Miracle-dz/UniFAR-FTUs huggingface dataset:
Enhanced Dendritic Cell Antigen Uptake via α2 Adrenoceptor-Mediated PI3K Activation Following Brief Exposure to Noradrenaline

Although noradrenaline (NA), a stress-associated neurotransmitter, seems to affect the immune system, the precise mechanisms underlying NA-mediated immunoregulation are not fully understood. We examined the effect of NA on Ag uptake (endocytosis) by dendritic cells (DCs) using murine bone marrow-derived DCs and fluorescence-labeled endocytic tracers (dextran and OVA). Ag uptake by DCs notably increased following a very brief treatment (3 min) with NA. NA-induced endocytosis was completely blocked by treatment with α2-adrenoceptor antagonist yohimbine. Neither α1-adrenoceptor antagonist prazosin nor β-adrenoceptor antagonist propranolol affected NA-induced endocytosis by DCs. A selective α2-adrenoceptor agonist, azepexole (B-HT 933), also significantly increased endocytosis by DCs. Thus, the α2-adrenoceptor seems to be responsible for NA-induced DC endocytosis. In parallel, NA markedly activated intracellular signaling pathways of PI3K and ERK1/2 in DCs. NA-mediated activation of these pathways was completely inhibited by yohimbine treatment. Blocking PI3K activation significantly reduced NA-induced endocytosis by DCs. Based on these results, NA rapidly enhances Ag capture by DCs via α2 adrenoceptor-mediated PI3K activation, which may be associated with immune enhancement following acute stress.
Sémantique et syntaxe dans l'acquisition des classes de mots : l'exemple des noms et des verbes en français

D. Bassano, Semantic and syntax in word classes acquisition: Nouns and verbs in French This paper investigates semantic and syntactic aspects in the acquisition of word classes in early French during the 2nd and 3rd years of life. Using analyses of children's naturalistic productions, it provides an overview of the emergence of the lexicon, and focuses on the development of two central word classes, nouns and verbs. Developmental processes in the construction of both the notional-semantic and the grammatical classes are analysed for both nouns and verbs, and the relationships among all of these processes are examined in the light of an integrative conception of language acquisition.
Seroprevalence and Risk Factors Associated with Escherichia coli O157 in a Farming Population

Evidence suggests that frequent and direct exposure to domestic animals has made farmers less susceptible to symptomatic Escherichia coli O157 infection than other members of the community. We have quantified the seroprevalence of antibodies to E. coli O157 lipopolysaccharide (LPS) from a representative cohort of farm workers in three geographically distinct regions of the United Kingdom during two sampling rounds over a 2‐year period. All participants completed a questionnaire to determine the range and extent of recent animal contact alongside other potential occupational and environmental exposure routes. A total of 31/946 (3.3%) serum samples contained antibodies to E. coli O157 LPS (from both rounds combined). On the second sampling round, a significant difference in seropositivity was apparent between the three regions, with enhanced seroprevalence linked to recent contact with beef cattle, having a private water supply and contact with a child under 5 years old. Only five seropositive people reported symptoms of a gastrointestinal tract infection, although these symptoms were mild. These results further support the premise of acquired immunity to E. coli O157 associated with prolonged antigenic exposures within the farming environment.
Molecular basis of high viscosity in concentrated antibody solutions: Strategies for high concentration drug product development

ABSTRACT Effective translation of breakthrough discoveries into innovative products in the clinic requires proactive mitigation or elimination of several drug development challenges. These challenges can vary depending upon the type of drug molecule. In the case of therapeutic antibody candidates, a commonly encountered challenge is high viscosity of the concentrated antibody solutions. Concentration-dependent viscosity behaviors of mAbs and other biologic entities may depend on pairwise and higher-order intermolecular interactions, non-native aggregation, and concentration-dependent fluctuations of various antibody regions. This article reviews our current understanding of molecular origins of viscosity behaviors of antibody solutions. We discuss general strategies and guidelines to select low viscosity candidates or optimize lead candidates for lower viscosity at early drug discovery stages. Moreover, strategies for formulation optimization and excipient design are also presented for candidates already in advanced product development stages. Potential future directions for research in this field are also explored.
Casein kinase I « in the Wnt pathway : Regulation of b-catenin function

