The Early Asexual Development Regulator fluG Codes for a Putative Bifunctional Enzyme

FluG is a long recognized early regulator of asexual development in Aspergillus nidulans. fluG null mutants show profuse aerial growth and no conidial production. Initial studies reported sequence homology of FluG with a prokaryotic type I glutamine synthetase, but catalytic activity has not been demonstrated. In this study, we conducted an in-depth analysis of the FluG sequence, which revealed a single polypeptide containing a putative N-terminal amidohydrolase region linked to a putative C-terminal γ-glutamyl ligase region. Each region corresponded, separately and completely, to respective single function bacterial enzymes. Separate expression of these regions confirmed that the C-terminal region was essential for asexual development. The N-terminal region alone did not support conidial development, but contributed to increased conidial production under high nutrient availability. Point mutations directed at respective key catalytic residues in each region demonstrated that they were essential for biological function. Moreover, the substitution of the N- and C-terminal regions with homologs from Lactobacillus paracasei and Pseudomonas aeruginosa, respectively, maintained functionality, albeit with altered characteristics. Taken together, the results lead us to conclude that FluG is a bifunctional enzyme that participates in an as yet unidentified metabolic or signaling pathway involving a γ-glutamylated intermediate that contributes to developmental fate

DisProt: the Database of Disordered Proteins

The Database of Protein Disorder (DisProt) links structure and function information for intrinsically disordered proteins (IDPs). Intrinsically disordered proteins do not form a fixed three-dimensional structure under physiological conditions, either in their entireties or in segments or regions. We define IDP as a protein that contains at least one experimentally determined disordered region. Although lacking fixed structure, IDPs and regions carry out important biological functions, being typically involved in regulation, signaling and control. Such functions can involve high-specificity low-affinity interactions, the multiple binding of one protein to many partners and the multiple binding of many proteins to one partner. These three features are all enabled and enhanced by protein intrinsic disorder. One of the major hindrances in the study of IDPs has been the lack of organized information. DisProt was developed to enable IDP research by collecting and organizing knowledge regarding the experimental characterization and the functional associations of IDPs. In addition to being a unique source of biological information, DisProt opens doors for a plethora of bioinformatics studies. DisProt is openly available at

The Glasgow Norms:Ratings of 5,500 words on nine scales

The Glasgow Norms are a set of normative ratings for 5,553 English words on nine psycholinguistic dimensions: arousal, valence, dominance, concreteness, imageability, familiarity, age of acquisition, semantic size, and gender association. The Glasgow Norms are unique in several respects. First, the corpus itself is relatively large, while simultaneously providing norms across a substantial number of lexical dimensions. Second, for any given subset of words, the same participants provided ratings across all nine dimensions (33 participants/word, on average). Third, two novel dimensions—semantic size and gender association—are included. Finally, the corpus contains a set of 379 ambiguous words that are presented either alone (e.g., toast) or with information that selects an alternative sense (e.g., toast (bread), toast (speech)). The relationships between the dimensions of the Glasgow Norms were initially investigated by assessing their correlations. In addition, a principal component analysis revealed four main factors, accounting for 82% of the variance (Visualization, Emotion, Salience, and Exposure). The validity of the Glasgow Norms was established via comparisons of our ratings to 18 different sets of current psycholinguistic norms. The dimension of size was tested with megastudy data, confirming findings from past studies that have explicitly examined this variable. Alternative senses of ambiguous words (i.e., disambiguated forms), when discordant on a given dimension, seemingly led to appropriately distinct ratings. Informal comparisons between the ratings of ambiguous words and of their alternative senses showed different patterns that likely depended on several factors (the number of senses, their relative strengths, and the rating scales themselves). Overall, the Glasgow Norms provide a valuable resource—in particular, for researchers investigating the role of word recognition in language comprehension

The British Lexicon Project: Lexical decision data for 28,730 monosyllabic and disyllabic English words

