The Possible "Proton Sponge " Effect of Polyethylenimine (PEI) Does Not Include Change in Lysosomal pH.

Polycations such as polyethylenimine (PEI) are used in many novel nonviral vector designs and there are continuous efforts to increase our mechanistic understanding of their interactions with cells. Even so, the mechanism of polyplex escape from the endosomal/lysosomal pathway after internalization is still elusive. The “proton sponge ” hypothesis remains the most generally accepted mechanism, although it is heavily debated. This hypothesis is associated with the large buffering capacity of PEI and other polycations, which has been interpreted to cause an increase in lysosomal pH even though no conclusive proof has been provided. In the present study, we have used a nanoparticle pH sensor that was developed for pH measurements in the endosomal/lysosomal pathway. We have carried out quantitative measurements of lysosomal pH as a function of PEI content and correlate the results to the “proton sponge ” hypothesis. Our measurements show that PEI does not induce change in lysosomal pH as previously suggested and quantification of PEI concentrations in lysosomes makes it uncertain that the “proton sponge ” effect is the dominant mechanism of polyplex escape

The Making of a Mobile Caliphate State in the African Sahel

The goal of this chapter is to thoroughly understand the context of the dominant jihadist narratives and the nature of their appeal in the Sahelian region. All these jihadist ideologies are based on a peculiar Salafi Radicalism that aimed to transform the state and society by methods of preaching and violence. Therefore, studying and analyzing the principles of the Salafist discourse as a political project helps us to understand its points of strengths and weaknesses. In addition, we can be better look at the future trends and prospects of violent jihadist groups in the African Sahel. The roots of this Islamic discourse as a political project may be attributed to what Lunay and Suarez call the “Islamic domain.” The rise of violent radical Islamism represents drive from the internal political and socioeconomic dynamics evolving in each Sahelian state. However, the struggle and rivalry of jihadist ideologies after the military defeat of Daesh in Mosul is important at a time when thousands of fighters who have survived the civil wars in Iraq, Syria, and Libya are looking for new jihadist fields

Diverging phenological responses of Arctic seabirds to an earlier spring

The timing of annual events such as reproduction is a critical component of how free‐living organisms respond to ongoing climate change. This may be especially true in the Arctic, which is disproportionally impacted by climate warming. Here, we show that Arctic seabirds responded to climate change by moving the start of their reproduction earlier, coincident with an advancing onset of spring and that their response is phylogenetically and spatially structured. The phylogenetic signal is likely driven by seabird foraging behavior. Surface‐feeding species advanced their reproduction in the last 35 years while diving species showed remarkably stable breeding timing. The earlier reproduction for Arctic surface‐feeding birds was significant in the Pacific only, where spring advancement was most pronounced. In both the Atlantic and Pacific, seabirds with a long breeding season showed a greater response to the advancement of spring than seabirds with a short breeding season. Our results emphasize that spatial variation, phylogeny, and life history are important considerations in seabird phenological response to climate change and highlight the key role played by the species' foraging behavior

Identifying Key Factors Associated with Aggression on Acute Inpatient Psychiatric Wards

Aggressive behaviour is a critical issue for modern acute psychiatric services, not just because of the adverse impact it has on patients and staff, but also because it puts a financial strain on service providers. The aim of this study was to assess the relationship of patient violence to other variables: patient characteristics, features of the service and physical environment, patient routines, staff factors, the use of containment methods, and other patient behaviours. A multivariate cross sectional design was utilised. Data were collected for a six month period on 136 acute psychiatric wards in 26 NHS Trusts in England. Multilevel modelling was conducted to ascertain those factors most strongly associated with verbal aggression, aggression toward objects, and physical aggression against others. High levels of aggression were associated with a high proportion of patients formally detained under mental health legislation, high patient turnover, alcohol use by patients, ward doors being locked, and higher staffing numbers (especially qualified nurses). The findings suggest that the imposition of restrictions on patients exacerbates the problem of violence, and that alcohol management strategies may be a productive intervention. Insufficient evidence is available to draw conclusions about the nature of the link between staffing numbers and violence

Broad and narrow personality traits as markers of one-time and repeated suicide attempts: A population-based study