Wnt and its intracellular effector b-catenin regulate developmental and oncogenic processes. Using expression cloning to identify novel components of the Wnt pathway, we isolated casein kinase I« (CKI«). CKI« mimicked Wnt in inducing a secondary axis in Xenopus, stabilizing b-catenin, and stimulating gene transcription in cells. Inhibition of endogenous CKI« by kinase-defective CKI« or CKI« antisense-oligonucleotides attenuated Wnt signaling. CKI« was in a complex with axin and other downstream components of the Wnt pathway, including Dishevelled. CKI« appears to be a positive regulator of the pathway and a link between upstream signals and the complexes that regulate b-catenin.
An 8-year single-centre experience of cardiac resynchronisation therapy: procedural success, early and late complications, and left ventricular lead performance.

AIMS Despite the increasing number of device implants worldwide, little is known about the early and late complications of cardiac resynchronisation therapy (CRT) or the incidence of these complications in patients with different heart failure aetiologies. We aim to determine procedural success and early and late complications in CRT patients. METHODS AND RESULTS All early (<90 days) and late (>90 days) complications occurring over 490 consecutive CRT procedures in 402 patients, from a large single-centre registry between 2000 and 2009 were analysed. Mean follow-up duration was 1012 ± 610 days. In addition, procedural data and long-term left ventricular (LV) lead performance were examined. The mean age of patients was 65 ± 15 years, 31% were female. The majority of devices (70%) were CRT-defibrillators. Left ventricular lead implantation was achieved after one or more than one attempt in 96.7% of patients (first procedure was successful in 95.1%). The incidence of early and late complications was 9.4% and 6.1% respectively. Infection and lead displacement were the most common complications. Dilated cardiomyopathy (DCM) was associated with significantly more complications than ischaemic cardiomyopathy (P = 0.01) and these occurred later in the DCM population. Long-term LV lead performance was comparable with that of right atrial and ventricular leads. CONCLUSION Transvenous implantation of the LV lead is safe and achievable for CRT with high procedural success rates. For the first time we describe the late complications from CRT in different heart failure populations. This group of patients must be kept under surveillance, not only for heart failure events but also for device-related issues. The reasons for higher complication rates in DCM patients require further evaluation.
Inhibition of the cytokine response does not protect against lethal H5N1 influenza infection

Because proinflammatory cytokines are markedly elevated during H5N1 influenza virus infection, the “cytokine storm” is hypothesized to be the main cause of mortality. Here, we demonstrate that mice deficient in the hallmark inflammatory cytokines TNF-α, IL-6, or CC chemokine ligand 2 succumb to infection with A/Vietnam/1203/04 (H5N1) virus, as do wild-type mice treated with glucocorticoids for suppression of cytokines. Because cytokine inhibition does not protect against death, therapies that target the virus rather than cytokines may be preferable.
From the old to the new: Is forensic mental health nursing in transition?

&NA; This study adopts a qualitative research strategy (Interpretative Phenomenological Analysis) to explore in‐depth the lived experience of six forensic mental health nurses working within Scotland. This paper examines one of the core themes uncovered through analyzing the transcripts, “From the Old to the New. ” This theme, it is suggested, reflects these nurses' experience as they move from the previously accepted culture and practice of forensic nursing to a new “humanistic” and “interpersonal” perspective.
Determination of renal arterial stenosis severity: comparison of pressure gradient and vessel diameter.

PURPOSE To determine the hemodynamic significance of arteriographically detected renal arterial stenosis by obtaining pressure gradients with a miniaturized pressure guide wire. MATERIALS AND METHODS Forty-six renal arterial stenoses in 38 patients were assessed in terms of severity and then subjected to gradient determination before and after angioplasty. The patients (mean age, 63 years) had a mean serum creatinine value of 1.3 mg/dL +/- 0.4 (114.9 micromol/L +/- 35.4 [SD]) and required on average three medications for blood pressure control. The mean degree of stenosis diameter was 51% +/- 17 (range, 12%-85%). RESULTS The systolic and mean arterial pressure gradients with and those without vasodilatation were highly correlated with stenosis severity, systolic blood pressure, and serum creatinine as a curvilinear fit (r = 0.9, P <.01). At 50% stenosis severity, the mean pressure gradient was 22 mm Hg. CONCLUSION Patients with a pressure gradient greater than 20 mm Hg should be good candidates for renal arterial dilatation, and use of the pressure guide wire will facilitate interventional decisions.
Family interaction and a supportive social network as salutogenic factors in childhood atopic illness

