Cholesterol- and actin-centered view of the plasma membrane: updating the Singer–Nicolson fluid mosaic model to commemorate its 50th anniversary

Two very polarized views exist for understanding the cellular plasma membrane (PM). For some, it is the simple fluid described by the original Singer–Nicolson fluid mosaic model. For others, due to the presence of thousands of molecular species that extensively interact with each other, the PM forms various clusters and domains that are constantly changing and therefore, no simple rules exist that can explain the structure and molecular dynamics of the PM. In this article, we propose that viewing the PM from its two predominant components, cholesterol and actin filaments, provides an excellent and transparent perspective of PM organization, dynamics, and mechanisms for its functions. We focus on the actin-induced membrane compartmentalization and lipid raft domains coexisting in the PM and how they interact with each other to perform PM functions. This view provides an important update of the fluid mosaic model

A Brief Measure of Fidelity for Mindfulness Programs: Development and Evaluation of the Concise Fidelity for Mindfulness-Based Interventions Tool

BackgroundMindfulness research and clinical programs are widespread, and it is important that mindfulness-based interventions are delivered with fidelity, or as intended, across settings. The MBI:TAC is a comprehensive system for assessing teacher competence, yet it can be complex to implement. A standardized, simple fidelity/engagement tool to address treatment delivery is needed.ObjectiveWe describe the development, evaluation, and outcomes of a brief, practical tool for assessing fidelity and engagement in online mindfulness-based programs. The tool contains questions about session elements such as meditation guidance and group discussion, and questions about participant engagement and technology-based barriers to engagement.MethodsThe fidelity rating tool was developed and tested in OPTIMUM, Optimizing Pain Treatment in Medical settings Using Mindfulness. The OPTIMUM study is a 3-site pragmatic randomized trial of group medical visits and adapted mindfulness-based stress reduction for primary care patients with chronic low back pain, delivered online. Two trained study personnel independently rated 26 recorded OPTIMUM sessions to determine inter-rater reliability of the Concise Fidelity for Mindfulness-Based Interventions (CoFi-MBI) tool. Trained raters also completed the CoFi-MBI for 105 sessions. Raters provided qualitative data via optional open text fields within the tool.ResultsInter-rater agreement was 77-100% for presence of key session components, and 69-88% for Likert ratings of participant engagement and challenges related to technology, with discrepancies only occurring within 2 categories: ‘very much’ and ‘quite a bit’. Key session components occurred as intended in 94-100% of the 105 sessions, and participant engagement was rated as ‘very much’ or ‘quite a bit’ in 95% of the sessions. Qualitative analysis of rater comments revealed themes related to engagement challenges and technology failures.ConclusionThe CoFi-MBI provides a practical way to assess basic adherence to online delivery of mindfulness session elements, participant engagement, and extent of technology obstacles. Optional text can guide strategies to improve engagement and reduce technology barriers

Theories for influencer identification in complex networks

In social and biological systems, the structural heterogeneity of interaction networks gives rise to the emergence of a small set of influential nodes, or influencers, in a series of dynamical processes. Although much smaller than the entire network, these influencers were observed to be able to shape the collective dynamics of large populations in different contexts. As such, the successful identification of influencers should have profound implications in various real-world spreading dynamics such as viral marketing, epidemic outbreaks and cascading failure. In this chapter, we first summarize the centrality-based approach in finding single influencers in complex networks, and then discuss the more complicated problem of locating multiple influencers from a collective point of view. Progress rooted in collective influence theory, belief-propagation and computer science will be presented. Finally, we present some applications of influencer identification in diverse real-world systems, including online social platforms, scientific publication, brain networks and socioeconomic systems.Comment: 24 pages, 6 figure

Possible origins of macroscopic left-right asymmetry in organisms

I consider the microscopic mechanisms by which a particular left-right (L/R) asymmetry is generated at the organism level from the microscopic handedness of cytoskeletal molecules. In light of a fundamental symmetry principle, the typical pattern-formation mechanisms of diffusion plus regulation cannot implement the "right-hand rule"; at the microscopic level, the cell's cytoskeleton of chiral filaments seems always to be involved, usually in collective states driven by polymerization forces or molecular motors. It seems particularly easy for handedness to emerge in a shear or rotation in the background of an effectively two-dimensional system, such as the cell membrane or a layer of cells, as this requires no pre-existing axis apart from the layer normal. I detail a scenario involving actin/myosin layers in snails and in C. elegans, and also one about the microtubule layer in plant cells. I also survey the other examples that I am aware of, such as the emergence of handedness such as the emergence of handedness in neurons, in eukaryote cell motility, and in non-flagellated bacteria.Comment: 42 pages, 6 figures, resubmitted to J. Stat. Phys. special issue. Major rewrite, rearranged sections/subsections, new Fig 3 + 6, new physics in Sec 2.4 and 3.4.1, added Sec 5 and subsections of Sec

Forward production of charged pions with incident π±\pi^{\pm} on nuclear targets measured at the CERN PS

Measurements of the double-differential $\pi^{\pm}$ production cross-section in the range of momentum 0.5 \GeVc \leq p \le 8.0 \GeVc and angle 0.025 \rad \leq \theta \le 0.25 \rad in interactions of charged pions on beryllium, carbon, aluminium, copper, tin, tantalum and lead are presented. These data represent the first experimental campaign to systematically measure forward pion hadroproduction. The data were taken with the large acceptance HARP detector in the T9 beam line of the CERN PS. Incident particles, impinging on a 5% nuclear interaction length target, were identified by an elaborate system of beam detectors. The tracking and identification of the produced particles was performed using the forward spectrometer of the HARP detector. Results are obtained for the double-differential cross-sections ${{\mathrm{d}^2 \sigma}}/{{\mathrm{d}p\mathrm{d}\Omega}}$ mainly at four incident pion beam momenta (3 \GeVc, 5 \GeVc, 8 \GeVc and 12 \GeVc). The measurements are compared with the GEANT4 and MARS Monte Carlo simulationComment: to be published on Nuclear Physics

