Miracle-dz/UniFAR-FTUs huggingface dataset:
The arrestin‐like protein ArtA is essential for ubiquitination and endocytosis of the UapA transporter in response to both broad‐range and specific signals

We investigated the role of all arrestin‐like proteins of Aspergillus nidulans in respect to growth, morphology, sensitivity to drugs and specifically for the endocytosis and turnover of the uric acid‐xanthine transporter UapA. A single arrestin‐like protein, ArtA, is essential for HulARsp5‐dependent ubiquitination and endocytosis of UapA in response to ammonium or substrates. Mutational analysis showed that residues 545–563 of the UapA C‐terminal region are required for efficient UapA endocytosis, whereas the N‐terminal region (residues 2–123) and both PPxY motives are essential for ArtA function. We further show that ArtA undergoes HulA‐dependent ubiquitination at residue Lys‐343 and that this modification is critical for UapA ubiquitination and endocytosis. Lastly, we show that ArtA is essential for vacuolar turnover of transporters specific for purines (AzgA) or l‐proline (PrnB), but not for an aspartate/glutamate transporter (AgtA). Our results are discussed within the frame of recently proposed mechanisms on how arrestin‐like proteins are activated and recruited for ubiquitination of transporters in response to broad range signals, but also put the basis for understanding how arrestin‐like proteins, such as ArtA, regulate the turnover of a specific transporter in the presence of its substrates.
A conserved ClpP‐like protease involved in spore outgrowth in Bacillus subtilis

Germination and outgrowth of endospores of the Gram‐positive bacterium Bacillus subtilis involves the degradation and conversion to free amino acids of abundant proteins located in the spore core known as small acid‐soluble proteins (SASP). This degradation is mediated primarily by the germination protease Gpr. Here we show that YmfB, a distant homologue of ClpP serine proteases that is highly conserved among endospore‐forming bacteria, contributes to SASP degradation but that its function is normally masked by Gpr. Spores from a ymfB gpr double mutant were more delayed in spore outgrowth and more impaired in SASP degradation than were spores from a gpr single mutant. The activity of YmfB relied on three putative active‐site residues as well as on the product of a small gene ylzJ located immediately downstream of, and overlapping with, ymfB. We propose that YmfB is an orphan ClpP protease that is dedicated to the degradation of a specialized family of small protein substrates.
Cerebral glucose metabolism in adults with hyperactivity of childhood onset.

Abstract Background and Methods. The cause of childhood hyperactivity (attention deficit–hyperactivity disorder) is unknown. We investigated the hypothesis that cerebral glucose metabolism might differ between normal adults (controls) and adults with histories of hyperactivity in childhood who continued to have symptoms. Each patient was also the biologic parent of a hyperactive child. None of the adults had ever been treated with stimulant medication. To measure cerebral glucose metabolism, we administered 148 to 185 MBq (4 to 5 mCi) of [18F]fluoro-2-deoxy-D-glucose intravenously to 50 normal adults and 25 hyperactive adults while they performed an auditory-attention task. Images were obtained for 30 minutes with a Scanditronix positron-emission tomograph with a resolution of 5 to 6 mm. Whole-brain and regional rates of glucose metabolism were measured with computer assistance by two trained research assistants, working independently, who were blinded to the subjects' status (control or hyperactive). Res.
Biochemical analysis and structure determination of Paucimonas lemoignei poly(3‐hydroxybutyrate) (PHB) depolymerase PhaZ7 muteins reveal the PHB binding site and details of substrate–enzyme interactions