The role of psycho‐social factors in the development of allergy was studied prospectively in 82 infants with a family history of atopy. The family participated in a standardized family test when the children were 18 months old. The ability to adjust to demands of the situation (‘adaptability’), and the balance between emotional closeness and distance (‘cohesion’), were assessed from videotapes by independent raters. Families rated as functional in both of these aspects were classified as ‘functional’, otherwise as ‘dysfunctional’. The social network, life events, atopic symptoms (based on postal inquiries regarding symptoms answered by the parents, and on physical examinations), psychiatric symptoms, and socio‐economic circumstances of the families were evaluated when the children were 18 months and 3 years of age. The children were classified as atopic (asthmatic symptoms or eczema) or as non‐atopic. All but two children with atopic disease at 3 years of age had atopic disease before 18 months of age, while 32 of 60 children with atopic disease at 18 months of age had no problems by 3 years of age. An unbalanced family interplay at 18 months was associated with a relative risk (RR) of 1.99 for continuing atopic illness at 3 years of age (1.18 < RR < 3.37, p = 0.01). There was a weak positive confounding effect for smoking (RR reduced by 7%), eczema on three or more localizations (RR reduced by 4.5%), and the amount of cat allergen in household dust (RR reduced by 3%). Recovery from atopic illness between 18 months and 3 years of age was four times as probable in families with functional interaction and a good social supportive network when children were 18 months of age, than in dysfunctional families with a poor social network (74% versus 20% p < 0.01). Children with asthmatic symptoms showed more signs of emotional distress than did healthy children (p = 0.02). Dysfunctional family interaction patterns were more commonly observed in families of children who at 3 years of age still had atopic symptoms, than in children who had recovered. The patterns included expression of emotion and reaction to the needs of others, alternating between total disinterest and over‐involvement (p = 0.02), lack of support and rejection of offered support (p = 0.01), a greater number of individual decisions without regard to the other family members (p = 0.04), and indistinct ‘generational boundaries’ (p = 0.04). We conclude that psychosocial factors, such as family interaction and a supportive social network, play a significant role in the course of atopic illness in early childhood and that measures which enhance family interaction and the social network could influence the course of the disease favorably.
Field condition reliability assessment for SnPb and SnAgCu solder joints in power cycling including mini cycles

Actual field conditions that computer components such as microprocessors experience are different from the accelerated thermal cycling tests typically used to perform reliability assessment. Field conditions can include longer dwell times, different temperature ramp rates driven by power ON/OFF events, and temperature fluctuations during the power ON state due to workload patterns. Series of numerical simulations have been performed to study the effect of the field conditions on the solder joint fatigue life of electronic packaging. The simulation results show that SnPb and SnAgCu solders respond differently with respect to dwell time and mini cycles. Without considering the effect of mini-cycles, it is possible that SnAgCu may fail earlier than SnPb with very long dwell time. However, it is important to note if mini-cycles contribute to damage as seen in this analysis, the SnPb solder will probably still fail before SnAgCu solder
Rocking ratchets in two-dimensional Josephson networks: collective effects and current reversal.

A detailed numerical study on the directed motion of ac-driven vortices and antivortices in 2D Josephson junction arrays with an asymmetric periodic pinning potential is reported. dc-voltage rectification shows a strong dependence on vortex density as well as an inversion of the vortex flow direction with ac amplitude for a wide range of vortex density around f = 1/2 (f = Ha(2)/Phi(0)), in good agreement with recent experiments by Shalóm and Pastoriza [Phys. Rev. Lett. 94, 177001 (2005)10.1103/PhysRevLett.94. 177001]. The study of vortex structures, spatial and temporal correlations, and vortex-antivortex pairs formation gives insight into a purely collective mechanism behind the current reversal effect.
Anxiogenic effects in the rat elevated plus-maze of 5-HT2C agonists into ventral but not dorsal hippocampus

