Highlights • The relationship between colonic bacteria and the host is not commensal but mutual. • Bacterial fermentation products serve as the messengers in this relationship. • The fermentation ...products protect against inflammation and cancer in colon. • SLC5A8 is critical for bacteria–host communication only when fiber intake is low. • GPR109A and GPR43 are critical for the communication even with optimal fiber intake.
Human pancreatic cancer does not respond to immune check point blockade immunotherapy. One key feature of pancreatic cancer is the association between its progression and chronic inflammation. ...Emerging evidence supports a key role for the JAK-STAT pathway in pancreatic cancer inflammation. We aimed at testing the hypothesis that sustained JAK-STAT signaling suppresses cytotoxic T lymphocyte (CTL) activation to counteract anti-PD-1 immunotherapy-induced CTL activity in pancreatic cancer. We show that human pancreatic carcinomas express high level of PD-L1 and exhibit low level of CTL infiltration. JAK-STAT inhibitor Ruxolitinib selectively inhibits STAT1 and STAT3 activation and increases CTL infiltration to induce a Tc1/Th1 immune response in the tumor microenvironment in an orthotopic pancreatic cancer mouse model. Ruxilitinib-mediated tumor suppressive efficacy diminishes in T-cell-deficient mice. Pancreatic tumor grows significantly faster in IFNγ-deficient mice. However, neutralizing IFNγ does not alter tumor growth but diminishes Ruxolitinib-induced tumor suppression in vivo, indicating that lymphocytes and IFNγ are essential for Ruxolitinib-induced host antitumor immune response. Both type I and type II interferons upregulate PD-L1 expression through the JAK-STAT signaling pathway in mouse pancreatic tumor cells. Tumor cells respond to activated T cells by activating STAT3. The inhibition of STAT3 downregulates immune suppressive cytokines production by tumor cells, resulting in increased T cell activation and effector function. Consequently, Ruxolitinib significantly improves the efficacy of anti-PD-1 immunotherapy. Our data demonstrate that Ruxolitinib is effective in the inhibition of systemic inflammation in the tumor microenvironment and therefore upregulates CTL infiltration and activation to overcome pancreatic cancer resistance to anti-PD-1 immunotherapy.
Rice is staple food for more than half of the world's population including two billion Asians, who obtain 60-70% of their energy intake from rice and its derivatives. To meet the growing demand from ...human population, rice varieties with higher yield potential and greater yield stability need to be developed. The favourable alleles for yield and yield contributing traits are distributed among two subspecies i.e., indica and japonica of cultivated rice (Oryza sativa L.). Identification of novel favourable alleles in indica/japonica will pave way to marker-assisted mobilization of these alleles in to a genetic background to break genetic barriers to yield.
A new plant type (NPT) based mapping population of 310 recombinant inbred lines (RILs) was used to map novel genomic regions and QTL hotspots influencing yield and eleven yield component traits. We identified major quantitative trait loci (QTLs) for days to 50% flowering (R2 = 25%, LOD = 14.3), panicles per plant (R2 = 19%, LOD = 9.74), flag leaf length (R2 = 22%, LOD = 3.05), flag leaf width (R2 = 53%, LOD = 46.5), spikelets per panicle (R2 = 16%, LOD = 13.8), filled grains per panicle (R2 = 22%, LOD = 15.3), percent spikelet sterility (R2 = 18%, LOD = 14.24), thousand grain weight (R2 = 25%, LOD = 12.9) and spikelet setting density (R2 = 23%, LOD = 15) expressing over two or more locations by using composite interval mapping. The phenotypic variation (R2) ranged from 8 to 53% for eleven QTLs expressing across all three locations. 19 novel QTLs were contributed by the NPT parent, Pusa1266. 15 QTL hotpots on eight chromosomes were identified for the correlated traits. Six epistatic QTLs effecting five traits at two locations were identified. A marker interval (RM3276-RM5709) on chromosome 4 harboring major QTLs for four traits was identified.
The present study reveals that favourable alleles for yield and yield contributing traits were distributed among two subspecies of rice and QTLs were co-localized in different genomic regions. QTL hotspots will be useful for understanding the common genetic control mechanism of the co-localized traits and selection for beneficial allele at these loci will result in a cumulative increase in yield due to the integrative positive effect of various QTLs. The information generated in the present study will be useful to fine map and to identify the genes underlying major robust QTLs and to transfer all favourable QTLs to one genetic background to break genetic barriers to yield for sustained food security.