Five amino acids (Y105, Y176, Y189, Y189, W207) that constitute the substrate binding site of PHB depolymerase PhaZ7 were identified. All residues are located at a single surface‐exposed location of PhaZ7. Exchange of these amino acids by less hydrophobic, hydrophilic or negatively charged residues reduced binding of PhaZ7 to PHB. Modifications of other residues at the PhaZ7 surface (F9, Y66, Y103, Y124, Y169, Y172, Y173, F198, Y203, Y204, F251, W252) had no effect on substrate binding. The PhaZ7 wild‐type protein, three muteins with single amino acid exchanges (Y105A, Y105E, Y190E), a PhaZ7 variant with deletion of residues 202–208, and PhaZ7 in which the active‐site serine had been replaced by alanine (S136A) were crystallized and their structures were determined at 1.6–2.0 Å resolution. The structures were almost identical but revealed flexibility of some regions. Structural analysis of PhaZ7 (S136A) with bound 3‐hydroxybutyrate tetramer showed that the substrate binds in a cleft that is composed of Y105, Y176, Y189 and Y190 and thus confirmed the data obtained by site‐directed mutagenesis. To the best of our knowledge this is the first example in which the substrate binding site of a PHB depolymerase is documented at a molecular and structural level.
IusWare: a methodology for the evaluation and selection of software products

IusWare (IUStitia SoftWARis) is a methodology designed to evaluate software products in a formal and rigorous way. The methodology is based on the multicriteria decision aid approach and encompasses activities such as the comparison, assessment and selection of software artefacts. The methodology defines an evaluation process which consists of two main phases: designing an evaluation model and applying it. The design phase is made up of the following activities: (1) identifying the actors that are relevant to the evaluation, their roles, the purpose of the evaluation, the resources available and the object(s) of the evaluation; (2) identifying the type of evaluation required: either a formal description of products or the ranking of products from the most preferred to the least preferred, or a partitioning into two sets of the best and the remaining products; (3) defining a nonredundant hierarchy of evaluation attributes, often corresponding with the quality characteristics of quality models; (4) associating a measure, a criterion scale and a function to transform the measure scale into the criterion scale to each basic attribute; and (5) choosing an aggregation technique so as to aggregate values on criteria to form a recommendation for the selection. In the application phase, attributes of products are measured, the measures are transformed into values on criteria and aggregated to form a recommendation.
Supporting dynamic QoS management functions in a reflective middleware platform

Reflection has recently been applied in a variety of settings to introduce more openness and flexibility into designs. The paper builds on the authors' previous work in applying reflection to the design of middleware platforms by considering the role of reflection in supporting the dynamic QoS management functions of monitoring and adaptation. It is argued that reflection provides strong support for such functions and indeed, the approach offers important benefits over alternative implementation strategies. A pilot implementation of a QoS management scheme is discussed and evaluated, and examples of the use of this approach are given.
Directional reversal of saccadic dysmetria and gain adaptivity in a patient with a superior l6 cerebellar artery infarction

Saccadic horizontal eye movements were explored in a 46-year old patient with a unilateral infarction in the cortico-cerebellar territory of the right superior cerebellar artery, involving vermal folia VI and VII. Eye movements were recorded with the search coil method ten days, and eight and 20 months after the infarction. Gain adaptivity of saccades was tested in the chronic stage only with the double target step paradigm which experimentally induced hypermetria of saccades.The patient had persistent and direction-specific saccadic dysmetria. Acutely, i.e., ten days after the stroke, saccades to the lesion side were strongly hypometric and those to the normal side tended to be hypermetric. In the chronic stage, i.e., months later, the directionality of saccadic dysmetria was reversed: ipsiversive saccades were now hypermetric whereas contraversive saccades tended to be hypometric.There is strong evidence that gain adaptivity of saccades in the chronic stage was diminished (it has not been tested in the .
The CcmFH complex is the system I holocytochrome c synthetase: engineering cytochrome c maturation independent of CcmABCDE

Cytochrome c maturation (ccm) in many bacteria, archaea and plant mitochondria requires eight membrane proteins, CcmABCDEFGH, called system I. This pathway delivers and attaches haem covalently to two cysteines (of Cys‐Xxx‐Xxx‐Cys‐His) in the cytochrome c. All models propose that CcmFH facilitates covalent attachment of haem to the apocytochrome; namely, that it is the synthetase. However, holocytochrome c synthetase activity has not been directly demonstrated for CcmFH. We report formation of holocytochromes c by CcmFH and CcmG, a periplasmic thioredoxin, independent of CcmABCDE (we term this activity CcmFGH‐only). Cytochrome c produced in the absence of CcmABCDE is indistinguishable from cytochrome c produced by the full system I, with a cleaved signal sequence and two covalent bonds to haem. We engineered increased cytochrome c production by CcmFGH‐only, with yields approaching those from the full system I. Three conserved histidines in CcmF (TM‐His1, TM‐His2 and P‐His1) are required for activity, as are the conserved cysteine pairs in CcmG and CcmH. Our findings establish that CcmFH is the system I holocytochrome c synthetase. Although we discuss why this engineering would likely not replace the need for CcmABCDE in nature, these results provide unique mechanistic and evolutionary insights into cytochrome c biosynthesis.
Streptococcus pneumoniae PBP2x mid‐cell localization requires the C‐terminal PASTA domains and is essential for cell shape maintenance

