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71,229 result(s) for "Das, P"
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Silencing NOTCH signaling causes growth arrest in both breast cancer stem cells and breast cancer cells
Background: Breast cancer stem cells (BCSCs) are characterized by high aldehyde dehydrogenase (ALDH) enzyme activity and are refractory to current treatment modalities, show a higher risk for metastasis, and influence the epithelial to mesenchymal transition (EMT), leading to a shorter time to recurrence and death. In this study, we focused on examination of the mechanism of action of a small herbal molecule, psoralidin (Pso) that has been shown to effectively suppress the growth of BSCSs and breast cancer cells (BCCs), in breast cancer (BC) models. Methods: ALDH − and ALDH + BCCs were isolated from MDA-MB-231 cells, and the anticancer effects of Pso were measured using cell viability, apoptosis, colony formation, invasion, migration, mammosphere formation, immunofluorescence, and western blot analysis. Results: Psoralidin significantly downregulated NOTCH1 signaling, and this downregulation resulted in growth inhibition and induction of apoptosis in both ALDH − and ALDH + cells. Molecularly, Pso inhibited NOTCH1 signaling, which facilitated inhibition of EMT markers ( β -catenin and vimentin) and upregulated E-cadherin expression, resulting in reduced migration and invasion of both ALDH − and ALDH + cells. Conclusion: Together, our results suggest that inhibition of NOTCH1 by Pso resulted in growth arrest and inhibition of EMT in BCSCs and BCCs. Psoralidin appears to be a novel agent that targets both BCSCs and BCCs.
Mutations inhibiting KDM4B drive ALT activation in ATRX-mutated glioblastomas
Alternative Lengthening of Telomeres (ALT) is a telomere maintenance pathway utilised in 15% of cancers. ALT cancers are strongly associated with inactivating mutations in ATRX ; yet loss of ATRX alone is insufficient to trigger ALT, suggesting that additional cooperating factors are involved. We identify H3.3 G34R and IDH1/2 mutations as two such factors in ATRX-mutated glioblastomas. Both mutations are capable of inactivating histone demethylases, and we identify KDM4B as the key demethylase inactivated in ALT. Mouse embryonic stem cells inactivated for ATRX, TP53, TERT and KDM4B (KDM4B knockout or H3.3 G34R ) show characteristic features of ALT. Conversely, KDM4B over-expression in ALT cancer cells abrogates ALT-associated features. In this work, we demonstrate that inactivation of KDM4B, through H3.3 G34R or IDH1/2 mutations, acts in tandem with ATRX mutations to promote ALT in glioblastomas. Alternative Lengthening of Telomeres (ALT) is a telomere maintenance pathway utilised in 15% of cancers that have been associated with mutations in ATRX. Here the authors reveal a functional role of histone demethylases KDM4B in regulating ALT activation.
Strong cooperative coupling of pressure-induced magnetic order and nematicity in FeSe
A hallmark of the iron-based superconductors is the strong coupling between magnetic, structural and electronic degrees of freedom. However, a universal picture of the normal state properties of these compounds has been confounded by recent investigations of FeSe where the nematic (structural) and magnetic transitions appear to be decoupled. Here, using synchrotron-based high-energy x-ray diffraction and time-domain Mössbauer spectroscopy, we show that nematicity and magnetism in FeSe under applied pressure are indeed strongly coupled. Distinct structural and magnetic transitions are observed for pressures between 1.0 and 1.7 GPa and merge into a single first-order transition for pressures ≳1.7 GPa, reminiscent of what has been found for the evolution of these transitions in the prototypical system Ba(Fe 1− x Co x ) 2 As 2 . Our results are consistent with a spin-driven mechanism for nematic order in FeSe and provide an important step towards a universal description of the normal state properties of the iron-based superconductors. Whilst strong coupling between structure and magnetism is a signature of many of the Fe-based superconductors, no evidence for this has been reported in the normal state of FeSe. Here, the authors demonstrate strong coupling between nematicity and magnetism in FeSe under applied pressure.
Probiotics in fish and shellfish culture: immunomodulatory and ecophysiological responses
Aquaculture is emerging as one of the most viable and promising enterprises for keeping pace with the surging need for animal protein, providing nutritional and food security to humans, particularly those residing in regions where livestock is relatively scarce. With every step toward intensification of aquaculture practices, there is an increase in the stress level in the animal as well as the environment. Hence, disease outbreak is being increasingly recognized as one of the most important constraints to aquaculture production in many countries, including India. Conventionally, the disease control in aquaculture has relied on the use of chemical compounds and antibiotics. The development of non-antibiotic and environmentally friendly agents is one of the key factors for health management in aquaculture. Consequently, with the emerging need for environmentally friendly aquaculture, the use of alternatives to antibiotic growth promoters in fish nutrition is now widely accepted. In recent years, probiotics have taken center stage and are being used as an unconventional approach that has numerous beneficial effects in fish and shellfish culture: improved activity of gastrointestinal microbiota and enhanced immune status, disease resistance, survival, feed utilization and growth performance. As natural products, probiotics have much potential to increase the efficiency and sustainability of aquaculture production. Therefore, comprehensive research to fully characterize the intestinal microbiota of prominent fish species, mechanisms of action of probiotics and their effects on the intestinal ecosystem, immunity, fish health and performance is reasonable. This review highlights the classifications and applications of probiotics in aquaculture. The review also summarizes the advancement and research highlights of the probiotic status and mode of action, which are of great significance from an ecofriendly, sustainable, intensive aquaculture point of view.
