Miracle-dz/UniFAR-FTUs huggingface dataset:
The medium is the messenger

Enteropathogenic Escherichia coli (EPEC), like many bacterial pathogens, employ a type III secretion system to deliver effector proteins across the bacterial cell. In EPEC, four proteins are known to be exported by a type III secretion system--EspA, EspB and EspD required for subversion of host cell signal transduction pathways and a translocated intimin receptor (Tir) protein (formerly Hp90) which is tyrosine-phosphorylated following transfer to the host cell to become a receptor for intimin-mediated intimate attachment and "attaching and effacing" (A/E) lesion formation. The structural basis for protein translocation has yet to be fully elucidated for any type III secretion system. Here, we describe a novel EspA-containing filamentous organelle that is present on the bacterial surface during the early stage of A/E lesion formation, forms a physical bridge between the bacterium and the infected eukaryotic cell surface and is required for the translocation of EspB into infected epithelial cells.
Introducing the fit-criteria assessment plot – A visualisation tool to assist class enumeration in group-based trajectory modelling

Background and objective Group-based trajectory modelling is a model-based clustering technique applied for the identification of latent patterns of temporal changes. Despite its manifold applications in clinical and health sciences, potential problems of the model selection procedure are often overlooked. The choice of the number of latent trajectories (class-enumeration), for instance, is to a large degree based on statistical criteria that are not fail-safe. Moreover, the process as a whole is not transparent. To facilitate class enumeration, we introduce a graphical summary display of several fit and model adequacy criteria, the fit-criteria assessment plot. Methods An R-code that accepts universal data input is presented. The programme condenses relevant group-based trajectory modelling output information of model fit indices in automated graphical displays. Examples based on real and simulated data are provided to illustrate, assess and validate fit-criteria assessment plot’s utility. Results Fit-criteria assessment plot provides an overview of fit criteria on a single page, placing users in an informed position to make a decision. Fit-criteria assessment plot does not automatically select the most appropriate model but eases the model assessment procedure. Conclusions Fit-criteria assessment plot is an exploratory, visualisation tool that can be employed to assist decisions in the initial and decisive phase of group-based trajectory modelling analysis. Considering group-based trajectory modelling’s widespread resonance in medical and epidemiological sciences, a more comprehensive, easily interpretable and transparent display of the iterative process of class enumeration may foster group-based trajectory modelling’s adequate use.
Anomalous nuclear enhancement in deeply inelastic scattering and photoproduction.

We derive the anomalous nuclear dependence of jet cross sections in deeply inelastic scattering and photoproduction, in terms of twist-four parton distributions in nuclei. This paper presents details of the use of factorization at higher twist to describe multiple scattering in nuclei, and the methods described here are applicable to a variety of other high-[ital p][sub [ital T]] cross sections.
Electron microscopic studies on developing cartilage. I. The membrane system related to the synthesis and secretion of extracellular materials.

The present communication describes the changing developmental pattern of the cellular organelles concerned with the synthesis and transfer of the extracellular materials during the process of chondrogenesis in chick limb-buds. Cartilage consists of a large amount of extracellular phase interspersed with chondrocytes. Chemically it is well established (Eastoe, 1961) that the main constituents of the extracellular phase are collagen and protein-polysaccharides. The latter are made up of a non-collagenous protein and acid mucopolysaccharides. The acid mucopolysaccharides are chondroitin sulphate A and C (Godman & Porter, 1960; Jackson, 1964). In electron micrographs, the extracellular phase is seen as an amorphous electron-translucent ground substance interlaced by fibrous material overlaid with electron-dense granules. The chemical interpretation of this ultrastructure is still dubious (Matukas, Panner & Orbison, 1967). It is usually considered that the amorphous ground substance consists of the acid mucopolysaccharides, the noncollagenous proteins and tropocollagen, which is a soluble form of collagen (Godman & Porter, 1960).
Effects of cypermethrin on Allium cepa

