Search

The target of rapamycin (TOR) protein phosphorylates its downstream effector p70kDa ribosomal protein S6 kinases (S6K1) for ribosome biogenesis and translation initiation in eukaryotes. However, the molecular mechanism of TOR-S6K1-ribosomal protein (RP) signaling is not well understood in plants. In the present study, we report the transcriptional upregulation of ribosomal protein large and small subunit (RPL and RPS) genes in the previously established TOR overexpressing transgenic lines of rice (in Oryza sativa ssp. indica, variety BPT-5204, TR-2.24 and TR-15.1) and of Arabidopsis thaliana (in Col 0 ecotype, ATR-1.4.27 and ATR-3.7.32). The mRNA levels of RP genes from this study were compared with those previously available in transcriptomic datasets on the expression of RPs in relation to TOR inhibitor and in the TOR-RNAi lines of Arabidopsis thaliana. We further analyzed TOR activity, i.e., S6K1 phosphorylation in SALK lines of Arabidopsis with mutation in rpl6, rpl18, rpl23, rpl24 and rps28C, where the rpl18 mutant showed inactivation of S6K1 phosphorylation. We also predicted similar putative Ser/Thr phosphorylation sites for ribosomal S6 kinases (RSKs) in the RPs of Oryza sativa ssp. indica and Arabidopsis thaliana. The findings of this study indicate that the TOR pathway is possibly interlinked in a cyclic manner via the phosphorylation of S6K1 as a modulatory step for the regulation of RP function to switch ‘on’/‘off’ the translational regulation for balanced plant growth.

The yellow stem borer (YSB), Scirpophaga incertulas, is a prominent pest in rice cultivation causing serious yield losses. The larval stage is an important stage in YSB, responsible for maximum infestation. However, limited knowledge exists on the biology and mechanisms underlying the growth and differentiation of YSB. To understand and identify the genes involved in YSB development and infestation, so as to design pest control strategies, we performed de novo transcriptome analysis at the first, third, fifth, and seventh larval developmental stages employing Illumina Hi-seq. High-quality reads (HQR) of ∼229 Mb were assembled into 24,775 transcripts with an average size of 1485 bp. Genes associated with various metabolic processes, i.e., detoxification mechanism [CYP450, GSTs, and carboxylesterases (CarEs)], RNA interference (RNAi) machinery (Dcr-1, Dcr-2, Ago-1, Ago-2, Sid-1, Sid-2, Sid-3, and Sid-1-related gene), chemoreception (CSPs, GRs, OBPs, and ORs), and regulators [transcription factors (TFs) and hormones] were differentially regulated during the developmental stages. Identification of stage-specific transcripts made it possible to determine the essential processes of larval development. Comparative transcriptome analysis revealed that YSB has not evolved much with respect to the detoxification mechanism, but showed the presence of distinct RNAi machinery. The presence of strong specific visual recognition coupled with chemosensory mechanisms supports the monophagous nature of YSB. Designed expressed sequenced tags-simple-sequence repeats (EST-SSRs) will facilitate accurate estimation of the genetic diversity of YSB. This is the first report on characterization of the YSB transcriptome and the identification of genes involved in key processes, which will help researchers and industry to devise novel pest control strategies. This study also opens up a new avenue to develop next-generation resistant rice using RNAi or genome editing approaches.

