Themis regulates metabolic signaling and effector functions in CD4+ T cells by controlling NFAT nuclear translocation

10.1038/s41423-020-00578-4Cellular and Molecular Immunology1892249-226

Using natural language processing and machine learning to classify health literacy from secure messages: The ECLIPPSE study.

Limited health literacy is a barrier to optimal healthcare delivery and outcomes. Current measures requiring patients to self-report limitations are time-consuming and may be considered intrusive by some. This makes widespread classification of patient health literacy challenging. The objective of this study was to develop and validate "literacy profiles" as automated indicators of patients' health literacy to facilitate a non-intrusive, economic and more comprehensive characterization of health literacy among a health care delivery system's membership. To this end, three literacy profiles were generated based on natural language processing (combining computational linguistics and machine learning) using a sample of 283,216 secure messages sent from 6,941 patients to their primary care physicians. All patients were participants in Kaiser Permanente Northern California's DISTANCE Study. Performance of the three literacy profiles were compared against a gold standard of patient self-reported health literacy. Associations were analyzed between each literacy profile and patient demographics, health outcomes and healthcare utilization. T-tests were used for numeric data such as A1C, Charlson comorbidity index and healthcare utilization rates, and chi-square tests for categorical data such as sex, race, poor adherence and severe hypoglycemia. Literacy profiles varied in their test characteristics, with C-statistics ranging from 0.61-0.74. Relations between literacy profiles and health outcomes revealed patterns consistent with previous health literacy research: patients identified via literacy profiles indicative of limited health literacy: (a) were older and more likely of minority status; (b) had poorer medication adherence and glycemic control; and (c) exhibited higher rates of hypoglycemia, comorbidities and healthcare utilization. This represents the first successful attempt to employ natural language processing to estimate health literacy. Literacy profiles can offer an automated and economical way to identify patients with limited health literacy and greater vulnerability to poor health outcomes

A study of CCD8 genes/proteins in seven monocots and eight dicots.

In plants, the enzyme CCD8 (carotenoid cleavage dioxygenase 8) is involved in the synthesis of an important hormone, strigolactone, and therefore, plays an important role in controlling growth and development. Using cDNA and protein sequence derived from the gene ZmCCD8 from maize, we identified putative orthologs of the gene encoding CCD8 in six other monocots and eight dicots; the sequence similarity ranged from 52-75.9% at the gene level and 60.9-93.7% at the protein level. The average length of the gene was ~3.3 kb (range: 2.08 to 3.98 kb), although the number of introns within the genes differed (4 or 5 in dicots and 3 or 4 in monocots, except in T. urartu with 6 introns). Several cis-acting regulatory elements were identified in the promoters of CCD8 genes, which are known to respond to biotic and abiotic stresses. The N-terminal end (up to ~70 amino acids) of CCD8 proteins was highly variable due to insertions, deletions and mismatches. The variation in genes and proteins were particularly conspicuous in T. urartu and Ae. tauschii among the monocots and A. thaliana and P. persica among the dicots. In CCD8 proteins, 12 motifs were also identified, of which 6 were novel; 4 of these novel motifs occurred in all the 15 species. The 3D structures of proteins had the characteristic features of the related enzyme apocarotenoid oxygenase (ACO) of Synechocystis (a representative of cyanobacteria). The results of qRT-PCR in wheat revealed that under phosphorous (P)-starved condition (relative to expression under optimum P used as control), the expression of TaCCD8 genes increased ~37 fold in root tissue of the cultivar C306 and ~33 fold in shoot tissue of the cultivar HUW468 (the two cultivars differed in their P-use efficiency). This suggested that expression of TaCCD8 genes is genotype-dependent and tissue-specific and is regulated under different levels of P supply

Genome-wide identification and characterization of gene family for RWP-RK transcription factors in wheat (Triticum aestivum L.).

RWP-RKs represent a small family of transcription factors (TFs) that are unique to plants and function particularly under conditions of nitrogen starvation. These RWP-RKs have been classified in two sub-families, NLPs (NIN-like proteins) and RKDs (RWP-RK domain proteins). NLPs regulate tissue-specific expression of genes involved in nitrogen use efficiency (NUE) and RKDs regulate expression of genes involved in gametogenesis/embryogenesis. During the present study, using in silico approach, 37 wheat RWP-RK genes were identified, which included 18 TaNLPs (2865 to 7340 bp with 4/5 exons), distributed on 15 chromosomes from 5 homoeologous groups (with two genes each on 4B,4D and 5A) and 19 TaRKDs (1064 to 5768 bp with 1 to 6 exons) distributed on 12 chromosomes from 4 homoeologous groups (except groups 1, 4 and 5); 2-3 splice variants were also available in 9 of the 37 genes. Sixteen (16) of these genes also carried 24 SSRs (simple sequence repeats), while 11 genes had targets for 13 different miRNAs. At the protein level, MD simulation analysis suggested their interaction with nitrate-ions. Significant differences were observed in the expression of only two (TaNLP1 and TaNLP2) of the nine representative genes that were used for in silico expression analysis under varying levels of N at post-anthesis stage (data for other genes was not available for in silico expression analysis). Differences in expression were also observed during qRT-PCR, when expression of four representative genes (TaNLP2, TaNLP7, TaRKD6 and TaRKD9) was examined in roots and shoots of seedlings (under different conditions of N supply) in two contrasting genotypes which differed in NUE (C306 with low NUE and HUW468 with high NUE). These four genes for qRT-PCR were selected on the basis of previous literature, level of homology and the level of expression (in silico study). In particular, the TaNLP7 gene showed significant up-regulation in the roots and shoots of HUW468 (with higher NUE) during N-starvation; this gene has already been characterized in Arabidopsis and tobacco, and is known to be involved in nitrate-signal transduction pathway