Reactive syringofibroadenoma
A 45-year-old diabetic and hypertensive man from Bihar presented with multiple, asymptomatic, elevated lesions on his right foot that developed over a period of 6 months. The lesions started developing gradually after auto-amputation of toes and have been increasing in size and thickness since then. He was treated with multi-drug therapy for Hansen's disease, 8 years before presenting to us. The further course was uneventful until he started developing auto-amputation of the toes of his right foot and he lost all of them over a period of 2 years. Cutaneous examination showed multiple, firm, slightly erythematous plaques and nodules having smooth surface, without any scaling or verrucosity, present over the distal aspect and dorsum of the right foot [Figure - 1].
Ascertaining the morpho-molecular diversity in buckwheat germplasm and identification of high yielding, stable genotypes with superior biochemical quality
Buckwheat, an underutilized crop, is a multipurpose crop with great potential and high nutritive values. Therefore, this study aimed to evaluate the genetic variability of 102 génotypes of common ( Fagopyrum esculentum) and tartaty buckwheat ( Fagopyrum tataricum) based on agro-morphological traits and microsatellite markers with the identification of high-yielding and stable genotypes with superior nutritive values. The accessions varied significantly in terms of morpho-molecular and biochemical traits. Key traits with agronomic relevance namely, number of seeds per plant, hundred seed weight, and petiole length were identified to exhibit positive correlations with direct positive path coefficient on yield per plant. Both the agro-morphological and SSR based clustering grouped the genotypes into five major clusters. The SSR polymorphism analysis, gene diversity and heterozygosity revealed substantial genetic diversity among the populations. The first three principal components explained about 61.05% of the total variance indicating trait under study contribute maximum of the variations. The model-based structure and PCoA analysis differentiated the population into two sub-populations. The genetic variation, as shown by analysis of molecular variance (AMOVA) indicates higher variability within population than among population in the analyzed set. Further, the AMMI stability analysis identified five promising accessions. Based on the multi-trait stability index, combining all the morphological traits together, IC37275, IC26592, IC13139, IC36919, and IC26606 were identified with a selection efficiency of 20%. Overall, the study revealed deep insights into genetic diversity, population differentiation vis-à-vis the identification of high yielding and stable accessions with higher nutritive values. Taking into account the nutritional values with yield and stability, the following four accessions namely IC16550, IC26586, Shimla B-1, and Local teethey were identified as most promising and thus exhibit a great potential to be utilized in buckwheat improvement programs.
Inhibition of a K9/K36 demethylase by an H3.3 point mutation found in paediatric glioblastoma
An array of oncogenic histone point mutations have been identified across a number of different cancer studies. It has been suggested that some of these mutant histones can exert their effects by inhibiting epigenetic writers. Here, we report that the H3.3 G34R (glycine to arginine) substitution mutation, found in paediatric gliomas, causes widespread changes in H3K9me3 and H3K36me3 by interfering with the KDM4 family of K9/K36 demethylases. Expression of a targeted single-copy of H3.3 G34R at endogenous levels induced chromatin alterations that were comparable to a KDM4 A/B/C triple-knockout. We find that H3.3 G34R preferentially binds KDM4 while simultaneously inhibiting its enzymatic activity, demonstrating that histone mutations can act through inhibition of epigenetic erasers. These results suggest that histone point mutations can exert their effects through interactions with a range of epigenetic readers, writers and erasers. Recent studies have identified a number of oncogenic histone point mutations in different cancers. Here the authors provide evidence that H3.3 G34R substitution mutation, which is found in paediatric gliomas, causes changes in H3K9me3 and H3K36me3 by interfering with the KDM4 family of K9/K36 demethylases.
De novo assembly, transcriptome characterization and marker discovery in Indian major carp, Labeo rohita through pyrosequencing
Labeo rohita, one of the Indian major carps, is the most popular culture species in Indian subcontinent due to its consumer preference and delicacy. A selective breeding program for harvest body weight has resulted in an average genetic gain of 17% per generation. Transcriptome resource for this species is scanty. Here, we have characterized the liver and muscle transcriptomes of rohu using Roche 454 GS-FLX next generation sequencing platform. In total, 1.2 million reads were generated, de novo assembly and clustering resulted in 4171 transcripts. Out of these, 4171 had significant blast hit against NCBI nr database, and 2130 transcripts were successfully annotated. In total, 289 SSRs were identified with an identification rate of 5.8%, and dinucleotide repeat motifs were observed to be the most abundant SSRs. Further, 2231 putative SNPs were identified with high confidence. Validation of eight putative SNPs using Sanger sequencing resulted in 100% true SNPs. Significant allelic imbalance of M1, M4 and M5 loci between growth selected and control individual were observed. Furthermore, 13 transcription factors were identified in the present study belonging to six different transcription factor families. The present study demonstrated the utility of RNAseq to develop genomics resources in non-model fish species, and the marker resources developed would support the genetic improvement program of this species.
Application of grey correlation-based EDAS method for parametric optimization of non-traditional machining processes
Higher dimensional accuracy along with better surface finish of various advanced engineering materials has turned out to be the prime desideratum for the presentday manufacturing industries. To this end, Non-Traditional Machining (NTM) processes have become quite popular because of their ability to produce intricate shape geometries on diverse difficult-to-machine materials. To allow these processes to operate at their fullest capability, it is often recommended to set their different input parameters at optimal levels. Thus, in this paper, a new technique combining grey correlation method with evaluation based on distance from average solution is applied for simultaneous optimization of three NTM processes, i.e., photochemical machining process, laser-assisted jet electrochemical machining process, and abrasive water jet drilling process. The derived optimal parametric combinations outperform those as identified by other popular multi-objective optimization techniques with respect to the considered response values. The results of analysis of variance also identify the most influencing parameters for the said NTM processes. Finally, the developed surface plots would help the process engineers investigate the effects of different NTM process parameters on the corresponding grey appraisal scores.