Miracle-dz/UniFAR-FTUs huggingface dataset:
Dot/Icm Effector Translocation by Legionella longbeachae Creates a Replicative Vacuole Similar to That of Legionella pneumophila despite Translocation of Distinct Effector Repertoires

ABSTRACT Legionella organisms are environmental bacteria and accidental human pathogens that can cause severe pneumonia, termed Legionnaires' disease. These bacteria replicate within a pathogen-derived vacuole termed the Legionella-containing vacuole (LCV). Our understanding of the development and dynamics of this vacuole is based on extensive analysis of Legionella pneumophila. Here, we have characterized the Legionella longbeachae replicative vacuole (longbeachae-LCV) and demonstrated that, despite important genomic differences, key features of the replicative LCV are comparable to those of the LCV of L. pneumophila (pneumophila-LCV). We constructed a Dot/Icm-deficient strain by deleting dotB and demonstrated the inability of this mutant to replicate inside THP-1 cells. L. longbeachae does not enter THP-1 cells as efficiently as L. pneumophila, and this is reflected in the observation that translocation of BlaM-RalFLLO (where RalFLLO is the L. longbeachae homologue of RalF) into THP-1 cells by the L. longbeachae Dot/Icm system is less efficient than that by L. pneumophila. This difference is negated in A549 cells where L. longbeachae and L. pneumophila infect with similar entry dynamics. A β-lactamase assay was employed to demonstrate the translocation of a novel family of proteins, the Rab-like effector (Rle) proteins. Immunofluorescence analysis confirmed that these proteins enter the host cell during infection and display distinct subcellular localizations, with RleA and RleC present on the longbeachae-LCV. We observed that the host Rab GTPase, Rab1, and the v-SNARE Sec22b are also recruited to the longbeachae-LCV during the early stages of infection, coinciding with the LCV avoiding endocytic maturation. These studies further our understanding of the L. longbeachae replicative vacuole, highlighting phenotypic similarities to the vacuole of L. pneumophila as well as unique aspects of LCV biology.
Declining financial capacity in patients with mild Alzheimer disease: a one-year longitudinal study.

OBJECTIVE The objective of this study was to investigate change over time in financial abilities in patients with mild Alzheimer disease (AD). METHODS The authors conducted a prospective 1-year longitudinal study at a large southern U.S. metropolitan-area medical school university. Participants included healthy older adults (N=63) and patients with mild AD (N=55). The authors conducted a standardized performance measure of financial capacity. Performance was assessed on 18 financial tasks, nine domains of financial activity, and overall financial capacity. Capacity outcomes classifications (capable, marginally capable, or incapable) for domains and overall performance were made using cut scores referenced to comparison group performance. RESULTS At baseline, patients with mild AD performed significantly below healthy older adults on 16 of 18 tasks, on all nine domains, and on overall financial capacity. At one-year follow up, comparison group performance was stable on all variables. In contrast, patients with mild AD showed substantial declines in overall financial capacity, on eight of nine domains, and on 12 of 18 tasks. Similarly, the proportion of the mild AD group classified as marginally capable and incapable increased substantially over one year for the two overall scores and for five financial domains. CONCLUSIONS Financial capacity is already substantially impaired in patients with mild AD at baseline and undergoes rapid additional decline over one year. Relative to the comparison group, overall financial capacity performance in the AD group declined 10%, from approximately 80% of the comparison group performance at baseline to 70% at follow up. Financial skills showed differential rates of decline on both simple and complex tasks. Of clinical and public policy interest was the declining judgment of patients with mild AD regarding simple fraud schemes. The study supports the importance of prompt financial supervision and planning for patients newly diagnosed with AD.
Impedance Characterization and Modeling of Lithium-Ion Batteries Considering the Internal Temperature Gradient

