Editorial: Homeostatic and retrograde signaling mechanisms modulating presynaptic function and plasticity

Dynamic reorganization of neural circuits can occur through the selective strengthening of synapses between neurons that are coactive in response to the encoded information (Shatz, 1990). However, the positive feedback resulting from synaptic strengthening and neuronal coactivity can lead to the destabilization of neuronal networks. Thus, synapses must maintain the capacity for change necessary for learning and memory, yet constrain this inherently destabilizing flexibility to enable stable neural function throughout life. Evidence has emerged in recent years that activity within neural circuits can shape the synaptic properties of component neurons in a manner that maintains stable excitatory drive, a process referred to as homeostatic synaptic plasticity (Turrigiano and Nelson, 2000; Pozo and Goda, 2010; Davis, 2013). Potent and adaptive homeostatic mechanisms have been demonstrated in a variety of systems to modulate activity at the level of an individual neuron, synapse, circuit, or entire network, and dysregulation at some or all of these levels may contribute to neuropsychiatric disorders, intellectual disability, and epilepsy (Wondolowski and Dickman, 2013). Greater mechanistic understanding of homeostatic plasticity will provide key insights into the etiology of these disorders, which may result from network instability and synaptic dysfunction. Over the past 15 years, the molecular mechanisms of this form of plasticity have been intensely studied in various model organisms, including invertebrates and vertebrates (Davis and Müller, 2015). Though, once thought to have a predominantly postsynaptic basis, emerging evidence suggests that homeostatic mechanisms act on both sides of the synapse, through mechanisms such as retrograde signaling, to orchestrate compensatory adaptations that maintain stable network function (Vitureira et al., 2012). These trans-synaptic signaling systems ultimately alter neurotransmitter release probability by a variety of mechanisms including changes in vesicle pool size and calcium influx (Davis and Müller, 2015). These adaptations are not expected to occur homogenously at all terminals of a pre-synaptic neuron, as they might synapse with neurons in non-overlapping circuits. However, the factors that govern the homeostatic control of synapse-specific plasticity are only beginning to be understood.National Institutes of Health (U.S.) (Grant NS019546

Synaptic Loss in Alzheimer's Disease: Mechanistic Insights Provided by Two-Photon in vivo Imaging of Transgenic Mouse Models

Synapse loss is the strongest correlate for cognitive decline in Alzheimer's disease. The mechanisms underlying synapse loss have been extensively investigated using mouse models expressing genes with human familial Alzheimer's disease mutations. In this review, we summarize how multiphoton in vivo imaging has improved our understanding of synapse loss mechanisms associated with excessive amyloid in the living animal brain. We also discuss evidence obtained from these imaging studies for the role of cell-intrinsic calcium dyshomeostasis and cell-extrinsic activities of microglia, which are the immune cells of the brain, in mediating synapse loss

Experimental investigation on the influences of varying injection timing on the performance of a B20 JOME biodiesel fueled diesel engine / S. Jaichandar and K. Annamalai

This experimental study aims to optimize the injection timing to achieve higher performance from biodiesel fueled Direct Injection (DI) diesel engine. Experiments were performed using a naturally-aspirated single cylinder DI diesel engine equipped with a conventional jerk type injection system to study the effects of varying injection timing on the combustion, performance and exhaust emissions using a blend of 20% Jatropha Oil Methyl Ester (JOME) by volume with diesel. The test results showed that improvement in terms of brake thermal efficiency and specific fuel consumption for the engine operated at retarded injection timing, particularly at 21o bTDC. Substantial improvements in reduction of emission levels particularly oxides of nitrogen (NOx) were observed for retarded injection timing of 21o bTDC. Compared to the engine operated at standard injection timing of 23o bTDC, the retarded injection timing of 21o bTDC provided a better performance of 2.27% and 3.4% in terms of BTE and BSFC respectively and NOx emission level improvement of 4.5%. However, CO, UBHC and smoke emission levels were slightly deteriorated compared to standard injection timing operation. It has also been found that retarding the injection timing lowers marginally ignition delay, peak in-cylinder pressure and maximum heat release rate

An Intelligent FPGA Based Anti-Sweating System for Bed Sore Prevention in a Clinical Environment