We present a new database of lexical decision times for English words and nonwords, for which two groups of British participants each responded to 14,365 monosyllabic and disyllabic words and the same number of nonwords for a total duration of 16 h (divided over multiple sessions). This database, called the British Lexicon Project (BLP), fills an important gap between the Dutch Lexicon Project (DLP; Keuleers, Diependaele, & Brysbaert, Frontiers in Language Sciences. Psychology, 1, 174, 2010) and the English Lexicon Project (ELP; Balota et al., 2007), because it applies the repeated measures design of the DLP to the English language. The high correlation between the BLP and ELP data indicates that a high percentage of variance in lexical decision data sets is systematic variance, rather than noise, and that the results of megastudies are rather robust with respect to the selection and presentation of the stimuli. Because of its design, the BLP makes the same analyses possible as the DLP, offering researchers with a new interesting data set of word-processing times for mixed effects analyses and mathematical modeling. The BLP data are available at http://crr.ugent.be/blp and as Electronic Supplementary Materials

Variables with time-varying effects and the Cox model: Some statistical concepts illustrated with a prognostic factor study in breast cancer

International audienceBACKGROUND: The Cox model relies on the proportional hazards (PH) assumption, implying that the factors investigated have a constant impact on the hazard - or risk - over time. We emphasize the importance of this assumption and the misleading conclusions that can be inferred if it is violated; this is particularly essential in the presence of long follow-ups. METHODS: We illustrate our discussion by analyzing prognostic factors of metastases in 979 women treated for breast cancer with surgery. Age, tumour size and grade, lymph node involvement, peritumoral vascular invasion (PVI), status of hormone receptors (HRec), Her2, and Mib1 were considered. RESULTS: Median follow-up was 14 years; 264 women developed metastases. The conventional Cox model suggested that all factors but HRec, Her2, and Mib1 status were strong prognostic factors of metastases. Additional tests indicated that the PH assumption was not satisfied for some variables of the model. Tumour grade had a significant time-varying effect, but although its effect diminished over time, it remained strong. Interestingly, while the conventional Cox model did not show any significant effect of the HRec status, tests provided strong evidence that this variable had a non-constant effect over time. Negative HRec status increased the risk of metastases early but became protective thereafter. This reversal of effect may explain non-significant hazard ratios provided by previous conventional Cox analyses in studies with long follow-ups. CONCLUSIONS: Investigating time-varying effects should be an integral part of Cox survival analyses. Detecting and accounting for time-varying effects provide insights on some specific time patterns, and on valuable biological information that could be missed otherwise

Scaling of charged particle multiplicity in Pb-Pb collisions at SPS energies

The charged particle multiplicity distribution $dN_{ch}/d\eta$ has been measured by the NA50 experiment in Pb--Pb collisions at the CERN SPS. Measurements were done at incident energies of 40 and 158 GeV per nucleon over a broad impact parameter range. The multiplicity distributions are studied as a function of centrality using the number of participating nucleons ($N_{part}$), or the number of binary nucleon--nucleon collisions ($N_{coll}$). Their values at midrapidity exhibit a power law scaling behaviour given by $N_{part}^{1.00}$ and $N_{coll}^{0.75}$ at 158 GeV. Compatible results are found for the scaling behaviour at 40 GeV. The width of the $dN_{ch}/d\eta$ distributions is larger at 158 than at 40 GeV/nucleon and decreases slightly with centrality at both energies. Our results are compared to similar studies performed by other experiments both at the CERN SPS and at RHIC.

The DEEP2 Galaxy Redshift Survey: Environments of Poststarburst Galaxies at z~0.1 and z~0.8

