Hapten contact hypersensitivity (CHS) elicits a well-documented inflammation response that can be used to illustrate training of immune cells through hapten-specific CHS memory. The education of ...hapten-specific memory T cells has been well-established, recent research in mice has expanded the "adaptive" characteristic of a memory response from solely a function of the adaptive immune system, to innate cells as well. To test whether similar responses are seen in a non-rodent model, we used hapten-specific CHS to measure the ear inflammation response of outbred pigs to dinitrofluorobenzene (DNFB), oxazolone (OXA), or vehicle controls. We adapted mouse innate memory literature protocols to the domestic pig model. Animals were challenged up to 32 days post initial sensitization exposure to the hapten, and specific ear swelling responses to this challenge were significant for 7, 21, and 32 days post-sensitization. We established hapten-specific CHS memory exists in a non-rodent model. We also developed a successful protocol for demonstrating these CHS responses in a porcine system.
Mycobacterium bovis (
M. bovis
) is the zoonotic bacterium responsible for bovine tuberculosis. An attenuated form of
M. bovis
, Bacillus Calmette-Guerin (BCG), is a modified live vaccine known to ...provide variable protection in cattle and other species. Protection for this vaccine is defined as a reduction in disease severity rather than prevention of infection and is determined by evaluation of the characteristic lesion of tuberculosis: the granuloma. Despite its recognized ability to decrease disease severity, the mechanism by which BCG imparts protection remains poorly understood. Understanding the histopathologic differences between granulomas which form in BCG vaccinates compared to non-vaccinates may help identify how BCG imparts protection and lead to an improved vaccine. Utilizing special stains and image analysis software, we examined 88 lymph nodes obtained from BGC-vaccinated and non-vaccinated animals experimentally infected with
M. bovis
. We evaluated the number of granulomas, their size, severity (grade), density of multinucleated giant cells (MNGC), and the amounts of necrosis, mineralization, and fibrosis. BCG vaccinates had fewer granulomas overall and smaller high-grade granulomas with less necrosis than non-vaccinates. The relative numbers of high- and low- grade lesions were similar as were the amounts of mineralization and the density of MNGC. The amount of fibrosis was higher in low-grade granulomas from vaccinates compared to non-vaccinates. Collectively, these findings suggest that BCG vaccination reduces bacterial establishment, resulting in the formation of fewer granulomas. In granulomas that form, BCG has a protective effect by containing their size, reducing the relative amount of necrosis, and increasing fibrosis in low-grade lesions. Vaccination did not affect the amount of mineralization or density of MNGC.
Introduction
Childhood trauma (CT) is associated with severe sequelae, including personality disorders and stress-related mental health disorders that can perpetuate long into adulthood.
Objectives
...We aimed to investigate (1) whether childhood trauma is associated with anger in adulthood, and, if so, (2) to explore which types of childhood trauma predominate in the prediction of anger, and (3) to explore whether the association is independent of psychopathology in a cohort that included participants without lifetime psychiatric disorders, with current or remitted depressive and anxiety disorders, or comorbid depressive and anxiety disorders.
Methods
In the Netherlands Study of Depression and Anxiety (NESDA), childhood trauma was assessed with a semi-structured Childhood Trauma Interview (CTI) at baseline, and analyzed in relation to anger as measured at 4-year follow-up with the Spielberger Trait Anger Subscale (STAS), the Anger Attacks Questionnaire, and cluster B personality traits (i.e., borderline, antisocial) of the Personality Disorder Questionnaire 4 (PDQ-4), using analysis of covariance (ANCOVA) and multivariable logistic regression analyses. Post-hoc analyses comprised cross-sectional regression analyses, using the Childhood Trauma Questionnaire – Short Form (CTQ-SF) obtained at 4-year follow-up.
Results
Participants (
n
= 2,276) were on average 42.1 years (
SD
= 13.1), and 66.3% were female. Childhood trauma showed a dose-response association with all anger constructs. Zooming in, all types of childhood trauma except for sexual abuse were associated with higher levels of trait anger, and a higher prevalence of anger attacks and antisocial personality traits in adulthood, independently of depression and anxiety. Additionally, all types of childhood trauma were significantly associated with borderline personality traits. Cross-sectionally, the effect sizes were larger compared to the analyses with the childhood trauma measured four years prior to the anger measures.
Conclusions
Childhood trauma is linked with anger in adulthood, most strongly for trait anger and borderline personality traits. It is of clinical importance to explore childhood traumatic experience and start trauma-focused interventions when appropriate.
