The dural venous sinuses play an integral role in draining venous blood from the cranial cavity. As a result of the sinuses anatomical location, they are of significant importance when evaluating the ...mechanopathology of traumatic brain injury (TBI). Despite the importance of the dural venous sinuses in normal neurophysiology, no mechanical analyses have been conducted on the tissues. In this study, we conduct mechanical and structural analysis on porcine dural venous sinus tissue to help elucidate the tissues' function in healthy and diseased conditions. With longitudinal elastic moduli values ranging from 33 to 58 MPa, we demonstrate that the sinuses exhibit higher mechanical stiffness than that of native dural tissue, which may be of interest to the field of TBI modelling. Furthermore, by employing histological staining and a colour deconvolution protocol, we show that the sinuses have a collagen-dominant extracellular matrix, with collagen area fractions ranging from 84 to 94%, which likely explains the tissue's large mechanical stiffness. In summary, we provide the first investigation of the dural venous sinus mechanical behaviour with accompanying structural analysis, which may aid in understanding TBI mechanopathology.
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IZUM, KILJ, NUK, PILJ, PNG, SAZU, UL, UM, UPUK
Great efforts have been made to increase accessibility of HIV antiretroviral therapy (ART) in low and middle-income countries. The threat of wide-scale emergence of drug resistance could severely ...hamper ART scale-up efforts. Population-based surveillance of transmitted HIV drug resistance ensures the use of appropriate first-line regimens to maximize efficacy of ART programs where drug options are limited. However, traditional HIV genotyping is extremely expensive, providing a cost barrier to wide-scale and frequent HIV drug resistance surveillance.
We have developed a low-cost laboratory-scale next-generation sequencing-based genotyping method to monitor drug resistance. We designed primers specifically to amplify protease and reverse transcriptase from Brazilian HIV subtypes and developed a multiplexing scheme using multiplex identifier tags to minimize cost while providing more robust data than traditional genotyping techniques. Using this approach, we characterized drug resistance from plasma in 81 HIV infected individuals collected in São Paulo, Brazil. We describe the complexities of analyzing next-generation sequencing data and present a simplified open-source workflow to analyze drug resistance data. From this data, we identified drug resistance mutations in 20% of treatment naïve individuals in our cohort, which is similar to frequencies identified using traditional genotyping in Brazilian patient samples.
The developed ultra-wide sequencing approach described here allows multiplexing of at least 48 patient samples per sequencing run, 4 times more than the current genotyping method. This method is also 4-fold more sensitive (5% minimal detection frequency vs. 20%) at a cost 3-5× less than the traditional Sanger-based genotyping method. Lastly, by using a benchtop next-generation sequencer (Roche/454 GS Junior), this approach can be more easily implemented in low-resource settings. This data provides proof-of-concept that next-generation HIV drug resistance genotyping is a feasible and low-cost alternative to current genotyping methods and may be particularly beneficial for in-country surveillance of transmitted drug resistance.
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DOBA, IZUM, KILJ, NUK, PILJ, PNG, SAZU, SIK, UILJ, UKNU, UL, UM, UPUK
Public awareness of the rising importance of allergies and other respiratory diseases has led to increased scientific effort to accurately and rapidly monitor and predict pollen, fungal spores and ...other bioaerosols in our atmosphere. An important driving force for the increased social and scientific concern is the realisation that climate change will increasingly have an impact on worldwide bioaerosol distributions and subsequent human health. In this review we examine new developments in monitoring of atmospheric pollen as well as observation and source-orientated modelling techniques. The results of a Scopus® search for scientific publications conducted with the terms 'Pollen allergy' and 'Pollen forecast' included in the title, abstract or keywords show that the number of such articles published has increased year on year. The 12 most important allergenic pollen taxa in Europe as defined by COST Action ES0603 were ranked in terms of the most 'popular' for model-based forecasting and for forecasting method used. Betula, Poaceae and Ambrosia are the most forecast taxa. Traditional regression and phenological models (including temperature sum and chilling models) are the most used modelling methods, but it is notable that there are a large number of new modelling techniques being explored. In particular, it appears that Machine Learning techniques have become more popular and led to better results than more traditional observation-orientated models such as regression and time-series analyses.
