Role of Glia in Sculpting Synaptic Connections at the Drosophila Neuromuscular Junction: A Dissertation

Emerging evidence in both vertebrates and invertebrates is redefining glia as active players in the development and integrity of the nervous system. The formation of functional neuronal circuits requires the precise addition of new synapses. Mounting evidence implicates glial function in synapse remodeling and formation. However, the precise molecular mechanisms governing these functions are poorly understood. My thesis work begins to define the molecular mechanisms by which glia communicate with neurons at the Drosophila neuromuscular junction (NMJ). During development glia play a critical role in remodeling neuronal circuits in the CNS. In order to understand how glia remodel synapses, I manipulated a key component of the glial engulfment machinery, Draper. I found that during normal NMJ growth presynaptic boutons constantly shed membranes or debris. However, a loss of Draper resulted in an accumulation of debris and ghost boutons, which inhibited synaptic growth. I found that glia use the Draper pathway to engulf these excess membranes to sculpt synapses. Surprisingly, I found that muscle cells function as phagocytic cells as well by eliminating immature synaptic ghost boutons. This demonstrates that the combined efforts of glia and muscle are required for the addition of synapses and proper growth. My work establishes that glia play a crucial role in synapse development at the NMJ and suggests that there are other glial-derived molecules that regulate synapse function. I identified one glial derived molecule critical for the development of the NMJ, a TGF-β ligand called Maverick. Presynaptically, Maverick regulates the activation of BMP pathway confirmed by reducing the transcription of the known target gene Trio. Postsynaptically, it regulates the transcription of Glass bottom boat (Gbb) in the muscle suggesting that glia modulate the function of Gbb and consequently the activation of the BMP retrograde pathway at NMJ. Surprisingly, I also found that glial Maverick regulates the transcription of Shaker potassium channel, suggesting that glia potentially could regulate muscle excitability and consequently modulate synaptic transmission. Future work will elucidate such hypothesis. My work has demonstrated two novel roles for glia at the NMJ. First is that glia engulfing activity is important for proper synaptic growth. Second is that the secretion of glial-derived molecules are required to orchestrate synaptic development. This further supports that glia are critical active players in maintaining a functional nervous system

On the use of laser-scanning vibrometry for mechanical performance evaluation of 3D printed specimens

In this study, we explored the suitability of laser-scanning vibrometry (LSV) for evaluation of the mechanical behavior of rectangular prisms produced by Fused Filament Fabrication (FFF). Our hypothesis was that LSV would be able to discriminate the mechanical behavior of specimens fabricated with different process parameters combinations. Build orientation, raster angle, nozzle temperature, printing speed and layer thickness were the process parameters of interest. Based on a factorial design of experiment approach, 48 different process parameter combinations were taken into account and 96 polylactic acid (PLA) rectangular prisms were fabricated. The characterization of their dynamical behavior provided frequency data, making possible the computation of an equivalent elastic modulus metric. Statistical analysis of the equivalent elastic modulus dataset confirmed the significant influences of raster angle, build orientation and nozzle temperature. Moreover, multivariate regression models served to rank, not only the significant influences of individual process parameters, but also the significant quadratic and cubic interactions between them. The previous knowledge was then applied to generate an ad hoc model selecting the most important factors (linear and interactions). The predicted equivalent elastic moduli provided by our ad hoc model were used in modal analysis simulations of both 3D printed rectangular prisms and a complex part. The simulated frequencies thus obtained were generally closer to the experimental ones (=11%), as compared to modal analysis simulations based on internal geometry modelling (=33%). The use of LSV appears very promising in the characterization of the mechanical behavior and integrity of 3D printed parts. Other additive manufacturing technologies may benefit from the use of this technique and from the adoption of the presented methodology to test, simulate and optimize the properties of 3D printed products. © 2021 The Author

Uncertainties in gas kinematics arising from stellar continuum modelling in integral field spectroscopy data: the case of NGC2906 observed with MUSE/VLT