Disclosure of Interest
None Declared
Neutrophils are principal host innate immune cell responders to mastitis infections. Thus, therapies have been developed that target neutrophil expansion. This includes the neutrophil-stimulating ...cytokine granulocyte colony-stimulating factor (gCSF). Pegylated gCSF (PEG-gCSF; Imrestor, Elanco Animal Health, Greenfield, IN) has been shown to reduce the natural incidence of mastitis in periparturient cows in commercial settings and reduce severity of disease against experimental mastitis challenge. Pegylated gCSF stimulates neutrophil expansion but also induces changes in monocyte and lymphocyte circulating numbers, surface protein expression changes, or both. We hypothesized that PEG-gCSF modulates surface expression of monocytes and neutrophils and facilitates their migration to the mammary gland. We challenged 8 mid-lactation Holsteins with approximately 150 cfu of Staphylococcus aureus (Newbould 305) in a single quarter via intramammary infusion. All animals developed chronic infections as assessed by bacteria counts and somatic cell counts (SCC). Ten to 16 wk postchallenge, 4 of the animals were treated with 2 subcutaneous injections of PEG-gCSF 7 d apart. Complete blood counts, SCC, bacterial counts, milk yield, feed intake, neutrophils extracellular trap analysis, and flow cytometric analyses of milk and blood samples were performed at indicated time points for 14 d after the first PEG-gCSF injection. The PEG-gCSF-treated cows had significantly increased numbers of blood neutrophils and lymphocytes compared with control cows. Flow cytometric analyses revealed increased surface expression of myeloperoxidase (MPO) on neutrophils and macrophages in milk but not in blood of treated cows. Neutrophils isolated from blood of PEG-gCSF-treated cows had decreased surface expression of CD62L (L-selectin) in blood, consistent with cell activation. Surprisingly, CD62L cell surface expression was increased on neutrophils and macrophages sourced from milk from treated animals compared with cells isolated from controls. The PEG-gCSF-treated cows did not clear the S. aureus infection, nor did they significantly differ in SCC from controls. These findings provide evidence that PEG-gCSF therapy modifies cell surface expression of neutrophils and monocytes. However, although surface MPO+ cells accumulate in the mammary gland, the lack of bacterial control from these milk-derived cells suggests an incomplete role for PEG-gCSF treatment against chronic S. aureus infection and possibly chronic mammary infections in general.
Penguins are the most threatened group of seabirds after albatrosses. Although penguins are regularly captured in fishing gear, the threat to penguins as a group has not yet been assessed. We ...reviewed both published and grey literature to identify the fishing gear types that penguins are most frequently recorded in, the most impacted species and, for these susceptible species, the relative importance of bycatch compared to other threats. While quantitative estimates of overall bycatch levels are difficult to obtain, this review highlights that, of the worldís 18 species of penguins, 14 have been recorded as bycatch in fishing gear and that gillnets, and to a lesser extent trawls, are the gear types that pose the greatest threats to penguins. Bycatch is currently of greatest concern for yellow-eyed Megadyptes antipodes (Endangered), Humboldt Spheniscus humboldti (Vulnerable) and Magellanic Spheniscus magellanicus penguins (Near Threatened). Penguins face many threats; reducing bycatch mortality in fishing gear will greatly enhance the resilience of penguin populations to threats from habitat loss and climate change that are more difficult to address in the short term. Additional data are required to quantify the true extent of penguin bycatch, particularly for the most susceptible species. In the meantime, it is crucially important to manage the fisheries operating within known penguin foraging areas to reduce the risks to this already threatened group of seabirds.
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•Unique Al/Al2O3 multilayers produced by combining atomic layer and physical vapor deposition without breaking vacuum.•Deformation behavior investigated in situ in biaxial tension ...with Synchrotron X-ray diffraction on polymer substrates.•Observed weakening of Al layers with increasing oxide thickness (0.14–9.4 nm) in contrast to uniaxial tensile results.•FE model of TEM cross-sections shows strain heterogeneities induced by wavy interfaces and a high young's modulus contrast.•Model describing the full biaxial yield surface of the multilayers appears to be valid up to 2.4 nm oxide thickness.
A unique deposition approach combining atomic layer deposition (ALD) and magnetron sputtering was used to fabricate a series of thin film multilayer structures of Al (50 nm) and Al2O3 (ALD, 2.4–9.4 nm) on flexible polymer substrates without breaking vacuum. The multilayers together with 50 nm and 150 nm Al reference films were analyzed by cross-sectional TEM analysis and experimentally strained in biaxial tension to investigate their deformation behavior. Al film stresses and peak widths, measured in situ with Synchrotron X-ray diffraction, are in good agreement with post-mortem surface SEM and through-thickness FIB analysis of the multilayers. It was revealed that brittle cracking of the multilayer can be avoided, and that the lateral and through-thickness crack resistance improve as a function of decreasing oxide layer thickness. An attempt to model the full biaxial yield surface of the multilayers, which remains experimentally challenging, appears to be valid up to 2.4 nm oxide thickness. Model predictions are further compared to compression data, obtained from the unloading segments of the tensile tests. Describing the mechanical behaviour under multiaxial stress conditions is of utmost importance for a diverse understanding of these multilayers across a variety of potential carrier systems and loading cases.