North-East (NE) India, the probable origin of rice has diverse genetic resources. Many rice landraces of NE India were not yet characterized for blast resistance. A set of 232 landraces of NE India, were screened for field resistance at two different hotspots of rice blast, viz., IIRR-UBN, Hyderabad and ICAR-NEH, Manipur in two consecutive seasons. The phenotypic evaluation as well as gene profiling for 12 major blast resistance genes (Pitp, Pi33, Pi54, Pib, Pi20, Pi38, Pita2, Pi1, Piz, Pi9, Pizt, and Pi40) with linked as well as gene-specific markers, identified 84 resistant landraces possessing different gene(s) either in singly or in combinations and also identified seven resistant landraces which do not have the tested genes, indicating the valuable genetic resources for blast resistance. To understand the molecular diversity existing in the population, distance and model based analysis were performed using 120 SSR markers. Results of both analyses are highly correlated by forming two distinct subgroups and the existence of high diversity (24.9% among the subgroups; 75.1% among individuals of each subgroup) was observed. To practically utilize the diversity in the breeding program, a robust core set having an efficiency index of 0.82 which consists of 33 landraces were identified through data of molecular, blast phenotyping, and important agro-morphological traits. The association of eight novel SSR markers for important agronomic traits which includes leaf and neck blast resistance was determined using genome-wide association analysis. The current study focuses on identifying novel resources having field resistance to blast as well as markers which can be explored in rice improvement programs. It also entails the development of a core set which can aid in representing the entire diversity for efficiently harnessing its properties to broaden the gene pool of rice.

The yellow stem borer (YSB), Scirpophaga incertulas, is a prominent pest in rice cultivation causing serious yield losses. The larval stage is an important stage in YSB, responsible for maximum infestation. However, limited knowledge exists on the biology and mechanisms underlying the growth and differentiation of YSB. To understand and identify the genes involved in YSB development and infestation, so as to design pest control strategies, we performed de novo transcriptome analysis at the first, third, fifth, and seventh larval developmental stages employing Illumina Hi-seq. High-quality reads (HQR) of ~229 Mb were assembled into 24,775 transcripts with an average size of 1485 bp. Genes associated with various metabolic processes, i.e., detoxification mechanism [CYP450, GSTs, and carboxylesterases (CarEs)], RNA interference (RNAi) machinery (Dcr-1, Dcr-2, Ago-1, Ago-2, Sid-1, Sid-2, Sid-3, and Sid-1-related gene), chemoreception (CSPs, GRs, OBPs, and ORs), and regulators [transcription factors (TFs) and hormones] were differentially regulated during the developmental stages. Identification of stage-specific transcripts made it possible to determine the essential processes of larval development. Comparative transcriptome analysis revealed that YSB has not evolved much with respect to the detoxification mechanism, but showed the presence of distinct RNAi machinery. The presence of strong specific visual recognition coupled with chemosensory mechanisms supports the monophagous nature of YSB. Designed expressed sequenced tags-simple-sequence repeats (EST-SSRs) will facilitate accurate estimation of the genetic diversity of YSB. This is the first report on characterization of the YSB transcriptome and the identification of genes involved in key processes, which will help researchers and industry to devise novel pest control strategies. This study also opens up a new avenue to develop next-generation resistant rice using RNAi or genome editing approaches. [ABSTRACT FROM AUTHOR]

Nucleotide binding site leucine rich repeat (NBS-LRR) gene encoding proteins are the major biotic stress resistance genes of rice and Arabidopsis thaliana. Upstream sequences of 206 entire NBS-LRR genes of Arabidopsis and 120 genes of rice were analyzed with three highly reliable motif prediction tools for enhanced accuracy of prediction and characterization of potential transcription factor binding motifs (TFBMs). A total of 36 and 30 novel, strong TFBMs were discovered from NBS-LRR genes of rice and A. thaliana, respectively. All the motifs identifed in these sequences were analyzed for their positional conservation and the possible motif network associations were also identifed. Further, the probability of the presence of motifs in these NBS-LRR genes were validated and statistically tested. Although Arabidopsis NBS-LRR sequences showed 76.3% similarity with rice sequences at motif level, the analysis revealed that rice sequences have many unique TFBMs and are more evolved in gene expression mechanisms. The study also provided a list of novel candidate motifs for these genes, which will be a good resource for experimental validation. A novel strategy of prediction of gene expression based on motif arrangement was also demonstrated in this study. The findings of this study, such as the motifs' positional conservation, architecture, etc. offered new biological insights into the role of TFBMs in the regulation of resistance genes. [ABSTRACT FROM AUTHOR]