The transpeptidase activity of the essential penicillin‐binding protein 2x (PBP2x) of Streptococcus pneumoniae is believed to be important for murein biosynthesis required for cell division. To study the molecular mechanism driving localization of PBP2x in live cells, we constructed a set of N‐terminal GFP–PBP2x fusions under the control of a zinc‐inducible promoter. The ectopic fusion protein localized at mid‐cell. Cells showed no growth defects even in the absence of the genomic pbp2x, demonstrating that GFP–PBP2x is functional. Depletion of GFP–PBP2x resulted in severe morphological alterations, confirming the essentiality of PBP2x and demonstrating that PBP2x is required for cell division and not for cell elongation. A genetically or antibiotic inactivated GFP–PBP2x still localized at septal sites. Remarkably, the same was true for a GFP–PBP2x derivative containing a deletion of the central transpeptidase domain, although only in the absence of the protease/chaperone HtrA. Thus localization is independent of the catalytic transpeptidase domain but requires the C‐terminal PASTA domains, identifying HtrA as targeting GFP–PBP2x derivatives. Finally, PBP2x was positioned at the septum similar to PBP1a and the PASTA domain containing StkP protein, confirming that PBP2x is a key element of the divisome complex.
The spore‐associated protein BclA1 affects the susceptibility of animals to colonization and infection by Clostridium difficile

The BclA protein is a major component of the outermost layer of spores of a number of bacterial species and Clostridium difficile carries three bclA genes. Using insertional mutagenesis each gene was characterized and spores devoid of these proteins had surface aberrations, reduced hydrophobicity and germinated faster than wild‐type spores. Therefore the BclA proteins were likely major components of the spore surface and when absent impaired the protective shield effect of this outermost layer. Analysis of infection and colonization in mice and hamsters revealed that the 50% infectious dose (ID50) of spores was significantly higher (2‐logs) in the bclA1− mutant compared to the isogenic wild‐type control, but that levels of toxins (A and B) were indistinguishable from animals dosed with wild‐type spores. bclA1− spores germinated faster than wild‐type spores yet mice were less susceptible to infection suggesting that BclA1 must play a key role in the initial (i.e. pre‐spore germination) stages of infection. We also show that the ID50 was higher in mice infected with R20291, a ‘hypervirulent’ 027 strain, that carries a truncated BclA1 protein.
Software fault trees and weakest preconditions: a comparison and analysis

Software development in safety-critical systems demands techniques which provide both the precision of formal methods and the practicality of tried and trusted engineering methods, giving a measure of rigour as required by the application. In particular, reasoning about system behaviour in the presence of failures requires a realistic use of formal methods. We show how to capture the semantics implied by software fault trees using a form of weakest precondition programming in modelling the failure properties of different software expressions as an example. Leveson et al. [1] have used software fault trees to produce ‘failure templates’ at the statement level for the Ada programming language. These templates are concerned solely with logical program errors and not with compiler errors, control errors, memory errors etc. which could be captured by a system-wide view of the software. Furthermore, the notion of software fault tree ‘failure templates’ is confusing for safety engineers used to normal fault tree analysis; the trees are motivated by failures, rather than by working back from system hazards, and thus are much more akin to failure modes and effects analysis. We propose a more traditional view in the application of fault trees to software expressions, which leads to a difference in their expression in weakest precondition semantics.
The circumstellar envelope around the S-type AGB star W Aql. Effects of an eccentric binary orbit.