We study how the use of several stellar subtraction methods and line fitting approaches can affect the derivation of the main kinematic parameters (velocity and velocity dispersion fields) of the ionized gas component. The target of this work is the nearby galaxy NGC 2906, observed with the MUSE instrument at Very Large Telescope. A sample of twelve spectra is selected from the inner (nucleus) and outer (spiral arms) regions, characterized by different ionization mechanisms. We compare three different methods to subtract the stellar continuum (FIT3D, STARLIGHT and pPXF), combined with one of the following stellar libraries: MILES, STELIB and GRANADA+MILES. The choice of the stellar subtraction method is the most important ingredient affecting the derivation of the gas kinematics, followed by the choice of the stellar library and by the line fitting approach. In our data, typical uncertainties in the observed wavelength and width of the H\alpha and [NII] lines are of the order of _rms \sim 0.1\AA\ and _rms \sim 0.2\AA\ (\sim 5 and 10km/s, respectively). The results obtained from the [NII] line seem to be slightly more robust, as it is less affected by stellar absorption than H\alpha. All methods considered yield statistically consistent measurements once a mean systemic contribution \Delta\bar\lambda=\Delta\bar\sigma=0.2xDelta_{MUSE} is added in quadrature to the line fitting errors, where \Delta_{MUSE} = 1.1\AA\ \sim 50 km/s denotes the instrumental resolution of the MUSE spectra. Although the subtraction of the stellar continuum is critical in order to recover line fluxes, any method (including none) can be used in order to measure the gas kinematics, as long as an additional component of 0.2 x Delta_MUSE is added to the error budget.Comment: 20 pages, 14 figure

Determination of Valanis model parameters in a bolted lap joint: Experimental and numerical analyses of frictional dissipation

In this work, Valanis model parameters, and their variation with bolt preload, were determined for a bolted lap joint, which consisted in two steel plates held together by a metric 12 screw. For this purpose, a series of transitory non-linear analyses were performed on the basis of a three dimensional finite element model of the bolted lap joint subjected to varying bolt preloads and tangential displacements. Curve fitting of hysteresis cycles obtained from numerical simulations allowed determination of Valanis model parameters as well as assessment of bolt preload influence on these parameters. In addition, the present numerical simulations provided information about the evolution of the contact state from stick to slip regimes between the bolted plates, reflecting the non-linear behaviour of the joint. Quasi-static tests at several preloads and tangential displacements conditions were conducted to validate Valanis model parameters previously obtained from numerical simulations. The present findings provided detailed information about the evolution of the aforementioned Valanis parameters with bolt preload. Thus, we confirmed that equivalent stiffness values corresponding to the macro-slip regime as well as the upper limit of the sticking regime (Et and σ0, respectively) are highly influenced by bolt preload levels. These results may prove useful to appropriately design bolted joints to be used under specific stiffness and damping criteria, and therefore reducing the vibration response of the joint.This work has been funded with project MYCT/FEDER Ref. BIA2006-15266-C02-02, and by Diputación General de Aragón (Grant no. G.C.I.A. 2011.T67).Peer Reviewe

Improved wear performance of ultra high molecular weight polyethylene coated with hydrogenated diamond like carbon

Hydrogenated diamond like carbon (DLCH) thin films were deposited on medical grade ultra high molecular weight polyethylene (UHMWPE) by radio frequency plasma enhanced chemical vapor deposition. The DLCH coating thicknesses ranged from 250 to 700. nm. The substrates were disks made of UHMWPEs typically used for soft components in artificial joints, namely virgin GUR 1050 and highly crosslinked (gamma irradiated in air to 100. kGy) UHMWPEs. Mechanical and tribological properties under bovine serum lubrication at body temperature were assessed on coated and uncoated polyethylenes by means of nano-hardness and ball-on-disk tests, respectively. Morphological features of the worn surfaces were obtained by confocal microscopy and scanning electron microscopy. This study confirms an increase in surface hardness and good wear resistance for coated materials after 24. h of sliding test compared to uncoated polyethylene. These results point out that to coat UHMWPE with DLCH films could be a potential method to reduce backside wear in total hip and knee arthroplasties.Ministerio de Ciencia y Educación MAT2006-12603- C02-01, CSD2008-0002

Estudio de laboratorio sobre utilización de zeolita natural versus zeolita sintética en la fabricación de mezclas semicalientes