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BFBNIB, DOBA, GIS, IJS, IZUM, KILJ, KISLJ, NUK, PILJ, PNG, SAZU, UILJ, UKNU, UL, UM, UPUK
Skin has a variety of functions that are incompletely understood at the molecular level. As the most accessible tissue in the body it often reveals the first signs of inflammation or infection and ...also represents a potentially valuable source of biomarkers for several diseases. In this study we surveyed the skin proteome qualitatively using gel electrophoresis, liquid chromatography tandem mass spectrometry (GeLC-MS/MS) and quantitatively using an isobaric tagging strategy (iTRAQ) to characterise the response of human skin following exposure to sodium dodecyl sulphate (SDS).
A total of 653 skin proteins were assigned, 159 of which were identified using GeLC-MS/MS and 616 using iTRAQ, representing the most comprehensive proteomic study in human skin tissue. Statistical analysis of the available iTRAQ data did not reveal any significant differences in the measured skin proteome after 4 hours exposure to the model irritant SDS.
This study represents the first step in defining the critical response to an irritant at the level of the proteome and provides a valuable resource for further studies at the later stages of irritant exposure.
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DOBA, IZUM, KILJ, NUK, PILJ, PNG, SAZU, SIK, UILJ, UKNU, UL, UM, UPUK
The rhesus macaque is an important animal model for AIDS and other infectious diseases; however, studies to address NK cell function in this species have been limited by the lack of defined ligands ...for killer cell Ig-like receptors (KIRs). To identify ligands for rhesus macaque KIRs, we adopted a novel approach based on a pair of stable cell lines. NFAT-responsive luciferase reporter cell lines expressing the extracellular domains of macaque KIRs fused to the transmembrane and cytoplasmic domains of CD28 and CD3ζ were incubated with target cells expressing individual MHC class I molecules, and ligand recognition was detected by the MHC class I-dependent upregulation of luciferase. Using this approach, we found that Mamu-KIR3DL01, -KIR3DL06, -KIR3DL08 and –KIR3DSw08 all recognize Mamu-Bw4 molecules, but with varying allotype specificity. In contrast, Mamu-KIR3DL05 recognizes Mamu-A and -A-related molecules, including Mamu-A1*002 and A3*13, Mamu-B*036, the product of a recombinant
Mamu-B
allele with α1 and α2 domain sequences derived from a
MHC-A
gene, and Mamu-AG*01, a non-classical molecule expressed on placental trophoblasts that originated from an ancestral duplication of a
MHC-A
gene. These results reveal an expansion of the lineage II KIRs in macaques that recognize Bw4 ligands, and identify a non-classical molecule implicated in placental development and pregnancy as a ligand for Mamu-KIR3DL05. In addition to offering new insights into KIR-MHC class I co-evolution, these findings provide an important foundation for investigating the role of NK cells in the rhesus macaque as an animal model for infectious diseases and reproductive biology.
Background and aims
Susceptibility to use of addictive substances may result, in part, from a greater preference for an immediate small reward relative to a larger delayed reward or relative ...insensitivity to punishment. This functional magnetic resonance imaging (fMRI) study examined the neural basis of inhibiting an immediately rewarding stimulus to obtain a larger delayed reward in smokers. We also investigated whether punishment could modulate inhibitory control.
Design
The Monetary Incentive Go/NoGo (MI‐Go/NoGo) task was administered that provided three types of reward outcomes contingent upon inhibitory control performance over rewarding stimuli: inhibition failure was either followed by no monetary reward (neutral condition), a small monetary reward with immediate feedback (reward condition) or immediate monetary punishment (punishment condition). In the reward and punishment conditions, successful inhibitory control resulted in larger delayed rewards.
