Miracle-dz/UniFAR-FTUs huggingface dataset:
Functional Analysis of PDX2 from Arabidopsis, a Glutaminase Involved in Vitamin B6 Biosynthesis1[W][OA]

Vitamin B6 is an essential metabolite in all organisms, being required as a cofactor for a wide variety of biochemical reactions. De novo biosynthesis of the vitamin occurs in microorganisms and plants, but animals must obtain it from their diet. Two distinct and mutually exclusive de novo pathways have been identified to date, namely deoxyxylulose 5-phosphate dependent, which is restricted to a subset of eubacteria, and deoxyxylulose 5-phosphate independent, present in archaea, fungi, plants, protista, and most eubacteria. In these organisms, pyridoxal 5′-phosphate (PLP) formation is catalyzed by a single glutamine amidotransferase (PLP synthase) composed of a glutaminase domain, PDX2, and a synthase domain, PDX1. Despite plants being an important source of vitamin B6, very little is known about its biosynthesis. Here, we provide information for Arabidopsis thaliana. The functionality of PDX2 is demonstrated, using both in vitro and in vivo analyses. The expression pattern of PDX2 is assessed at both the RNA and protein level, providing insight into the spatial and temporal pattern of vitamin B6 biosynthesis. We then provide a detailed biochemical analysis of the plant PLP synthase complex. While the active sites of PDX1 and PDX2 are remote from each other, coordination of catalysis is much more pronounced with the plant proteins than its bacterial counterpart, Bacillus subtilis. Based on a model of the PDX1/PDX2 complex, mutation of a single residue uncouples enzyme coordination and in turn provides tangible evidence for the existence of the recently proposed ammonia tunnel through the core of PDX1.
Mesure de la masse maigre sur les examens tomodensitométriques initiaux chez des patients de réanimation chirurgicale et traumatologique :lien avec la dépense énergétique et amélioration de sa prédiction

Introduction : en reanimation la determination de la depense energetique (DE) peut etre realise par le biais d’equation predictive (EP) ou en realisant des mesures de calorimetrie indirect (CI). La CI possede de nombreuses limites et beaucoup de services se servent des EP pour definir les besoins caloriques de leurs patients. Les EP et particulierement celle recommandee dans les guides de bonne pratique sont imprecises. La masse maigre (MM) est le determinant principal de la variabilite des la DE entre les personnes et elle peut etre mesuree precisement sur des examens tomodensitometriques. L’objectif principal de cette etude etait d’evaluer la correlation entre DE mesuree par CI et la MM mesuree sur des scanners, puis d’essayer d’ameliorer la prediction de la DE a partir des elements obtenus par l’analyse scanographique. Methode : nous avons conduit une etude retrospective monocentrique incluant les patients hospitalises dans notre reanimation chirurgicale et traumatologique. Les patients etaient inclus s'ils etaient ventiles, sedates, nourris par nutrition artificielle. La DE a ete evaluee par 5 equations predictives et mesuree par CI. Si une difference superieure a 15% etait retrouvee entre les resultats de la CI et la prediction par l’equation de Penn state les scanners initiaux des patients etaient analyses pour determiner la MM et masse grasse au niveau de la 3eme vertebre lombaire. Notre objectif principal etait de determiner la correlation entre la MM et la DE mesuree (DEM) par CI. Dans un second temps nous avons essaye d’ameliorer la precision de l’evaluation de la DE une EP incluant les donnees mesurees sur les scanners. Resultats : un total de 147 patients ont ete inclus. 68 presentaient une difference de plus de 15% entre la DEM et la DE predite (DEP) par l’equation de Penn state. Un total de 67 scanners initiaux permettant une analyse au niveau de L3 etaient disponibles. Il y avait une correlation statistiquement significative entre la MM et la DE (R=0,453 ; p = 0,0001) et nous avons cree une formule prenant en compte les donnees des analyses scanographiques presentant un r² = 0,63. Conclusion : il existe une correlation faible entre la MM et la DE des patients hospitalises en reanimation pour des motifs chirurgicaux ou traumatologiques. Cette correlation est moins importante que dans la population.
On the Spectral Slopes of Hard X-ray Emission from Black Hole Candidates