In this study, toxic effects of the cypermethrin in Allium cepa L. cells were investigated. For this aim, we investigated the changes in pigment contents, antioxidant enzymes, mitotic index and chromosomal abnormalities as indicators of toxicity. The seeds were treated with different doses (1.5, 3.0, 6.0 ppm) of cypermethrin for 72 h. The result showed that there was a significant alteration in the tested parameters depending on treatment dose in the seeds exposed to cypermethrin when compared to the control group. Cypermethrin exposure significantly reduced the carotenoid, chlorophyll a and b pigments in all treatment groups. The activity of superoxide dismutase showed a concentration‐time dependent increase and the maximum increase was observed on day 15 of treatment at 6.0 ppm cypermethrin exposure. The activity of catalase increased gradually with increasing cypermethrin concentration, but a soft decrease in CAT activity was decreased after 15 days of 1.5 ppm and 3.0 ppm cypermethrin treatment. In the roots treated with 1.5, 3.0, and 6.0 ppm cypermethrin, the level of malondialdehyde was about 1.8, 2.4, and 3.4 times higher than the control group, respectively. It was also found that cypermethrin has a mitodepressive action on mitosis, and the MI was decreased depending on the dose of cyprmethrin. All of the concentrations of cypermethrin induced chromosomal abnormalities and the most common abnormality observed in the present study was chromosome bridges. © 2011 Wiley Periodicals, Inc. Environ Toxicol 2012.
Blocking Virus Replication during Acute Murine Cytomegalovirus Infection Paradoxically Prolongs Antigen Presentation and Increases the CD8+ T Cell Response by Preventing Type I IFN–Dependent Depletion of Dendritic Cells

Increasing amounts of pathogen replication usually lead to a proportionate increase in size and effector differentiation of the CD8+ T cell response, which is attributed to increased Ag and inflammation. Using a murine CMV that is highly sensitive to the antiviral drug famciclovir to modulate virus replication, we found that increased virus replication drove increased effector CD8+ T cell differentiation, as expected. Paradoxically, however, increased virus replication dramatically decreased the size of the CD8+ T cell response to two immunodominant epitopes. The decreased response was due to type I IFN–dependent depletion of conventional dendritic cells and could be reproduced by specific depletion of dendritic cells from day 2 postinfection or by sterile induction of type I IFN. Increased virus replication and type I IFN specifically inhibited the response to two immunodominant epitopes that are known to be dependent on Ag cross-presented by DCs, but they did not inhibit the response to “inflationary” epitopes whose responses can be sustained by infected nonhematopoietic cells. Our results show that type I IFN can suppress CD8+ T cell responses to cross-presented Ag by depleting cross-presenting conventional dendritic cells.
A single tyrosine prevents insertion of ribonucleotides in the eukaryotic-type phi29 DNA polymerase.

Three conserved motifs (named A, B and C) have been proposed to form the polymerization active site in all classes of DNA-dependent polymerases. In eukaryotic-type (alpha-like) DNA polymerases, motif A is characterized by the consensus "Dx2SLYP". Mutants in phi29 DNA polymerase residue Tyr254 of this conserved motif had been previously shown to be affected in dNTP binding. Here, we show that a single substitution of Tyr254 into a valine residue enables the enzyme to incorporate ribonucleotide substrates, without affecting its wild-type affinity for dNTPs. Whereas the wild-type enzyme preferred dNTPs more than two million-fold over rNTPs, the mutation of Tyr254 into valine reduced the discrimination for rNTPs up to 1000-fold. In addition to this discrimination mechanism, based on sugar selection, phi29 DNA polymerase is very inefficient when extending an RNA primer terminus, allowing its exonucleolytic degradation. These results indicate that the Tyr254 of phi29 DNA polymerase is responsible for the discrimination against the 2'-OH group of an incoming ribonucleotide. This is the first time that the invariant tyrosine residue of motif A is involved in ribo- versus deoxyribonucleotide discrimination in an eukaryotic-type DNA polymerase.
Cloning of a putative voltage-gated sodium channel from the turbellarian flatworm Bdelloura candida

The neuromuscular sodium currents of early invertebrates such as platyhelminths display distinctive kinetic and pharmacological properties. We have cloned a cDNA from the horseshoe crab flatworm Bdelloura candida that encodes a protein homologous to the primary subunit of voltage-gated sodium channels. The B. candida protein, named BdNa1, exhibits amino acid identity of 40–47% to sodium channels of vertebrates and higher invertebrates. BdNa1 has the multidomain structure characteristic of sodium channels, and is most highly conserved in the hydrophobic transmembrane segments and the regions that form the pore of the channel. Northern blot analysis confirms the presence of a 5·4 kb BdNa1 transcript in B. candida tissue. The information provided by analysis of the BdNa1 sequence offers insight into the physiology of platyhelminth sodium currents.
Expression of the Sox11 gene in mouse embryos suggests roles in neuronal maturation and epithelio‐mesenchymal induction