Comparison of large-angle production of charged pions with incident protons on cylindrical long and short targets

The HARP collaboration has presented measurements of the double-differential pi+/pi- production cross-section in the range of momentum 100 MeV/c <= p 800 MeV/c and angle 0.35 rad <= theta <= 2.15 rad with proton beams hitting thin nuclear targets. In many applications the extrapolation to long targets is necessary. In this paper the analysis of data taken with long (one interaction length) solid cylindrical targets made of carbon, tantalum and lead is presented. The data were taken with the large acceptance HARP detector in the T9 beam line of the CERN PS. The secondary pions were produced by beams of protons with momenta 5 GeV/c, 8 GeV/c and 12 GeV/c. The tracking and identification of the produced particles were performed using a small-radius cylindrical time projection chamber (TPC) placed inside a solenoidal magnet. Incident protons were identified by an elaborate system of beam detectors. Results are obtained for the double-differential yields per target nucleon d2 sigma / dp dtheta. The measurements are compared with predictions of the MARS and GEANT4 Monte Carlo simulations.Comment: 43 pages, 20 figure

Metabolic reprogramming during neuronal differentiation.

Newly generated neurons pass through a series of well-defined developmental stages, which allow them to integrate into existing neuronal circuits. After exit from the cell cycle, postmitotic neurons undergo neuronal migration, axonal elongation, axon pruning, dendrite morphogenesis and synaptic maturation and plasticity. Lack of a global metabolic analysis during early cortical neuronal development led us to explore the role of cellular metabolism and mitochondrial biology during ex vivo differentiation of primary cortical neurons. Unexpectedly, we observed a huge increase in mitochondrial biogenesis. Changes in mitochondrial mass, morphology and function were correlated with the upregulation of the master regulators of mitochondrial biogenesis, TFAM and PGC-1α. Concomitant with mitochondrial biogenesis, we observed an increase in glucose metabolism during neuronal differentiation, which was linked to an increase in glucose uptake and enhanced GLUT3 mRNA expression and platelet isoform of phosphofructokinase 1 (PFKp) protein expression. In addition, glutamate-glutamine metabolism was also increased during the differentiation of cortical neurons. We identified PI3K-Akt-mTOR signalling as a critical regulator role of energy metabolism in neurons. Selective pharmacological inhibition of these metabolic pathways indicate existence of metabolic checkpoint that need to be satisfied in order to allow neuronal differentiation

Large-angle production of charged pions by 3 GeV/c - 12 GeV/c protons on carbon, copper and tin targets

A measurement of the double-differential $\pi^{\pm}$ production cross-section in proton--carbon, proton--copper and proton--tin collisions in the range of pion momentum 100 \MeVc \leq p < 800 \MeVc and angle 0.35 \rad \le \theta <2.15 \rad is presented. The data were taken with the HARP detector in the T9 beam line of the CERN PS. The pions were produced by proton beams in a momentum range from 3 \GeVc to 12 \GeVc hitting a target with a thickness of 5% of a nuclear interaction length. The tracking and identification of the produced particles was done using a small-radius cylindrical time projection chamber (TPC) placed in a solenoidal magnet. An elaborate system of detectors in the beam line ensured the identification of the incident particles. Results are shown for the double-differential cross-sections at four incident proton beam momenta (3 \GeVc, 5 \GeVc, 8 \GeVc and 12 \GeVc)

Absolute Momentum Calibration of the HARP TPC

In the HARP experiment the large-angle spectrometer is using a cylindrical TPC as main tracking and particle identification detector. The momentum scale of reconstructed tracks in the TPC is the most important systematic error for the majority of kinematic bins used for the HARP measurements of the double-differential production cross-section of charged pions in proton interactions on nuclear targets at large angle. The HARP TPC operated with a number of hardware shortfalls and operational mistakes. Thus it was important to control and characterize its momentum calibration. While it was not possible to enter a direct particle beam into the sensitive volume of the TPC to calibrate the detector, a set of physical processes and detector properties were exploited to achieve a precise calibration of the apparatus. In the following we recall the main issues concerning the momentum measurement in the HARP TPC, and describe the cross-checks made to validate the momentum scale. As a conclusion, this analysis demonstrates that the measurement of momentum is correct within the published precision of 3%.Comment: To be published by JINS

Large-angle production of charged pions by 3 GeV/c - 12.9 GeV/c protons on beryllium, aluminium and lead targets

Measurements of the double-differential $\pi^{\pm}$ production cross-section in the range of momentum 100 \MeVc \leq p < 800 \MeVc and angle 0.35 \rad \leq \theta < 2.15 \rad in proton--beryllium, proton--aluminium and proton--lead collisions are presented. The data were taken with the HARP detector in the T9 beam line of the CERN PS. The pions were produced by proton beams in a momentum range from 3 \GeVc to 12.9 \GeVc hitting a target with a thickness of 5% of a nuclear interaction length. The tracking and identification of the produced particles was performed using a small-radius cylindrical time projection chamber (TPC) placed inside a solenoidal magnet. Incident particles were identified by an elaborate system of beam detectors. Results are obtained for the double-differential cross-sections at six incident proton beam momenta (3 \GeVc, 5 \GeVc, 8 \GeVc, 8.9 \GeVc (Be only), 12 \GeVc and 12.9 \GeVc (Al only)) and compared to previously available data