Downregulation of Integrin β4 Decreases the Ability of Airway Epithelial Cells to Present Antigens

Airway epithelial cells have been demonstrated to be accessory antigen presentation cells (APC) capable of activating T cells and may play an important role in the development of allergic airway inflammation of asthma. In asthmatic airways, loss of expression of the adhesion molecule integrin β4 (ITGB4) and an increase in Th2 inflammation bias has been observed in our previous study. Given that ITGB4 is engaged in multiple signaling pathways, we studied whether disruption of ITGB4-mediated cell adhesion may contribute to the adaptive immune response of epithelial cells, including their ability to present antigens, induce the activate and differentiate of T cells. We silenced ITGB4 expression in bronchial epithelial cells with an effective siRNA vector and studied the effects of ITGB4 silencing on the antigen presentation ability of airway epithelial cells. T cell proliferation and cytokine production was investigated after co-culturing with ITGB4-silenced epithelial cells. Surface expression of B7 homologs and the major histocompatibility complex (MHC) class II was also detected after ITGB4 was silenced. Our results demonstrated that silencing of ITGB4 resulted in impaired antigen presentation processes and suppressed T cell proliferation. Meanwhile, decrease in Th1 cytokine production and increase in Th17 cytokine production was induced after co-culturing with ITGB4-silenced epithelial cells. Moreover, HLA-DR was decreased and the B7 homologs expression was different after ITGB4 silencing. Overall, this study suggested that downregulation of ITGB4 expression in airway epithelial cells could impair the antigen presentation ability of these cells, which further regulate airway inflammation reaction in allergic asthma

Highly porous flame-retardant and sustainable biofoams based on wheat gluten and in situ polymerized silica

Wheat gluten from ethanol production is presented as flame-retardant silica hybrid biofoams for insulation. The porosity of 90% and self-extinguishing nature make them an attractive alternative to petroleum-based foams.</p

The temporal relationship between the neural and vascular actions of kallidin within the nose

The time course of effect of the B2-receptor agonist kallidin (K) on induced changes of nasal airflow, rhinorrhoea, nasal pain, sneezing and nasal microvascular leakage has been examined and compared with its B2 metabolite agonist bradykinin (B) and the B1-agonist [des-arg9]-bradykinin (D). When administered as a single dose K and B induced an immediate sensation of pain, rhinorrhoea, elevations in lavage albumin and protein levels and a sustained increase in nasal airways resistance (NAR) for 5–40 min post-challenge. [des-arg9]-Bradykinin and vehicle placebo (V) were without effect on any of these indices. These studies identify the action of K and B within the nose and differentiate the neural and vascular effects of these kinins in addition to suggesting the potential that nasal blockage and nasal microvascular leakage represent alterations in differing vascular compartments. These findings have implications for the understanding and therapeutic manipulation of rhinitis

A retrospective review of Listeria monocytogenes infection at Tygerberg Children’s Hospital, Cape Town, South Africa, from 2006 to 2016: Is empirical ampicillin still indicated after the first month of life?

Background. Ampicillin to treat Listeria monocytogenes (LM) infection is empirically added to the treatment of infants (&lt;3 months) with suspected sepsis or meningitis.Objectives. In view of limited LM cases, the paucity of South African (SA) data and an ampicillin shortage, our objective was to describe the occurrence of LM infections at Tygerberg Hospital (TBH), Cape Town, with the aim of rationalising the paediatric antibiotic policy.Methods. An 11-year (2006 - 2016) retrospective descriptive study of children (&lt;13 years) from TBH and referral hospitals with a positive blood or cerebrospinal fluid (CSF) culture for LM was conducted.Results. Of 26 children with positive cultures for LM, 23 (88.5%) were &lt;3 months of age; all were &lt;10 days old. Approximately half (56.5%, 13/23) were born at or referred to TBH. Presentation was on the day of delivery in 46.2% (6/13), 92.3% were admitted to the neonatal intensive care unit (NICU), and 61.5% (8/13) died. Neonates treated at peripheral hospitals were statistically more likely than those treated at TBH to have a CSF culture obtained (90.0% v. 30.8%; p=0.005), and had higher platelet counts (239 × 109/L v. 107 × 109/L; p=0.004), lower C-reactive protein levels (64 mg/L v. 137 mg/L; p=0.013) and a lower mortality rate (0% v. 61.5%; p=0.002). The incidence of LM at TBH was 0.04/1 000 live births and 2.3/1 000 NICU admissions.Conclusions. As in other countries, the local neonatal LM incidence is low. Neonates present in the first week of life with severe disease and a high mortality rate. These data support a change in antibiotic policy, in keeping with international guidelines, limiting empirical ampicillin prescription to infants &lt;1 month of age.