Postststarburst (K+A) galaxies are candidates for galaxies in transition from a star-forming phase to a passively-evolving phase. We have spectroscopically identified large samples of K+A galaxies both in the SDSS at z~0.1 and in the DEEP2 survey at z~0.8, using a robust selection method based on a cut in Hbeta emission rather than the more problematic [OII] 3727. Based on measurements of the overdensity of galaxies around each object, we find that K+A galaxies brighter than 0.4L*_B at low-z have a similar, statistically indistinguishable environment distribution as blue galaxies, preferring underdense environments, but dramatically different from that of red galaxies. However, at higher-z, the environment distribution of K+A galaxies is more similar to red galaxies than to blue galaxies. We conclude that the quenching of star formation and the build-up of the red sequence through the K+A phase is happening in relatively overdense environments at z~1 but in relatively underdense environments at z~0. Although the relative environments where quenching occurs are decreasing with time, the corresponding absolute environment may have stayed the same along with the quenching mechanisms, because the mean absolute environments of all galaxies has to grow with time. In addition, we do not find any significant dependence on luminosity in the environment distribution of K+As. The existence of a large K+A population in the field at both redshifts indicates that cluster-specific mechanisms cannot be the dominant route by which these galaxies are formed. We also demonstrates that studying K+A-environment relations by measuring the K+A fraction in different environments is highly non-robust. Statistical comparisons of the overall environment distributions of different populations are much better behaved.Comment: 21 pages, 13 figures, 4 tables, submitted to MNRAS; v2: major revision in Sec 5, 6, 7, and 9. Implemented robust statistical techniques in place of K+A fraction measurements; conclusions on the environment distribution of poststarbursts at z~0.8 have changed. Completely new discussion added. v3: minor changes matching the accepted versio

Psychiatric and cognitive phenotype in children and adolescents with myotonic dystrophy

Myotonic dystrophy type 1 (DM1) is the most frequent inherited neuromuscular disorder. The juvenile form has been associated with cognitive and psychiatric dysfunction, but the phenotype remains unclear. We reviewed the literature to examine the psychiatric phenotype of juvenile DM1 and performed an admixture analysis of the IQ distribution of our own patients, as we hypothesised a bimodal distribution. Two-thirds of the patients had at least one DSM-IV diagnosis, mainly attention deficit/ hyperactivity disorder and anxiety disorder. Two-thirds had learning disabilities comorbid with mental retardation on one hand, but also attention deficit, low cognitive speed and visual spatial impairment on the other. IQ showed a bi-modal distribution and was associated with parental transmission. The psychiatric phenotype in juvenile DM1 is complex. We distinguished two different phenotypic subtypes: one group characterised by mental retardation, severe developmental delay and maternal transmission; and another group characterised by borderline full scale IQ, subnormal development and paternal transmission

It is time to define an organizational model for the prevention and management of infections along the surgical pathway : a worldwide cross-sectional survey

Background The objectives of the study were to investigate the organizational characteristics of acute care facilities worldwide in preventing and managing infections in surgery; assess participants' perception regarding infection prevention and control (IPC) measures, antibiotic prescribing practices, and source control; describe awareness about the global burden of antimicrobial resistance (AMR) and IPC measures; and determine the role of the Coronavirus Disease 2019 pandemic on said awareness. Methods A cross-sectional web-based survey was conducted contacting 1432 health care workers (HCWs) belonging to a mailing list provided by the Global Alliance for Infections in Surgery. The self-administered questionnaire was developed by a multidisciplinary team. The survey was open from May 22, 2021, and June 22, 2021. Three reminders were sent, after 7, 14, and 21 days. Results Three hundred four respondents from 72 countries returned a questionnaire, with an overall response rate of 21.2%. Respectively, 90.4% and 68.8% of participants stated their hospital had a multidisciplinary IPC team or a multidisciplinary antimicrobial stewardship team. Local protocols for antimicrobial therapy of surgical infections and protocols for surgical antibiotic prophylaxis were present in 76.6% and 90.8% of hospitals, respectively. In 23.4% and 24.0% of hospitals no surveillance systems for surgical site infections and no monitoring systems of used antimicrobials were implemented. Patient and family involvement in IPC management was considered to be slightly or not important in their hospital by the majority of respondents (65.1%). Awareness of the global burden of AMR among HCWs was considered very important or important by 54.6% of participants. The COVID-19 pandemic was considered by 80.3% of respondents as a very important or important factor in raising HCWs awareness of the IPC programs in their hospital. Based on the survey results, the authors developed 15 statements for several questions regarding the prevention and management of infections in surgery. The statements may be the starting point for designing future evidence-based recommendations. Conclusion Adequacy of prevention and management of infections in acute care facilities depends on HCWs behaviours and on the organizational characteristics of acute health care facilities to support best practices and promote behavioural change. Patient involvement in the implementation of IPC is still little considered. A debate on how operationalising a fundamental change to IPC, from being solely the HCWs responsibility to one that involves a collaborative relationship between HCWs and patients, should be opened.Peer reviewe