Battery impedance is essential to the management of lithium-ion batteries for electric vehicles (EVs), and impedance characterization can help to monitor and predict the battery states. Many studies have been undertaken to investigate impedance characterization and the factors that influence impedance. However, few studies regarding the influence of the internal temperature gradient, which is caused by heat generation during operation, have been presented. We have comprehensively studied the influence of the internal temperature gradient on impedance characterization and the modeling of battery impedance, and have proposed a discretization model to capture battery impedance characterization considering the temperature gradient. Several experiments, including experiments with artificial temperature gradients, are designed and implemented to study the influence of the internal temperature gradient on battery impedance. Based on the experimental results, the parameters of the non-linear impedance model are obtained, and the relationship between the parameters and temperature is further established. The experimental results show that the temperature gradient will influence battery impedance and the temperature distribution can be considered to be approximately linear. The verification results indicate that the proposed discretization model has a good performance and can be used to describe the actual characterization of the battery with an internal temperature gradient.
Bedeuten die Grenzen meiner Sprache die Grenzen meiner Welt

Die Sprachfahigkeit als Gattungsmerkmal des homo sapiens erzeugt Zeichen, durch die linear akustische Signale mit begrifflich strukturierten Umwelterfahrungen verbunden werden. Diese Verbindung beruht weder (ikonisch) auf Ahnlichkeit noch (indexikalisch) auf direktem Situationsbezug, sondern ist (symbolisch) konventionell begrundet. Sie ermoglicht durch freie Kombination die Bildung komplexer Zeichen. Damit sind entscheidende Eigenschaften der Sprache gegeben. Einerseits sind sprachliche Ausdrucke uber alle Erfahrungsbereiche moglich, naturliche Sprachen sind unbegrenzt und vollstandig, andererseits sind sie zwangslaufig abstrakt, sie konnen nur den klassifizierend begrifflichen Aspekt der Erfahrungswelt wiedergeben. Diese Begrenztheit liegt innerhalb der Sprache selbst. Zugleich ist durch die Moglichkeit, uber alles, also auch uber Sprache zu sprechen, die Basis fur Reflexion und explizite Bewusstheit, also Selbstbewusstsein gegeben. - Das Ineinandergreifen der verschiedenen Aspekte wird abschliesend an Brentanos Wiegenlied demonstriert.
TLR 7 ligand prevents allergen-induced airway hyperresponsiveness and eosinophilia in allergic asthma by a MYD 88-dependent and MK 2-independent pathway

J. Moisan, P. Camateros, T. Thuraisingam, D. Marion, H. Koohsari, P. Martin, M. L. Boghdady, A. Ding, M. Gaestel, M. C. Guiot, J. G. Martin, and D. Radzioch McGill University, Department of Experimental Medicine, Montreal, Quebec, Canada; Department of Microbiology and Immunology, Weill Medical College of Cornell University, New York, New York; Medical School Hannover, Institute of Biochemistry, Hannover, Germany; McGill University, Department of Pathology, Montreal Neurological Hospital, Montreal, Quebec, Canada; and McGill University, Department of Human Genetics, Montreal, Quebec, Canada
Comment on: Antifungal therapy: drug-drug interactions at your fingertips.

We are writing in response to an article entitled ‘Antifungal therapy: drug–drug interactions at your ﬁngertips’, which was published online on 8 November 2015. 1 The article highlights the compilation of adverse drug–drug interactions (DDIs) with antifungal medicines as a knowledge database. They describe the construction of a database online and the development of a smartphone app to access the data for paired DDIs and antifungal drugs. Thepaper has omitted to mention a similar and pre-existing database, which was developed and made available online in 2012, using similar data sources. 2 It also omitted reference to two smartphone apps for assessing DDIs with antifungal medicines, which have been available since early 2013. 3,4 All these are free resources; both apps, named ‘Antifungal Interactions’, are available for Android or iOS platforms. The apps and the database have been presented at several international conferences. 5,6
De novo microdeletion of BCL11A is associated with severe speech sound disorder

