarking was undertaken using available experimental structures of effector-host receptor complexes to optimise simulation parameters, which were then used to predict the structures and mediating interactions of effector proteins with host receptor binding partners that have not yet been characterised experimentally. Rigid docking was applied for both the so-called bound and unbound docking of MAX effectors with plant HMA domain protein partners. All bound complexes used for benchmarking were correctly predicted, with 84% being ranked as the top docking pose using the ZDOCK scoring function. In the case of unbound complexes, a minimum of 95% of known residues were predicted to be part of the interacting interface on the host receptor binding partner, and at least 87% of known residues were predicted to be part of the interacting interface on the effector protein. Hydrophobic interactions were found to dominate the formation of effector-plant protein complexes. An optimised set of docking parameters based on the use of ZDOCK and ZRANK scoring functions were established to enable the prediction of near-native docking poses involving different binding interfaces on plant HMA domain proteins. Whilst this study was limited by the availability of the experimentally determined complexed structures of effectors and host receptor binding partners, we demonstrated the potential of molecular docking simulations to predict the likely interactions between effectors and their respective host receptor binding partners. This computational approach may accelerate the process of the discovery of putative interacting plant partners of effector proteins and contribute to effector-assisted marker discovery, thereby supporting the breeding of disease-resistant crops.

A Genome-Wide Identification and Comparative Analysis of the Heavy-Metal-Associated Gene Family in Cucurbitaceae Species and Their Role in Cucurbita pepo under Arsenic Stress.

The heavy-metal-associated (HMA) proteins are a class of PB1-type ATPases related to the intracellular transport and detoxification of metals. However, due to a lack of information regarding the HMA gene family in the Cucurbitaceae family, a comprehensive genome-wide analysis of the HMA family was performed in ten Cucurbitaceae species: Citrullus amarus, Citrullus colocynthis, Citrullus lanatus, Citrullus mucosospermus, Cucumis melo, Cucumis sativus, Cucurbita maxima, Cucurbita moschata, Cucurbita pepo, and Legenaria siceraria. We identified 103 Cucurbit HMA proteins with various members, ranging from 8 (Legenaria siceraria) to 14 (Cucurbita pepo) across species. The phylogenetic and structural analysis confirmed that the Cucurbitaceae HMA protein family could be further classified into two major clades: Zn/Co/Cd/Pb and Cu/Ag. The GO-annotation-based subcellular localization analysis predicted that all HMA gene family members were localized on membranes. Moreover, the analysis of conserved motifs and gene structure (intron/exon) revealed the functional divergence between clades. The interspecies microsynteny analysis demonstrated that maximum orthologous genes were found between species of the Citrullus genera. Finally, nine candidate HMA genes were selected, and their expression analysis was carried out via qRT-PCR in root, leaf, flower, and fruit tissues of C. pepo under arsenic stress. The expression pattern of the CpeHMA genes showed a distinct pattern of expression in root and shoot tissues, with a remarkable expression of CpeHMA6 and CpeHMA3 genes from the Cu/Ag clade. Overall, this study provides insights into the functional analysis of the HMA gene family in Cucurbitaceae species and lays down the basic knowledge to explore the role and mechanism of the HMA gene family to cope with arsenic stress conditions.

ZmHMA3, a Member of the Heavy-Metal-Transporting ATPase Family, Regulates Cd and Zn Tolerance in Maize.