Zeolite can be used as an ingredient in warm bituminous mixes to reduce manufacturing temperatures. The zeolite for this purpose is usually synthetic, but natural zeolite can also be used. The research presented in this paper analyzed the use of natural zeolite from Cuba in the form of sand and filler as an additive in warm asphalt mixes and compared it to asphalt mixes with synthetic zeolite. The mixes were given the Marshall tests, and their moisture sensitivity and stiffness modulus values were also obtained. The results showed that both types of mix had a similar performance, which was only slightly lower than that of the reference mix. The use of different dosages of natural zeolite in the mixes gave the best results when the zeolite was incorporated as filler. This study demonstrated that the use of natural zeolite is an effective way of reducing the temperature of bituminous mixes.Las mezclas semicalientes permiten una reducción de la temperatura de fabricación respecto a las mezclas tradicionales, mediante la modificación del proceso de producción en planta o el empleo de aditivos. En esta investigación se analiza el empleo de zeolita natural procedente de Cuba como aditivo para la fabricación de mezclas semicalientes, en comparación con el empleo de zeolitas artificiales. Para ello, a través de pruebas de estabilidad Marshall, sensibilidad al agua y módulos de rigidez se realiza un estudio comparativo. El resultado obtenido mostró un comportamiento similar entre las mezclas con zeolita natural y la sintética, resultando en ambos casos ligeramente inferior al obtenido por la mezcla patrón. Además, se evaluó la influencia de la adición de zeolita natural a la mezcla en diferentes porcentajes, como filler o como arena, obteniendo mejores resultados con la incorporación en la fracción filler

AGN Feedback in SDSS-IV MaNGA: AGNs have Suppressed Central Star Formation Rates

Despite the importance of feedback from active galactic nuclei (AGNs) in models of galaxy evolution, observational constraints on the influence of AGN feedback on star formation remain weak. To this end, we have compared the star formation trends of 279 low-redshift AGN galaxies with 558 inactive control galaxies using integral field unit spectroscopy from the SDSS-IV MaNGA survey. With a Gaussian process-based methodology, we reconstruct nonparametric star formation histories in spatially resolved spaxels covering the face of each galaxy. Based on galaxy-wide star formation rates (SFRs) alone, we find no obvious signatures of AGN feedback. However, the AGN galaxies have significantly suppressed central (kiloparsec-scale) SFRs, lying up to a factor of $2$ below those of the control galaxies, providing direct observational evidence of AGN feedback suppressing star formation. The suppression of central SFRs in the AGN galaxies began in the central regions ${\sim} 6$ Gyr ago (redshift $z {\sim} 0.7$), taking place over a few gigayears. A small subset of the AGN galaxies were rapidly driven to quiescence shortly before being observed (in the last $500$ Myr), potentially indicating instances of AGN-driven feedback. More frequently, however, star formation continues in the AGN galaxies, with suppression primarily in the central regions. This is suggestive of a picture in which integrated (Gyr-timescale) AGN feedback can significantly affect central star formation, but may be inefficient in driving galaxy-wide quenching in low-redshift galaxies, instead leaving them in the green valley.Comment: 22 pages, 15 figures. Accepted for publication in Ap

Neuroimagen y neurobiología de la adicción:un estudio sobre los cambios funcionales cerebrales en personas adictas a las cocaína

Decenes Jornades de Foment de la Investigació de la FCHS (Any 2004-2005)El consumo crónica de cocaína produce una reducción de la dopamina en ciertas áreas cerebrales, provocando una alteración en este sistema. (Volkow y cols., 1999; Wu y cols., 1997). El objetivo de este trabajo es estudiar mediante Resonancia Magnética Funcional, los efectos que el consumo crónico de cocaína provoca sobre el procesamiento emocional. Los participantes (10 pacientes adictos a la cocaína y 10 personas no adictas) realizaron una tarea de procesamiento emocional en la que visualizaban fotografías con contenido emocional positivo, negativo y neutro (Adaptación española del International Affective Pictures System, IAPS, moltó y cols. 2001) como fondo en un tarea de discriminación de letras. Los resultados muestran una menor activación en el núcleo accumbens, giro cingulado anterior y cortex orbitofrontal en personas adictas a la cocaína en comparación al grupo control, ante la visión de imágenes positivas. Mientras que, se observa una menor activación del giro cingulado anterior en pacientes en comparación a los controles, para la visión de imágenes negativas. Estos resultados sugieren que la tarea del IAPS es una buena tarea para activar áreas específicas de recompensa (N.acc y giro orbitofrontal). Y que los pacientes presentan una disfunción en el sistema de recompensa, lugar donde actúa la cocaína tras su administración, liberando dopamina. Esto podría tener como consecuencia una menor sensibilidad de estas personas para los reforzadores naturales