Miracle-dz/UniFAR-FTUs huggingface dataset:
Origins and Recombination of the Bacterial-Sized Multichromosomal Mitochondrial Genome of Cucumber[C][W]

This work presents the cucumber mitochondrial genome sequence. Its extremely large size reflects the proliferation of dispersed repeats, large introns, and an abundance of chloroplast and nuclear DNA. The genome has an unusual multichromosomal structure, and computational analyses reveal a large number of recombinationally active repeats. Members of the flowering plant family Cucurbitaceae harbor the largest known mitochondrial genomes. Here, we report the 1685-kb mitochondrial genome of cucumber (Cucumis sativus). We help solve a 30-year mystery about the origins of its large size by showing that it mainly reflects the proliferation of dispersed repeats, expansions of existing introns, and the acquisition of sequences from diverse sources, including the cucumber nuclear and chloroplast genomes, viruses, and bacteria. The cucumber genome has a novel structure for plant mitochondria, mapping as three entirely or largely autonomous circular chromosomes (lengths 1556, 84, and 45 kb) that vary in relative abundance over a twofold range. These properties suggest that the three chromosomes replicate independently of one another. The two smaller chromosomes are devoid of known functional genes but nonetheless contain diagnostic mitochondrial features. Paired-end sequencing conflicts reveal differences in recombination dynamics among chromosomes, for which an explanatory model is developed, as well as a large pool of low-frequency genome conformations, many of which may result from asymmetric recombination across intermediate-sized and sometimes highly divergent repeats. These findings highlight the promise of genome sequencing for elucidating the recombinational dynamics of plant mitochondrial genomes.
An extended IUPAC nomenclature code for polymorphic nucleic acids

UNLABELLED The International Union of Pure and Applied Chemistry (IUPAC) code specified nearly 25 years ago provides a nomenclature for incompletely specified nucleic acids. However, no system currently exists that allows for the informatics representation of the relative abundance at polymorphic nucleic acids (e.g. single nucleotide polymorphisms) in a single specified character, or a string of characters. Here, I propose such an information code as a natural extension to the IUPAC nomenclature code, and present some potential uses and limitations to such a code. The primary anticipated use of this extended nomenclature code is to assist in the representation of the rapidly growing space of information in human genetic variation. CONTACT johnsonad2@nhlbi.nih. gov SUPPLEMENTARY INFORMATION Supplementary data are available at Bioinformatics online.
JUNGBRUNNEN1, a Reactive Oxygen Species–Responsive NAC Transcription Factor, Regulates Longevity in Arabidopsis[W][OA]

Aging in plants is an intricate process that balances vegetative growth with flowering and reproductive success. This work describes the identification of JUNGBRUNNEN1, a NAC transcription factor that regulates this process in Arabidopsis thaliana and additionally affects abiotic stress tolerance by activating expression of the DREB2A transcription factor. The transition from juvenility through maturation to senescence is a complex process that involves the regulation of longevity. Here, we identify JUNGBRUNNEN1 (JUB1), a hydrogen peroxide (H2O2)-induced NAC transcription factor, as a central longevity regulator in Arabidopsis thaliana. JUB1 overexpression strongly delays senescence, dampens intracellular H2O2 levels, and enhances tolerance to various abiotic stresses, whereas in jub1-1 knockdown plants, precocious senescence and lowered abiotic stress tolerance are observed. A JUB1 binding site containing a RRYGCCGT core sequence is present in the promoter of DREB2A, which plays an important role in abiotic stress responses. JUB1 transactivates DREB2A expression in mesophyll cell protoplasts and transgenic plants and binds directly to the DREB2A promoter. Transcriptome profiling of JUB1 overexpressors revealed elevated expression of several reactive oxygen species–responsive genes, including heat shock protein and glutathione S-transferase genes, whose expression is further induced by H2O2 treatment. Metabolite profiling identified elevated Pro and trehalose levels in JUB1 overexpressors, in accordance with their enhanced abiotic stress tolerance. We suggest that JUB1 constitutes a central regulator of a finely tuned control system that modulates cellular H2O2 level and primes the plants for upcoming stress through a gene regulatory network that involves DREB2A.
Dorland's Illustrated Medical Dictionary.