<p>Abstract</p> <p>Background</p> <p>Studying personality traits with the potential to differentiate between individuals engaging in suicide attempts of different degrees of severity could help us to understand the processes underlying the link of personality and nonfatal suicidal behaviours and to identify at-risk groups. One approach may be to examine whether narrow, i.e., lower-order personality traits may be more useful than their underlying, broad personality trait dimensions.</p> <p>Methods</p> <p>We investigated qualitative and quantitative differences in broad and narrow personality traits between one-time and repeated suicide attempters in a longitudinal, population-based sample of young French Canadian adults using two multivariate regression models.</p> <p>Results</p> <p>One broad (Compulsivity: OR = 2.0; 95% CI 1.2–3.5) and one narrow personality trait (anxiousness: OR = 1.1; 95% CI 1.01–1.1) differentiated between individuals with histories of repeated and one-time suicide attempts. Affective instability [(OR = 1.1; 95% CI 1.04–1.1)] and anxiousness [(OR = .92; 95% CI .88–.95)], on the other hand, differentiated between nonattempters and one-time suicide attempters.</p> <p>Conclusion</p> <p>Emotional and cognitive dysregulation and associated behavioural manifestations may be associated with suicide attempts of different severity. While findings associated with narrow traits may be easier to interpret and link to existing sociobiological theories, larger effect sizes associated with broad traits such as Compulsivity may be better suited to objectives with a more clinical focus.</p

Charting the course for a Blue Economy in Peru: A Research Agenda

Ocean- and coastal-based economic activities are increasingly recognised as key drivers for supporting global economies. This move towards the “blue economy” is becoming globally widespread, with the recognition that if ocean-based activities are to be sustainable, they will need to move beyond solely extractive and exploitative endeavours, aligning more closely with marine conservation and effective marine spatial planning. In this paper we define the “blue economy” as a “platform for strategic, integrated and participatory coastal and ocean development and protection that incorporates a low carbon economy, the ecosystem approach and human well-being through advancing regional industries, services and activities”. In Peru, while the seas contribute greatly to the national economy, the full potential of the blue economy has yet to be realised. This paper presents the findings of an early career scientist workshop in Lima, Peru, in March 2016. The workshop “Advancing Green Growth in Peru” brought together researchers to identify challenges and opportunities for green growth across three Peruvian economic sectors—tourism, transport and the blue economy with this paper exploring in detail the priorities generated from the “blue economy” stream. These priorities include themes such as marine spatial planning, detailed evaluations of existing maritime industries (e.g. guano collection and fisheries), development of an effective MPA network, support for sustainable coastal tourism, and better inclusion of social science disciplines in understanding societal and political support for a Peruvian blue economy. In addition, the paper discusses the research requirements associated with these priorities. While not a comprehensive list, these priorities provide a starting point for future dialogue on a co-ordinated scientific platform supporting the blue growth agenda in Peru, and in other regions working towards a successful “blue economy”

Pre-clinical imaging of transgenic mouse models of neuroblastoma using a dedicated 3-element solenoid coil on a clinical 3T platform.

Background The use of clinical MRI scanners to conduct pre-clinical research facilitates comparisons with clinical studies. Here the utility and sensitivity of anatomical and functional MRI data/biomarkers acquired from transgenic mouse models of neuroblastoma using a dedicated radiofrequency (RF) coil on a clinical 3T scanner was evaluated.Methods Multiparametric MRI of transgenic mice bearing abdominal neuroblastomas was performed at 3T, and data cross-referenced to that acquired from the same mice on a pre-clinical 7T MRI system. T2-weighted imaging, quantitation of the native longitudinal relaxation time (T1) and the transverse relaxation rate (R2*), and dynamic contrast-enhanced (DCE)-MRI, was used to assess tumour volume, phenotype and response to cyclophosphamide or cabozantinib.Results Excellent T2-weighted image contrast enabled clear tumour delineation at 3T. Significant correlations of tumour volume (R=0.98, P2* (R=0.87, P2* (Ptrans for each tumour (median Ktrans values of 0.202, 0.168 and 0.114 min-1). Cyclophosphamide elicited a significant reduction in both tumour burden (P1 (P<0.01), whereas cabozantinib induced significant (P<0.01) tumour growth delay.Conclusions Simultaneous multiparametric MRI of multiple tumour-bearing animals using this coil arrangement at 3T can provide high efficiency/throughput for both phenotypic characterisation and evaluation of novel therapeutics, and facilitate the introduction of functional MRI biomarkers into aligned imaging-embedded clinical trials