4,758 research outputs found
A synthetic sex ratio distortion system for the control of the human malaria mosquito.
It has been theorized that inducing extreme reproductive sex ratios could be a method to suppress or eliminate pest populations. Limited knowledge about the genetic makeup and mode of action of naturally occurring sex distorters and the prevalence of co-evolving suppressors has hampered their use for control. Here we generate a synthetic sex distortion system by exploiting the specificity of the homing endonuclease I-PpoI, which is able to selectively cleave ribosomal gene sequences of the malaria vector Anopheles gambiae that are located exclusively on the mosquito's X chromosome. We combine structure-based protein engineering and molecular genetics to restrict the activity of the potentially toxic endonuclease to spermatogenesis. Shredding of the paternal X chromosome prevents it from being transmitted to the next generation, resulting in fully fertile mosquito strains that produce >95% male offspring. We demonstrate that distorter male mosquitoes can efficiently suppress caged wild-type mosquito populations, providing the foundation for a new class of genetic vector control strategies
Autologous hematopoietic cell transplantation in multiple sclerosis.
INTRODUCTION: Autologous haematopoietic cell transplantation (AHCT) is an evolving treatment avenue in multiple sclerosis (MS), which may be highly effective in controlling disease activity and improving disability. However, AHCT is associated with intrinsic toxicities and risks compared with conventional therapies. With growing experience in patient selection and treatment delivery, AHCT is increasingly considered an option in patients with aggressive disease that's responding poorly to disease modifying therapy. AREAS COVERED: This article provides an introduction to AHCT and looks at its development as a treatment for MS over the last 20 years. It also highlights potential mechanisms of action, patient selection, and future trends for this treatment approach. EXPERT OPINION: Currently published data suggest that AHCT's use is associated with significant reduction in MS disease activity and marked improvement in disability when used in patients with highly active relapsing remitting disease. Its long term safety and efficacy have not been fully evaluated but as increasing clinical trial data are published, its use is likely to grow. Further randomised controlled studies are needed to compare AHCT with standard disease modifying therapies and to optimise transplant regimens. Mechanistic studies may provide potential markers for response and a better understanding of disease pathogenesis
The "Unfriending" Problem: The Consequences of Homophily in Friendship Retention for Causal Estimates of Social Influence
An increasing number of scholars are using longitudinal social network data
to try to obtain estimates of peer or social influence effects. These data may
provide additional statistical leverage, but they can introduce new inferential
problems. In particular, while the confounding effects of homophily in
friendship formation are widely appreciated, homophily in friendship retention
may also confound causal estimates of social influence in longitudinal network
data. We provide evidence for this claim in a Monte Carlo analysis of the
statistical model used by Christakis, Fowler, and their colleagues in numerous
articles estimating "contagion" effects in social networks. Our results
indicate that homophily in friendship retention induces significant upward bias
and decreased coverage levels in the Christakis and Fowler model if there is
non-negligible friendship attrition over time.Comment: 26 pages, 4 figure
Participatory Security: Citizen Security, Participation, and the Inequities of Citizenship in Urban Peru
Peer Reviewedhttp://deepblue.lib.umich.edu/bitstream/2027.42/90078/1/j.1470-9856.2011.00656.x.pd
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From seafood waste to active seafood packaging: An emerging opportunity of the circular economy
Sustainable development is an overarching objective that requires an interdisciplinary approach in order to address the societal challenge concerning climate action, environment, resource efficiency and raw materials. In this context, valorization of abundant and available bio-wastes with high potential to manufacture value-added products is the first step to close the loop between waste and consumption in line with the main goal of the circular economy. In the last years, many research works have been published in the literature regarding novel food packaging. However, most of them are focused on packaging composition (scientific aspects) and some of them on the packaging manufacture (technological aspects), but very few studies are concerned about the influence of bringing novel food packaging systems into the market on environmental, social and economic issues. In this regard, this review intends to fill this gap, considering the potential of developing food packaging from food processing waste in order to create business for food industries, being aware of the food quality demanded by consumers and the environmental care demanded by institutions and society
Optimal measurement of visual motion across spatial and temporal scales
Sensory systems use limited resources to mediate the perception of a great
variety of objects and events. Here a normative framework is presented for
exploring how the problem of efficient allocation of resources can be solved in
visual perception. Starting with a basic property of every measurement,
captured by Gabor's uncertainty relation about the location and frequency
content of signals, prescriptions are developed for optimal allocation of
sensors for reliable perception of visual motion. This study reveals that a
large-scale characteristic of human vision (the spatiotemporal contrast
sensitivity function) is similar to the optimal prescription, and it suggests
that some previously puzzling phenomena of visual sensitivity, adaptation, and
perceptual organization have simple principled explanations.Comment: 28 pages, 10 figures, 2 appendices; in press in Favorskaya MN and
Jain LC (Eds), Computer Vision in Advanced Control Systems using Conventional
and Intelligent Paradigms, Intelligent Systems Reference Library,
Springer-Verlag, Berli
APOE Δ4 moderates abnormal CSF-abeta-42 levels, while neurocognitive impairment is associated with abnormal CSF tau levels in HIV+ individuals â a cross-sectional observational study
Background: Cerebrospinal fluid (CSF) biomarkers AÎČ1-42, t-tau and p-tau have a characteristic pattern in Alzheimerâs Disease (AD). Their roles in HIV-associated neurocognitive disorder (HAND) remains unclear.