Identification of full length genes along with upstream regulatory elements is important to understand its expression. Here, we report preparation of high titre genomic library and identification of a genomic clone containing Pi-k h gene with its complete upstream and downstream sequences from the rice blast resistant line Tetep. Structural analysis of protein revealed that Pi-k h has a central nucleotide binding site domain, leucine-rich repeats domain and a unique zinc-finger domain. Comparative analysis of Pi-k h protein sequence showed 64% and 45% similarity with the protein sequences of rice blast resistance genes Pi-b and Pi-ta, respectively. [ABSTRACT FROM AUTHOR]

Rice blast is a continuous threat in rice ecosystems across the globe; its dynamics is becoming complex in the changing climatic conditions. Host resistance is still a viable option; hence, the exploration of resistance genes and their novel alleles is indispensable. The majority of the blast resistance genes belong to nucleotide-binding site and leucine-rich repeat (LRR) domain. In the present study, diverse LRR alleles of five major blast resistance genes (Pi2, Pi9, Pib, Pita, and Pi37) were cloned from 13 different Oryza species to determine the nucleotide diversity as well as to identify the single nucleotide polymorphisms, InDels, conserved domains, and protein functional sites. Although Pi9 and Pi2 are homologous genes, significant nucleotide variations and variants in the motifs distribution were observed. Among the five genes, Pi37 showed the highest nucleotide diversity and Pita showed the least diversity. The phylogenetic groups of alleles were correlated with the identified haplotypes. The motif (xxLxLxx) was present among all the alleles of blast R gene sequences across various Oryza species, indicating its importance. The appearance of post-translational modification sites in the protein sequences of these alleles also indicates its nature of involvement in host-pathogen interactions. The present study offers clues in further understanding the molecular evolution of the LRR domain of resistance genes, which is a key determinant of host-pathogen interactions. [ABSTRACT FROM AUTHOR]

Background: The risk of recurrent adverse birth outcomes has been reported worldwide, but there are limited estimates of these risks by social subgroups such as race and ethnicity in the United States. We assessed racial and ethnic disparities in the risk of recurrent adverse birth outcomes, including preterm birth, low birthweight, fetal growth restriction, small for gestational age, stillbirth, and neonatal mortality in the U.S., Methods: We searched MEDLINE, CINAHL Complete, Web of Science, and Scopus from the date of inception to April 5, 2022. We identified 3,540 articles for a title and abstract review, of which 80 were selected for full-text review. Studies were included if they focused on the recurrence of any of the six outcomes listed in the objectives. Study quality was assessed using the NIH Study Quality Assessment Tool. Heterogeneity across studies was too large for meta-analysis, but race and ethnicity-stratified estimates and tests for homogeneity results were reported., Results: Six studies on recurrent preterm birth and small for gestational age were included. Pooled comparisons showed a higher risk of recurrent preterm birth and small for gestational age for all women. Stratified race comparisons showed a higher but heterogeneous risk of recurrence of preterm birth across Black and White women. Relative risks of recurrent preterm birth ranged from 2.02 [1.94, 2.11] to 2.86 [2.40, 3.39] for Black women and from 3.23 [3.07, 3.39] to 3.92 [3.35, 4.59] for White women. The evidence was weak for race and ethnicity stratification for Hispanic and Asian women for both outcomes., Conclusions: Disparities exist in the recurrence of preterm birth, and race/ethnicity-concordant comparisons suggest race is an effect modifier for recurrent preterm birth for Black and White women. Due to the small number of studies, no conclusions could be made for small for gestational age or Hispanic and Asian groups. The results pose new research areas to better understand race-based differences in recurrent adverse birth outcomes., (© 2024. The Author(s).)

