Computation predicts rapidly adapting mechanotransduction currents cannot account for tactile encoding in Merkel cell-neurite complexes

Distinct firing properties among touch receptors are influenced by multiple, interworking anatomical structures. Our understanding of the functions and crosstalk of Merkel cells and their associated neurites—the end organs of slowly adapting type I (SAI) afferents—remains incomplete. Piezo2 mechanically activated channels are required both in Merkel cells and in sensory neurons for canonical SAI responses in rodents; however, a central unanswered question is how rapidly inactivating currents give rise to sustained action potential volleys in SAI afferents. The computational model herein synthesizes mechanotransduction currents originating from Merkel cells and neurites, in context of skin mechanics and neural dynamics. Its goal is to mimic distinct spike firing patterns from wildtype animals, as well as Atoh1 knockout animals that completely lack Merkel cells. The developed generator function includes a Merkel cell mechanism that represents its mechanotransduction currents and downstream voltage-activated conductances (slower decay of current) and a neurite mechanism that represents its mechanotransduction currents (faster decay of current). To mimic sustained firing in wildtype animals, a longer time constant was needed than the 200 ms observed for mechanically activated membrane depolarizations in rodent Merkel cells. One mechanism that suffices is to introduce an ultra-slowly inactivating current, with a time constant on the order of 1.7 s. This mechanism may drive the slow adaptation of the sustained response, for which the skin’s viscoelastic relaxation cannot account. Positioned within the sensory neuron, this source of current reconciles the physiology and anatomical characteristics of Atoh1 knockout animals

Computation predicts rapidly adapting mechanotransduction currents cannot account for tactile encoding in Merkel cell-neurite complexes

Distinct firing properties among touch receptors are influenced by multiple, interworking anatomical structures. Our understanding of the functions and crosstalk of Merkel cells and their associated neurites—the end organs of slowly adapting type I (SAI) afferents—remains incomplete. Piezo2 mechanically activated channels are required both in Merkel cells and in sensory neurons for canonical SAI responses in rodents; however, a central unanswered question is how rapidly inactivating currents give rise to sustained action potential volleys in SAI afferents. The computational model herein synthesizes mechanotransduction currents originating from Merkel cells and neurites, in context of skin mechanics and neural dynamics. Its goal is to mimic distinct spike firing patterns from wildtype animals, as well as Atoh1 knockout animals that completely lack Merkel cells. The developed generator function includes a Merkel cell mechanism that represents its mechanotransduction currents and downstream voltage-activated conductances (slower decay of current) and a neurite mechanism that represents its mechanotransduction currents (faster decay of current). To mimic sustained firing in wildtype animals, a longer time constant was needed than the 200 ms observed for mechanically activated membrane depolarizations in rodent Merkel cells. One mechanism that suffices is to introduce an ultra-slowly inactivating current, with a time constant on the order of 1.7 s. This mechanism may drive the slow adaptation of the sustained response, for which the skin’s viscoelastic relaxation cannot account. Positioned within the sensory neuron, this source of current reconciles the physiology and anatomical characteristics of Atoh1 knockout animals

Poster Session II, July 14th 2010 — Abstracts Improvements in the design of a kayak-ergometer using a sliding footrest-seat complex

AbstractAs observed previously in rowing, kayaking an ergometer becomes more and more popular. Nowadays, indoor kayak championships are organized performed on ergometer designed with a fixed footrest-seat complex. The main goal when one designs ergometers is to reproduce as closest as possible the on-water conditions. The reliability with on-water condition is usually assessed using both physiological and kinematics parameters. The previous studies of our research group have shown that the dynamics of the in situ movement has also to be reproduced. In other words, major muscular groups (who generated the joint torque and by the way the contact forces) involved in kayaking should be recruit with the same timing during on-water and ergometer kayaking. At the 7th ISEA conference, our research group presented a method based on numerical optimization to design a kayak ergometer equipped with a sliding footrest-seat complex that reproduces the acceleration generated in flatwater kayak. Based on these preliminary results, we have constructed a new ergometer. Then, the purpose of this study was to present the last developments performed on this ergometer and preliminary 3D kinematics analysis from elite kayakers. The characteristics (stiffness and damping) of the bungee cord linking the back of the frame with the trolley were determined using our previous results. An air brake, composed of a flywheel with a heavy wheel and two freewheel-pulleys on a shaft, simulated the water drag on the blades. However, a magnetic brake was added for specific training sessions. The paddle was linked to the pulleys by two ropes. Each side of the frame is equipped with one slide (1 dof in translation) in order to always keep the directions of the ropes parallel to the long axis of the ergometer whatever the instant of the cycle. First trials performed with elite athlete showed the robustness of all the mechanisms developed. 3D kinematic analysis showed the relevance of the adding slides when compared with on-water paddle trajectories observed during the propulsion phase. An instrumentation (3D force sensors at each contact) coupled with a specific interface that allows real time feedback is under development. This innovative ergometer will be used to collect dynamic and kinematic parameters. They will serve as input data of our simulator in order to carry out intra-athlete comparisons and to still improve the design of kayak ergometers

