287 research outputs found
Accessing social media: help or hindrance for people with social anxiety?
Despite increasing use of social media and the potential benefits for people with social anxiety (SA) disorder, little is known about the online experience of people with SA. Our study aimed to investigate the occurrence of cognitive and behavioral processes during a series of online and off-line Facebook (FB)-based tasks among individuals with high and low levels of SA. Sixty-one undergraduates with low or high SA were asked to use FB in a laboratory setting, to make an FB post, and to imagine three ambiguous FB scenarios. Participants with high SA reported higher anxiety throughout the study with an interaction effect, indicating greater relative increases in anxiety for those with high SA over low SA across tasks. The high SA group were more likely to negatively interpret the ambiguous FB scenarios than the low SA group. They also reported using more safety-seeking behaviors and having more negative thoughts. The findings suggest that the cognitive and behavioral processes that characterize socially anxious face-to-face interaction are also evident in online communication. Suggestions are made for the clinical implications of such findings
The impact of DMARD and anti-TNF therapy on functional characterization of short-term T-cell activation in patients with rheumatoid arthritis - A follow-up study
Rheumatoid arthritis (RA) is a chronic autoimmune disease characterized by a systemic dysfunction of T-cells. In this study we tested the impact of DMARD and anti-TNF agents on short-term activation characteristics of T-cells. We enrolled 12 patients with newly diagnosed RA (naïve RA) who were treated with methothrexate (MTX) and glucocorticsteroid (GCS) and 22 patients with established RA non responding to conventional DMARD therapy who were treated with different anti-TNF agents. Nine healthy volunteers served as controls. Blood samples were taken at baseline, then at 4th and 8th week of therapy. The characteristics of several intracellular activation processes during short-term activation of T-cells including cytoplasmic Ca2+ level, mitochondrial Ca2+ level, reactive oxygen species (ROS) and nitric oxide (NO) generation were determined by a novel flow-cytometry technique. At baseline, the tested processes were comparable to controls in naïve RA. During GCS therapy, cytoplasmic Ca2+ level and ROS generation decreased. After the addition of MTX to GCS cytoplasmic Ca2+ level became comparable to controls, while ROS generation decreased further. In DMARD non responders, cytoplasmic Ca2+ level was higher than controls at baseline. The cytoplasmic Ca2+ level became comparable to controls and ROS generation decreased during each of the three anti-TNF-α agent therapies. Mitochondrial Ca2+ level and NO generation were unaltered in all of the patient groups. These results indicate that intracellular machinery is affected in T-cells of RA patients. This may alter the behavior of T-cells during activation. Different therapeutic approaches may modulate the abnormal T-cell functions. © 2014 Szalay et al
Toxoplasma gondii-Induced Activation of EGFR Prevents Autophagy Protein-Mediated Killing of the Parasite
Toxoplasma gondii resides in an intracellular compartment (parasitophorous vacuole) that excludes transmembrane molecules required for endosome-lysosome recruitment. Thus, the parasite survives by avoiding lysosomal degradation. However, autophagy can re-route the parasitophorous vacuole to the lysosomes and cause parasite killing. This raises the possibility that T. gondii may deploy a strategy to prevent autophagic targeting to maintain the non-fusogenic nature of the vacuole. We report that T. gondii activated EGFR in endothelial cells, retinal pigment epithelial cells and microglia. Blockade of EGFR or its downstream molecule, Akt, caused targeting of the parasite by LC3(+) structures, vacuole-lysosomal fusion, lysosomal degradation and killing of the parasite that were dependent on the autophagy proteins Atg7 and Beclin 1. Disassembly of GPCR or inhibition of metalloproteinases did not prevent EGFR-Akt activation. T. gondii micronemal proteins (MICs) containing EGF domains (EGF-MICs; MIC3 and MIC6) appeared to promote EGFR activation. Parasites defective in EGF-MICs (MIC1 ko, deficient in MIC1 and secretion of MIC6; MIC3 ko, deficient in MIC3; and MIC1-3 ko, deficient in MIC1, MIC3 and secretion of MIC6) caused impaired EGFR-Akt activation and recombinant EGF-MICs (MIC3 and MIC6) caused EGFR-Akt activation. In cells treated with autophagy stimulators (CD154, rapamycin) EGFR signaling inhibited LC3 accumulation around the parasite. Moreover, increased LC3 accumulation and parasite killing were noted in CD154-activated cells infected with MIC1-3 ko parasites. Finally, recombinant MIC3 and MIC6 inhibited parasite killing triggered by CD154 particularly against MIC1-3 ko parasites. Thus, our findings identified EGFR activation as a strategy used by T. gondii to maintain the non-fusogenic nature of the parasitophorous vacuole and suggest that EGF-MICs have a novel role in affecting signaling in host cells to promote parasite survival
Spatial Targeting for Bovine Tuberculosis Control: Can the Locations of Infected Cattle Be Used to Find Infected Badgers?