The effect of the non-selective 5-HT2C receptor agonist trifluoromethyl-phenylpiperazine (TFMPP, 0.75, 1.5 and 3.0 lg) and the preferential 5-HT2C agonist 6-chloro-2 (1-piperazinyl)pyrazine (MK-212, 0.1, 0.3 and 1.0 lg) microinjected into the ventral or dorsal hippocampus was investigated in anxiety measures of rats exposed to the elevated plus-maze test. Ventral hippocampal (VH) microinjections of the 0.75 or 1.5 lg doses of TFMPP reduced open-arm exploration without affecting the number of closed-arm entries, indicating a selective anxiogenic profile. The highest dose (3.0 lg) reduced openand closed-arm entries, suggesting interference in locomotor activity. The 0.1 lg dose of MK-212 also caused a selective anxiogenic effect when microinjected into the ventral hippocampus, without disturbing locomotor activity. Microinjections of the two higher doses of MK-212 (0.3 or 1.0 lg) into the ventral hippocampus led to a decrease of exploration in both arms of the maze. In contrast to the anxiogenic effect observed in the VH, neither TFMPP nor MK-212 significantly changed anxiety measures when microinjected into the dorsal hippocampus. These results suggest that activation of 5-HT2C postsynaptic receptors located in the ventral, but not in the dorsal, hippocampus play an important role in anxiety triggered by the elevated plus-maze test. Behavioural Pharmacology 15:37–43 c 2004 Lippincott Williams & Wilkins.
Mitochondrial apoptotic cell death and moderate superoxide generation upon selective activation of non‐desensitizing AMPA receptors in hippocampal cultures

In the present work we investigated the effect of selective stimulation of non‐desensitizing α‐amino‐3‐hydroxy‐5‐methyl‐4‐isoxazolepropionate (AMPA) receptors in the intracellular processes leading to hippocampal neuronal death and production of reactive oxygen species (ROS). Activation of AMPA receptors in the presence of cyclothiazide (CYZ), a blocker of AMPA receptor desensitization, resulted in the death of approximately 25% of neurones, which was prevented by 2,3‐dihydroxy‐6‐nitro‐7‐sulphamoyl‐benzo(f)quinoxaline (NBQX), an AMPA‐preferring receptor antagonist. (+)‐5‐Methyl‐10,11‐dihydro‐5H‐dibenzo[a,d]cyclohepten‐5,10‐imine hydrogen maleate (MK‐801) protected the neurones from necrotic death induced by AMPA or NMDA receptor activation. Neurodegeneration caused by selective activation of non‐desensitizing AMPA receptors, in the presence of AMPA, CYZ and MK‐801, significantly decreased the number of Co2+‐positive neurones, used as a cytochemical marker of Ca2+‐permeable AMPA receptors, but maintained intracellular ATP/ADP. The AMPA‐mediated apoptotic cell death involved mitochondrial cytochrome c release and the activation of caspases‐1 and ‐3, which was prevented by NBQX. Interestingly, although selective activation of AMPA receptors was not associated with production of intracellular peroxides, a moderate increase in superoxide production was observed upon exposure to antimycin A (AA). Furthermore, increased activity of Mn‐ superoxide dismutase (SOD) was observed on selective activation of non‐desensitizing AMPA receptors. Taken together, these data make important contributions to the elucidation of the downstream pathways activated in AMPA receptor‐mediated excitotoxicity in cultured rat hippocampal neurones.
Tecarfarin, a Novel Vitamin K Reductase Antagonist, Is Not Affected by CYP2C9 and CYP3A4 Inhibition Following Concomitant Administration of Fluconazole in Healthy Participants

Comparative pharmacokinetics of vitamin K epoxide reductase antagonists tecarfarin and warfarin were assessed before and after coadministration for 21 days of the CYP450 inhibitor fluconazole in a randomized, open‐label, single‐center drug interaction study. Twenty healthy adult participants were randomized 1:1 to receive approximately equipotent single oral doses of tecarfarin (50 mg) or warfarin (17.5 mg). Following 7 days of baseline serial blood level collections, each participant received oral fluconazole 400 mg daily for 21 days. A second identical single oral dose of tecarfarin or warfarin was given 14 days after starting fluconazole with serial pharmacokinetic sampling. Key pharmacokinetic parameters Cmax, tmax, AUC0–168, apparent clearance, and t1/2 demonstrated no tecarfarin‐fluconazole interaction but a strong warfarin‐fluconazole interaction. The ratio of log‐transformed mean AUC0–168 with versus without fluconazole for tecarfarin was 91.2% (90% confidence interval [CI]: 83.3–99.8) and for racemic warfarin was 213% (90% CI: 202–226). The 90% CI was entirely within the standard 80% to 125% bioequivalence interval for tecarfarin but well outside the bioequivalence interval for warfarin, confirming a clinically significant pharmacokinetic interaction between warfarin and fluconazole. In contrast, tecarfarin pharmacokinetics were apparently unchanged by fluconazole.
The cellular concentration of the sigma S subunit of RNA polymerase in Escherichia coli is controlled at the levels of transcription, translation, and protein stability.

