Miracle-dz/UniFAR-FTUs huggingface dataset:
Coordination of the Vernalization Response through a VIN3 and FLC Gene Family Regulatory Network in Arabidopsis[C][W]

Winter annual and biennial plants use the prolonged period of winter cold as an environmental cue to ensure proper floral transition in early spring. This work demonstrates that a sophisticated regulatory network by two gene families coordinates the proper vernalization response in Arabidopsis. Vernalization is an environmentally induced epigenetic switch in which winter cold triggers epigenetic silencing of floral repressors and thus provides competence to flower in spring. Vernalization triggers the recruitment of chromatin-modifying complexes to a clade of flowering repressors that are epigenetically silenced via chromatin modifications. In Arabidopsis thaliana, VERNALIZATION INSENSITIVE3 (VIN3) and its related plant homeodomain finger proteins act together with Polycomb Repressive Complex 2 to increase repressive histone marks at floral repressor loci, including FLOWERING LOCUS C (FLC) and its related genes, by vernalization. Here, we show that VIN3 family of proteins nonredundantly functions to repress different subsets of the FLC gene family during the course of vernalization. Each VIN3 family protein binds to modified histone peptides in vitro and directly associates with specific sets of FLC gene family chromatins in vivo to mediate epigenetic silencing. In addition, members of the FLC gene family are also differentially regulated during the course of vernalization to mediate proper vernalization response. Our results show that these two gene families cooperated during the course of evolution to ensure proper vernalization response through epigenetic changes.
Target of Rapamycin Signaling Regulates Metabolism, Growth, and Life Span in Arabidopsis[W][OA]

This work examines the postembryonic functions of Target of Rapamycin (TOR) in Arabidopsis by generating rapamycin-sensitive Arabidopsis plants via transgenic expression of a yeast protein. Examination of these lines indicates that in plants, as in animals, TOR acts in the integration of metabolism, nutrition, and life span. Target of Rapamycin (TOR) is a major nutrition and energy sensor that regulates growth and life span in yeast and animals. In plants, growth and life span are intertwined not only with nutrient acquisition from the soil and nutrition generation via photosynthesis but also with their unique modes of development and differentiation. How TOR functions in these processes has not yet been determined. To gain further insights, rapamycin-sensitive transgenic Arabidopsis thaliana lines (BP12) expressing yeast FK506 Binding Protein12 were developed. Inhibition of TOR in BP12 plants by rapamycin resulted in slower overall root, leaf, and shoot growth and development leading to poor nutrient uptake and light energy utilization. Experimental limitation of nutrient availability and light energy supply in wild-type Arabidopsis produced phenotypes observed with TOR knockdown plants, indicating a link between TOR signaling and nutrition/light energy status. Genetic and physiological studies together with RNA sequencing and metabolite analysis of TOR-suppressed lines revealed that TOR regulates development and life span in Arabidopsis by restructuring cell growth, carbon and nitrogen metabolism, gene expression, and rRNA and protein synthesis. Gain- and loss-of-function Ribosomal Protein S6 (RPS6) mutants additionally show that TOR function involves RPS6-mediated nutrition and light-dependent growth and life span in Arabidopsis.
Crosstown Trafficking: The Retromer Complex Component VPS29 and Recycling of the Vacuolar Sorting Receptor

For plant growth and development to proceed normally, cellular trafficking of proteins must flow more smoothly than the cars on the crosstown expressway (reviewed in [De Marcos Lousa et al., 2012][1]). Cargo proteins move from the endoplasmic reticulum, via the Golgi, through the trans-Golgi network
Positional integratomic approach in identification of genomic candidate regions for Parkinson's disease