As the authors state in the preface, the twenty-third edition of this medical classic does indeed usher in a new era in the history of "The American Illustrated Medical Dictionary. " Dr. W. A. Newman Dorland, whose name has been inseparably linked with that of the dictionary since its first edition, died in 1956. The present editorial board has made his name an official part of the title, and the volume will henceforth be known as "Dorland's Illustrated Medical Dictionary. " A large and distinguished board of editors and consultants have taken over the task of keeping the dictionary current. The basic format of the previous volumes remains unchanged. In spite of the fact that four thousand definitions have been added, the new edition is 138 pages shorter than its predecessor. This has been accomplished by increasing the page size and by eliminating some definitions, especially those of words not in the
PHO2-Dependent Degradation of PHO1 Modulates Phosphate Homeostasis in Arabidopsis[C][W][OA]

PHO2, a ubiquitin-conjugating E2 enzyme, maintains phosphate homeostasis by regulating phosphate uptake and translocation. This work identifies PHO1, a membrane-spanning protein implicated in xylem loading of phosphate, as a PHO2-interacting protein in the endomembrane system and shows that PHO1 degradation is PHO2 dependent and involves multivesicular body–mediated vacuolar proteolysis. The Arabidopsis thaliana pho2 mutant, which is defective in a ubiquitin-conjugating E2 enzyme, displays inorganic phosphate (Pi) toxicity as a result of enhanced uptake and root-to-shoot translocation of Pi. To elucidate downstream components of the PHO2-dependent regulatory pathway, we identified two pho2 suppressors as carrying missense mutations in PHO1, which has been implicated in Pi loading to the xylem. In support of the genetic interaction between PHO1 and PHO2, we found that the protein level of PHO1 is increased in pho2, whereas such accumulation is ameliorated in both pho2 suppressors. Results from cycloheximide and endosomal Cys protease inhibitor E-64d treatments further suggest that PHO1 degradation is PHO2 dependent and involves multivesicular body–mediated vacuolar proteolysis. Using the transient expression system of tobacco (Nicotiana tabacum) leaves, we demonstrated that PHO1 and PHO2 are partially colocalized and physically interact in the endomembranes, where the ubiquitin conjugase activity of PHO2 is required for PHO1 degradation. In addition, reduced PHO1 expression caused by PHO1 mutations impede Pi uptake, indicating a functional association between xylem loading and acquisition of Pi. Together, our findings uncover a pivotal molecular mechanism by which PHO2 modulates the degradation of PHO1 in the endomembranes to maintain Pi homeostasis in plants.
ETPOD (European Training Program on Organ Donation): a successful training program to improve organ donation

Advanced training of healthcare professionals active in organ donation is highlighted as a major means to overcome organ shortage. The objective of this study was to improve donation rates in the selected European target areas (TAs) by providing an advanced training program. A prospective intervention study was conducted in 25 TAs with active donor programs from 17 European countries, between 2007 and 2009. A training program based on collaborative methodology was designed at three different professional levels (health workers awareness, junior transplant coordinators, managers). Courses evaluation scores and donation figures in each TA were collected and compared before and after intervention. Courses with new developed training tools were implemented reaching out 3286 healthcare professionals. Feed‐back questionnaires revealed a high degree of satisfaction among participants (average of 4.35 on a 1–5 scale). The number of utilized donors in the TAs increased from 15.7 ± 14.3 (95% CI: 9.8–21.6) to 20.0 ± 17.1 (95% CI: 13–27.1) (P = 0.014) and the number of organs recovered increased from 49.7 ± 48.5 (95% CI: 29.6–69.7) to 59.3 ± 52.1 (95% CI: 37.8–80.8) (P = 0.044). The European Training Program on Organ Donation is a successful training program, achieving a significant increase in organ donation figures.
Impact of basal heart rate on long‐term prognosis of heart transplant patients