In pancreatic ductal adenocarcinoma (PDAC), glutamine is a critical nutrient that drives a wide array of metabolic and biosynthetic processes that support tumor growth. Here, we elucidate how 6-diazo-5-oxo-L-norleucine (DON), a glutamine antagonist that broadly inhibits glutamine metabolism, blocks PDAC tumor growth and metastasis. We find that DON significantly reduces asparagine production by inhibiting asparagine synthetase (ASNS), and that the effects of DON are rescued by asparagine. As a metabolic adaptation, PDAC cells upregulate ASNS expression in response to DON, and we show that ASNS levels are inversely correlated with DON efficacy. We also show that L-asparaginase (ASNase) synergizes with DON to affect the viability of PDAC cells, and that DON and ASNase combination therapy has a significant impact on metastasis. These results shed light on the mechanisms that drive the effects of glutamine mimicry and point to the utility of cotargeting adaptive responses to control PDAC progression., (© 2023. The Author(s), under exclusive licence to Springer Nature America, Inc.)

Purpose: The RefleXion X1 is a novel radiotherapy machine designed for image-guided radiotherapy (IGRT) and biology-guided radiotherapy (BgRT). Its treatment planning system (TPS) generates IMRT and SBRT plans for a 6MV-FFF beam delivered axially via 50 firing positions with the couch advancing every 2.1 mm. The purpose of this work is to report the TPS commissioning results for the first clinical installation of RefleXion™ X1., Methods: CT images of multiple phantoms were imported into the RefleXion TPS to evaluate the accuracy of data transfer, anatomical modeling, plan evaluation, and dose calculation. Comparisons were made between the X1, Eclipse™, and MIM™. Dosimetric parameters for open static fields were evaluated in water and heterogeneous slab phantoms. Representative clinical IMRT and SBRT cases were planned and verified with ion chamber, film, and ArcCHECK @ measurements. The agreement between TPS and measurements for various clinical plans was evaluated using Gamma analysis with a criterion of 3%/2 mm for ArcCHECK @ and film. End-to-end (E2E) testing was performed using anthropomorphic head and lung phantoms., Results: The average difference between the TPS-reported and known HU values was -1.4 ± 6.0 HU. For static fields, the agreements between the TPS-calculated and measured PDD 10 , crossline profiles, and inline profiles (FWHM) were within 1.5%, 1.3%, and 0.5 mm, respectively. Measured output factors agreed with the TPS within 1.3%. Measured and calculated dose for static fields in heterogeneous phantoms agreed within 2.5%. The ArcCHECK @ mean absolute Gamma passing rate was 96.4% ± 3.4% for TG 119 and TG 244 plans and 97.8% ± 3.6% for the 21 clinical plans. E2E film analysis showed 0.8 mm total targeting error for isocentric and 1.1 mm for off-axis treatments., Conclusions: The TPS commissioning results of the RefleXion X1 TPS were within the tolerances specified by AAPM TG 53, MPPG 5.a, TG 119, and TG 148. A subset of the commissioning tests has been identified as baseline data for an ongoing QA program., (© 2022 The Authors. Journal of Applied Clinical Medical Physics published by Wiley Periodicals, LLC on behalf of The American Association of Physicists in Medicine.)

Background: Public health nurses (PHNs) engage in home visiting services and documentation of care services for at-risk clients. To increase efficiency and decrease documentation burden, it would be useful for PHNs to identify critical data elements most associated with patient care priorities and outcomes. Machine learning techniques can aid in retrospective identification of critical data elements., Objective: We used two different machine learning feature selection techniques of minimum redundancy-maximum relevance (mRMR) and LASSO (least absolute shrinkage and selection operator) and elastic net regularized generalized linear model (glmnet in R)., Methods: We demonstrated application of these techniques on the Omaha System database of 205 data elements (features) with a cohort of 756 family home visiting clients who received at least one visit from PHNs in a local Midwest public health agency. A dichotomous maternal risk index served as the outcome for feature selection., Application: Using mRMR as a feature selection technique, out of 206 features, 50 features were selected with scores greater than zero, and generalized linear model applied on the 50 features achieved highest accuracy of 86.2% on a held-out test set. Using glmnet as a feature selection technique and obtaining feature importance, 63 features had importance scores greater than zero, and generalized linear model applied on them achieved the highest accuracy of 95.5% on a held-out test set., Discussion: Feature selection techniques show promise toward reducing public health nursing documentation burden by identifying the most critical data elements needed to predict risk status. Further studies to refine the process of feature selection can aid in informing PHNs' focus on client-specific and targeted interventions in the delivery of care.

