Implementing Cancer Registry Data With the PCORnet Common Data Model: The Greater Plains Collaborative Experience.

Purpose: Electronic health records (EHRs) comprise a rich source of real-world data for cancer studies, but they often lack critical structured data elements such as diagnosis date and disease stage. Fortunately, such concepts are available from hospital cancer registries. We describe experiences from integrating cancer registry data with EHR and billing data in an interoperable data model across a multisite clinical research network.

Medication Reconciliation during Transitions of Care Across Institutions: A Quantitative Analysis of Challenges and Opportunities.

Objective: Medication discrepancies between clinical systems may pose a patient safety hazard. In this paper, we identify challenges and quantify medication discrepancies across transitions of care.

Methods: We used structured clinical data and free-text hospital discharge summaries to compare active medications' lists at four time points: preadmission (outpatient), at-admission (inpatient), at-discharge (inpatient), and postdischarge (outpatient).

Rate of change in investigational treatment options: An analysis of reports from a large precision oncology decision support effort.

Purpose: Genomic analysis of individual patients is now affordable, and therapies targeting specific molecular aberrations are being tested in clinical trials. Genomically-informed therapy is relevant to many clinical domains, but is particularly applicable to cancer treatment. However, even specialized clinicians need help to interpret genomic data, to navigate the complicated space of clinical trials, and to keep up with the rapidly expanding biomedical literature.

Over-expression of SINAL7 increases biomass and drought tolerance, and also delays senescence in Arabidopsis.

The seven in absentia like 7 gene (At5g37890, SINAL7) from Arabidopsis thaliana encodes a RING finger protein belonging to the SINA superfamily that possesses E3 ubiquitin-ligase activity. SINAL7 has the ability to self-ubiquitinate and to mono-ubiquitinate glyceraldehyde-3-P dehydrogenase 1 (GAPC1), suggesting a role for both proteins in a hypothetical signaling pathway in Arabidopsis. In this study, the in vivo effects of SINAL7 on plant physiology were examined by over-expressing SINAL7 in transgenic Arabidopsis plants.

Automated identification of molecular effects of drugs (AIMED).

Introduction: Genomic profiling information is frequently available to oncologists, enabling targeted cancer therapy. Because clinically relevant information is rapidly emerging in the literature and elsewhere, there is a need for informatics technologies to support targeted therapies. To this end, we have developed a system for Automated Identification of Molecular Effects of Drugs, to help biomedical scientists curate this literature to facilitate decision support.

The E3 ubiquitin-ligase SEVEN IN ABSENTIA like 7 mono-ubiquitinates glyceraldehyde-3-phosphate dehydrogenase 1 isoform in vitro and is required for its nuclear localization in Arabidopsis thaliana.

The E3 ubiquitin-protein ligases are associated to various processes such as cell cycle control and diverse developmental pathways. Arabidopsis thaliana SEVEN IN ABSENTIA like 7, which has ubiquitin ligase activity, is located in the nucleus and cytosol and is expressed at several stages in almost all plant tissues suggesting an important role in plant functions. However, the mechanism underlying the regulation of this protein is unknown.

Frataxin Is Localized to Both the Chloroplast and Mitochondrion and Is Involved in Chloroplast Fe-S Protein Function in Arabidopsis.

Frataxin plays a key role in eukaryotic cellular iron metabolism, particularly in mitochondrial heme and iron-sulfur (Fe-S) cluster biosynthesis. However, its precise role has yet to be elucidated. In this work, we studied the subcellular localization of Arabidopsis frataxin, AtFH, using confocal microscopy, and found a novel dual localization for this protein.

Characterization of the Arabidopsis thaliana E3 ubiquitin-ligase AtSINAL7 and identification of the ubiquitination sites.