Digital Art as ‘Monetised Graphics:’ Enforcing Intellectual Property on the Blockchain
In a global economic landscape of hyper-commodification and financialisation, efforts to assimilate digital art into the high-stakes commercial art market have so far been rather unsuccessful, presumably because digital art works cannot easily assume the status of precious object worthy of collection. This essay explores the use of blockchain technologies in attempts to create proprietary digital art markets in which uncommodifiable digital art works are financialised as artificially scarce commodities. Using the decentralisation techniques and distributed database protocols underlying current cryptocurrency technologies, such efforts, exemplified here by the platform Monegraph, tend to be presented as concerns with the interest of digital artists and with shifting ontologies of the contemporary work of art. I challenge this characterisation, and argue, in a discussion that combines aesthetic theory, legal and philosophical theories of intellectual property, rhetorical analysis, and research in the political economy of new media, that the formation of proprietary digital art markets by emerging commercial platforms such as Monegraph constitutes a worrisome amplification of long-established, on-going efforts to fence in creative expression as private property. As I argue, the combination of blockchain-based protocols with established ambitions of intellectual property policy yields hybrid conceptual-computational financial technologies (such as self-enforcing smart contracts attached to digital artefacts) that are unlikely to empower artists, but which serve to financialise digital creative practices as a whole, curtailing the critical potential of the digital as an inherently dynamic and potentially uncommodifiable mode of production and artistic expression
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Meta-analysis reveals that pollinator functional diversity and abundance enhance crop pollination and yield
How insects promote crop pollination remains poorly understood in terms of the contribution of functional trait differences between species. We used meta-analyses to test for correlations between community abundance, species richness and functional trait metrics with oilseed rape yield, a globally important crop. While overall abundance is consistently important in predicting yield, functional divergence between species traits also showed a positive correlation. This result supports the complementarity hypothesis that pollination function is maintained by non-overlapping trait distributions. In artificially constructed communities (mesocosms), species richness is positively correlated with yield, although this effect is not seen under field conditions. As traits of the dominant species do not predict yield above that attributed to the effect of abundance alone, we find no evidence in support of the mass ratio hypothesis. Management practices increasing not just pollinator abundance, but also functional divergence, could benefit oilseed rape agriculture
Vaccination with Recombinant Microneme Proteins Confers Protection against Experimental Toxoplasmosis in Mice
Toxoplasmosis, a zoonotic disease caused by Toxoplasma gondii, is an important public health problem and veterinary concern. Although there is no vaccine for human toxoplasmosis, many attempts have been made to develop one. Promising vaccine candidates utilize proteins, or their genes, from microneme organelle of T. gondii that are involved in the initial stages of host cell invasion by the parasite. In the present study, we used different recombinant microneme proteins (TgMIC1, TgMIC4, or TgMIC6) or combinations of these proteins (TgMIC1-4 and TgMIC1-4-6) to evaluate the immune response and protection against experimental toxoplasmosis in C57BL/6 mice. Vaccination with recombinant TgMIC1, TgMIC4, or TgMIC6 alone conferred partial protection, as demonstrated by reduced brain cyst burden and mortality rates after challenge. Immunization with TgMIC1-4 or TgMIC1-4-6 vaccines provided the most effective protection, since 70% and 80% of mice, respectively, survived to the acute phase of infection. In addition, these vaccinated mice, in comparison to non-vaccinated ones, showed reduced parasite burden by 59% and 68%, respectively. The protective effect was related to the cellular and humoral immune responses induced by vaccination and included the release of Th1 cytokines IFN-γ and IL-12, antigen-stimulated spleen cell proliferation, and production of antigen-specific serum antibodies. Our results demonstrate that microneme proteins are potential vaccines against T. gondii, since their inoculation prevents or decreases the deleterious effects of the infection
Judgment of Learning Accuracy in High-functioning Adolescents and Adults with Autism Spectrum Disorder