The pollution of heavy metals is extremely serious in China, including zinc (Zn), copper (Cu), lead (Pb), and cadmium (Cd). Heavy-metal-transporting ATPase (HMA) belongs to a subfamily of the P-ATPase family, which absorbs and transports Zn, Cu, Pb, and Cd in plants. Here, we describe a ZmHMA-encoding HMA family protein that positively regulates Cd and Zn tolerance. The real-time fluorescence quantification (RT-PCR) results revealed that ZmHMA3 had a high expression in B73, and the expression of ZmHMA3 was sensitive to Cd in yeast cells, which was related to Cd accumulation in yeast. Additionally, the Arabidopsis thaliana homologous mutants of AtHMA2 showed Cd sensitivity compared with WT. The overexpressing ZmHMA3 plants showed higher tolerance under Cd and Zn stresses than the wild type. The overexpression of ZmHMA3 led to higher Cd and Zn accumulation in tissues based on the subcellular distribution analysis. We propose that ZmHMA3 improves maize tolerance to Cd and Zn stresses by absorbing and transporting Cd and Zn ions. This study elucidates the gene function of the ZmHMA3 response to Cd and Zn stress and provides a reference for improving the characteristics of heavy metals enrichment in existing maize varieties and the plant remediation technology of heavy-metal-contaminated soil.

Organosilicon Compounds in Hot-Melt Adhesive Technologies.

Hot-melt adhesives (HMAs) are thermoplastic materials that can bond various substrates by solidifying rapidly upon cooling from the molten state, and their modification with organosilicon compounds can result in crosslinking behavior, characteristic of gels. Organosilicon compounds are hybrid molecules that have both inorganic and organic components and can enhance the properties and performance of HMAs. The gel aspect of HMA with and without organosilicon modifiers can be considered in organosilicon-modified systems, the modifiers are often either sol-gel condensation products or their mechanism of action on the adherent surface can be considered of sol-gel type. The purpose of this manuscript is to present the current state of the art on the formulation, characterization, and application of HMAs and optimize their performance with organosilicon compounds for application in various industries such as automotive, construction, and photovoltaics. This review covers articles published within the period of 2018-2022. The article is divided into sections, in which information about hot-melt adhesives is described at the beginning. The following part of the presented review focuses on the composition of hot-melt adhesives, which takes into account the use of organosilicon compounds. The last part of this review outlines the future trends in hot-melt adhesives.

Mitotic perturbation is a key mechanism of action of decitabine in myeloid tumor treatment.

Decitabine (DAC) is clinically used to treat myelodysplastic syndrome (MDS) and acute myeloid leukemia (AML). Our genome-wide CRISPR-dCas9 activation screen using MDS-derived AML cells indicates that mitotic regulation is critical for DAC resistance. DAC strongly induces abnormal mitosis (abscission failure or tripolar mitosis) in human myeloid tumors at clinical concentrations, especially in those with TP53 mutations or antecedent hematological disorders. This DAC-induced mitotic disruption and apoptosis are significantly attenuated in DNMT1-depleted cells. In contrast, overexpression of Dnmt1, but not the catalytically inactive mutant, enhances DAC-induced mitotic defects in myeloid tumors. We also demonstrate that DAC-induced mitotic disruption is enhanced by pharmacological inhibition of the ATR-CLSPN-CHK1 pathway. These data challenge the current assumption that DAC inhibits leukemogenesis through DNMT1 inhibition and subsequent DNA hypomethylation and highlight the potent activity of DAC to disrupt mitosis through aberrant DNMT1-DNA covalent bonds.

Browsers or Grazers? New Insights into Feral Burro Diet Using a Non-Invasive Sampling and Plant DNA Metabarcoding Approach.

Ungulates play a large role in shaping ecosystems and communities by influencing plant composition, structure, and productivity. We investigated the summer diets of feral burros in two ecosystems in which they are found in the United States: a subtropical desert in Arizona and a temperate juniper shrubland in Utah. Between 24 June and 16 July of 2019, we gathered 50 burro fecal samples from each location and used plant DNA metabarcoding to determine the burros' diets. We found that during our sampling period the burros in the Sonoran Desert consumed a higher proportion of woody browse and had a narrower dietary niche breadth and lower degree of diet diversity compared to the burros in the juniper shrubland ecosystem, where the burros consumed higher proportions of graminoids and forbs and had a higher diet diversity index and broader dietary niche breadth. The burros in the Sonoran Desert relied primarily on Prosopis spp. (mesquite) and Poaceae grasses, whereas the burros in the juniper shrubland relied on a wider variety of forb and grass species, likely due to the greater variability in the forage species temporally and spatially available in that temperate ecosystem. We found that feral burros are highly adaptable with respect to diet and appear to be employing a mixed feeding strategy, similar to their ancestor, the African wild ass, to meet their nutritional needs in whichever ecosystem they are found.