Protein ubiquitination leading to degradation by the proteasome is an important mechanism in regulating key cellular functions. Protein ubiquitination is carried out by a three step process involving ubiquitin (Ub) activation by a E1 enzyme, the transfer of Ub to a protein E2, finally an ubiquitin ligase E3 catalyzes the transfer of the Ub peptide to an acceptor protein. The E3 component is responsible for the specific recognition of the target, making the unveiling of E3 components essential to understand the mechanisms regulating fundamental cell processes through the protein degradation pathways.

The nucleocytoplasmic conflict, a driving force for the emergence of plant organellar RNA editing.

RNA editing challenges the central dogma of molecular biology by changing the genetic information at the transcript level. In plant organelles, RNAs are modified by deamination of some specific cytosine residues, but the origin of this process remains puzzling. Different from the generally accepted neutral model to explain the emergence of RNA editing in plant organelles, we propose a new hypothesis based on the nucleocytoplasmic conflict theory.

Mitochondrial dysfunction affects chloroplast functions.

The transcriptomic response of A9:u-ATP9 and apetala3:u-ATP9 lines carrying a mitochondrial dysfunction in flower tissues has been characterized. Both lines showed an alteration in the transcription of several genes involved in carbon and nitrogen metabolism, stress responses, transcription factors and DNA binding proteins. Interestingly, several transcripts of photosynthetic-related genes were also affected in their expression such as the mRNAs encoding for chlorophyllase, chlorophyll binding proteins and a PSII.

RNA editing restores critical domains of a group I intron in fern mitochondria.

In the leptosporangiate fern Osmunda regalis, cox1 gene is disrupted by a 1071-nucleotide-long group I intron that is homologous to the Marchantia polymorpha cox1 intron 4 (cox1i395g1). This intron, which shares 89% sequence identity with its bryophyte counterpart, lost the capacity to encode for a maturase due to insertion/deletion mutations. The cox1 coding region is interrupted by a stop codon in both exons.

The RNA editing pattern of cox2 mRNA is affected by point mutations in plant mitochondria.

The mitochondrial transcriptome from land plants undergoes hundreds of specific C-to-U changes by RNA editing. These events are important since most of them occur in the coding region of mRNAs. One challenging question is to understand the mechanism of recognition of a selected C residue (editing sites) on the transcript.

The mitochondrial protein frataxin is essential for heme biosynthesis in plants.

Frataxin, a conserved mitochondrial protein implicated in cellular iron homeostasis, has been involved as the iron chaperone that delivers iron for the Fe-S cluster and heme biosynthesis. However, its role in iron metabolism remains unclear, especially in photosynthetic organisms. In previous work, we found that frataxin deficiency in Arabidopsis results in decreased activity of the mitochondrial Fe-S proteins aconitase and succinate dehydrogenase, despite the increased expression of the respective genes, indicating an important role for Arabidopsis thaliana frataxin homolog (AtFH).

Effect of mitochondrial dysfunction on carbon metabolism and gene expression in flower tissues of Arabidopsis thaliana.

We characterized the transcriptomic response of transgenic plants carrying a mitochondrial dysfunction induced by the expression of the unedited form of the ATP synthase subunit 9. The u-ATP9 transgene driven by A9 and APETALA3 promoters induce mitochondrial dysfunction revealed by a decrease in both oxygen uptake and adenine nucleotides (ATP, ADP) levels without changes in the ATP/ADP ratio. Furthermore, we measured an increase in ROS accumulation and a decrease in glutathione and ascorbate levels with a concomitant oxidative stress response.

Intron RNA editing is essential for splicing in plant mitochondria.

Most plant mitochondria messenger RNAs (mRNAs) undergo editing through C-to-U conversions located mainly in exon sequences. However, some RNA editing events are found in non-coding regions at critical positions in the predicted secondary and tertiary structures of introns, suggesting that RNA editing could be important for splicing. Here, we studied the relationships between editing and splicing of the mRNA encoding the ribosomal protein S10 (rps10), which has a group II intron and five editing sites.

A nuclear gene encoding the iron-sulfur subunit of mitochondrial complex II is regulated by B3 domain transcription factors during seed development in Arabidopsis.

