Extracellular vesicle-induced differentiation of neural stem progenitor cells

Neural stem progenitor cells (NSPCs) from E13.5 mouse embryos can be maintained in culture under proliferating conditions. Upon growth-factor removal, they may differentiate toward either neuronal or glial phenotypes or both. Exosomes are small extracellular vesicles that are part of the cell secretome; they may contain and deliver both proteins and genetic material and thus play a role in cell–cell communication, guide axonal growth, modulate synaptic activity and regulate peripheral nerve regeneration. In this work, we were interested in determining whether NSPCs and their progeny can produce and secrete extracellular vesicles (EVs) and if their content can affect cell differentiation. Our results indicate that cultured NSPCs produce and secrete EVs both under proliferating conditions and after differentiation. Treatment of proliferating NSPCs with EVs derived from differentiated NSPCs triggers cell differentiation in a dose-dependent manner, as demonstrated by glial-and neuronal-marker expression

Dystonia: sparse synapses for D2 receptors in striatum of a DYT1 knock-out mouse model

Dystonia pathophysiology has been partly linked to downregulation and dysfunction of dopamine D2 receptors in striatum. We aimed to investigate the possible morpho-structural correlates of D2 receptor downregulation in the striatum of a DYT1 Tor1a mouse model. Adult control Tor1a+/+ and mutant Tor1a+/− mice were used. The brains were perfused and free-floating sections of basal ganglia were incubated with polyclonal anti-D2 antibody, followed by secondary immune-fluorescent antibody. Confocal microscopy was used to detect immune-fluorescent signals. The same primary antibody was used to evaluate D2 receptor expression by western blot. The D2 receptor immune-fluorescence appeared circumscribed in small disks (~0.3–0.5 μm diameter), likely representing D2 synapse aggregates, densely distributed in the striatum of Tor1a+/+ mice. In the Tor1a+/− mice the D2 aggregates were significantly smaller (μm2 2.4 ± SE 0.16, compared to μm2 6.73 ± SE 3.41 in Tor1a+/+) and sparse, with ~30% less number per microscopic field, value correspondent to the amount of reduced D2 expression in western blotting analysis. In DYT1 mutant mice the sparse and small D2 synapses in the striatum may be insufficient to “gate” the amount of presynaptic dopamine release diffusing in peri-synaptic space, and this consequently may result in a timing and spatially larger nonselective sphere of influence of dopamine action

Combining electrostatic, hindrance and diffusive effects for predicting particle transport and separation efficiency in deterministic lateral displacement microfluidic devices

Microfluidic separators based on Deterministic Lateral Displacement (DLD) constitute a promising technique for the label-free detection and separation of mesoscopic objects of biological interest, ranging from cells to exosomes. Owing to the simultaneous presence of different forces contributing to particle motion, a feasible theoretical approach for interpreting and anticipating the performance of DLD devices is yet to be developed. By combining the results of a recent study on electrostatic effects in DLD devices with an advection-diffusion model previously developed by our group, we here propose a fully predictive approach (i.e., ideally devoid of adjustable parameters) that includes the main physically relevant effects governing particle transport on the one hand, and that is amenable to numerical treatment at affordable computational expenses on the other. The approach proposed, based on ensemble statistics of stochastic particle trajectories, is validated by comparing/contrasting model predictions to available experimental data encompassing different particle dimensions. The comparison suggests that at low/moderate values of the flowrate the approach can yield an accurate prediction of the separation performance, thus making it a promising tool for designing device geometries and operating conditions in nanoscale applications of the DLD technique

Whetting disadvantaged adults’ appetite for nutrition education

Objective: To identify the features of a nutrition education programme for disadvantaged adults deemed most attractive and useful by participants. Design: A two-year, multi-method, qualitative evaluation of pre and post data collected from programme participants. Data were imported into NVivo10 for coding to facilitate a thematic analysis. Setting: Western Australia. Participants: Individuals attending the Western Australian FOODcents nutrition education programme that is designed to provide knowledge and skills needed to consume a healthy diet on a budget. Focus groups were conducted several weeks after course completion (five groups, forty-seven participants), observations were conducted during FOODcents sessions (thirty-one observation episodes, 237 participants), and open-ended questions were asked in pre–post hard-copy surveys administered in sessions (n 927) and an online survey administered on average six weeks after course completion (n 114). Results: The course attributes that were found to be especially important to participants were: (i) user-friendly, practical information that could be immediately translated to their daily lives; (ii) experiential learning that involved direct contact with food products; and (iii) opportunities for social interaction. These aspects of nutrition education were described as being highly influential in the decision to participate in the course, the application of the information in their subsequent food purchase and preparation activities, and their word-of-mouth communications with others about the course. Conclusions: Incorporating aspects of most importance to participants into nutrition education programme delivery and promotion may increase joining rates, enjoyment, satisfaction with course content and, ultimately, the uptake of recommended behaviours

Fractionation of a three-particle mixture by Brownian sieving hydrodynamic chromatography