MOTIVATION Recent abundance of data from studies employing high-throughput technologies to reveal alterations in human disease on genomic, transcriptomic, proteomic and other levels, offer the possibility to integrate this information into a comprehensive picture of molecular events occurring in human disease. Diversity of data originating from these studies presents a methodological obstacle in the integration process, also due to difficulties in choosing the optimal unified denominator that would allow inclusion of variables from various types of studies. We present a novel approach for integration of such multi-origin data based on positions of genetic alterations occurring in human diseases. Parkinson's disease (PD) was chosen as a model for evaluation of our methodology. METHODS Datasets from various types of studies in PD (linkage, genome-wide association, transcriptomic and proteomic studies) were obtained from online repositories or were extracted from available research papers. Subsequently, human genome assembly was subdivided into 10 kb regions, and significant signals from aforementioned studies were arranged into their corresponding regions according to their genomic position. For each region, rank product values were calculated and significance values were estimated by permuting the original dataset. RESULTS Altogether, 179 regions (representing 33 contiguous genomic regions) had significant accumulation of signals when P-value cut-off was set at 0.0001. Identified regions with significant accumulation of signals contained 29 plausible candidate genes for PD. In conclusion, we present a novel approach for identification of candidate regions and genes for various human disorders, based on the positional integration of data across various types of omic studies.
An Arabidopsis Soil-Salinity–Tolerance Mutation Confers Ethylene-Mediated Enhancement of Sodium/Potassium Homeostasis[W]

The soil salinity tolerance of an Arabidopsis mutant is shown to be caused by a mutation in the ETO1 gene that results in ethylene overproduction. Increased ethylene causes root stele reactive oxygen species (ROS)–dependent reductions in root Na influx and xylem loading and stelar ROS-independent enhancement of root K status, thus improving plant Na/K homeostasis and salinity tolerance. High soil Na concentrations damage plants by increasing cellular Na accumulation and K loss. Excess soil Na stimulates ethylene-induced soil-salinity tolerance, the mechanism of which we here define via characterization of an Arabidopsis thaliana mutant displaying transpiration-dependent soil-salinity tolerance. This phenotype is conferred by a loss-of-function allele of ETHYLENE OVERPRODUCER1 (ETO1; mutant alleles of which cause increased production of ethylene). We show that lack of ETO1 function confers soil-salinity tolerance through improved shoot Na/K homeostasis, effected via the ETHYLENE RESISTANT1–CONSTITUTIVE TRIPLE RESPONSE1 ethylene signaling pathway. Under transpiring conditions, lack of ETO1 function reduces root Na influx and both stelar and xylem sap Na concentrations, thereby restricting root-to-shoot delivery of Na. These effects are associated with increased accumulation of RESPIRATORY BURST OXIDASE HOMOLOG F (RBOHF)–dependent reactive oxygen species in the root stele. Additionally, lack of ETO1 function leads to significant enhancement of tissue K status by an RBOHF-independent mechanism associated with elevated HIGH-AFFINITY K+ TRANSPORTER5 transcript levels. We conclude that ethylene promotes soil-salinity tolerance via improved Na/K homeostasis mediated by RBOHF-dependent regulation of Na accumulation and RBOHF-independent regulation of K accumulation.
Getting There Faster: Genome-Wide Association Studies Point the Way to Increasing Nutritional Values

What if you were plunked down in front of a flying saucer and told to make it faster? Once you figured out how it moves at all, you could best choose your modifications if you knew what factors affect the saucer’s speed and which of them you could readily control. Scientists aiming to understand and alter characteristics such as crop yield or nutritional value similarly need to decide where tofocus their efforts.Asyou prepared to tinker with your saucer, you might wish you could check a slew of saucers and see what the faster (or slower) ones had in common. Plant scientists now can do just that using genome-wide association study (GWAS), wherein trait variation in diverse germplasm is associated with specific genomic differences. In contrast to traditional linkage mapping, in which relatively large quantitative trait loci are identified based on recombinant inbred populations produced from only two parental lines, GWAS takes advantage of historical recombination within
Identification of a Sphingolipid α-Glucuronosyltransferase That Is Essential for Pollen Function in Arabidopsis[C][W][OPEN]