Sry, the mammalian Y‐linked testis determining gene, is a member of a family of genes known as Sox genes, which encode transcription factors related by a DNA‐binding motif termed the HMG box. Sox genes are known to have diverse roles in vertebrate differentiation and development. We report here the cloning and characterisation of one of these genes, Sox11, in mice. In addition to an N‐terminal HMG box domain, the deduced SOX11 protein contains a number of highly conserved C‐terminal motifs, which may function in transcriptional regulation. Expression of Sox11 in mouse embryos was prominent in the periventricular cells of the central nervous system, suggesting a role in neuronal maturation. Expression was also observed in a wide range of tissues involved in epithelial‐mesenchymal interactions, suggesting an additional role in tissue modelling during development. Dev. Dyn. 1997;210:79–86. © 1997 Wiley‐Liss, Inc.
Real Time IoT Stream Processing and Large-scale Data Analytics for Smart City Applications

Smart cities are evolving into a larger interconnected ecosystems and many applications and services in these ecosystems are going on-line. A key challenge in smart city applications is aggregation and processing of streaming information from various domains. In fact, large amounts of valuable data and sensor information remain still unused or are limited to specific application domains due to large number of specific technologies and format, and efficient adaptive stream processing for high-level events is still a hard task. We present a smart city framework for processing large-scale IoT data streams by enriching data streams with semantic annotations, enabling adaptive processing, aggregation and federation of data. We also address the challenges of smart adaptation, user centric decision support and reliable information processing for smart city applications.
Perinatal risk factors in young adult‐onset type 1 and type 2 diabetes – a population‐based case‐control study

Objective. To examine the effects of the size of the mother and the newborn, including placental weight and gestational age at delivery, on the risk for young adult‐onset type 1 diabetes (T1DM) and type 2 diabetes (T2DM). Design. Case‐control study. Setting. Finland. Population. Subjects with T1DM and T2DM aged 15–39 at diagnosis between the years 1992 and 1996. The number of case‐control pairs was 858 for T1DM and 355 for T2DM. Methods. Diabetic subjects were identified from the Finnish national healthcare registers and reports from diabetes nurses. Control subjects were obtained from the population register. Data on perinatal factors were obtained from the original healthcare records. The odds ratios (ORs) for both types of diabetes were estimated using conditional logistic regression. Results. The risk for early‐onset T2DM decreased with increasing birthweight until 4.2 kg (OR 0.49 (95% confidence interval 0.37–0.66) per 1 kg), but with birthweight above 4.2 kg the risk increased (OR 4.8 (1.3–17.6) per 1 kg). The risk for T2DM decreased also with increasing birth length (OR 0.88 (0.81–0.95) per 1 cm), body mass index at birth (OR 0.81 (0.73–0.90) per 1 kg/m2), and placental weight (OR 0.77 (0.61–0.98) per 100 g). The latter was not significant when adjusted for birthweight. The examined perinatal factors did not affect the risk for T1DM in young adults. Conclusions. Birth size significantly affects the risk for T2DM diagnosed in young adulthood but no evidence was found of an association between late‐onset T1DM and perinatal factors.
Concept of Pharmacogenomics and Future Considerations

Council of Scientiﬁc and Industrial Research-Institute of Genomics and Integrative Biology (CSIR-IGIB), Delhi, IndiaCorrespondenceRitushree Kukreti,Genomics and Molecular Medicine Unit,Council of Scientiﬁc and Industrial Research-Institute of Genomics and Integrative Biology(CSIR-IGIB), Mall Road, Delhi 110 007, India.Tel. : 91-11-27662201;Fax: 91-11-27667471;E-mail: ritus@igib.res.inReceived 7 June 2013; revision 3 July 2013;accepted 4 July 2013doi: 10.1111/cns.12157
Vérification et dépliages de réseaux de Petri temporels paramétrés. (Model-checking and unfoldings of parametric time Petri nets)