In 10 cases of 2p15p16.1 microdeletions reported worldwide to date, shared phenotypes included growth retardation, craniofacial and skeletal dysmorphic traits, internal organ defects, intellectual disability, nonverbal or low verbal status, abnormal muscle tone, and gross motor delays. The size of the deletions ranged from 0.3 to 5.7 Mb, where the smallest deletion involved the BCL11A, PAPOLG, and REL genes. Here we report on an 11‐year‐old male with a heterozygous de novo 0.2 Mb deletion containing a single gene, BCL11A, and a phenotype characterized by childhood apraxia of speech and dysarthria in the presence of general oral and gross motor dyspraxia and hypotonia as well as expressive language and mild intellectual delays. BCL11A is situated within the dyslexia susceptibility candidate region 3 (DYX3) candidate region on chromosome 2. The present case is the first to involve a single gene within the microdeletion region and a phenotype restricted to a subset of the traits observed in other cases with more extensive deletions. © 2014 Wiley Periodicals, Inc.
Genomic selection: A paradigm shift in animal breeding

• Traditional marker-assisted selection (MAS) did not result in a widespread use of DNA information in animal breeding. The main reason was that the traits of interest in livestock production were much more complex than expected: they were determined by thousands of genes with small effects on phenotype. These effects were usually too small to be statistically significant and so were ignored. • Genomic selection (GS) assumes that all markers might be linked to a gene affecting the trait and concentrates on estimating their effect rather than testing its significance. Three technological breakthroughs resulted in the current wide-spread use of DNA information in animal breeding: the development of the genomic selection technology, the discovery of massive numbers of genetic markers (single nucleotide polymorphisms; SNPs), and high-throughput technology to genotype animals for (hundreds of) thousands of SNPs in a cost-effective manner. • Here we review current methods for GS, including how they deal with practical data, where genotypes are missing on a large scale. The use of whole-genome sequence data is anticipated, and its advantages and disadvantages are depicted. Current and predicted future impacts of GS on dairy and beef cattle, pigs, and poultry breeding are described. Finally, future directions for GS are discussed. • It is anticipated that future GS applications will either be: within breed (wbGS), where accuracy is obtained by maintaining huge withinbreed reference populations; or across breed (abGS) where accuracy is obtained from across-breed reference populations and high-density GS methods that focus on causative genomic regions. We argue that future GS applications will increasingly turn toward abGS.
A Mutant of Burkholderia pseudomallei, Auxotrophic in the Branched Chain Amino Acid Biosynthetic Pathway, Is Attenuated and Protective in a Murine Model of Melioidosis

ABSTRACT Using a transposon mutagenesis approach, we have identified a mutant of Burkholderia pseudomallei that is auxotrophic for branched chain amino acids. The transposon was shown to have interrupted the ilvI gene encoding the large subunit of the acetolactate synthase enzyme. Compared to the wild type, this mutant was significantly attenuated in a murine model of disease. Mice inoculated intraperitoneally with the auxotrophic mutant, 35 days prior to challenge, were protected against a challenge dose of 6,000 median lethal doses of wild-type B. pseudomallei.
Diseases caused by mutations in ORAI1 and STIM1

Ca2+ release‐activated Ca2+ (CRAC) channels mediate a specific form of Ca2+ influx called store‐operated Ca2+ entry (SOCE) that contributes to the function of many cell types. CRAC channels are composed of ORAI1 proteins located in the plasma membrane, which form its ion‐conducting pore. ORAI1 channels are activated by stromal interaction molecule (STIM) 1 and STIM2 located in the endoplasmic reticulum. Loss‐ and gain‐of‐function gene mutations in ORAI1 and STIM1 in human patients cause distinct disease syndromes. CRAC channelopathy is caused by loss‐of‐function mutations in ORAI1 and STIM1 that abolish CRAC channel function and SOCE; it is characterized by severe combined immunodeficiency (SCID)‐like disease, autoimmunity, muscular hypotonia, and ectodermal dysplasia, with defects in sweat gland function and dental enamel formation. The latter defect emphasizes an important role of CRAC channels in tooth development. By contrast, autosomal dominant gain‐of‐function mutations in ORAI1 and STIM1 result in constitutive CRAC channel activation, SOCE, and increased intracellular Ca2+ levels that are associated with an overlapping spectrum of diseases, including nonsyndromic tubular aggregate myopathy (TAM) and York platelet and Stormorken syndromes. The latter two syndromes are defined, besides myopathy, by thrombocytopenia, thrombopathy, and bleeding diathesis. The fact that myopathy results from both loss‐ and gain‐of‐function mutations in ORAI1 and STIM1 highlights the importance of CRAC channels for Ca2+ homeostasis in skeletal muscle function. The cellular dysfunction and clinical disease spectrum observed in mutant patients provide important information about the molecular regulation of ORAI1 and STIM1 proteins and the role of CRAC channels in human physiology.
Detecting memory performance validity with DETECTS: A computerized performance validity test

