Tumor metastasis is the leading cause of death among breast cancer patients. PELP1 (proline, glutamic acid and leucine rich protein 1) is a nuclear receptor coregulator that is upregulated during ...breast cancer progression to metastasis and is an independent prognostic predictor of shorter survival of breast cancer patients. Here, we show that PELP1 modulates expression of metastasis-influencing microRNAs (miRs) to promote cancer metastasis. Whole genome miR array analysis using PELP1-overexpressing and PELP1-underexpressing model cells revealed that miR-200 and miR-141 levels inversely correlated with PELP1 expression. Consistent with this, PELP1 knockdown resulted in lower expression of miR-200a target genes ZEB1 and ZEB2. PELP1 knockdown significantly reduced tumor growth and metastasis compared with parental cells in an orthotopic xenograft tumor model. Furthermore, re-introduction of miR-200a and miR-141 mimetics into PELP1-overexpressing cells reversed PELP1 target gene expression, decreased PELP1-driven migration/invasion in vitro and significantly reduced in vivo metastatic potential in a preclinical model of experimental metastasis. Our results demonstrated that PELP1 binds to miR-200a and miR-141 promoters and regulates their expression by recruiting chromatin modifier histone deacetylase 2 (HDAC2) as revealed by chromatin immunoprecipitation, small interfering RNA and HDAC inhibitor assays. Taken together, our results suggest that PELP1 regulates tumor metastasis by controlling the expression and functions of the tumor metastasis suppressors miR-200a and miR-141.
The North-Eastern region (NER) of India, comprising of Arunachal Pradesh, Assam, Manipur, Meghalaya, Mizoram, Nagaland and Tripura, is a hot spot for genetic diversity and the most probable origin of ...rice. North-east rice collections are known to possess various agronomically important traits like biotic and abiotic stress tolerance, unique grain and cooking quality. The genetic diversity and associated population structure of 6,984 rice accessions, originating from NER, were assessed using 36 genome wide unlinked single nucleotide polymorphism (SNP) markers distributed across the 12 rice chromosomes. All of the 36 SNP loci were polymorphic and bi-allelic, contained five types of base substitutions and together produced nine types of alleles. The polymorphic information content (PIC) ranged from 0.004 for Tripura to 0.375 for Manipur and major allele frequency ranged from 0.50 for Assam to 0.99 for Tripura. Heterozygosity ranged from 0.002 in Nagaland to 0.42 in Mizoram and gene diversity ranged from 0.006 in Arunachal Pradesh to 0.50 in Manipur. The genetic relatedness among the rice accessions was evaluated using an unrooted phylogenetic tree analysis, which grouped all accessions into three major clusters. For determining population structure, populations K = 1 to K = 20 were tested and population K = 3 was present in all the states, with the exception of Meghalaya and Manipur where, K = 5 and K = 4 populations were present, respectively. Principal Coordinate Analysis (PCoA) showed that accessions were distributed according to their population structure. AMOVA analysis showed that, maximum diversity was partitioned at the individual accession level (73% for Nagaland, 58% for Arunachal Pradesh and 57% for Tripura). Using POWERCORE software, a core set of 701 accessions was obtained, which accounted for approximately 10% of the total NE India collections, representing 99.9% of the allelic diversity. The rice core set developed will be a valuable resource for future genomic studies and crop improvement strategies.
Aging into later life is often accompanied by social disconnection, anxiety, and sadness. Negative emotions are self-focused states with detrimental effects on aging and longevity. Awe-a positive ...emotion elicited when in the presence of vast things not immediately understood-reduces self-focus, promotes social connection, and fosters prosocial actions by encouraging a "small self." We investigated the emotional benefits of a novel "awe walk" intervention in healthy older adults. Sixty participants took weekly 15-min outdoor walks for 8 weeks; participants were randomly assigned to an awe walk group, which oriented them to experience awe during their walks, or to a control walk group. Participants took photographs of themselves during each walk and rated their emotional experience. Each day, they reported on their daily emotional experience outside of the walk context. Participants also completed pre- and postintervention measures of anxiety, depression, and life satisfaction. Compared with participants who took control walks, those who took awe walks experienced greater awe during their walks and exhibited an increasingly "small self" in their photographs over time. They reported greater joy and prosocial positive emotions during their walks and displayed increasing smile intensity over the study. Outside of the walk context, participants who took awe walks reported greater increases in daily prosocial positive emotions and greater decreases in daily distress over time. Postintervention anxiety, depression, and life satisfaction did not change from baseline in either group. These results suggest cultivating awe enhances positive emotions that foster social connection and diminishes negative emotions that hasten decline.
In the present study, a total of 53 promising salt-tolerant genotypes were tested across 18 salt-affected diverse locations for three years. An attempt was made to identify ideal test locations and ...mega-environments using GGE biplot analysis. The CSSRI sodic environment was the most discriminating location in individual years as well as over the years and could be used to screen out unstable and salt-sensitive genotypes. Genotypes CSR36, CSR-2K-219, and CSR-2K-262 were found ideal across years. Overall, Genotypes CSR-2K-219, CSR-2K-262, and CSR-2K-242 were found superior and stable among all genotypes with higher mean yields. Different sets of genotypes emerged as winners in saline soils but not in sodic soils; however, Genotype CSR-2K-262 was the only genotype that was best under both saline and alkaline environments over the years. The lack of repeatable associations among locations and repeatable mega-environment groupings indicated the complexity of soil salinity. Hence, a multi-location and multi-year evaluation is indispensable for evaluating the test sites as well as identifying genotypes with consistently specific and wider adaptation to particular agro-climatic zones. The genotypes identified in the present study could be used for commercial cultivation across edaphically challenged areas for sustainable production.
