677 research outputs found
Sleep-related attentional bias for tired faces in insomnia: evidence from a dot-probe paradigm
People with insomnia often display an attentional bias for sleep-specific stimuli. However, prior studies have mostly utilized sleep-related words and images, and research is yet to examine whether people with insomnia display an attentional bias for sleep-specific (i.e. tired appearing) facial stimuli. This study aimed to examine whether individuals with insomnia present an attentional bias for sleep-specific faces depicting tiredness compared to normal-sleepers. Additionally, we aimed to determine whether the presence of an attentional bias was characterized by vigilance or disengagement. Forty-one individuals who meet the DSM-5 criteria for Insomnia Disorder and 41 normal-sleepers completed a dot-probe task comprising of neutral and sleep-specific tired faces. The results demonstrated that vigilance and disengagement scores differed significantly between the insomnia and normal-sleeper groups. Specifically, individuals with insomnia displayed difficulty in both orienting to and disengaging attention from tired faces compared to normal-sleepers. Using tired facial stimuli, the current study provides novel evidence that insomnia is characterized by a sleep-related attentional bias. These outcomes support cognitive models of insomnia by suggesting that individuals with insomnia monitor tiredness in their social environment
Measuring chlorine bleach in biology and medicine
Background: Chlorine bleach, or hypochlorous acid, is the most reactive two-electron oxidant produced in appreciable amounts in our bodies. Neutrophils are the main source of hypochlorous acid. These champions of the innate immune system use it to fight infection but also direct it against host tissue in inflammatory diseases.
Neutrophils contain a rich supply of the enzyme myeloperoxidase. It uses hydrogen peroxide to convert chloride
to hypochlorous acid.
Scope of review: We give a critical appraisal of the best methods to measure production of hypochlorous acid by
purified peroxidases and isolated neutrophils. Robust ways of detecting it inside neutrophil phagosomes where
bacteria are killed are also discussed. Special attention is focused on reaction-based fluorescent probes but their
visual charm is tempered by stressing their current limitations. Finally, the strengths and weaknesses of biomarker assays that capture the footprints of chlorine in various pathologies are evaluated.
Major conclusions: Detection of hypochlorous acid by purified peroxidases and isolated neutrophils is best
achieved by measuring accumulation of taurine chloramine. Formation of hypochlorous acid inside neutrophil
phagosomes can be tracked using mass spectrometric analysis of 3-chlorotyrosine and methionine sulfoxide in
bacterial proteins, or detection of chlorinated fluorescein on ingestible particles. Reaction-based fluorescent probes
can also be used to monitor hypochlorous acid during phagocytosis. Specific biomarkers of its formation during inflammation include 3-chlorotyrosine, chlorinated products of plasmalogens, and glutathione sulfonamide.
General significance: These methods should bring new insights into how chlorine bleach is produced by peroxidases, reacts within phagosomes to kill bacteria, and contributes to inflammation. This article is part of a Special
Issue entitled Current methods to study reactive oxygen species - pros and cons and biophysics of membrane proteins. Guest Editor: Christine Winterbourn
Oxidation contributes to low glutathione in the airways of children with cystic fibrosis
Glutathione is an important antioxidant in the lungs but its concentration is low in the
airways of patients with cystic fibrosis. Whether this deficit occurs from an early age or how oxidative stress
contributes to lowering glutathione is unknown.
We measured glutathione, its oxidation products, myeloperoxidase, and biomarkers of hypochlorous
acid in bronchoalveolar lavage from children with cystic fibrosis and disease controls using mass
spectrometry and immunological techniques.
The concentration of glutathione was lower in bronchoalveolar lavage from children with cystic fibrosis,
whereas glutathione sulfonamide, a specific oxidation product of hypochlorous acid, was higher. Oxidised
glutathione and glutathione sulfonamide correlated with myeloperoxidase and a biomarker of hypochlorous
acid. The percentage of glutathione attached to proteins was higher in children with cystic fibrosis than
controls. Pulmonary infections in cystic fibrosis resulted in lower levels of glutathione but higher levels of
oxidised glutathione and glutathione sulfonamide in bronchoalveolar lavage.
The concentration of glutathione is low in the airways of patients with cystic fibrosis from an early age.