Previous studies in patients with heart failure have shown that an elevated basal heart rate (HR) is associated with a poor outcome. Our aim with this study was to investigate if this relationship is also present in heart transplantation (HTx) recipients. From 2003 until 2010, 256 HTx performed in our center were recruited. Patients who required pacemaker, heart‐lung transplants, pediatrics, retransplants, and those patients with a survival of less than 1 year were excluded. The final number included in the analysis was 191. Using the HR obtained by EKG during elective admission at 1 year post‐HTx and the survival rate, an ROC‐curve was performed. The best point under the curve was achieved with 101 beats per minute (bpm), so patients were divided in two groups according to their HR. A comparison between survival curves of both groups was performed (Kaplan–Meier). Subsequently, a multivariate analysis considering HR and other variables with influence on survival according to the literature was carried out. A total of 136 patients were included in the group with HR ≤100 bpm, and 55 in the one with HR >100 bpm. There were no basal differences in both groups except for primary graft failure, which was more frequent in the >100 bpm group (30.9 vs. 17%, P = 0.033). Patients with ≤100 bpm had a better long prognosis (P < 0.001). The multivariate analysis proved that high HR was an independent predictor of mortality. Our study shows that HR should be considered as a prognosis factor in HTx patients.
Determination of the safe range of graft size mismatch using body surface area index in deceased liver transplantation

In live donor liver transplantation, rigorous standardized criteria for matching of liver volume between donor and recipient have prevented graft loss because of size mismatch. In deceased whole liver transplantation, the safe donor–recipient size mismatch range remains unknown. We developed a multivariate survival model (generalized additive model) to estimate hazard risk of body surface area index (BSAi) for 3‐year graft survival using data derived from the national registry database between 2005 and 2010. BSAi was calculated by BSA of donor divided by BSA of recipient. 24 509 patients were included in the analysis. Small‐for‐size (SFS) grafts with BSAi less than 0.78 had a significant impact on graft dysfunction with progressive increase of hazard risk toward the lowest end and a higher incidence of primary graft nonfunction and vascular thrombosis. Large‐for‐size (LFS) grafts with BSAi greater than 1.24 had a significant impact on graft dysfunction with progressive increase of hazard risk toward the largest end. Our findings suggest that donor grafts with BSAi < 0.78 could be considered ‘SFS’ and donor grafts with BSAi > 1.24 could be considered ‘LFS’, with both extremes resulting in decreased graft survival. Therefore, BSAi > 0.78 and <1.24 appears to be a safe range to avoid adverse outcome associated with size mismatch.
Tendência da epidemia de AIDS em usuários de drogas injetáveis no Município de São Paulo de 1985 a 1997

OBJECTIVE: To analyze trends of AIDS epidemic among adults, from 1985 to 1997, in the city of Sao Paulo, focussing primarily on intravenous drug users (IDU), owing to the major impact of the epidemic on this population group. METHODOLOGY: Data from the AIDS surveillance of Sao Paulo State were analyzed. The statistical method applied to analyze the time series of the 8,558 cases of AIDS among IDU and of the 16,756 cases among non-IDU was polynomial regression. RESULTS: From 1985 to 1992 there was a increase in AIDS cases both in IDU and non-IDU. Thereafter there was a decrease in cases among IDU, while cases among non-IDU leveled off owing to the constant growth trend among heterosexual men and women. Adjusted regression coefficients (R2a) for all models remained higher than 70%, and the second-order (parabolic) models explained better the trends, except in the case of heterosexual non-IDU, in which the model was linear. CONCLUSION: At the end of the period under study the data suggest a decrease in the epidemic among IDU, while the trend among non-IDU keep flat at high level, and showed a constant increase among heterosexual.
Phylobiochemical Characterization of Class-Ib Aspartate/Prephenate Aminotransferases Reveals Evolution of the Plant Arogenate Phenylalanine Pathway[W]