Methods: Adults with chronic treated HIV disease were recruited (n = 43, aged 56.7 ± 7.9; 32% aged 60+; median HIV duration 20 years, \u3e95% plasma and CSF HIV RNA \u3c50 cp/mL, on cART for a median 24 months). All underwent standard neuropsychological testing (61% had HAND), APOE genotyping (30.9% carried APOE Δ4 and 7.1% were Δ4 homozygotes) and a lumbar puncture. Concentrations of AÎČ1-42, t-tau and p-tau were assessed in the CSF using commercial ELISAs. Current neurocognitive status was defined using the continuous Global Deficit Score, which grades impairment in clinically relevant categories. History of HAND was recorded. Univariate correlations informed multivariate models, which were corrected for nadir CD4-T cell counts and HIV duration.
Results: Carriage of APOE Δ4 predicted markedly lower levels of CSF AÎČ1-42 in univariate (r = -.50; p = .001) and multivariate analyses (R2 = .25; p \u3c .0003). Greater levels of neurocognitive impairment were associated with higher CSF levels of p-tau in univariate analyses (r = .32; p = .03) and multivariate analyses (R2 = .10; p = .03). AD risk prediction cut-offs incorporating all three CSF biomarkers suggested that 12.5% of participants had a high risk for AD. Having a CSF-AD like profile was more frequent in those with current (p = .05) and past HIV-associated dementia (p = .03).
Conclusions: Similarly to larger studies, APOE Δ4 genotype was not directly associated with HAND, but moderated CSF levels of AÎČ1-42 in a minority of participants. In the majority of participants, increased CSF p-tau levels were associated with current neurocognitive impairment. Combined CSF biomarker risk for AD in the current HIV+ sample is more than 10 times greater than in the Australian population of the same age. Larger prospective studies are warranted
Left gaze bias in humans, rhesus monkeys and domestic dogs
While viewing faces, human adults often demonstrate a natural gaze bias towards the left visual field, that is, the right side of the vieweeâs face is often inspected first and for longer periods. Using a preferential looking paradigm, we demonstrate that this bias is neither uniquely human nor limited to primates, and provide evidence to help elucidate its biological function within a broader social cognitive framework. We observed that 6-month-old infants showed a wider tendency for left gaze preference towards objects and faces of different species and orientation, while in adults the bias appears only towards upright human faces. Rhesus monkeys showed a left gaze bias towards upright human and monkey faces, but not towards inverted faces. Domestic dogs, however, only demonstrated a left gaze bias towards human faces, but not towards monkey or dog faces, nor to inanimate object images. Our findings suggest that face- and species-sensitive gaze asymmetry is more widespread in the animal kingdom than previously recognised, is not constrained by attentional or scanning bias, and could be shaped by experience to develop adaptive behavioural significance
Phenoloxidase activity acts as a mosquito innate immune response against infection with semliki forest virus
Several components of the mosquito immune system including the RNA interference (RNAi), JAK/STAT, Toll and IMD pathways have previously been implicated in controlling arbovirus infections. In contrast, the role of the phenoloxidase (PO) cascade in mosquito antiviral immunity is unknown. Here we show that conditioned medium from the Aedes albopictus-derived U4.4 cell line contains a functional PO cascade, which is activated by the bacterium Escherichia coli and the arbovirus Semliki Forest virus (SFV) (Togaviridae; Alphavirus). Production of recombinant SFV expressing the PO cascade inhibitor Egf1.0 blocked PO activity in U4.4 cell- conditioned medium, which resulted in enhanced spread of SFV. Infection of adult female Aedes aegypti by feeding mosquitoes a bloodmeal containing Egf1.0-expressing SFV increased virus replication and mosquito mortality. Collectively, these results suggest the PO cascade of mosquitoes plays an important role in immune defence against arboviruses
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