ABSTRACT Evaluating performance validity is essential in neuropsychological and forensic assessments. Nonetheless, most psychological assessment tests are unable to detect performance validity and other methods must be used for this purpose. A new Performance Validity Test (DETECTS – Memory Performance Validity Test) was developed with several characteristics that enhance test utility. Moreover, precise response time measurement was added to DETECTS. Two groups of participants (normative and simulator group) completed DETECTS and three memory tests from the Wechsler Memory Scale III. Simulators achieved considerably lower scores (hits) and higher response times in DETECTS compared with the normative group. All participants in the normative group were classified correctly and no simulator was classified as having legitimate memory deficits. Thus, DETECTS seems to be a valuable computerized Performance Validity Test with reduced application time and effective cut-off scores as well as high sensitivity, specificity, and positive and negative predictive power values. Lastly, response time may be a very useful measure for detecting memory malingering.
NF-κB downregulation may be involved the depression of tumor cell proliferation mediated by human mesenchymal stem cells

AbstractAim:It has been reported that stem cells are able to home to tumorigenesis and inhibit the proliferation of tumor cells. The purpose of our study was to demonstrate the molecular mechanism of the inhibitory proliferation of hepatoma cells and breast cancer cells mediated by human mesenchymal stem cells (hMSCs). Methods:The proliferation of H7402 human hepatoma cells and MCF-7 human breast cancer cells was measured by the 5-bromodeoxyuridine (BrdU) incorporation assay and flow cytometry assay after the treatment with conditioned media from hMSCs culture, such as Z3 cells or BMMS-03 cells. The role of NF-κB or the phosphorylation of inhibitor κBα (p-IκBα) in the depression of hepatoma or breast cancer cells treated with conditioned media from Z3 cells or BMMS-03 cells was examined by reporter gene assay, quantitative real-time PCR, and Western blot analysis, respectively.Results:The proliferation of H7402 cells and MCF-7 cells was decreased significantly by the BrdU incorporation assay and flow cytometry assay after treatment. The transcriptional activity and mRNA level of NF-κB were downregulated in the treated cells by reporter gene assay and quantitative real-time PCR in a dose-dependent manner. At the protein level, NF-κB and p-IκBα decreased in the treated cells by Western blot analysis.Conclusion:Conditioned media from hMSCs are able to inhibit the proliferation of tumor cells. NF-κB downregulation is one of reasons for the depression of tumor cell proliferation mediated by hMSCs.
Droplet fate in indoor environments, or can we prevent the spread of infection?