This study explored whether adults and adolescents with autism spectrum disorder (ASD) demonstrate difficulties making metacognitive judgments, specifically judgments of learning. Across two experiments, the study examined whether individuals with ASD could accurately judge whether they had learnt a piece of information (in this case word pairs). In Experiment 1, adults with ASD demonstrated typical accuracy on a standard ‘cue-alone’ judgment of learning (JOL) task, compared to age- and IQmatched neurotypical adults. Additionally, in Experiment 2, adolescents with ASD demonstrated typical accuracy on both a standard ‘cue-alone’ JOL task, and a ‘cue-target’ JOL task. These results suggest that JOL accuracy is unimpaired in ASD. These results have important implications for both theories of metacognition in ASD and educational practise
Long-term efficacy of botulinum toxin A for treatment of blepharospasm,hemifacial spasm, and spastic entropion: a multicentre study using two drug-dose escalation indexes
PURPOSE: To investigate the long-term effectiveness and safety of botulinum
neurotoxin A (BoNT-A) treatment in patients with blepharospasm (BEB), hemifacial
spasm (HFS), and entropion (EN) and to use for the first time two modified indexes, 'botulin toxin escalation index-U' (BEI-U) and 'botulin toxin escalation
index percentage' (BEI-%), in the dose-escalation evaluation. METHODS: All
patients in this multicentre study were followed for at least 10 years and main
outcomes were clinical efficacy, duration of relief, BEI-U and BEI-%, and
frequency of adverse events. RESULTS: BEB, HFS, and EN patients received a mean
BoNT-A dose with a significant inter-group difference (P<0.0005, respectively).
The mean (+/-SD) effect duration was statistically different (P=0.009) among
three patient groups. Regarding the BoNT-A escalation indexes, the mean (+/-SD)
values of BEI-U and BEI-% were statistically different (P=0.035 and 0.047,
respectively) among the three groups. In BEB patients, the BEI-% was
significantly increased in younger compared with older patients (P=0.008). The
most frequent adverse events were upper lid ptosis, diplopia, ecchymosis, and
localized bruising. CONCLUSIONS: This long-term multicentre study supports a high
efficacy and good safety profile of BoNT-A for treatment of BEB, HFS, and EN. The
BEI indexes indicate a significantly greater BoNT-A-dose escalation for BEB
patients compared with HFS or EN patients and a significantly greater BEI-% in
younger vsolder BEB patients. These results confirm a greater efficacy in the
elderly and provide a framework for long-term studies with a more flexible and
reliable evaluation of drug-dose escalation
A systematic genome-wide analysis of zebrafish protein-coding gene function
Since the publication of the human reference genome, the identities of specific genes associated with human diseases are being discovered at a rapid rate. A central problem is that the biological activity of these genes is often unclear. Detailed investigations in model vertebrate organisms, typically mice, have been essential for understanding the activities of many orthologues of these disease-associated genes. Although gene-targeting approaches1, 2, 3 and phenotype analysis have led to a detailed understanding of nearly 6,000 protein-coding genes3, 4, this number falls considerably short of the more than 22,000 mouse protein-coding genes5. Similarly, in zebrafish genetics, one-by-one gene studies using positional cloning6, insertional mutagenesis7, 8, 9, antisense morpholino oligonucleotides10, targeted re-sequencing11, 12, 13, and zinc finger and TAL endonucleases14, 15, 16, 17 have made substantial contributions to our understanding of the biological activity of vertebrate genes, but again the number of genes studied falls well short of the more than 26,000 zebrafish protein-coding genes18. Importantly, for both mice and zebrafish, none of these strategies are particularly suited to the rapid generation of knockouts in thousands of genes and the assessment of their biological activity. Here we describe an active project that aims to identify and phenotype the disruptive mutations in every zebrafish protein-coding gene, using a well-annotated zebrafish reference genome sequence18, 19, high-throughput sequencing and efficient chemical mutagenesis. So far we have identified potentially disruptive mutations in more than 38% of all known zebrafish protein-coding genes. We have developed a multi-allelic phenotyping scheme to efficiently assess the effects of each allele during embryogenesis and have analysed the phenotypic consequences of over 1,000 alleles. All mutant alleles and data are available to the community and our phenotyping scheme is adaptable to phenotypic analysis beyond embryogenesis
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