This study found that IPUT1 is an enzyme required for the biosynthesis of glycosyl inositol phosphorylceramide sphingolipids in plants. These glycolipids are highly abundant and have many important cellular roles. IPUT1 adds glucuronic acid residues to the lipids. When the glucuronic acid residues are not incorporated in the sphingolipids, the pollen is unable to mediate fertilization. Glycosyl inositol phosphorylceramide (GIPC) sphingolipids are a major class of lipids in fungi, protozoans, and plants. GIPCs are abundant in the plasma membrane in plants, comprising around a quarter of the total lipids in these membranes. Plant GIPCs contain unique glycan decorations that include a conserved glucuronic acid (GlcA) residue and various additional sugars; however, no proteins responsible for glycosylating GIPCs have been identified to date. Here, we show that the Arabidopsis thaliana protein INOSITOL PHOSPHORYLCERAMIDE GLUCURONOSYLTRANSFERASE1 (IPUT1) transfers GlcA from UDP-GlcA to GIPCs. To demonstrate IPUT1 activity, we introduced the IPUT1 gene together with genes for a UDP-glucose dehydrogenase from Arabidopsis and a human UDP-GlcA transporter into a yeast mutant deficient in the endogenous inositol phosphorylceramide (IPC) mannosyltransferase. In this engineered yeast strain, IPUT1 transferred GlcA to IPC. Overexpression or silencing of IPUT1 in Nicotiana benthamiana resulted in an increase or a decrease, respectively, in IPC glucuronosyltransferase activity in vitro. Plants in which IPUT1 was silenced accumulated IPC, the immediate precursor, as well as ceramides and glucosylceramides. Plants overexpressing IPUT1 showed an increased content of GIPCs. Mutations in IPUT1 are not transmitted through pollen, indicating that these sphingolipids are essential in plants.
Comprehensive Annotation of Physcomitrella patens Small RNA Loci Reveals That the Heterochromatic Short Interfering RNA Pathway Is Largely Conserved in Land Plants[OPEN]

The moss Physcomitrella patens has over 1000 small RNA loci that produce 23- to 24-nucleotide heterochromatic short interfering RNAs, some of which are dependent upon a minimal Dicer-Like gene. Many plant small RNAs are sequence-specific negative regulators of target mRNAs and/or chromatin. In angiosperms, the two most abundant endogenous small RNA populations are usually 21-nucleotide microRNAs (miRNAs) and 24-nucleotide heterochromatic short interfering RNAs (siRNAs). Heterochromatic siRNAs are derived from repetitive regions and reinforce DNA methylation at targeted loci. The existence and extent of heterochromatic siRNAs in other land plant lineages has been unclear. Using small RNA-sequencing (RNA-seq) of the moss Physcomitrella patens, we identified 1090 loci that produce mostly 23- to 24-nucleotide siRNAs. These loci are mostly in intergenic regions with dense DNA methylation. Accumulation of siRNAs from these loci depends upon P. patens homologs of DICER-LIKE3 (DCL3), RNA-DEPENDENT RNA POLYMERASE2, and the largest subunit of DNA-DEPENDENT RNA POLYMERASE IV, with the largest subunit of a Pol V homolog contributing to expression at a smaller subset of the loci. A MINIMAL DICER-LIKE (mDCL) gene, which lacks the N-terminal helicase domain typical of DCL proteins, is specifically required for 23-nucleotide siRNA accumulation. We conclude that heterochromatic siRNAs, and their biogenesis pathways, are largely identical between angiosperms and P. patens, with the notable exception of the P. patens-specific use of mDCL to produce 23-nucleotide siRNAs.
Flavonoids and Auxin Transport Inhibitors Rescue Symbiotic Nodulation in the Medicago truncatula Cytokinin Perception Mutant cre1

The inability of the cytokinin perception mutant cre1 to form symbiotic nodules in Medicago truncatula was linked to a deficiency in auxin transport regulation mediated by endogenous flavonoids. Initiation of symbiotic nodules in legumes requires cytokinin signaling, but its mechanism of action is largely unknown. Here, we tested whether the failure to initiate nodules in the Medicago truncatula cytokinin perception mutant cre1 (cytokinin response1) is due to its altered ability to regulate auxin transport, auxin accumulation, and induction of flavonoids. We found that in the cre1 mutant, symbiotic rhizobia cannot locally alter acro- and basipetal auxin transport during nodule initiation and that these mutants show reduced auxin (indole-3-acetic acid) accumulation and auxin responses compared with the wild type. Quantification of flavonoids, which can act as endogenous auxin transport inhibitors, showed a deficiency in the induction of free naringenin, isoliquiritigenin, quercetin, and hesperetin in cre1 roots compared with wild-type roots 24 h after inoculation with rhizobia. Coinoculation of roots with rhizobia and the flavonoids naringenin, isoliquiritigenin, and kaempferol, or with the synthetic auxin transport inhibitor 2,3,5,-triiodobenzoic acid, rescued nodulation efficiency in cre1 mutants and allowed auxin transport control in response to rhizobia. Our results suggest that CRE1-dependent cytokinin signaling leads to nodule initiation through the regulation of flavonoid accumulation required for local alteration of polar auxin transport and subsequent auxin accumulation in cortical cells during the early stages of nodulation.
Ein neues Laser-Scan-System für die Fernseh-Ophthalmoskopie