As new data sources including individuals' strengths emerge in electronic health records, such data provide whole-person oriented information to generate integrated knowledge for person-centered practice. The purpose of this study is to describe older adults' strengths and problems within a wellbeing context documented by the Omaha System. The Wellbeing Model is employed as a conceptual framework for wellbeing and is operationalized by the Omaha System Problem Classification Scheme. This study has a retrospective, descriptive design using de-identified EHR data of wellbeing assessments including problems, strengths, and signs/symptoms for a convenience sample of 440 assisted-living residents in a Midwest metropolitan area. Descriptive statistics and data visualization were used to summarize and display strength and signs/symptom attributes within wellbeing contexts. The study reveals cutting-edge knowledge regarding older adults' strengths and wellbeing, and creates a platform for further research use of a strength-based ontology in clinical practice and electronic system of documentation.

Background: Dermatological conditions have an impact on psychology of the patients. There is a dearth of studies regarding this field in Rural population of India., Aims and Objectives: The primary objective of this study is to evaluate the psychiatric morbidity in patients affected with Dermatological condition in a rural population and secondary objective is to assess the morbidity in dimensions of Depression Severity and the quality of life in the Emotional Sphere, Physical Symptoms, Psychosocial Functioning., Subjects and Methods: Seventy three rural patients were included in the study. PHQ9 and SKINDEX-29 was used to assess the psychiatric morbidity and quality of life. Statistical analysis was done using SPSS V 20. Chi-square test was used as a test of significance., Results: Significance has been found for duration of suffering from a dermatological condition and quality of life (p=0.03). Correlation has also been established between dermatological diagnosis with depression severity (p=0.004) or quality of life (p=0.004). In the sub scales of SKINDEX it was noted that overall dysfunction was notably more marked in Emotional Sphere and Psychosocial Functions than the Physical symptoms. Eczema was the most affected diagnosis in Skindex indicating a poor quality of life followed by psoriasis, Acne vulgaris and Seborrhoeic Dermatitis however, It was found that the majorly affected condition in depression severity was Psoriasis followed by Eczema, Acne Vulgaris and Seborrhoeic Dermatitis., Conclusion: There seems to be an increased morbidity among the rural population in depression severity and that of quality of life in terms of emotional sphere and psychosocial functioning.

Interleukin (IL)-11 is a cytokine with thrombopoietic activity that has been shown to increase plasma von Willebrand factor (vWf) in preliminary clinical studies. This led to further evaluation of the effect of recombinant human (rh)IL-11 on vWf and factor VIII (FVIII) secretion. In vitro, rhIL-11 did not increase vWf production by cultured endothelial cells, which suggests an indirect mechanism. Also, in vivo, plasma vWf was not elevated in mice shortly after a single intravenous (IV) bolus injection of 250 or 1000 microg/kg rhIL-11. The effect of continuous exposure to rhIL-11 was accessed by treating wild type mice for 7 consecutive days with subcutaneous 250 microg/kg/d rhIL-11. Platelet counts increased by 25% and 40% after 4 and 7 days, respectively. Plasma vWf and FVIII levels increased 2-fold after 4 and 7 days. Surprisingly, no effect of rhIL-11 on vWf or FVIII messenger RNA was observed, which suggests that the regulation by rhIL-11 occurs after transcription. No increase in soluble P-selectin was observed after rhIL-11 treatment, indicating that platelet activation is not the source of elevated vWf. Similarly to wild type mice, vWf heterozygous mice responded to rhIL-11 treatment by a significant increase in platelet counts and vWf and FVIII levels. Importantly, in vWf-deficient mice, rhIL-11 also induced a significant increase in FVIII independent of vWf and was able to reduce skin bleeding time. These results suggest that a clinical evaluation of the effects of rhIL-11-induced vWf/FVIII elevation in maintaining hemostasis in mild hemophilia A or von Willebrand disease would be worthwhile.