Context Recent observations at subarcsecond resolution, now possible also at submillimeter wavelengths, have shown intricate circumstellar structures around asymptotic giant branch (AGB) stars, mostly attributed to binary interaction. The results presented here are part of a larger project aimed at investigating the effects of a binary companion on the morphology of circumstellar envelopes (CSEs) of AGB stars. Aims AGB stars are characterized by intense stellar winds that build CSEs around the stars. Here, the CO(J = 3→2) emission from the CSE of the binary S-type AGB star W Aql has been observed at subarcsecond resolution using ALMA. The aim of this paper is to investigate the wind properties of the AGB star and to analyse how the known companion has shaped the CSE. Methods The average mass-loss rate during the creation of the detected CSE is estimated through modelling, using the ALMA brightness distribution and previously published single-dish measurements as observational constraints. The ALMA observations are presented and compared to the results from a 3D smoothed particle hydrodynamics (SPH) binary interaction model with the same properties as the W Aql system and with two different orbital eccentricities. Three-dimensional radiative transfer modelling is performed and the response of the interferometer is modelled and discussed. Results The estimated average mass-loss rate of W Aql is Ṁ = 3.0×10-6 M⊙ yr-1 and agrees with previous results based on single-dish CO line emission observations. The size of the emitting region is consistent with photodissociation models. The inner 10″ of the CSE is asymmetric with arc-like structures at separations of 2-3″ scattered across the denser sections. Further out, weaker spiral structures at greater separations are found, but this is at the limit of the sensitivity and field of view of the ALMA observations. Conclusions The CO(J = 3→2) emission is dominated by a smooth component overlayed with two weak arc patterns with different separations. The larger pattern is predicted by the binary interaction model with separations of ~10″ and therefore likely due to the known companion. It is consistent with a binary orbit with low eccentricity. The smaller separation pattern is asymmetric and coincides with the dust distribution, but the separation timescale (200 yrs) is not consistent with any known process of the system. The separation of the known companions of the system is large enough to not have a very strong effect on the circumstellar morphology. The density contrast across the envelope of a binary with an even larger separation will not be easily detectable, even with ALMA, unless the orbit is strongly asymmetric or the AGB star has a much larger mass-loss rate.
Involvement of reductases IruO and NtrA in iron acquisition by Staphylococcus aureus

To obtain host iron, Staphylococcus aureus secretes siderophores staphyloferrin A (SA) or staphyloferrin B (SB), and accesses heme iron through use of iron‐regulated surface determinant proteins. While iron transport in S. aureus is well documented, there is scant information about proteins required to access iron from complexes in the cytoplasm. In vitro studies identified a pyridine nucleotide‐disulfide oxidoreductase, named IruO, as an electron donor for the heme monooxygenases IsdG and IsdI, promoting heme degradation. Here, we show that an iruO mutant was not debilitated for growth on heme, suggesting involvement of another reductase. NtrA is an iron‐regulated nitroreductase and, as with the iruO mutant, a ntrA mutant grew on heme comparable with wild type (WT). In contrast, a iruO ntrA double mutant was severely debilitated for growth on heme, a phenotype that was complemented by expression of either iruO or ntrA in trans, demonstrating their overlapping role in heme‐iron utilization. Contrasting the involvement of multiple reductases for heme iron utilization, ntrA was shown essential for iron utilization using SA, although not SB or other siderophores tested, and an iruO mutant was incapable of deferoxamine‐mediated growth. Accordingly, virulence of WT S. aureus, but not an iruO mutant, was enhanced in mice receiving deferoxamine.
Effect of cooking and soaking on physical, nutrient composition and sensory evaluation of indigenous and foreign rice varieties in Nigeria