Uber den klinischen Einsatz eines Laser-Scan-Systems fur die Ophthalmoskopie und die fernsehtechnische Darstellung von Fundusaufnahmen wird berichtet. Beurteilt werden die Abbildungsqualitat (Kontrast, Tiefenscharfe) und die Abbildungsmoglichkeiten (konfokale Blende). Aufnahmen mit unterschiedlichen Lasern (Argon, He-Ne) oder Aufnahmeanderungen, die durch konfokale Bedingungen moglich sind, werden diskutiert. Aufnahmen mit dem Scanning-Laser-Ophthalmoskop werden auch in Abhangigkeit von fernsehtechnischen Problemen fur die Dokumentation der Bildbefunde mit Funduskamera-Aufnahmen verglichen. An Beispielen werden Moglichkeiten der direkten Bildverarbeitung und -restaurierung von digital gespeicherten Video-Aufnahmen des Augenhintergrundes demonstriert. Anderungsvorstellungen fur ein dem Prototyp folgendes endgultig zu bauendes Laser-Scan-System werden aufgefuhrt. The clinical advantages of a scanning laser ophthalmoscope (SLO) and video imaging of fundus pictures are described. Image quality (contrast, depth of field) and imaging possibilities (confocal stop) are assessed. Imaging with different lasers (argon, He-Ne) and changes in imaging rendered possible by confocal alignment of the imaging optics are discussed. Hard copies from video images are still of inferior quality compared to fundus photographs. Methods of direct processing and retrieval of digitally stored SLO video fundus images are illustrated by examples. Modifications for a definitive laser scanning system - in regard to the field of view and the quality of hard copies - are proposed.
Transcranial Doppler Ultrasound: Technique and Application

Abstract Transcranial Doppler (TCD) ultrasound provides rapid, noninvasive, real-time measures of cerebrovascular function. TCD can be used to measure flow velocity in the basal arteries of the brain to assess relative changes in flow, diagnose focal vascular stenosis, or to detect embolic signals within these arteries. TCD can also be used to assess the physiologic health of a particular vascular territory by measuring blood flow responses to changes in blood pressure (cerebral autoregulation), changes in end-tidal CO2 (cerebral vasoreactivity), or cognitive and motor activation (neurovascular coupling or functional hyperemia). TCD has established utility in the clinical diagnosis of a number of cerebrovascular disorders such as acute ischemic stroke, vasospasm, subarachnoid hemorrhage, sickle cell disease, as well as other conditions such as brain death. Clinical indication and research applications for this mode of imaging continue to expand. In this review, the authors summarize the basic principles and clinical utility of TCD and provide an overview of a few TCD research applications.
Assessment of hypertension in 40 cats with left ventricular hypertrophy by Doppler‐shift sphygmomanometry

Forty cats with left ventricular hypertrophic disease had blood pressure evaluated indirectly by Doppler-shift sphygmomanometry. Disease categories included hyperthyroidism, chronic renal insufficiency and hypertrophic cardiomyopathy unrelated to either of the first two disorders. Nineteen (47-5 per cent) of the 40 cats had systemic hypertension, nine had high systolic blood pressure only, 10 had high systolic and diastolic blood pressure, and none had only isolated diastolic hypertension. Blood pressure did not correlate with the degree of left ventricular thickness. The results of this study suggest a high prevalence of both left ventricular hypertrophy and systemic hypertension. Cause and effect relationships require further evaluation.
Polar Localization of the NIP5;1 Boric Acid Channel Is Maintained by Endocytosis and Facilitates Boron Transport in Arabidopsis Roots