Structural mechanism of heavy metal-associated integrated domain engineering of paired nucleotide-binding and leucine-rich repeat proteins in rice.

Plant nucleotide-binding and leucine-rich repeat (NLR) proteins are immune sensors that detect pathogen effectors and initiate a strong immune response. In many cases, single NLR proteins are sufficient for both effector recognition and signaling activation. These proteins possess a conserved architecture, including a C-terminal leucine-rich repeat (LRR) domain, a central nucleotide-binding (NB) domain, and a variable N-terminal domain. Nevertheless, many paired NLRs linked in a head-to-head configuration have now been identified. The ones carrying integrated domains (IDs) can recognize pathogen effector proteins by various modes; these are known as sensor NLR (sNLR) proteins. Structural and biochemical studies have provided insights into the molecular basis of heavy metal-associated IDs (HMA IDs) from paired NLRs in rice and revealed the co-evolution between pathogens and hosts by combining naturally occurring favorable interactions across diverse interfaces. Focusing on structural and molecular models, here we highlight advances in structure-guided engineering to expand and enhance the response profile of paired NLR-HMA IDs in rice to variants of the rice blast pathogen MAX-effectors (Magnaporthe oryzae AVRs and ToxB-like). These results demonstrate that the HMA IDs-based design of rice materials with broad and enhanced resistance profiles possesses great application potential but also face considerable challenges.

Efficacy and safety of an HDACi- and HMA-based protocol in adults with acute myeloid leukemia of intermediate- and adverse-risk categories: a retrospective study.

OBJECTIVE: Anthracyclines and cytarabine have comprised standard induction therapy for acute myeloid leukemia (AML) for decades. Low overall survival of AML is due to non-remission or relapse after remission. Hypomethylating agent (HMA) decitabine combined with low-dose chemotherapy or other targeted agents has shown promising effect for AML in clinical trials, especially in t(8;21) acute myeloid leukemia. We previously investigated histone deacetylase inhibitor (HDACi) chidamide could regulate Wnt/ß-catenin signaling pathway in leukemia cell lines. METHODS: Adult patients with de novo or relapsed/refractory AML who were treated with chidamide and decitabine in combination with chemotherapy (chidamide group, n = 23) or only decitabine combination with chemotherapy (decitabine group, n = 17) were analyzed. RESULTS: Chidamide group represented higher complete response rate (82.6% and 52.9%, p = 0.0430, vs. decitabine group), progression-free survival and overall survival rates (p = 0.0088 and p = 0.0139, respectively), especially for patients with de novo AML. Hematological toxicity and infections were the most common adverse events (AEs) in both groups, and they were manageable by supportive treatments. CONCLUSIONS: This HDACi- and HMA-based protocol is an effective and tolerable therapy for patients with AML. The comprehensive mechanism and effects of chidamide in combination with decitabine are worth to be further explored in AML.

Effects of sponge-to-sponge contact on the microbiomes of three spatially competing Caribbean coral reef species.

Sponges perform important ecosystem functions, host diverse microbial symbiont communities (microbiomes), and have been increasing in density on Caribbean coral reefs over the last decade. Sponges compete for space in coral reef communities through both morphological and allelopathic strategies, but no studies of microbiome impacts during these interactions have been conducted. Microbiome alterations mediate spatial competition in other coral reef invertebrates and may similarly impact competitive outcomes for sponges. In this study, we characterized the microbiomes of three common Caribbean sponges (Agelas tubulata, Iotrochota birotulata, and Xestospongia muta) observed to naturally interact spatially in Key Largo, Florida (USA). For each species, replicate samples were collected from sponges in contact with neighbors at the site of contact (contact) and distant from the site of contact (no contact), and from sponges spatially isolated from neighbors (control). Next-generation amplicon sequencing (V4 region of 16S rRNA) revealed significant differences in microbial community structure and diversity among sponge species, but no significant effects were observed within sponge species across all contact states and competitor pairings, indicating no large community shifts in response to direct contact. At a finer scale, particular symbiont taxa (operational taxonomic units at 97% sequence identity, OTUs) were shown to decrease significantly in some interaction pairings, suggesting localized effects for specific sponge competitors. Overall, these results revealed that direct contact during spatial competition does not significantly alter microbial community composition or structure of interacting sponges, suggesting that allelopathic interactions and competitive outcomes are not mediated by microbiome damage or destabilization.