Most black hole candidates exhibit characteristic power-law like hard X-ray emission above $\sim$ 10 keV. In the {\em high state}, in which 2 -- 10 keV luminosity is relatively high, the energy index of the hard X-ray emission is usually greater than 1 --- typically $\sim 1.5$. On the other hand, in the {\em low state}, the hard X-ray energy index is 0.3 -- 0.9. In this paper, we suggest that this difference of the hard X-ray spectral slopes may be due to two different Comptonization mechanisms. We propose that, in the high state, the hard component is governed by the Comptonization due to the bulk motion of the almost freely falling (convergent accretion) flow close to the black hole, rather than thermal Comptonization. The spectral slope of the hard component is insensitive to the disk accretion rate governing the soft component, hence is nearly invariant in spite of the soft component variations. The power-law component due to the bulk motion Comptonization has a sharp cut-off at around the electron rest mass energy, which is consistent with high energy observations of the high state. In the low state, the spectrum is formed due to thermal Comptonization of the low-frequency disk radiation by a sub-Keplerian component (possibly undergoing a centrifugally-supported shock) which is originated from the Keplerian disk. In the limit of low disk accretion rate, the power law index is uniquely determined by the mass accretion rate of the sub-Keplerian component.
Interaction of Tumor Necrosis Factor Receptor-Associated Factor Signaling Proteins with the Latent Membrane Protein 1 PXQXT Motif Is Essential for Induction of Epidermal Growth Factor Receptor Expression

ABSTRACT The Epstein-Barr virus latent membrane protein 1 (LMP1) oncoprotein causes multiple cellular changes, including induction of epidermal growth factor receptor (EGFR) expression and activation of the NF-κB transcription factor. LMP1 and the cellular protein CD40, which also induces EGFR expression, interact with the tumor necrosis factor receptor-associated factor (TRAF) proteins. The LMP1 carboxy-terminal activation region 1 signaling domain interacts specifically with the TRAFs and is essential for EGFR induction through a mechanism independent of NF-κB alone. LMP1 and CD40 share a common TRAF binding motif, PXQXT. In this study, the PXQXT motifs in both LMP1 and CD40 were altered and mutant proteins were analyzed for induction of EGFR expression. Replacement of the T residue with A in CD40 completely blocked induction of the EGFR, while the same mutation in LMP1 did not affect EGFR induction. Replacement of both P and Q residues with A’s in LMP1 reduced EGFR induction by >75%, while deletion of PXQXT blocked EGFR induction. These results genetically link EGFR induction by LMP1 to the TRAF signaling pathway. Overexpression of TRAF2 potently activates NF-κB, although TRAF2 did not induce expression of the EGFR either alone or in combination with TRAF1 and TRAF3. In vivo analyses of the interaction of the TRAFs with LMP1 variants mutated in the PXQXT domain indicate that high-level induction of EGFR expression requires interaction with TRAF1, -2, and -3. However, exogenous expression of TRAF3 decreased EGFR induction mediated by either LMP1 or CD40. These data suggest that TRAF-mediated activation of EGFR expression requires assembly of a complex containing the appropriate stoichiometry of TRAF proteins clustered at the cell membrane with LMP1.
Spasmodic torticollis due to a midbrain lesion in a case of multiple sclerosis

A case of multiple sclerosis is described in which spasmodic torticollis occurred abruplty and abated after 1 year. Magnetic resonance imaging (MRI) demonstrated a lesion in the mesencephalon. Other symptoms and physical signs that developed at the same time as the spasmodic torticollis were compatible with the lesion that had not been present on MRI 18 months previously. There are very few reports of spasmodic torticollis due to an identified focal lesion; there is evidence form experimental work on animals that midbrain lesions may cause spasmodic torticollis but there has been no previous human example.
Hematopoietic growth factors—use in normal blood and stem cell donors: clinical and ethical issues