AA5083 with ultrafine grain structure was produced through equal channel angular pressing using different levels of ECAP tensions, underwent a series of tensile tests. The superplasticity temperature ...573 K at low temperatures. This study investigate how varying the ECAP strain influences the distinctive microstructure of the alloy and its impact on deformation mechanisms within the low-temperature superplasticity range. A fraction of the high angle borders increased when the equal channel angular pressing strain was increased from 1 to 2, while the sub-grain size stayed nearly same. This was the most applicable microstructural evolution. After double passes, the material showed superplastic elongations, but after single pass, it did not show low temperature superplasticity. Upon analyzing the mechanical data using typical deformation mechanisms, it was determined that dislocation climb controlled the samples deformation after the first pass, whereas grain boundary sliding was responsible for the sample's low temperature superplasticity after the second pass. In the present study, we explored the differences in deformation mechanisms by considering the microstructures formed under various ECAP strains. Equal channel angular pressing with a BC route and an effective strain of 1∼2, we created an ultrafine-grained AA5083. A significant increase was seen in the fraction of particles measuring 1.8–3.8 μm under the current ECAP conditions. The implementation of equal channel angular pressing, there was a significant increase in the occurrence of voids with sizes ranging from 0.8 to 1.8 μm. According to the current analysis and results, if moderate superplastic elongation is guaranteed, it may be preferable to have fewer equal channel angular pressing passes than those that result in the largest elongation while taking into account cavitation damage and the low temperature superplasticity of ultrafine grained AA5083 used in commercial applications.
•Identifying equal channel angular pressing techniques related to different properties in the existing literature on AA5083.•To find out the mechanical properties and data using typical deformation mechanisms of AA5083.•Low temperature superplasticity, identified by grain sizes of different sample is primarily associated with a nearly equiaxed ultrafine-grained structure formed.•To find strength and behaviour of material through ECAP Technique for various materials.•Identifying different microstructure deformation of body for various materials through ECAP technique.
Pigeonpea is a major source of dietary protein to the vegetarian population of the Indian sub-continent. Crop improvement to mitigate biotic and abiotic stresses for realization of its potential ...yield and bridging yield gap is the need of the hour. Availability of limited genomic resources in the cultivated germplasm, however, is a serious bottleneck towards successful molecular breeding for the development of superior genotypes in pigeonpea. In view of this, improvement of pigeonpea can be attempted through transgenesis or by exploiting genetic resources from its wild relatives. Pigeonpea wild relatives are known to be bestowed with agronomic traits of importance; discovery and deployment of genes from them can provide a lucrative option for crop improvement. Understanding molecular signatures of wild relatives would not only provide information about the mechanism behind desired traits but also enable us to extrapolate the information to cultivated pigeonpea. The present study deals with the characterization of leaf transcriptomes of Cajanus cajan and one of its wild relatives, Cajanus platycarpus. Illumina sequencing revealed 0.11 million transcripts in both the species with an annotation of 0.09 million (82%) transcripts using BLASTX. Comparative transcriptome analyses on the whole, divulged cues about the wild relative being vigilant and agile. Gene ontology and Mapman analysis depicted higher number of transcripts in the wild relative pertaining to signaling, transcription factors and stress responsive genes. Further, networking between the differentially expressed MapMan bins demonstrated conspicuous interactions between different bins through 535 nodes (512 Genes and 23 Pathways) and 1857 edges. The authenticity of RNA-seq analysis was confirmed by qRT-PCR. The information emanating from this study can provide valuable information and resource for future translational research including genome editing to alleviate varied stresses. Further, this learning can be a platform for in-depth investigations to decipher molecular mechanisms for mitigation of various stresses in the wild relative.