Polar localization of the NIP5;1 boric acid channel is mediated by phosphorylation, maintained by clathrin-dependent endocytosis, and is required for efficient boron transport in Arabidopsis roots. Boron uptake in Arabidopsis thaliana is mediated by nodulin 26-like intrinsic protein 5;1 (NIP5;1), a boric acid channel that is located preferentially on the soil side of the plasma membrane in root cells. However, the mechanism underlying this polar localization is poorly understood. Here, we show that the polar localization of NIP5;1 in epidermal and endodermal root cells is mediated by the phosphorylation of Thr residues in the conserved TPG (ThrProGly) repeat in the N-terminal region of NIP5;1. Although substitutions of Ala for three Thr residues in the TPG repeat did not affect lateral diffusion in the plasma membrane, these substitutions inhibited endocytosis and strongly compromised the polar localization of GFP-NIP5;1. Consistent with this, the polar localization was compromised in µ subunit mutants of the clathrin adaptor AP2. The Thr-to-Ala substitutions did not affect the boron transport activity of GFP-NIP5;1 in Xenopus laevis oocytes but did inhibit the ability to complement boron translocation to shoots and rescue growth defects in nip5;1-1 mutant plants under boron-limited conditions. These results demonstrate that the polar localization of NIP5;1 is maintained by clathrin-mediated endocytosis, is dependent on phosphorylation in the TPG repeat, and is necessary for the efficient transport of boron in roots.
Hyperscape: visualization for complex biological networks

MOTIVATION Network biology has emerged as a powerful tool to uncover the organizational properties of living systems through the application of graph theoretic approaches. However, due to limitations in underlying data models and visualization software, knowledge relating to large molecular assemblies and biologically active fragments is poorly represented. RESULTS Here, we demonstrate a novel hypergraph implementation that better captures hierarchical structures, using components of elastic fibers and chromatin modification as models. These reveal unprecedented views of the biology of these systems, demonstrating the unique capacity of hypergraphs to resolve overlaps and uncover new insights into the subfunctionalization of variant complexes. AVAILABILITY AND IMPLEMENTATION Hyperscape is available as a web application at http://www.compsysbio. org/hyperscape. Source code, examples and a tutorial are freely available under a GNU license. CONTACTS john.parkinson@utoronto.ca or graham.cromar@gmail.com SUPPLEMENTARY INFORMATION Supplementary data are available at Bioinformatics online.
LONG CONTINUED, LOW GRADE, IDIOPATHIC FEVER: ANALYSIS OF ONE HUNDRED CASES

Undoubtedly every experienced clinician has at one time or another been baffled diagnostically or therapeutically by patients suffering from long continued, low grade fever of unknown origin. The patient, although not seriously ill, realizes that she is below par and, fearful lest the fever spells impending disaster, consults her family physician, insisting on cure of the fever or at least on knowing its cause. The subsequent story of most of these patients is similar. After considerable investigation, study, and futile therapy, the patient leaves her family physician and starts on the rounds of consultants and specialists. In the vast majority of instances she visits hospital after hospital, wasting her time and substance without obtaining either satisfaction or relief. Such cases are not rare. A hundred of these patients were subjected to careful routine examination in the Mayo Clinic from June 1919 to June 1930 and, in addition, in most instances
A mutation profile for top-k patient search exploiting Gene-Ontology and orthogonal non-negative matrix factorization

Motivation : As the quantity of genomic mutation data increases, the likelihood of ﬁnding patients with similar genomic proﬁles, for various disease inferences, increases. However, so does the difﬁ-culty in identifying them. Similarity search based on patient mutation proﬁles can solve various translational bioinformatics tasks, including prognostics and treatment efﬁcacy predictions for better clinical decision making through large volume of data. However, this is a challenging problem due to heterogeneous and sparse characteristics of the mutation data as well as their high dimensionality. Results : To solve this problem we introduce a compact representation and search strategy based on Gene-Ontology and orthogonal non-negative matrix factorization. Statistical signiﬁcance be-tween the identiﬁed cancer subtypes and their clinical features are computed for validation; results show that our method can identify and characterize clinically meaningful tumor subtypes comparable or better in most datasets than the recently introduced Network-Based Stratiﬁcation method while enabling real-time search. To the best of our knowledge, this is the ﬁrst attempt to simultaneously characterize and represent somatic mutational data for efﬁcient search purposes. Availability : The implementations are available at: https://sites.google. com/site/postechdm/research/ implementation/orgos.