475. 99. Bussel JB, Kuter DJ, George LN, McMillan R, Aledort LM, Conklin GT, Lichtin AE, Lyons RM, Nieva J, Wasser JS, Wiznitzer I, Kelly R, Chen CF, Nichol JL. AMG 531, a thrombopoiesis-stimulating protein, for chronic ITP. N Engl J Med 2006;355:1672-81. 100. Kuter D, Bussel J, George J, Aledort L, Lichtin A, Lyons R, Nieva J, Wasser J, Bourgeois E, Kappers-Klunne M, Lefrere F, Schipperus M, Kelly R, Christal J, Guo M, Nichol J. Longterm dosing of AMG 531 in thrombocytopenic patients with immune thrombocytopenic purpura: 48-week update [abstract]. Blood 2006;108:144a, abstract #476. 101. McHutchison JG, Dusheiko G, Shiffman ML, RodriguezTorres M, Sigal S, Bourliere M, Berg T, Gordon SC, Campbell FM, Theodore D, Blackman N, Jenkins J, Afdhal NH; TPL102357 Study Group. Eltrombopag for thrombocytopenic in patients with cirrhosis associated with hepatitis C. N Engl J Med 2007;357:2227-36. 102. Spivak JL. Recombinant human erythropoietin and its role in transfusion medicine. Transfusion 1994;34:1-4. 103. Fullerton DA, Campbell DN, Whitman GJ. Use of human recombinant erythropoietin to correct severe preoperative anemia. Ann Thorac Surg 1991;51:825-6. 104. Gaudiani VA, Mason HD. Preoperative erythropoietin in Jehovah’s Witnesses who require cardiac procedures. Ann Thorac Surg 1991;41:823-4. 105. Shi PA, Ness PM. Two-unit red cell apheresis and its potential advantages over traditional whole blood donation: a review. Transfusion 1999;39:218-25. 106. Bahlmann FH, Groot K, Spandau J-M, Landry AL, Hertel B, Duckert T, Boehm SM, Menne J, Haller H, Fliser D. Erythropoietin regulates endothelial progenitor cells. Blood 2004;103:921-6. 107. Anagnostou A, Liu Z, Steiner M, Chin K, Lee ES, Kessimian N, Noguchi CT. Erythropoietin receptor mRNA expression in human endothelial cells. Proc Natl Acad Sci U S A 1994;
Endothelial cell–cell adhesion during zebrafish vascular development

The vertebrate vasculature is an essential organ network with major roles in health and disease. The establishment of balanced cell–cell adhesion in the endothelium is crucial for the functionality of the vascular system. Furthermore, the correct patterning and integration of vascular endothelial cell–cell adhesion drives the morphogenesis of new vessels, and is thought to couple physical forces with signaling outcomes during development. Here, we review insights into this process that have come from studies in zebrafish. First, we describe mutants in which endothelial adhesion is perturbed, second we describe recent progress using in vivo cell biological approaches that allow the visualization of endothelial cell–cell junctions. These studies underline the profound potential of this model system to dissect in great detail the function of both known and novel regulators of endothelial cell–cell adhesion.
Engineering or food? mechanisms of facilitation by a habitat-forming invasive seaweed

Nonnative species that form novel habitats strongly affect ecosystem processes. The effects of these ecosystem engineers can be both positive and negative but the mechanisms behind their effects are not well described. In this study we determined the relative importance of three main mechanisms by which invasive ecosystem engineers can facilitate native fauna. The engineer may provide new physical structure that reduces harsh abiotic conditions or gives refuge from predation (both engineering mechanisms), or provide a new profitable food resource (a trophic mechanism). The invasive seaweed Gracilaria vermiculophylla is a novel addition to estuarine intertidal mudflats of the southeastern United States. The epifaunal amphipod Gammarus mucronatus is up to 100 times more abundant on Gracilaria-invaded mudflats compared to uninvaded mudflats. Feeding assays, a survivorship experiment and stable isotope analysis demonstrated that Gammarus consumes little Gracilaria and cannot survive on Gracilaria alone. However, the structural engineering effects of Gracilaria greatly enhanced the survivorship of Gammarus in the presence of predators during high tide and when exposed to harsh abiotic conditions during low tide. Our results demonstrate that invasive ecosystem engineers can dramatically affect the distribution and abundance of native species by providing a novel protective structure.
Identification and Characterization of a Potent Activator of p53-Independent Cellular Senescence via a Small-Molecule Screen for Modifiers of the Integrated Stress Response