An alternate method of alloying is to use extreme plastic deformation on commercially available AA5083 to generate an ultrafinegrained microstructure. The objective of this approach is to improve ...mechanical characteristics without sacrificing corrosion resistance and biocompatibility. Anisotropy in mechanical properties is introduced by plastic deformation leading to the production of a distinct texture. This is a crucial concept to understand in order to build and model structural devices and components from a perspective based approach. The ultrafine-grained structure of AA5083, which was obtained by equal channel angular pressing, is examined in this work. Ex-situ and indirect in-situ thermal studies are used to supplement this investigation while the material is heat treated at different annealing temperatures. The results show that the elastic properties undergo very small change during the annealing process, in contrast to other parameters as thermal expansion, internal friction, or hardness. The strong relationship between the elastic anisotropy and texture highlights the importance and possibilities of using texture into the design and customization of mechanical characteristics. Pure deforms plastically in order to improve mechanical qualities while maintaining biocompatibility and corrosion resistance. Analysis of the materials elastic inhomogeneity and crunchiness in detail. In comparison to other characteristics like as inner conflict thermal enlargement or hardness, the results demonstrate that elastic properties barely marginally change during annealing. The microstructure fragmentation had no influence on the conductivity of the AA5083, which oscillated at 18 MS/m after the ECAP procedure. According to the findings, all deformed specimens strain hardening exponent and capacity were lower than they were in their as-received state. Investigated was the effect of size of grains on the strain hardening comportment of the ECAPed AA5083.
The submicrometer range of grain sizes was reached for AA5083 by using equal channel angular pressing at room temperature. While the submicrometer grains of AA5083 were stable up to annealing ...temperatures of 300 °C, the stability of these grains was only moderately maintained up to annealing temperatures of about 200 °C. Tensile tests conducted after one pass of equal channel angular pressing—that is, strain introduction of roughly one—showed a significant increase in the 0.2% proof stress and ultimate tensile stress values for each alloy. Concurrent with this improvement, the elongations to failure decreased. The analysis shows that the square root of the magnesium content in each alloy corresponds with the magnitudes of these stresses. In samples that were cold rolled, comparable values of proof stresses and ultimate tensile stress were obtained at equivalent strains. However, because of the induction of a very small grain size, elongations to failure were higher after applying equal channel angular pressing to similar strains greater than one. The effects of material constitutive behaviour, tool design, and friction conditions on metal flow, stress fields, and the tendency for tensile fracture during the equal channel angular pressing process were studied using a finite element modelling technique. A degree of non-uniform flow was noted that extended past the head and tail of the extrusion when materials were subjected to equal channel angular pressing with varying constitutive behaviours or when utilising tooling with a radiused front leg. It is anticipated that tool design and material qualities will have a considerable effect on tensile stresses and, in turn, the development of tensile damage during equal channel angular pressing.
Rice blast caused by Magnaporthe oryzae is one of the most important diseases of rice. Pi54, a rice gene that imparts resistance to M. oryzae isolates prevalent in India, was already cloned but its ...avirulent counterpart in the pathogen was not known. After decoding the whole genome of an avirulent isolate of M. oryzae, we predicted 11440 protein coding genes and then identified four candidate effector proteins which are exclusively expressed in the infectious structure, appresoria. In silico protein modeling followed by interaction analysis between Pi54 protein model and selected four candidate effector proteins models revealed that Mo-01947_9 protein model encoded by a gene located at chromosome 4 of M. oryzae, interacted best at the Leucine Rich Repeat domain of Pi54 protein model. Yeast-two-hybrid analysis showed that Mo-01947_9 protein physically interacts with Pi54 protein. Nicotiana benthamiana leaf infiltration assay confirmed induction of hypersensitive response in the presence of Pi54 gene in a heterologous system. Genetic complementation test also proved that Mo-01947_9 protein induces avirulence response in the pathogen in presence of Pi54 gene. Here, we report identification and cloning of a new fungal effector gene which interacts with blast resistance gene Pi54 in rice.
AA5083 bars processed by four pass ambient Equal Channel Angular Pressing were subjected to intersection annealing, where time and temperature were varied after each pass. The microstructures, ...texturing and compressive characteristics of the samples were meticulously examined. Due to the high annealing temperatures, both ultimate tensile strength and compressive stresses decreased with increasing grain size. However, intersection annealing at room temperature resulted in the best compressive yield strength. The deformation behavior of AA5083 billets was investigated using finite element analysis. Electron back scatter diffraction was employed to examine the texture of the Equal Channel Angular Pressed billet crystals. Extensive research was conducted on the tensile properties and Vickers microhardness. The finite element simulations revealed that the 90 0 die exhibited a significantly more uniform dispersion of plastic strain compared to the 120 0 die. The renewal of additional slip mechanisms during the four Pass process was attributed to the grain refining that occurred after the 1-Pass and 2-Pass stages. Equal Channel Angular Pressing successfully produced a homogeneously ultra-fine grained microstructure. The increase in strength was attributed to grain refining and dislocation strengthening. Molecular dynamics simulations were employed to study the ECAPed approach of AA5083 providing insights into the deformation behavior and polycrystal formation.
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