Genome-wide analysis toward the epigenetic aetiology of myelodysplastic syndrome disease progression and pharmacoepigenomic basis of hypomethylating agents drug treatment response.

Myelodysplastic syndromes (MDS) consist of a group of hematological malignancies characterized by ineffective hematopoiesis, cytogenetic abnormalities, and often a high risk of transformation to acute myeloid leukemia (AML). So far, there have been only a very limited number of studies assessing the epigenetics component contributing to the pathophysiology of these disorders, but not a single study assessing this at a genome-wide level. Here, we implemented a generic high throughput epigenomics approach, using methylated DNA sequencing (MeD-seq) of LpnPI digested fragments to identify potential epigenomic targets associated with MDS subtypes. Our results highlighted that PCDHG and ZNF gene families harbor potential epigenomic targets, which have been shown to be differentially methylated in a variety of comparisons between different MDS subtypes. Specifically, CpG islands, transcription start sites and post-transcriptional start sites within ZNF124, ZNF497 and PCDHG family are differentially methylated with fold change above 3,5. Overall, these findings highlight important aspects of the epigenomic component of MDS syndromes pathogenesis and the pharmacoepigenomic basis to the hypomethylating agents drug treatment response, while this generic high throughput whole epigenome sequencing approach could be readily implemented to other genetic diseases with a strong epigenetic component.

Genome-wide survey of HMA gene family and its characterization in wheat (Triticum aestivum).

Background: Abiotic stresses, particularly drought and heavy metal toxicity, have presented a significant risk to long-term agricultural output around the world. Although the heavy-metal-associated domain (HMA) gene family has been widely explored in Arabidopsis and other plants, it has not been thoroughly studied in wheat (Triticum aestivum). This study was proposed to investigate the HMA gene family in wheat. Methods: To analyze the phylogenetic relationships, gene structure, gene ontology, and conserved motifs, a comparative study of wheat HMA genes with the Arabidopsis genome was performed. Results: A total of 27 T. aestivum proteins belonging to the HMA gene family were identified in this study, with amino acid counts ranging from 262 to 1,071. HMA proteins were found to be grouped into three subgroups in a phylogenetic tree, and closely related proteins in the tree showed the same expression patterns as motifs found in distinct subgroups. Gene structural study elucidated that intron and exon arrangement differed by family. Conclusion: As a result, the current work offered important information regarding HMA family genes in the T. aestivum genome, which will be valuable in understanding their putative functions in other wheat species.

Antifungal activity of 6-substituted amiloride and hexamethylene amiloride (HMA) analogs.

Fungal infections have become an increasing threat as a result of growing numbers of susceptible hosts and diminishing effectiveness of antifungal drugs due to multi-drug resistance. This reality underscores the need to develop novel drugs with unique mechanisms of action. We recently identified 5-(N,N-hexamethylene)amiloride (HMA), an inhibitor of human Na+/H+ exchanger isoform 1, as a promising scaffold for antifungal drug development. In this work, we carried out susceptibility testing of 45 6-substituted HMA and amiloride analogs against a panel of pathogenic fungi. A series of 6-(2-benzofuran)amiloride and HMA analogs that showed up to a 16-fold increase in activity against Cryptococcus neoformans were identified. Hits from these series showed broad-spectrum activity against both basidiomycete and ascomycete fungal pathogens, including multidrug-resistant clinical isolates.