The Integrated Stress Response (ISR) is a signaling program that enables cellular adaptation to stressful conditions like hypoxia and nutrient deprivation in the tumor microenvironment. An important effector of the ISR is activating transcription factor 4 (ATF4), a transcription factor that regulates genes involved in redox homeostasis and amino acid metabolism and transport. Because both inhibition and overactivation of the ISR can induce tumor cell death, modulators of ATF4 expression could prove to be clinically useful. In this study, chemical libraries were screened for modulators of ATF4 expression. We identified one compound, E235 (N-(1-benzyl-piperidin-4-yl)-2-(4-fluoro-phenyl)-benzo[d]imidazo[2,1-b]thiazole-7-carboxamide), that activated the ISR and dose-dependently increased levels of ATF4 in transformed cells. A dose-dependent decrease in viability was observed in several mouse and human tumor cell lines, and knockdown of ATF4 significantly increased the antiproliferative effects of E235. Interestingly, low μM doses of E235 induced senescence in many cell types, including HT1080 human fibrosarcoma and B16F10 mouse melanoma cells. E235-mediated induction of senescence was not dependent on p21 or p53; however, p21 conferred protection against the growth inhibitory effects of E235. Treatment with E235 resulted in an increase in cells arrested at the G2/M phase with a concurrent decrease in S-phase cells. E235 also activated DNA damage response signaling, resulting in increased levels of Ser15-phosphorylated p53, γ-H2AX, and phosphorylated checkpoint kinase 2 (Chk2), although E235 does not appear to cause physical DNA damage. Induction of γ-H2AX was abrogated in ATF4 knockdown cells. Together, these results suggest that modulation of the ISR pathway with the small molecule E235 could be a promising antitumor strategy.
Cerebellar control of fixation eye movements

Human subjects normally have miniature eye movements during tasks that require steady visual fixation. These eye movements were compared in 12 control subjects and 4 patients with degenerative cerebellar disorders. Slow drifts, small fixation saccades, square waves, saccadic oscillations, flutter, and vertical nystagmus occurred in both control subjects and patients. In the patients, however, fixation eye movements were enlarged and square waves and saccadic oscillations were more frequent. It appears that some forms of pathologic fixation instability are due to defective cerebellar control of fixation eye movements, and that precise measurements of these eye movements may quantitate disorders of cerebellar function.
Métodos de Umbralización de Imágenes Digitales Basados en Entropía de Shannon y Otros

La umbralizacion de imagenes es el proceso por el cual se busca un umbral optimo que permita distinguir en una imagen los objetos del fondo de los objetos del primer plano. Este umbral es el punto (o valor) en el cual el histograma de una imagen se divide en dos picos. En la mayoria de las imagenes este valor resulta un poco dificil de encontrar graficamente debido a la complejidad de estos histogramas. Es por eso que se usan metodos parametricos y no parametricos que modelizan el problema y encuentran diferentes maneras de obtener este umbral. Pun y Kapur utilizaron la entropia de Shannon, haciendo sus modificaciones de acuerdo a su analisis y plantearon sus propuestas en la busqueda de un umbral. Yen definio un metodo basado en entropia de la correlacion de acuerdo a los lineamientos de Shannon. Kittler e Illingworth, propusieron un metodo basado en clusterizacion de grupos mediante el minimo error del promedio de clasificacion de pixeles. Continuando un trabajo anterior se agregan estos metodos en el calculo del umbral en imagenes en gris, realizando luego la binarizacion por capas, y comparando cada una de estas binarizaciones con una realizada en escala de grises. Experimentalmente se encuentra que las imagenes por umbralizacion siguiendo el metodo de Pun (a partir de aquellas en escala de grises) da como resultado imagenes poco definidas, siendo aquellas obtenidas por los metodos de Kapur y Yen mas definidas en detalles. A la vez, el metodo propuesto por Kittler brinda resultados muy similares a Yen, umbralizaciones muy parejas. Tanto Yen como Kittler tienen un comportamiento sobresaliente respecto de los otros metodos.
The prognostic value of circulating microRNAs in heart failure: preliminary results from a genome-wide expression study

Introduction Recent studies have demonstrated the potential of microRNAs (miRNA) as biomarkers in various cardiovascular disorders. The aim of the present study was to quantitatively evaluate the expression levels of miRNAs in patients with chronic congestive heart failure (CHF) in order to identify differential expression profiles as biomarkers with prognostic values. Materials and method The study included 20 clinically stable [New York Heart Association (NYHA) II] and 22 decompensated (NYHA III and IV) CHF patients and 15 healthy controls. miRNA profiling was performed using a microarray method. Dysregulated miRNAs were evaluated for their biomarker potential. Results Microarray profiling revealed an increase in the expression of miR-21, miR-650, miR-744*, miR-516-5p, miR-1292, miR-182, miR-1228, miR-595, miR-663b, miR-1296, miR-1825, miR-299-3p, miR-662 miR-122*, miR-3148 and miR-518e* and a decrease in the expression of miR-129-3p, miR-3155, miR-3175, miR-583, miR-568, miR-30d, miR-200a-star, miR-1979, miR-371-3p, miR-155-star and miR-502-5p in sera of CHF patients. The prognostic value of miR-182 [area under the curve (AUC) 0.695] was found to be superior to pro-brain type natriuretic peptide (NT-proBNP; AUC 0.350) and high-sensitivity C-reactive protein (hs-CRP) (AUC 0.475) by receiver operator characteristic (ROC) analysis. Cox regression analysis showed that miR-182 could predict cardiovascular mortality (P = 0.032). Conclusion We demonstrated the increased expression levels of circulating miRNAs in CHF as compared with controls. Moreover, miR-182 was found to be a potential prognostic marker in CHF.
The Art of Peer‐Reviewing an Original Research Paper