Setting
Community sample of smokers in the Melbourne (Australia) area.
Participants
Nineteen smokers were compared with 17 demographically matched non‐smoking controls.
Measurements
Accuracy, reaction times and brain activation associated with the MI‐Go/NoGo task.
Findings
Smokers showed hyperactivation in the right insula (P < 0.01), inferior and middle frontal gyrus (P < 0.01), dorsolateral prefrontal cortex (P = 0.001) and inferior parietal lobe (P < 0.01) both during inhibition of an immediately rewarding stimulus to obtain a larger delayed reward, and during inhibition of neutral stimuli. Group differences in brain activity were not significant in the punishment condition in the right insula and dorsolateral prefrontal cortex, most probably as a result of increased activation in non‐smoking controls.
Conclusions
Compared with non‐smokers, smokers showed increased neural activation when resisting immediately rewarding stimuli and may be less sensitive to punishment as a strategy to increase control over rewarding stimuli.
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BFBNIB, DOBA, FSPLJ, FZAB, GIS, IJS, IZUM, KILJ, NLZOH, NUK, OILJ, PILJ, PNG, SAZU, SBCE, SBMB, SIK, UILJ, UKNU, UL, UM, UPUK, VSZLJ
Many studies have demonstrated that people will adjust their behavioral response to a reward on the basis of the time taken to receive the reward. Yet despite growing evidence that time and space are ...not mentally independent, there has been no examination of whether spatial distance may also affect the way people respond to rewarding objects. We examined speeded binary decisions about objects associated with high, low, or no reward for correct responses. Using a 3-D display, we varied perceived spatial distance so that objects appeared at distances near to or far from participants. Both the speed and the accuracy of responses were better for high-reward objects compared with lowand no-reward objects, but this difference occurred only when the objects appeared at near distance to participants. These results demonstrate that when people respond to rewarding objects, they show sensitivity to spatial-distance information even if the information is irrelevant to the task.
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BFBNIB, NMLJ, NUK, OILJ, PNG, SAZU, UKNU, UL, UM, UPUK
Aim
Few interventions address social cognition or functioning in individuals at clinical risk (CR) for psychosis. Theatre Improvisation Training to Promote Social Cognition (TIPS) is a manualized ...intervention based on drama therapy. We aim to describe TIPS, evaluate feasibility and acceptability, and present a preliminary investigation of outcomes in a quasi‐experimental design.
Methods
Thirty‐six CR participants (15‐25 years) were ascertained from the Philadelphia Neurodevelopmental Cohort. Twenty‐six completed the TIPS protocol: 18 weekly 2‐hour group sessions led by a theatre director and actor‐assistant. Participants engaged in collaborative acting and improvisation exercises. Baseline and follow‐up assessments included the Clinical Assessment Interview for Negative Symptoms (CAINS), Structured Interview for Prodromal Syndromes, Global Assessment of Functioning (GAF) and Penn Computerized Neurocognitive Battery (CNB), which includes social cognitive tests. Acceptability was assessed using focus groups. Preliminary outcomes were compared to CR controls who were not enrolled in the study but completed follow‐up assessments using the same methods.
Results
There were no significant differences in baseline demographics, psychosis symptoms, or cognition between those who did and did not complete the protocol. Overall, TIPS was considered feasible and acceptable among CR. Preliminary outcomes suggest that TIPS may be effective in improving positive and negative psychosis‐spectrum symptoms and GAF, but not performance on facial emotion processing.
Conclusions
TIPS is a promising and acceptable intervention that may improve symptoms and functioning in CR while providing a framework for participants to develop more empowered and confident ways of relating to others. Larger randomized controlled trials investigating TIPS efficacy are warranted.
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BFBNIB, FZAB, GIS, IJS, IZUM, KILJ, NLZOH, NUK, OILJ, PILJ, PNG, SAZU, SBCE, SBMB, UL, UM, UPUK
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