Plants use phenylalanine to produce abundant and diverse phenylpropanoid compounds, such as flavonoids, tannins, and lignin. Through phylogenetic, bioinformatic, and biochemical analyses of prephenate aminotransferase enzymes from deep taxonomic lineages, this study revealed unique evolutionary history and molecular changes of key enzymes responsible for phenylalanine biosynthesis in plants. The aromatic amino acid Phe is required for protein synthesis and serves as the precursor of abundant phenylpropanoid plant natural products. While Phe is synthesized from prephenate exclusively via a phenylpyruvate intermediate in model microbes, the alternative pathway via arogenate is predominant in plant Phe biosynthesis. However, the molecular and biochemical evolution of the plant arogenate pathway is currently unknown. Here, we conducted phylogenetically informed biochemical characterization of prephenate aminotransferases (PPA-ATs) that belong to class-Ib aspartate aminotransferases (AspAT Ibs) and catalyze the first committed step of the arogenate pathway in plants. Plant PPA-ATs and succeeding arogenate dehydratases (ADTs) were found to be most closely related to homologs from Chlorobi/Bacteroidetes bacteria. The Chlorobium tepidum PPA-AT and ADT homologs indeed efficiently converted prephenate and arogenate into arogenate and Phe, respectively. A subset of AspAT Ib enzymes exhibiting PPA-AT activity was further identified from both Plantae and prokaryotes and, together with site-directed mutagenesis, showed that Thr-84 and Lys-169 play key roles in specific recognition of dicarboxylic keto (prephenate) and amino (aspartate) acid substrates. The results suggest that, along with ADT, a gene encoding prephenate-specific PPA-AT was transferred from a Chlorobi/Bacteroidetes ancestor to a eukaryotic ancestor of Plantae, allowing efficient Phe and phenylpropanoid production via arogenate in plants today.
AraPath: a knowledgebase for pathway analysis in Arabidopsis

UNLABELLED Studying plants using high-throughput genomics technologies is becoming routine, but interpretation of genome-wide expression data in terms of biological pathways remains a challenge, partly due to the lack of pathway databases. To create a knowledgebase for plant pathway analysis, we collected 1683 lists of differentially expressed genes from 397 gene-expression studies, which constitute a molecular signature database of various genetic and environmental perturbations of Arabidopsis. In addition, we extracted 1909 gene sets from various sources such as Gene Ontology, KEGG, AraCyc, Plant Ontology, predicted target genes of microRNAs and transcription factors, and computational gene clusters defined by meta-analysis. With this knowledgebase, we applied Gene Set Enrichment Analysis to an expression profile of cold acclimation and identified expected functional categories and pathways. Our results suggest that the AraPath database can be used to generate specific, testable hypotheses regarding plant molecular pathways from gene expression data. AVAILABILITY http://bioinformatics.sdstate. edu/arapath/.
Identification and Characterization of a Golgi-Localized UDP-Xylose Transporter Family from Arabidopsis[OPEN]

Three nucleotide sugar transporters were shown to transport UDP-Xyl in vitro, demonstrating the existence of plant nucleotide sugar transporters with specificity for UDP-Xyl. UXT1 provides UDP-Xyl for cell wall biosynthesis. Most glycosylation reactions require activated glycosyl donors in the form of nucleotide sugars to drive processes such as posttranslational modifications and polysaccharide biosynthesis. Most plant cell wall polysaccharides are biosynthesized in the Golgi apparatus from cytosolic-derived nucleotide sugars, which are actively transferred into the Golgi lumen by nucleotide sugar transporters (NSTs). An exception is UDP-xylose, which is biosynthesized in both the cytosol and the Golgi lumen by a family of UDP-xylose synthases. The NST-based transport of UDP-xylose into the Golgi lumen would appear to be redundant. However, employing a recently developed approach, we identified three UDP-xylose transporters in the Arabidopsis thaliana NST family and designated them UDP-XYLOSE TRANSPORTER1 (UXT1) to UXT3. All three transporters localize to the Golgi apparatus, and UXT1 also localizes to the endoplasmic reticulum. Mutants in UXT1 exhibit ∼30% reduction in xylose in stem cell walls. These findings support the importance of the cytosolic UDP-xylose pool and UDP-xylose transporters in cell wall biosynthesis.
The Calcium-Dependent Protein Kinase CPK28 Regulates Development by Inducing Growth Phase-Specific, Spatially Restricted Alterations in Jasmonic Acid Levels Independent of Defense Responses in Arabidopsis[OPEN]