Mitochondrial complex II (succinate dehydrogenase) is part of the tricarboxylic acid cycle and the respiratory chain. Three nuclear genes encode its essential iron-sulfur subunit in Arabidopsis (Arabidopsis thaliana). One of them, SUCCINATE DEHYDROGENASE2-3 (SDH2-3), is specifically expressed in the embryo during seed maturation, suggesting that SDH2-3 may have a role as the complex II iron-sulfur subunit during embryo maturation and/or germination.

The horsetail Equisetum arvense mitochondria share two group I introns with the liverwort Marchantia, acquired a novel group II intron but lost intron-encoded ORFs.

We studied the genomic structure and RNA editing of mitochondrial cox1, cox2, cob and atp9 from the horsetail Equisetum arvense, a representative of an old fern lineage. Editing of cox1, cob and atp9 mRNAs occur only by C-to-U transitions. No changes were found in cox2 transcripts constituting one of the rare examples of unedited mitochondrial mRNA in land plants.

In organello gene expression and RNA editing studies by electroporation-mediated transformation of isolated plant mitochondria.

Plant mitochondrial gene expression is a complex process involving multiple steps such as transcription, cis- and trans-splicing, RNA trimming, RNA editing, and translation. One of the main hurdles in understanding more about these processes has been the inability to incorporate engineered genes into mitochondria. We recently reported an in organello approach on the basis of the introduction of foreign DNA into isolated plant mitochondria by electroporation.

Deficiency of Arabidopsis thaliana frataxin alters activity of mitochondrial Fe-S proteins and induces oxidative stress.

Frataxin, a protein crucial for the biogenesis of mitochondria in different organisms, was recently identified in Arabidopsis thaliana. To investigate the role of frataxin in higher plants, we analyze two knock-out and one knock-down T-DNA insertion mutants. The knock-out mutants present an embryo-lethal phenotype, indicating an essential role for frataxin.

RNA editing site recognition in heterologous plant mitochondria.

RNA editing is a process that modifies the information content of mitochondrial messenger RNAs in flowering plants changing specific cytosine residues into uridine. To gain insight into editing site recognition, we used electroporation to introduce engineered wheat (Triticum aestivum) or potato (Solanum tuberosum) mitochondrial cox2 genes, and an atp9-containing chimeric gene, into non-cognate mitochondria, and observed the efficiency of editing in these contexts. Both wheat and potato mitochondria were able to express "foreign" constructs, and their products were properly spliced.

Expression and one-step purification of recombinant Arabidopsis thaliana frataxin homolog (AtFH).

Frataxin, a nuclear-encoded mitochondrial protein, has been proposed to participate in Fe-S cluster assembly, mitochondrial energy metabolism, respiration, and iron homeostasis. However, its precise function remains elusive. Frataxin is highly conserved in living organisms with no major structural changes, in particular at the C-terminal protein domain, suggesting that it plays a key function in all organisms.

Nuclear-encoded mitochondrial complex I gene expression is restored to normal levels by inhibition of unedited ATP9 transgene expression in Arabidopsis thaliana.

Mitochondria play an important role during sporogenesis in plants. The steady state levels of the nuclear-encoded mitochondrial complex I (nCI), PSST, TYKY and NADHBP transcripts increase in flowers of male-sterile plants with impairment of mitochondrial function generated by the expression of the unedited version of ATP9 (u-ATP9). This suggests a nuclear control of nCI genes in response to the mitochondrial flaw.

Gene expression studies in isolated mitochondria: Solanum tuberosum rps10 is recognized by cognate potato but not by the transcription, splicing and editing machinery of wheat mitochondria.

The complex gene expression mechanisms that occur in plant mitochondria, such as RNA editing and splicing, are not yet well understood. RNA editing in higher plant mitochondria is a highly specific process which modifies mRNA sequences by C-to-U conversions. It has been suggested that in some cases this process is required for splicing.