The second vegetative sigma factor sigma S (encoded by the rpoS gene) is the master regulator in a complex regulatory network that governs the expression of many stationary phase-induced and osmotically regulated genes in Escherichia coli. Using a combination of gene-fusion technology and quantitative immunoblot, pulse-labeling, and immunoprecipitation analyses, we demonstrate here that rpoS/sigma S expression is not only transcriptionally controlled, but is also extensively regulated at the levels of translation and protein stability. rpoS transcription is inversely correlated with growth rate and is negatively controlled by cAMP-CRP. In complex medium rpoS transcription is stimulated during entry into stationary phase, whereas in minimal media, it is not significantly induced. rpoS translation is stimulated during transition into stationary phase as well as by an increase in medium osmolarity. A model involving mRNA secondary structure is suggested for this novel type of post-transcriptional growth phase-dependent and osmotic regulation. Furthermore, sigma S is a highly unstable protein in exponentially growing cells (with a half-life of 1.4 min), that is stabilized at the onset of starvation. When cells are grown in minimal glucose medium, translational induction and sigma S stabilization occur in a temporal order with the former being stimulated already in late exponential phase and the latter taking place at the onset of starvation. Although sigma S does not control its own transcription, it is apparently indirectly involved in a negative feedback control that operates on the post-transcriptional level. Our analysis also indicates that at least five different signals [cAMP, a growth rate-related signal (ppGpp? ), a cell density signal, an osmotic signal, and a starvation signal] are involved in the control of all these processes that regulate rpoS/sigma S expression.
Ongoing Activity of Toscana Virus Genotype A and West Nile Virus Lineage 1 Strains in Turkey: A Clinical and Field Survey

Toscana virus (TOSV), West Nile virus (WNV) and tickborne encephalitis virus (TBEV) are among major viral pathogens causing febrile disease and meningitis/encephalitis. The impact of these viruses was investigated at a referral centre in Ankara Province, Central Anatolia in 2012, where previous reports suggested virus circulation but with scarce information on clinical cases and vector activity. Serum and/or cerebrospinal fluid samples from 94 individuals were evaluated, in addition to field‐collected arthropod specimens that included 767 sandflies and 239 mosquitoes. Viral nucleic acids in clinical samples and arthropods were sought via specific and generic nested/real‐time PCRs, and antibody responses in clinical samples were investigated via commercial indirect immunofluorescence tests (IIFTs) and virus neutralization. A WNV antigen assay was also employed for mosquitoes. WNV neuroinvasive disease has been identified in a 63‐year‐old male via RNA detection, and the WNV strain was characterized as lineage 1. TOSV infections were diagnosed in six individuals (6.3%) via RNA or IgM detection. Partial sequences in a 23‐year‐old female, presented with fever and transient pancytopenia, were characterized as TOSV genotype A. Febrile disease with arthralgia and/or peripheral cranial nerve involvement was noted in cases with TOSV infections. Previous WNV and TOSV exposures have been observed in 5.3% and 2.1% of the subjects, respectively. No confirmed TBEV exposure could be identified. Morphological identification of the field‐collected mosquitoes revealed Culex pipiens sensu lato (74.4%), Anopheles maculipennis (20.9%), An. claviger (2.1%) and others. Sandfly species were determined as Phlebotomus papatasi (36.2%), P. halepensis (27.3%), P. major s. l. (19.3%), P. sergenti (8.9%), P. perfiliewi (4.4%), P. simici (2.6%) and others. Viral infections in arthropods could not be demonstrated. TOSV genotype A and WNV lineage 1 activity have been demonstrated as well as serologically proven exposure in patients. Presence of sandfly and mosquito species capable of virus transmission has also been revealed.