Increased oxidation of glutathione by hypochlorous acid and its attachment to proteins contribute to this
deficiency. Therapies targeted against myeloperoxidase may boost antioxidant defence and slow the onset
and progression of lung disease in cystic fibrosis
Sustaining Wildlife with Recreation on Public Lands: A Synthesis of Research Findings, Management Practices, and Research Needs
Humans and wildlife interact in multifaceted ways on public lands with both positive and negative outcomes for each group. When managed well, wildlife-based tourism and other forms of recreation can benefit conservation goals. Public lands planners and managers often must decide how to best manage recreational activities and wildlife habitats that overlap spatially and temporally. We conducted an extensive literature review and categorized recreational activity into five types based on the use of motorized equipment, season, and location (terrestrial vs. aquatic), expanding on findings summarized in prior reviews. Our findings provide a reference for public lands planners and managers who need information about how wildlife species respond to recreational activities and to associated changes in their habitats. We also describe management principles gleaned from the literature and outline priority research and administrative study areas to advance our understanding of recreation-wildlife interactions
Assessment of an LSDV-Vectored Vaccine for Heterologous Prime-Boost Immunizations against HIV
The modest protective effects of the RV144 HIV-1 vaccine trial have prompted the further exploration of improved poxvirus vector systems that can yield better immune responses and protection. In this study, a recombinant lumpy skin disease virus (LSDV) expressing HIV-1 CAP256.SU gp150 (Env) and a subtype C mosaic Gag was constructed (LSDVGC5) and compared to the equivalent recombinant modified vaccinia Ankara (MVAGC5). In vitro characterization confirmed that cells infected with recombinant LSDV produced Gag virus-like particles containing Env, and that Env expressed on the surface of the cells infected with LSDV was in a native-like conformation. This candidate HIV-1 vaccine (L) was tested in a rabbit model using different heterologous vaccination regimens, in combination with DNA (D) and MVA (M) vectors expressing the equivalent HIV-1 antigens. The four different vaccination regimens (DDMMLL, DDMLML, DDLMLM, and DDLLMM) all elicited high titers of binding and Tier 1A neutralizing antibodies (NAbs), and some regimens induced Tier 1B NAbs. Furthermore, two rabbits in the DDLMLM group developed low levels of autologous Tier 2 NAbs. The humoral immune responses elicited against HIV-1 Env by the recombinant LSDVGC5 were comparable to those induced by MVAGC5
Ceruloplasmin is an endogenous inhibitor of myeloperoxidase
Myeloperoxidase is a neutrophil enzyme that promotes oxidative stress in numerous inflammatory pathologies. It uses
hydrogen peroxide to catalyze the production of strong oxidants
including chlorine bleach and free radicals. A physiological
defense against the inappropriate action of this enzyme has yet
to be identified. We found that myeloperoxidase oxidized 75%
of the ascorbate in plasma from ceruloplasmin knock-out mice,
but there was no significant loss in plasma from wild type animals. When myeloperoxidase was added to human plasma it
became bound to other proteins and was reversibly inhibited.
Ceruloplasmin was the predominant protein associated with
myeloperoxidase. When the purified proteins were mixed, they
became strongly but reversibly associated. Ceruloplasmin was a
potent inhibitor of purified myeloperoxidase, inhibiting production of hypochlorous acid by 50% at 25 nM
Pathways to prevention: protocol for the CAP (Climate and Preventure) study to evaluate the long-term effectiveness of school-based universal, selective and combined alcohol misuse prevention into early adulthood
Background: Alcohol use and associated harms are among the leading causes of burden of disease among young
people, highlighting the need for effective prevention. The Climate and Preventure (CAP) study was the first trial of
a combined universal and selective school-based approach to preventing alcohol misuse among adolescents. Initial
results indicate that universal, selective and combined prevention were all effective in delaying the uptake of alcohol
use and binge drinking for up to 3 years following the interventions. However, little is known about the sustainability
of prevention effects across the transition to early adulthood, a period of increased exposure to alcohol and other drug
use. This paper describes the protocol for the CAP long-term follow-up study which will determine the effectiveness of
universal, selective and combined alcohol misuse prevention up to 7 years post intervention, and across the transition
from adolescence into early adulthood.
Methods: A cluster randomized controlled trial was conducted between 2012 and 2015 with 2190 students (mean
age: 13.3 yrs) from 26 Australian high schools. Participants were randomized to receive one of four conditions; universal
prevention for all students (Climate); selective prevention for high-risk students (Preventure); combined universal and
selective prevention (Climate and Preventure; CAP); or health education as usual (Control). The positive effect of the
interventions on alcohol use at 12-, 24- and 36-month post baseline have previously been reported. This study will
follow up the CAP study cohort approximately 5- and 7-years post baseline. The primary outcome will be alcohol use
and related harms. Secondary outcomes will be cannabis use, alcohol and other drug harms including violent behavior,
and mental health symptomatology. Analyses will be conducted using multi-level, mixed effects models within an
intention-to-treat framework. Discussion: This study will provide the first ever evaluation of the long-term effectiveness of combining universal and selective approaches to alcohol prevention and will examine the durability of intervention effects into the longer-term,
over a 7-year period from adolescence to early adulthood
LSDV-Vectored SARS-CoV-2 S and N Vaccine Protects against Severe Clinical Disease in Hamsters
The SARS-CoV-2 pandemic demonstrated the need for potent and broad-spectrum vaccines. This study reports the development and testing of a lumpy skin disease virus (LSDV)-vectored vaccine against SARS-CoV-2, utilizing stabilized spike and conserved nucleocapsid proteins as antigens to develop robust immunogenicity. Construction of the vaccine (LSDV-SARS2-S,N) was confirmed by polymerase chain reaction (PCR) amplification and sequencing. In vitro characterization confirmed that cells infected with LSDV-SARS2-S,N expressed SARS-CoV-2 spike and nucleocapsid protein. In BALB/c mice, the vaccine elicited high magnitude IFN-γ ELISpot responses (spike: 2808 SFU/106 splenocytes) and neutralizing antibodies (ID50 = 6552). Testing in hamsters, which emulate human COVID-19 disease progression, showed the development of high titers of neutralizing antibodies against the Wuhan and Delta SARS-CoV-2 variants (Wuhan ID50 = 2905; Delta ID50 = 4648). Additionally, hamsters vaccinated with LSDV-SARS2-S,N displayed significantly less weight loss, lung damage, and reduced viral RNA copies following SARS-CoV-2 infection with the Delta variant as compared to controls, demonstrating protection against disease. These data demonstrate that LSDV-vectored vaccines display promise as an effective SARS-CoV-2 vaccine and as a potential vaccine platform for communicable diseases in humans and animals. Further efficacy testing and immune response analysis, particularly in non-human primates, are warranted
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