The α5 Subunit Regulates the Expression and Function of α4*-Containing Neuronal Nicotinic Acetylcholine Receptors in the Ventral-Tegmental Area

Human genetic association studies have shown gene variants in the α5 subunit of the neuronal nicotinic receptor (nAChR) influence both ethanol and nicotine dependence. The α5 subunit is an accessory subunit that facilitates α4* nAChRs assembly in vitro. However, it is unknown whether this occurs in the brain, as there are few research tools to adequately address this question. As the α4*-containing nAChRs are highly expressed in the ventral tegmental area (VTA) we assessed the molecular, functional and pharmacological roles of α5 in α4*-containing nAChRs in the VTA. We utilized transgenic mice α5+/+(α4YFP) and α5-/-(α4YFP) that allow the direct visualization and measurement of α4-YFP expression and the effect of the presence (α5+/+) and absence of α5 (-/-) subunit, as the antibodies for detecting the α4* subunits of the nAChR are not specific. We performed voltage clamp electrophysiological experiments to study baseline nicotinic currents in VTA dopaminergic neurons. We show that in the presence of the α5 subunit, the overall expression of α4 subunit is increased significantly by 60% in the VTA. Furthermore, the α5 subunit strengthens baseline nAChR currents, suggesting the increased expression of α4* nAChRs to be likely on the cell surface. While the presence of the α5 subunit blunts the desensitization of nAChRs following nicotine exposure, it does not alter the amount of ethanol potentiation of VTA dopaminergic neurons. Our data demonstrates a major regulatory role for the α5 subunit in both the maintenance of α4*-containing nAChRs expression and in modulating nicotinic currents in VTA dopaminergic neurons. Additionally, the α5α4* nAChR in VTA dopaminergic neurons regulates the effect of nicotine but not ethanol on currents. Together, the data suggest that the α5 subunit is critical for controlling the expression and functional role of a population of α4*-containing nAChRs in the VTA

CD24 Expression Identifies Teratogen-Sensitive Fetal Neural Stem Cell Subpopulations: Evidence from Developmental Ethanol Exposure and Orthotopic Cell Transfer Models

Ethanol is a potent teratogen. Its adverse neural effects are partly mediated by disrupting fetal neurogenesis. The teratogenic process is poorly understood, and vulnerable neurogenic stages have not been identified. Identifying these is a prerequisite for therapeutic interventions to mitigate effects of teratogen exposures.We used flow cytometry and qRT-PCR to screen fetal mouse-derived neurosphere cultures for ethanol-sensitive neural stem cell (NSC) subpopulations, to study NSC renewal and differentiation. The identity of vulnerable NSC populations was validated in vivo, using a maternal ethanol exposure model. Finally, the effect of ethanol exposure on the ability of vulnerable NSC subpopulations to integrate into the fetal neurogenic environment was assessed following ultrasound guided, adoptive transfer.Ethanol decreased NSC mRNAs for c-kit, Musashi-1and GFAP. The CD24(+) NSC population, specifically the CD24(+)CD15(+) double-positive subpopulation, was selectively decreased by ethanol. Maternal ethanol exposure also resulted in decreased fetal forebrain CD24 expression. Ethanol pre-exposed CD24(+) cells exhibited increased proliferation, and deficits in cell-autonomous and cue-directed neuronal differentiation, and following orthotopic transplantation into naïve fetuses, were unable to integrate into neurogenic niches. CD24(depleted) cells retained neurosphere regeneration capacity, but following ethanol exposure, generated increased numbers of CD24(+) cells relative to controls.Neuronal lineage committed CD24(+) cells exhibit specific vulnerability, and ethanol exposure persistently impairs this population's cell-autonomous differentiation capacity. CD24(+) cells may additionally serve as quorum sensors within neurogenic niches; their loss, leading to compensatory NSC activation, perhaps depleting renewal capacity. These data collectively advance a mechanistic hypothesis for teratogenesis leading to microencephaly

Understanding Silicate Deposit Variability and its Implications for Evaluating TBCs and EBCs

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The osteological evidence for execution in Anglo-Saxon England

YesThis paper reviews the osteological evidence for execution in Anglo-Saxon England, which, in the cases of modern analysis, can reveal considerable detail about the methods of decapitation, in particular, and it also provides a critical appraisal of the considerably less reliable antiquarian reports. We suggest that secure evidence for execution, principally decapitation, can be identified through modern osteological analysis but it is limited, and we also argue that assertions made in antiquarian excavation reports about apparent examples of execution need to be treated with caution