Mutational analysis of βCOP (Sec26p) identifies an appendage domain critical for function

<p>Abstract</p> <p>Background</p> <p>The appendage domain of the γCOP subunit of the COPI vesicle coat bears a striking structural resemblance to adaptin-family appendages despite limited primary sequence homology. Both the γCOP appendage domain and an equivalent region on βCOP contain the FxxxW motif; the conservation of this motif suggested the existence of a functional appendage domain in βCOP.</p> <p>Results</p> <p>Sequence comparisons in combination with structural prediction tools show that the fold of the COOH-terminus of Sec26p is strongly predicted to closely mimic that of adaptin-family appendages. Deletion of the appendage domain of Sec26p results in inviability in yeast, over-expression of the deletion construct is dominant negative and mutagenesis of this region identifies residues critical for function. The ArfGAP Glo3p was identified via suppression screening as a potential downstream modulator of Sec26p in a manner that is independent of the GAP activity of Glo3p but requires the presence of the COOH-terminal ISS motifs.</p> <p>Conclusion</p> <p>Together, these results indicate an essential function for the predicted βCOP appendage and suggest that both COPI appendages perform a biologically active regulatory role with a structure related to adaptin-family appendage domains.</p

Characterization of a far-red analog of ghrelin for imaging GHS-R in P19-derived cardiomyocytes.

Ghrelin and its receptor, the growth hormone secretagogue receptor (GHS-R), are expressed in the heart, and may function to promote cardiomyocyte survival, differentiation and contractility. Previously, we had generated a truncated analog of ghrelin conjugated to fluorescein isothiocyanate for the purposes of determining GHS-R expression in situ. We now report the generation and characterization of a far-red ghrelin analog, [Dpr(3)(octanoyl), Lys(19)(Cy5)]ghrelin (1-19), and show that it can be used to image changes in GHS-R in developing cardiomyocytes. We also generated the des-acyl analog, des-acyl [Lys(19)(Cy5)]ghrelin (1-19) and characterized its binding to mouse heart sections. Receptor binding affinity of Cy5-ghrelin as measured in HEK293 cells overexpressing GHS-R1a was within an order of magnitude of that of fluorescein-ghrelin and native human ghrelin, while the des-acyl Cy5-ghrelin did not bind GHS-R1a. Live cell imaging in HEK293/GHS-R1a cells showed cell surface labeling that was displaced by excess ghrelin. Interestingly, Cy5-ghrelin, but not the des-acyl analog, showed concentration-dependent binding in mouse heart tissue sections. We then used Cy5-ghrelin to track GHS-R expression in P19-derived cardiomyocytes. Live cell imaging at different time points after DMSO-induced differentiation showed that GHS-R expression preceded that of the differentiation marker aMHC and tracked with the contractility marker SERCA 2a. Our far-red analog of ghrelin adds to the tools we are developing to map GHS-R in developing and diseased cardiac tissues

Free Space Laser Communication Experiments from Earth to the Lunar Reconnaissance Orbiter in Lunar Orbit

Laser communication and ranging experiments were successfully conducted from the satellite laser ranging (SLR) station at NASA Goddard Space Flight Center (GSFC) to the Lunar Reconnaissance Orbiter (LRO) in lunar orbit. The experiments used 4096-ary pulse position modulation (PPM) for the laser pulses during one-way LRO Laser Ranging (LR) operations. Reed-Solomon forward error correction codes were used to correct the PPM symbol errors due to atmosphere turbulence and pointing jitter. The signal fading was measured and the results were compared to the model

The transition to parenthood in obstetrics: Enhancing prenatal care for 2-generation impact

Obstetrics, the specialty overseeing infant and parent health before birth, could be expanded to address the interrelated areas of parents\u27 prenatal impact on children\u27s brain development and their own psychosocial needs during a time of immense change and neuroplasticity. Obstetrics is primed for the shift that is happening in pediatrics, which is moving from its traditional focus on physical health to a coordinated, whole-child, 2- or multigeneration approach. Pediatric care now includes developmental screening, parenting education, parent coaching, access to developmental specialists, brain-building caregiving skills, linkages to community resources, and tiered interventions with psychologists. Drawing on decades of developmental origins of health and disease research highlighting the prenatal beginnings of future health and new studies on the transition to parenthood describing adult development from pregnancy to early postpartum, we have proposed that, similar to pediatrics, the integration of education and intervention strategies into the prenatal care ecosystem should be tested for its potential to improve child cognitive and social-emotional development and parental mental health. Pediatric care programs can serve as models of change for the systematic development, testing and, incorporation of new content into prenatal care as universal, first-tier treatment and evidenced-based, triaged interventions according to the level of need. To promote optimal beginnings for the whole family, we have proposed an augmented prenatal care ecosystem that aligns with, and could build on, current major efforts to enhance perinatal care individualization through consideration of medical, social, and structural determinants of health