Les travaux presentes portent sur l'etude de methodes de verification parametree des systemes temps reels. La motivation pour ces recherches est de proposer des methodes formelles a appliquer sur des systemes dont les specifications ne sont pas encore completes. Des parametres sont donc introduits dans les modeles utilises afin de donner des degres de liberte a la modelisation. Le but est alors de guider la conception du systeme en determinant des valeurs satisfaisantes pour les parametres. Nous nous sommes focalise sur les parametres temporels qui sont en general parmi les plus complexes a definir. Nous avons ainsi defini le modele des reseaux de Petri a chronometres parametres. Dans une premiere approche, nous etendons les methodes d'analyse classiquement utilisees dans les reseaux de Petri temporels. L'espace d'etats du modele parametre est ainsi represente par le graphe des classes d'etats parametrees. Cela nous permet de proposer des semi-algorithmes de model-checking parametre avec lesquels nous verifions des formules de logique TCTL parametrees. Dans une seconde approche, nous etudions les methodes qui preservent le parallelisme des reseaux de Petri. L'interet est de limiter l'explosion combinatoire qui apparait lors de l'analyse de systemes distribues, en particulier avec des modeles parametres. Nous proposons pour cela une methode de depliage temporel parametre. Ce depliage est a priori infini, mais nous proposons de l'utiliser pour resoudre un probleme de supervision. La construction du depliage est alors guidee par des observations finies, et nous extrayons les explications de ces observations, ainsi que les contraintes sur les parametres qu'elles induisent.
THE ROLE OF WILD MAMMALS IN THE MAINTENANCE OF RIFT VALLEY FEVER VIRUS

Rift Valley fever virus (RVFV) is a zoonotic arbovirus affecting primarily domestic ruminants and humans. Numerous vector species are known or implicated in the transmission of RVFV. The role of mammals in the maintenance of RVFV, and the existence of a wild mammal reservoir in the epidemiologic cycle of RVFV, remain largely unknown. Our objective is to present a detailed review of studies undertaken on RVFV, often associated with wild mammals, with the aim of focusing future research on potential reservoirs of the virus. Natural and experimental infections related to RVFV in several mammalian orders, including Artiodactyla, Chiroptera, Rodentia, Primata (nonhuman), Perissodactyla, Carnivora, Proboscidea, Erinaceomorpha, and Lagomorpha, are reviewed; the first four orders have received the greatest attention. The possible role of wild ruminants, especially African buffalo (Syncerus caffer), is also discussed. Conflicting results have been published concerning rodents but, based on the literature, the likely candidate species include the African genera Arvicanthis and Micaelamys and the widely introduced roof rat (Rattus rattus). Members of the orders Chiroptera and Rodentia should receive greater attention associated with new research programs. For the other orders mentioned above, few data are available. We are unaware of any investigation concerning the orders Afrosoricida and Soricomorpha, which are represented in the geographic area of RVFV and can be abundant. As a first step to resolve the question of wild mammals as a reservoir of RVFV, serologic and virologic surveys should be promoted during epizootic periods to document infected wild animals and, in the case of positive results, extended to interepidemic periods to explore the role of wild animals as possible reservoirs.
Stimulation of P2X7 receptors elevates Ca2+ and kills retinal ganglion cells.

PURPOSE Retinal ganglion cells are known to express ionotropic P2X(7) receptors for ATP. Stimulation of these receptors in other cells can elevate Ca(2+) and sometimes lead to cell death. This study asked whether P2X(7) receptor stimulation alters the Ca(2+) levels and viability of retinal ganglion cells. METHODS P2X(7) agonists were applied to retinal ganglion cells from neonatal rats loaded with fura-2 to examine their effect on intracellular Ca(2+) levels. The effect of P2X(7) receptor stimulation on cell viability was examined in rat retinal ganglion cells back-labeled with aminostilbamidine. RESULTS The P2X(7) agonist benzoylbenzoyl adenosine triphosphate (BzATP) led to a large, sustained increase in Ca(2+). BzATP was >100-fold more effective than ATP at raising intracellular Ca(2+), when both agonists were applied at 10 microM. The response to BzATP was enhanced threefold by removal of extracellular Mg(2+), was dependent on extracellular Ca(2+), and was prevented by brilliant blue G (BBG). BzATP led to a concentration-dependent reduction in the number of cells with a median lethal dose (LD(50)) of 35 muM. Cell death was prevented by the P2X(7) antagonists BBG and oxidized ATP, but not by 30 microM suramin, consistent with the actions of the P2X(7) receptor. BzATP activated caspases in ganglion cells, but did not lead to membrane blebbing or increased permeability to Yo-Pro-1. The L-type Ca(2+) channel blocker nifedipine attenuated cell death, suggesting excessive Ca(2+) influx contributes to the lethal effects of BzATP. CONCLUSION Short-term stimulation of the P2X(7) receptor can raise Ca(2+) in rat retinal ganglion cells, whereas sustained stimulation of the receptor can kill them.
ACE inhibitors versus diuretics: ALLHAT versus ANBP2