Purpose – The objective of this study is to ascertain the effect of cooking and soaking on the physical characteristics, nutrient composition and sensory evaluation of an indigenous “ofada” rice and a foreign “aroso” rice varieties in Nigeria.Design/methodology/approach – The two rice varieties were freshly purchased in the raw state, soaked in water and cooked. The physical characteristics, such as length, width, weight, colour, purity, breakage, cooking time, dispersability and swelling capacity of the raw rice varieties were determined according to official methods. The raw, soaked and cooked rice varieties were oven‐dried at 60○C for 4 h and milled to obtain a uniform surface area. The proximate composition and some minerals of the raw, soaked and cooked rice varieties and the sensory evaluation of the cooked rice were determined. Findings–The physical characteristics showed that “ofada” and “aroso” rice varieties were brown and creamy in colour, respectively. There were significant (p<0.01) differenc.
Reduction of Hospital Physicians' Workflow Interruptions: A Controlled Unit-Based Intervention Study

Highly interruptive clinical environments may cause work stress and suboptimal clinical care. This study features an intervention to reduce workflow interruptions by re-designing work and organizational practices in hospital physicians providing ward coverage. A prospective, controlled intervention was conducted in two surgical and two internal wards. The intervention was based on physician quality circles - a participative technique to involve employees in the development of solutions to overcome work-related stressors. Outcome measures were the frequency of observed workflow interruptions. Workflow interruptions by fellow physicians and nursing staff were significantly lower after the intervention. However, a similar decrease was also observed in control units. Additional interviews to explore process-related factors suggested that there might have been spill-over effects in the sense that solutions were not strictly confined to the intervention group. Recommendations for further research on the effectiveness and consequences of such interventions for professional communication and patient safety are discussed.
Evidence of Shared Genome-Wide Additive Genetic Effects on Interpersonal Trauma Exposure and Generalized Vulnerability to Drug Dependence in a Population of Substance Users.

Exposure to traumatic experiences is associated with an increased risk for drug dependence and poorer response to substance abuse treatment (Claus & Kindleberger, 2002; Jaycox, Ebener, Damesek, & Becker, 2004). Despite this evidence, the reasons for the observed associations of trauma and the general tendency to be dependent upon drugs of abuse remain unclear. Data (N = 2,596) from the Study of Addiction: Genetics and Environment were used to analyze (a) the degree to which commonly occurring single nucleotide polymorphisms (SNPs; minor allele frequency > 1%) in the human genome explains exposure to interpersonal traumatic experiences, and (b) the extent to which additive genetic effects on trauma are shared with additive genetic effects on drug dependence. Our results suggested moderate additive genetic influences on interpersonal trauma, h(2) SNP-Interpersonal = . 47, 95% confidence interval (CI) [. 10, . 85], that are partially shared with additive genetic effects on generalized vulnerability to drug dependence, h(2) SNP-DD = . 36, 95% CI [. 11, . 61]; rG-SNP = . 49, 95% CI [. 02, . 96]. Although the design/technique does not exclude the possibility that substance abuse causally increases risk for traumatic experiences (or vice versa), these findings raise the possibility that commonly occurring SNPs influence both the general tendency towards drug dependence and interpersonal trauma.
McmA‐dependent and ‐independent regulatory systems governing expression of ClrB‐regulated cellulase and hemicellulase genes in Aspergillus nidulans

Fungal cellulolytic and hemicellulolytic enzymes are promising tools for industrial hydrolysis of cellulosic biomass; however, the regulatory network underlying their production is not well understood. The recent discovery of the transcriptional activators ClrB and McmA in Aspergillus nidulans implied a novel regulatory mechanism driven by their interaction, experimental evidence for which was obtained from transcriptional and DNA‐binding analyses in this study. It was found that ClrB was essential for induced expression of all the genes examined in this study, while McmA dependency of their expression was gene‐dependent. DNA‐binding studies revealed McmA assisted in the recruitment of ClrB to the cellulose‐responsive element (CeRE) in the promoters of eglA and eglB, expression of which was significantly reduced in the mcmA mutant. The CCG triplet within the CeRE served as the recognition sequence for the ClrB monomer. In contrast, ClrB did not require McmA for binding as a homodimer to the CGGN8CCG sequences in the promoter of mndB, expression of which was affected less in the mcmA mutant than in all other examined genes. Thus, there are two types of ClrB‐mediated regulation: McmA‐assisted and McmA‐independent. This novel McmA–ClrB synergistic system provides new insights into the complex regulatory network involved in cellulase and hemicellulase production.