A central characteristic of living beings is the ability to learn from and respond to their environment leading to habit formation and decision making. This behavior, known as habituation, is ...universal among all forms of life with a central nervous system, and is also observed in single-cell organisms that do not possess a brain. Here, we report the discovery of habituation-based plasticity utilizing a perovskite quantum system by dynamical modulation of electron localization. Microscopic mechanisms and pathways that enable this organismic collective charge-lattice interaction are elucidated by first-principles theory, synchrotron investigations, ab initio molecular dynamics simulations, and in situ environmental breathing studies. We implement a learning algorithm inspired by the conductance relaxation behavior of perovskites that naturally incorporates habituation, and demonstrate learning to forget: a key feature of animal and human brains. Incorporating this elementary skill in learning boosts the capability of neural computing in a sequential, dynamic environment.Habituation is a learning mechanism that enables control over forgetting and learning. Zuo, Panda et al., demonstrate adaptive synaptic plasticity in SmNiO
perovskites to address catastrophic forgetting in a dynamic learning environment via hydrogen-induced electron localization.
Simple sequence repeat (SSR) and Single Nucleotide Polymorphic (SNP), the two most robust markers for identifying rice varieties were compared for assessment of genetic diversity and population ...structure. Total 375 varieties of rice from various regions of India archived at the Indian National GeneBank, NBPGR, New Delhi, were analyzed using thirty six genetic markers, each of hypervariable SSR (HvSSR) and SNP which were distributed across 12 rice chromosomes. A total of 80 alleles were amplified with the SSR markers with an average of 2.22 alleles per locus whereas, 72 alleles were amplified with SNP markers. Polymorphic information content (PIC) values for HvSSR ranged from 0.04 to 0.5 with an average of 0.25. In the case of SNP markers, PIC values ranged from 0.03 to 0.37 with an average of 0.23. Genetic relatedness among the varieties was studied; utilizing an unrooted tree all the genotypes were grouped into three major clusters with both SSR and SNP markers. Analysis of molecular variance (AMOVA) indicated that maximum diversity was partitioned between and within individual level but not between populations. Principal coordinate analysis (PCoA) with SSR markers showed that genotypes were uniformly distributed across the two axes with 13.33% of cumulative variation whereas, in case of SNP markers varieties were grouped into three broad groups across two axes with 45.20% of cumulative variation. Population structure were tested using K values from 1 to 20, but there was no clear population structure, therefore Ln(PD) derived Δk was plotted against the K to determine the number of populations. In case of SSR maximum Δk was at K=5 whereas, in case of SNP maximum Δk was found at K=15, suggesting that resolution of population was higher with SNP markers, but SSR were more efficient for diversity analysis.
Large area X-ray propositional counter (LAXPC) instrument on
AstroSat
is aimed at providing high time resolution X-ray observations in 3–80 keV energy band with moderate energy resolution. To achieve ...large collecting area, a cluster of three co-aligned identical LAXPC detectors, is used to realize an effective area in access of
∼
6000
cm
2
at 15 keV. The large detection volume of the LAXPC detectors, filled with xenon gas at
∼
2 atmosphere pressure, results in detection efficiency greater than 50%, above 30 keV. In this article, we present salient features of the LAXPC detectors, their testing and characterization in the laboratory prior to launch and calibration in the orbit. Some preliminary results on timing and spectral characteristics of a few X-ray binaries and other type of sources, are briefly discussed to demonstrate that the LAXPC instrument is performing as planned in the orbit.
The hemocompatibility of plasma-treated, silicon-incorporated, diamond-like carbon (Si-DLC) films was investigated. Si-DLC films with a Si concentration of 2at.% were prepared on Si (100) or Nitinol ...substrates using a capacitively coupled radiofrequency plasma-assisted chemical vapor deposition method using a mixed gas of benzene (C(6)H(6)) and diluted silane (SiH(4):H(2)=10:90). The Si-DLC films were then treated with O(2), CF(4) or N(2) glow discharge for surface modification. The plasma treatment revealed an intimate relationship between the polar component of the surface energy and its hemocompatibility. All in vitro characterizations, i.e. protein absorption behavior, activated partial thromboplastin time measurement and platelet adhesion behavior, showed improved hemocompatibility of the N(2-)- or O(2)-plasma-treated surfaces where the polar component of the surface energy was significantly increased. Si-O or Si-N surface bonds played an important role in improving hemocompatibility, as observed in a model experiment. These results support the importance of a negatively charged polar component of the surface in inhibiting fibrinogen adsorption and platelet adhesion.
The aim of this study was to identify stable rice genotypes tolerant to a salt stress environment and to identify ideal mega-environments using AMMI (additive main effects and multiplicative ...interaction) stability model analysis. A total of 13 rice genotypes and three salt tolerance checks were evaluated across 13 salt stress locations (alkaline and saline) for the two kharif seasons of 2014 and 2015. Genotype CSR 36 (CHK3) was found to be the most ideal of those tested. Genotypes CHK2 (CST 27) and IR 87952-1-1-1-2-3-B (G05) were found to be the most stable, with above average yields. The check CSR 36 (CHK3) genotype was the best performer in the majority of the environments studied, followed by CSR 27 (CHK2) and IR 87952-1-1-1-2-3-B (G05) which were the best genotypes in the mega-environment consisting of 21 environments evaluated across stress locations and year combinations. Overall, the most promising genotype (IR 87952-1-1-1-2-3-B) had high mean yield and stability and could be used for commercial cultivation or used as donor for breeding programs across salt-affected soils. The genotypes GN13 (IR 87938-1-1-2-1-3-B) and GN11 (IR 87938-1-2-2-1-3-B) showed 60–80% yield advantage at specific salt stress locations, showing that these genotypes could be used for specific environments of salt-affected soils in India.
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