The ALLHAT (The Antihypertensive and Lipid-Lowering treatment to prevent Heart Attack Trial) trial enrolled hypertensive patients with at least one additional risk factor for coronary heart disease (CHD) to a comparison of the diuretic chlorthalidone, the calcium channel blocker, amlodipine, and the angiotensin-converting enzyme (ACE) inhibitor, lisinopril. Throughout the study, chlorthalidone decreased the systolic blood pressure to a slightly, but significantly greater extent (0.8 – 3.1 mmHg) than amlodipine or lisinopril. No significance differences were reported for amlodipine versus chlorthalidone or lisinopril versus chlorthalidone on the primary outcome of combined incidence of fatal CHD and nonfatal myocardial infarction. The findings of ALLHAT support the use of thiazide-type diuretics as first choice pharmacological therapy in at risk patients with hypertension. ANBP2 (The Second Australian National Blood Pressure Study) was also a comparison between diuretics (hydrochlorothiazide) and ACE inhibitors (enalapril) but was performed in older hypertensives that had few previous cardiovascular events. Diastolic blood pressure reduction was similar in both groups at all times. The risk of the primary outcome of all cardiovascular events or death from any cause was 11% lower in the ACE group than the diuretic group and the benefit was predominantly in men. Thus, ANBP2 suggests that in relatively healthy elderly hypertensive patients, ACE inhibitors should be preferred to diuretics.
Inventing the User: EDSAC in Context

Electronic delay storage automatic calculator (EDSAC) is rightly celebrated as the first internal stored-program computer to provide useful problem solving services. This paper identifies the user as an emergent new class of practitioner, and locates EDSAC in the context of the history of the internal stored program widely held to be the defining feature of the modern digital computer. The significance of the stored-program concept is far from self-evident and an interpretation of its defining role, as well as EDSAC's part in this, is offered.
Alternative Splicing at the 3′‐cDNA of Human Tryptophan Hydroxylase

Abstract: Two alternatively spliced transcripts of human tryptophan hydroxylase (TPH) were identified that differed at the 3′ end of the open reading frame. Comparison of the human TPH cDNA and genomic sequences revealed that an intron containing an in‐frame stop codon could be alternatively spliced out of intron 11. This splicing would give rise to two human TPH isoforms with different C termini; the one that derives from the nonspliced intron contains a putative cyclic AMP‐dependent protein kinase site, whereas the other one, which is 22 amino acids longer, does not. Analysis of various human tissues by RT‐PCR revealed that the spliced TPH mRNA species was detected in all the postmortem tissues we tested, but the nonspliced species was expressed in only some tissues.
FGF‐4 signaling is involved in mir‐206 expression in developing somites of chicken embryos

The microRNAs (miRNAs) are recently discovered short, noncoding RNAs, that regulate gene expression in metazoans. We have cloned short RNAs from chicken embryos and identified five new chicken miRNA genes. Genome analysis identified 17 new chicken miRNA genes based on sequence homology to previously characterized mouse miRNAs. Developmental Northern blots of chick embryos showed increased accumulation of most miRNAs analyzed from 1.5 days to 5 days except, the stem cell–specific mir‐302, which was expressed at high levels at early stages and then declined. In situ analysis of mature miRNAs revealed the restricted expression of mir‐124 in the central nervous system and of mir‐206 in developing somites, in particular the developing myotome. In addition, we investigated how miR‐206 expression is controlled during somite development using bead implants. These experiments demonstrate that fibroblast growth factor (FGF) ‐mediated signaling negatively regulates the initiation of mir‐206 gene expression. This may be mediated through the effects of FGF on somite differentiation. These data provide the first demonstration that developmental signaling pathways affect miRNA expression. Thus far, miRNAs have not been studied extensively in chicken embryos, and our results show that this system can complement other model organisms to investigate the regulation of many other miRNAs. Developmental Dynamics 235:2185–2191, 2006. © 2006 Wiley‐Liss, Inc.