Background
Childhood trauma (CT) is associated with severe sequelae, including stress‐related mental health disorders that can perpetuate long into adulthood. A key mechanism in this relationship ...seems to be emotion regulation. We aimed to investigate (1) whether childhood trauma is associated with anger in adulthood, and, if so, (2) to explore which types of childhood trauma predominate in the prediction of anger in a cohort that included participants with and without current affective disorders.
Methods
In the Netherlands Study of Depression and Anxiety (NESDA), childhood trauma was assessed with a semi‐structured Childhood Trauma Interview (CTI) at baseline, and analyzed in relation to anger as measured at a 4‐year follow‐up with the Spielberger Trait Anger Subscale (STAS), the Anger Attacks Questionnaire, and cluster B personality traits (i.e., borderline, antisocial) of the Personality Disorder Questionnaire 4 (PDQ‐4), using analysis of covariance (ANCOVA) and multivariable logistic regression analyses. Post hoc analyses comprised cross‐sectional regression analyses, using the Childhood Trauma Questionnaire‐Short Form (CTQ‐SF) also obtained at a 4‐year follow‐up.
Results
Participants (n = 2271) were on average 42.1 years (SD = 13.1), and 66.2% were female. Childhood trauma showed a dose–response association with all anger constructs. All types of childhood trauma were significantly associated with borderline personality traits, independently of depression and anxiety. Additionally, all types of childhood trauma except for sexual abuse were associated with higher levels of trait anger, and a higher prevalence of anger attacks and antisocial personality traits in adulthood. Cross‐sectionally, the effect sizes were larger compared with the analyses with the childhood trauma measured 4 years prior to the anger measures.
Conclusions
Childhood trauma is linked with anger in adulthood, which could be of particular interest in the context of psychopathology. Focus on childhood traumatic experiences and adulthood anger may help to enhance the effectiveness of treatment for patients with depressive and anxiety disorders. Trauma‐focused interventions should be implemented when appropriate.
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•Novel high throughput methodology to understand atomistic structure of thin film metallic glass combinatorial libraries on polymer substrates.•Co-sputtered CuZr films exhibit ...dual-phase microstructure that could not be produced by conventional methods according to the CuZr phase diagram.•Linear phase ratio between amorphous Cu51Zr14 and nanocrystalline α-Zr as a function Zr content (25–80 at%), forming a mechanical mixture.•Real space HR-STEM analyses of representative composition substantiate XRD results.
We report for the first-time combinatorial synthesis of thin film metallic glass libraries via magnetron co-sputtering at the limit of crystallinity. Special care was taken to prepare extremely pure CuZr films (1–2 µm thickness) with large compositional gradients (Cu18.2Zr81.8 to Cu74.8Zr25.2) on X-ray transparent polymer substrates in high-vacuum conditions. Combined mapping of atomic structure (synchrotron radiation) and chemical composition (X-ray fluorescence spectroscopy) revealed that over the entire composition range, covering multiple renowned glass formers, two phases are present in the film. Our high-resolution Synchrotron approach identified the two phases as: untextured amorphous Cu51Zr14 (cluster size 1.3 nm) and textured, nanocrystalline α-Zr (grain size 1–5 nm). Real space HR-STEM analyses of a representative composition substantiate our XRD results. Determined cluster and grain sizes are below the resolution limit of conventional laboratory-scale X-ray diffractometers. The presented phase mixture is not permitted in the Cu-Zr phase diagram and contrary to existing literature. The phase ratio follows a linear trend with amorphous films on the Cu-rich side and increasing amounts of α-Zr with increasing Zr content. While cluster size and composition of the amorphous phase remain constant thorough the compositional gradient, crystallite size and texture of the nanocrystalline α-Zr change as a function of Zr content.
Comparative sequence analysis addresses the problem of RNA folding and RNA structural diversity, and is responsible for determining the folding of many RNA molecules, including 5S, 16S, and 23S ...rRNAs, tRNA, RNase P RNA, and Group I and II introns. Initially this method was utilized to fold these sequences into their secondary structures. More recently, this method has revealed numerous tertiary correlations, elucidating novel RNA structural motifs, several of which have been experimentally tested and verified, substantiating the general application of this approach. As successful as the comparative methods have been in elucidating higher-order structure, it is clear that additional structure constraints remain to be found. Deciphering such constraints requires more sensitive and rigorous protocols, in addition to RNA sequence datasets that contain additional phylogenetic diversity and an overall increase in the number of sequences. Various RNA databases, including the tRNA and rRNA sequence datasets, continue to grow in number as well as diversity. Described herein is the development of more rigorous comparative analysis protocols. Our initial development and applications on different RNA datasets have been very encouraging. Such analyses on tRNA, 16S and 23S rRNA are substantiating previously proposed associations and are now beginning to reveal additional constraints on these molecules. A subset of these involve several positions that correlate simultaneously with one another, implying units larger than a basepair can be under a phylogenetic constraint.
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