Particles ranging in size from a few nanometers (exosomes or viruses) to a few micrometers (bacteria or red blood cells) can be sorted using a size-based separation process. One of the simplest techniques is provided by hydrodynamic chromatography (HDC) which typically requires long channels to achieve adequate resolution. A new separation mechanism based on a Brownian sieving effect coupled with HDC has recently been proposed to overcome these limitations. An efficiency improvement of up to 2000 % has been predicted for a two-size mixture. The aim of this work is to study and optimize a modified geometry useful for obtaining the simultaneous separation of a three-size diluted suspension. The results suggest a significant performance improvement, up to 3000 %, over the standard HDC

Tuning the polarization states of optical spots at the nanoscale on the poincar´e sphere using a plasmonic nanoantenna

It is shown that the polarization states of optical spots at the nanoscale can be manipulated to various points on the Poincar´e sphere using a plasmonic nanoantenna. Linearly, circularly, and elliptically polarized near-field optical spots at the nanoscale are achieved with various polarization states on the Poincar´e sphere using a plasmonic nanoantenna. A novel plasmonic nanoantenna is illuminated with diffraction-limited linearly polarized light. It is demonstrated that the plasmonic resonances of perpendicular and longitudinal components of the nanoantenna and the angle of incident polarization can be tuned to obtain optical spots beyond the diffraction limit with a desired polarization and handedness

Non-Stationary Policy Learning for Multi-Timescale Multi-Agent Reinforcement Learning

In multi-timescale multi-agent reinforcement learning (MARL), agents interact across different timescales. In general, policies for time-dependent behaviors, such as those induced by multiple timescales, are non-stationary. Learning non-stationary policies is challenging and typically requires sophisticated or inefficient algorithms. Motivated by the prevalence of this control problem in real-world complex systems, we introduce a simple framework for learning non-stationary policies for multi-timescale MARL. Our approach uses available information about agent timescales to define a periodic time encoding. In detail, we theoretically demonstrate that the effects of non-stationarity introduced by multiple timescales can be learned by a periodic multi-agent policy. To learn such policies, we propose a policy gradient algorithm that parameterizes the actor and critic with phase-functioned neural networks, which provide an inductive bias for periodicity. The framework's ability to effectively learn multi-timescale policies is validated on a gridworld and building energy management environment.Comment: Accepted at IEEE CDC'23. 7 pages, 6 figure

Bulk Cr tips for scanning tunneling microscopy and spin-polarized scanning tunneling microscopy

A simple, reliable method for preparation of bulk Cr tips for Scanning Tunneling Microscopy (STM) is proposed and its potentialities in performing high-quality and high-resolution STM and Spin Polarized-STM (SP-STM) are investigated. Cr tips show atomic resolution on ordered surfaces. Contrary to what happens with conventional W tips, rest atoms of the Si(111)-7x7 reconstruction can be routinely observed, probably due to a different electronic structure of the tip apex. SP-STM measurements of the Cr(001) surface showing magnetic contrast are reported. Our results reveal that the peculiar properties of these tips can be suited in a number of STM experimental situations

Generalized Fourier Integral Operators on spaces of Colombeau type

Generalized Fourier integral operators (FIOs) acting on Colombeau algebras are defined. This is based on a theory of generalized oscillatory integrals (OIs) whose phase functions as well as amplitudes may be generalized functions of Colombeau type. The mapping properties of these FIOs are studied as the composition with a generalized pseudodifferential operator. Finally, the microlocal Colombeau regularity for OIs and the influence of the FIO action on generalized wave front sets are investigated. This theory of generalized FIOs is motivated by the need of a general framework for partial differential operators with non-smooth coefficients and distributional data

Potential in-class strategies to increase children’s vegetable consumption

Objective: The Crunch&Sip programme is a school-based nutrition initiative designed to increase the fruit, vegetable and water intakes of primary-school children. In recognition of the notable deficits in children’s vegetable consumption, the present study explored the receptivity of school staff to a realignment of the Crunch&Sip programme to feature a primary focus on vegetable consumption. This involved investigating school staff members’ perceptions of relevant barriers, motivators and facilitators. Design: A multi-method approach was adopted that involved four focus groups and a survey (administered in paper and online formats) containing a mixture of open- and closed-ended items. Setting: Western Australia. Subjects: Staff from Western Australian schools participated in the focus groups (n 37) and survey (n 620). Results: School staff were strongly supportive of modifying the Crunch&Sip programme to focus primarily on children’s vegetable consumption and this was generally considered to be a feasible change to implement. Possible barriers identified included children’s taste preferences and a perceived lack of parental support. Suggested strategies to overcome these barriers were education sessions for parents and children, teachers modelling vegetable consumption for their students and integrating vegetable-related topics into the school curriculum. Conclusions: School staff are likely to support the introduction of school-based nutrition programmes that specifically encourage the consumption of vegetables. Potential barriers may be overcome through strategies to engage parents and children