A calcium-dependent protein kinase plays dual roles, maintaining tissue-specific phytohormone levels in adult plants without affecting defense responses and regulating defense signaling in seedlings. Phytohormones play an important role in development and stress adaptations in plants, and several interacting hormonal pathways have been suggested to accomplish fine-tuning of stress responses at the expense of growth. This work describes the role played by the CALCIUM-DEPENDENT PROTEIN KINASE CPK28 in balancing phytohormone-mediated development in Arabidopsis thaliana, specifically during generative growth. cpk28 mutants exhibit growth reduction solely as adult plants, coinciding with altered balance of the phytohormones jasmonic acid (JA) and gibberellic acid (GA). JA-dependent gene expression and the levels of several JA metabolites were elevated in a growth phase-dependent manner in cpk28, and accumulation of JA metabolites was confined locally to the central rosette tissue. No elevated resistance toward herbivores or necrotrophic pathogens was detected for cpk28 plants, either on the whole-plant level or specifically within the tissue displaying elevated JA levels. Abolishment of JA biosynthesis or JA signaling led to a full reversion of the cpk28 growth phenotype, while modification of GA signaling did not. Our data identify CPK28 as a growth phase-dependent key negative regulator of distinct processes: While in seedlings, CPK28 regulates reactive oxygen species-mediated defense signaling; in adult plants, CPK28 confers developmental processes by the tissue-specific balance of JA and GA without affecting JA-mediated defense responses.
The signal within the noise: efficient inference of stochastic gene regulation models using fluorescence histograms and stochastic simulations

MOTIVATION In the noisy cellular environment, stochastic fluctuations at the molecular level manifest as cell-cell variability at the population level that is quantifiable using high-throughput single-cell measurements. Such variability is rich with information about the cell's underlying gene regulatory networks, their architecture and the parameters of the biochemical reactions at their core. RESULTS We report a novel method, called Inference for Networks of Stochastic Interactions among Genes using High-Throughput data (INSIGHT), for systematically combining high-throughput time-course flow cytometry measurements with computer-generated stochastic simulations of candidate gene network models to infer the network's stochastic model and all its parameters. By exploiting the mathematical relationships between experimental and simulated population histograms, INSIGHT achieves scalability, efficiency and accuracy while entirely avoiding approximate stochastic methods. We demonstrate our method on a synthetic gene network in bacteria and show that a detailed mechanistic model of this network can be estimated with high accuracy and high efficiency. Our method is completely general and can be used to infer models of signal-activated gene networks in any organism based solely on flow cytometry data and stochastic simulations. AVAILABILITY A free C source code implementing the INSIGHT algorithm, together with test data is available from the authors. CONTACT mustafa.khammash@bsse.ethz. ch SUPPLEMENTARY INFORMATION Supplementary data are available at Bioinformatics online.
Chemical structure informing statistical hypothesis testing in metabolomics

MOTIVATION Metabolomics has been shown as an effective tool to study various biological and biomedical phenotypes, whereas interrogating the inherently noisy metabolite concentration data with limited sample size remains a major challenge. Accumulating evidence suggests that metabolites' structures are relevant to their bioactivities. RESULTS We present a new strategy to boost the statistical power of hypothesis testing in metabolomics by incorporating quantitative molecular descriptors for each metabolite. The strategy selects potentially informative summary molecular descriptors and outputs chemical structure-informed false discovery rates. The effectiveness of the proposed strategy is demonstrated by both simulation studies and a real application. In a metabolomic study on Alzheimer's disease, the posterior inclusion probability for summary molecular descriptors reaches 0.97. By incorporating the structure data, our approach uniquely identifies multiple Alzheimer's disease signatures, which are consistent with existing evidence. These results evidently suggest the value of the proposed approach for metabolomic hypothesis-testing problems. AVAILABILITY AND IMPLEMENTATION A code package implementing the strategy is freely available at https://github.com/HongjieZhu/CIMA.git.