Bed sores, a common problem among immobile patients occur as a result of continuous sweating due to increase in skin to bed surface temperature in patients lying on same posture for prolonged period. If left untreated, the skin can break open and become infected. Currently adopted methods for bed sores prevention include: use of two hourly flip chat for repositioning patient or use of air fluidized beds. However, the setbacks of these preventive measures include either use of costly equipment or wastage of human resources. This paper introduces an intelligent low cost FPGA based anti-sweating system for bed sores prevention in a clinical environment. The developed system consists of bed surface implanted temperature sensors interfaced with an FPGA chip for sensing the temperature change in patient’s skin to bed surface. Based on the temperature change, the FPGA chip select the - mode (heater/cooler) and speed of the fan module. Furthermore, an alarm module was implemented to alert the nurse to reposition the patient only if patient’s skin to bed surface temperature exceeds a predefined threshold thereby saving human resources. By integrating the whole system into a single FPGA chip, we were able to build a low cost compact system without sacrificing processing power and flexibility

The Influence of Piston Bowl Geometries on In-Cylinder Air Flow in a Direct-Injection (DI) Diesel Engine for Biodiesel Operation / S. Jaichandar, E. James Gunasekaran and A. Gunabalan

Thermal efficiency improvement, fuel consumption and pollutant emissions reduction from biodiesel fueled engines are critical requirements in engine research. In order to achieve these, a rapid and better air-fuel mixing condition is desired. The mixing quality of biodiesel with air can be improved by selecting the best engine design particularly combustion chamber design and injection system parameters. The present work investigates the effect of varying the piston bowl geometry on the air flow characteristics such as swirl velocity, Swirl Ratio (SR), and Turbulent Kinetic Energy (TKE) inside the engine cylinder. The piston’s bowl geometry was modified into several configurations that include Shallow depth combustion chamber (SCC), Toroidal combustion chamber (TCC), Shallow depth reentrant combustion chamber (SRCC) and Toroidal re-entrant combustion chamber (TRCC) from the standard Hemispherical combustion chamber (HCC), without altering the compression ratio of the engine. A commercially available CFD code STAR-CD was used to analyze the in-cylinder flow at different conditions. Flow conditions inside the cylinder were predicted by solving momentum, continuity and energy equations. The results confirmed that the piston bowl geometry had little influence on the in-cylinder flow during the intake stroke and the first part of compression stroke i.e. up to 300oafter suction TDC. However, the piston bowl geometry plays a significant role in the latter stage of the compression stroke i.e. beyond 300oafter suction TDC to compression TDC. The intensity of maximum swirl velocity at the end of compression stroke for TRCC was observed higher as 18.95 m/s and a strong recirculation was observed due to the geometry. Compared to baseline HCC the TRCC had higher, maximum swirl ratio and turbulent kinetic energy by about 28% and 2.14 times respectively. From the analysis of results, it was found that TRCC configuration gives better in-cylinder flows

Non-descanned multifocal multiphoton microscopy with a multianode photomultiplier tube

Multifocal multiphoton microscopy (MMM) improves imaging speed over a point scanning approach by parallelizing the excitation process. Early versions of MMM relied on imaging detectors to record emission signals from multiple foci simultaneously. For many turbid biological specimens, the scattering of emission photons results in blurred images and degrades the signal-to-noise ratio (SNR). We have recently demonstrated that a multianode photomultiplier tube (MAPMT) placed in a descanned configuration can effectively collect scattered emission photons from each focus into their corresponding anodes significantly improving image SNR for highly scattering specimens. Unfortunately, a descanned MMM has a longer detection path resulting in substantial emission photon loss. Optical design constraints in a descanned geometry further results in significant optical aberrations especially for large field-of-view (FOV), high NA objectives. Here, we introduce a non-descanned MMM based on MAPMT that substantially overcomes most of these drawbacks. We show that we improve signal efficiency up to fourfold with limited image SNR degradation due to scattered emission photons. The excitation foci can also be spaced wider to cover the full FOV of the objective with minimal aberrations. The performance of this system is demonstrated by imaging interneuron morphological structures deep in the brains of living mice.Grant RO1 EY017656National Institutes of Health (U.S.) (9P41EB015871)5 R01 NS0513204R44EB012415National Science Foundation (U.S.) (CBET-0939511)Singapore-MIT Alliance for Research and TechnologyMIT Skoltech InitiativeHamamatsu CorporationDavid H. Koch Institute for Integrative Cancer Research at MIT (Bridge Project Initiative