Address correspondence to Anthony M. Vintzileos, MD, Department of Obstetrics and Gynecology, Winthrop University Hospital, 259 First St, Mineola, NY 11501 USA. E-mail: avintzileos@winthrop.org eer-reviewing is an art. One of the holy grails in academic medicine is the effective and efficient peer review of articles that are under consideration for publication in medical journals. Yet, most peer reviewers do not undergo any formal training in this extremely important role to act as referees. The process for becoming a referee is quite simple. The editor(s) chooses the referees based on some “qualifiers. ” A very important qualifier in choosing a referee is evidence of publications by the “referee-to-be. ” However, one or more publications by the referee on a topic similar to the manuscript in question indicate only one of the many prerequisites for being an effective and efficient reviewer. The ability to review critically and efficiently an original research article depends not only on the referee’s special area of expertise but also on his or her time availability, dedication, communication skills, and experience. Many of the seasoned referees may not have available time, whereas many of the young junior referees may not have the necessary skills for a critical and efficient review. In our view, this skill can be achieved by strict adherence to certain principles. There is no question that the quality of the articles published in the medical journals, as well as their impact, are as good as the referees who reviewed the articles in the first place. We recently provided guidelines for writing peerreviewed manuscripts in academic medicine.1 Of note is that there is considerable overlap between writing and peer-review guidelines. The aim of this article is to describe some tips that young referees may use as guidelines in reviewing an ultrasound research paper.
Synucleins Are Developmentally Expressed, and α-Synuclein Regulates the Size of the Presynaptic Vesicular Pool in Primary Hippocampal Neurons

α-, β-, and γ-Synuclein, a novel family of neuronal proteins, has become the focus of research interest because α-synuclein has been increasingly implicated in the pathogenesis of Parkinson's and Alzheimer's disease. However, the normal functions of the synucleins are still unknown. For this reason, we characterized α-, β-, and γ-synuclein expression in primary hippocampal neuronal cultures and showed that the onset of α- and β-synuclein expression was delayed after synaptic development, suggesting that these synucleins may not be essential for synapse formation. In mature cultured primary neurons, α- and β-synuclein colocalized almost exclusively with synaptophysin in the presynaptic terminal, whereas little γ-synuclein was expressed at all. To assess the function of α-synuclein, we suppressed expression of this protein with antisense oligonucleotide technology. Morphometric ultrastructural analysis of the α-synuclein antisense oligonucleotide-treated cultures revealed a significant reduction in the distal pool of synaptic vesicles. These data suggest that one function of α-synuclein may be to regulate the size of distinct pools of synaptic vesicles in mature neurons.
Biophysical properties of Penicillium stoloniferum virus S.

Summary Pencillium stoloniferum virus S has been fractionated into four particle classes, E, M, L and H, with sedimentation coefficients of 66, 87, 101 and 113 S, respectively. E particles were shown to be empty capsids, while M particles contained single-stranded RNA, L particles contained double-stranded RNA, and H particles contained both single-stranded RNA and double-stranded RNA. The mol. wt. of L particles was found from sedimentation and diffusion coefficients to be 6.0 × 106. Evidence is presented that the M, L, and H particle classes each contain two components, M 1, M 2, L 1, L 2, H 1 and H 2, respectively. It has been shown that the M 1, M 2, L 1 and L 2 particles each contain only one molecule of RNA with mol. wts. of 0.47 × 106, 0.56 × 106, 0.94 × 106 and 1.11 × 106, respectively, while H 1 and H 2 particles each contain one molecule of double-stranded RNA of mol. wts. 0.94 × 106 and 1.11 × 106, respectively, together with single-stranded RNA.