UNLABELLED When considering how people are infected and what can be done to prevent the infections, answers from many disciplines are sought: microbiology, epidemiology, medicine, engineering, and physics. There are many pathways to infection spread, and among the most significant from the epidemiological point of view is airborne transport. Microorganisms can become airborne when droplets are generated during speech, coughing, sneezing, vomiting, or atomization of feces during sewage removal. The fate of the droplets is governed by the physical principles of transport, with droplet size being the most important factor affecting their dispersion, deposition on surfaces and determining the survival of microorganisms within the droplets. In addition, physical characteristics of the indoor environment as well as the design and operation of building ventilation systems are of critical importance. Do we understand the mechanisms of infection spread and can we quantify the droplet dynamics under various indoor conditions? Unfortunately no, as this aspect of infection spread has attracted surprisingly little scientific interest. However, investigations of numerous cases in which a large number of people were infected show how critical the physics of microorganism spread can be. This paper reviews the state of knowledge regarding mechanisms of droplet spread and solutions available to minimize the spread and prevent infections. PRACTICAL IMPLICATIONS Every day tens of millions of people worldwide suffer from viral infections of different severity at immense economic cost. There is, however, only minimal understanding of the dynamics of virus-laden aerosols, and so the ability to control and prevent virus spread is severely reduced, as was clearly demonstrated during the recent severe acute respiratory syndrome epidemic. This paper proposes the direction to significantly advance fundamental and applied knowledge of the pathways of viral infection spread in indoor atmospheric systems, through a comprehensive multidisciplinary approach and application of state-of-the-art scientific methods. Knowledge gained will have the potential to bring unprecedented economical gains worldwide by minimizing/reducing the spread of disease.
Older (but not younger) siblings facilitate false belief understanding.

Results from 4 experiments and an analysis in which all data from 444 English and Japanese children are pooled show (a) a linear increase in understanding false belief with the number of older siblings, (b) no such effect for children younger than 3 years 2 months, (c) no helpful effect of younger siblings at any age (despite the large sample), (d) no effect of siblings' gender, and (e) no helpful effect of siblings on a task measuring children's understanding of how they know something. Discussion involves speculation about how older siblings may assist children (e.g., through pretend play and mental state language) and how different aspects of a theory of mind may develop through different means.
Investigating users' post-adoptive satisfaction and dissatisfaction toward an information system

An information system can be regarded as successful when a significant number of users use the system in a continued basis. Satisfaction is often regarded as the basis of continued usage, while dissatisfaction may cause users to discontinue the system use. While many studies of information system have investigated user satisfaction, user dissatisfaction seems to be ignored. The purpose of this study is to investigate the factors that influence user satisfaction and the factors that influence user dissatisfaction. Drawing the theoretical assumptions from Oliver’s expectation-confirmation theory and Herzberg’s twofactor theory, we propose a general theoretical framework that posits environmental factors and job-specific outcome factors may cause satisfaction and dissatisfaction. The framework extends our understanding of user satisfaction and dissatisfaction and helps to underpin and categorize the factors that are salient for causing user satisfaction and dissatisfaction during postadoption stage of information system usage. By collecting text data responses using open ended survey questions and qualitatively analyzing them, we identify a list of factors that cause educators’ satisfaction and a list of factors that cause dissatisfaction in the e-learning tool utilization context. Our study reveals that satisfaction is caused by both environmental and job-specific factors, while dissatisfaction is mainly caused by environmental factors.
Nuclear receptors and endobiotics glucuronidation: the good, the bad, and the UGT

The recent progresses in molecular biology and pharmacology approaches allowed the characterization of a series of nuclear receptors (NRs) as efficient regulators of uridine diphosphate glucuronosyltransferase (UGT) genes activity. These regulatory processes ensure an optimized UGT expression in response to specific endo- and/or exogenous stimuli. Many of these NRs are activated by endobiotics that also are substrates for UGTs. Thus, by activating their receptors, these endogenous substances control their own conjugation, leading to the concept that glucuronidation is an important part of feed-forward/feedback mechanisms by which bioactive molecules control their own concentrations. On the other hand, numerous studies have established the pharmacological relevance of NR-UGT regulatory pathways in the response to therapeutic ligands. The present review article aims at providing a comprehensive view of the physiological and pharmacological importance of the NR regulation of the expression and activity of endobiotics-conjugating UGT enzymes. Selected examples will illustrate how the organism profits from the feed-forward/feedback mechanisms involving NR-UGT pathways, but also how such regulatory processes are involved in the initiation and/or progression of several pathological situations. Finally, we will discuss how the present pharmacopeia involves NR-dependent regulation of endobiotics glucuronidation, and whether the unexploited NR-UGT axes could serve as pharmacological targets for novel therapeutics to restore endobiotics homeostasis.