Reassignment of Scattered Emission Photons in Multifocal Multiphoton Microscopy

Multifocal multiphoton microscopy (MMM) achieves fast imaging by simultaneously scanning multiple foci across different regions of specimen. The use of imaging detectors in MMM, such as CCD or CMOS, results in degradation of image signal-to-noise-ratio (SNR) due to the scattering of emitted photons. SNR can be partly recovered using multianode photomultiplier tubes (MAPMT). In this design, however, emission photons scattered to neighbor anodes are encoded by the foci scan location resulting in ghost images. The crosstalk between different anodes is currently measured a priori, which is cumbersome as it depends specimen properties. Here, we present the photon reassignment method for MMM, established based on the maximum likelihood (ML) estimation, for quantification of crosstalk between the anodes of MAPMT without a priori measurement. The method provides the reassignment of the photons generated by the ghost images to the original spatial location thus increases the SNR of the final reconstructed image.RO1 EY017656Singapore-MIT Alliance for Research and TechnologyNIH P41EB0158715 R01 NS0513204R44EB012415NSF CBET-0939511MIT Skoltech InitiativeDavid H. Koch Institute for Integrative Cancer Research at MI

Inhibitory Synapses Are Repeatedly Assembled and Removed at Persistent Sites In Vivo

Older concepts of a hard-wired adult brain have been overturned in recent years by in vivo imaging studies revealing synaptic remodeling, now thought to mediate rearrangements in microcircuit connectivity. Using three-color labeling and spectrally resolved two-photon microscopy, we monitor in parallel the daily structural dynamics (assembly or removal) of excitatory and inhibitory postsynaptic sites on the same neurons in mouse visual cortex in vivo. We find that dynamic inhibitory synapses often disappear and reappear again in the same location. The starkest contrast between excitatory and inhibitory synapse dynamics is on dually innervated spines, where inhibitory synapses frequently recur while excitatory synapses are stable. Monocular deprivation, a model of sensory input-dependent plasticity, shortens inhibitory synapse lifetimes and lengthens intervals to recurrence, resulting in a new dynamic state with reduced inhibitory synaptic presence. Reversible structural dynamics indicate a fundamentally new role for inhibitory synaptic remodeling—flexible, input-specific modulation of stable excitatory connections.National Eye Institute (Grant RO1 EY017656 and RO1 EY011894)National Institutes of Health (U.S.) (P41EB015871-26A1, 4R44EB012415-02, and NSF CBET-0939511)Singapore-MIT AllianceSingapore-MIT Alliance for Research and Technology CenterRuth L. Kirschstein National Research Service Award (F31AG044061)National Institutes of Health (U.S.) (Pre-Doctoral Training Grant T32GM007287

Experimental assessment of pre-turbo aftertreatment configurations in a single stage turbocharged diesel engine. Part 1: Steady-state operation

Diesel oxidation catalysts and diesel particulate filters are standard aftertreatment systems in Diesel engines which are traditionally placed downstream of the turbine. However, pre-turbo aftertreatment configurations are being approached as a way to improve the aftertreatment performance in terms of light-off and passive regeneration. This exhaust line architecture can also benefit fuel economy. The objective of this work is to analyse experimentally how the pre-turbo aftertreatment placement impacts on the performance of a single stage turbocharged Diesel engine. The work has been divided into two parts focused on steady-state and transient engine operation separately. The first part comprises the analysis of the experimental results corresponding to steady-state operating conditions. The range of operation covers different engine loads and speeds. The engine response with pre-turbo aftertreatment placement is mainly affected by the change in the pumping work caused by the aftertreatment pressure drop reduction and its new location, which avoids the multiplicative effect of the turbine expansion ratio when setting the engine back-pressure. These effects become more significant as the engine load increases benefiting fuel consumption from low to high loads. Concerning aftertreatment performance, the results evidence noticeable benefits in DPF passive regeneration and CO/HC emissions reduction at low engine load.This work has been partially supported by the Vicerrectorado de Investigacion de la Universitat Politenica de Valencia through grant number SP20120340-UPPTE/2012/96 and by the Conselleria de Educacio, Cultura i Esport of the Generalitat Valenciana through grant number GV/2013/043.Luján, JM.; Bermúdez, V.; Piqueras, P.; García Afonso, Ó. (2015). Experimental assessment of pre-turbo aftertreatment configurations in a single stage turbocharged diesel engine. Part 1: Steady-state operation. Energy. 80:599-613. https://doi.org/10.1016/j.energy.2014.05.048S5996138