An basilar motion, based on the cell’s RC time constant. This problem has been addressed by many investigators, and many ostensible resolutions to the RC time-constant problem have been proposed (15,25,59?2). However, we must now consider the slow kinetics of prestin at physiological chloride levels that we have uncovered. This can only make matters worse. To be sure, we have recently found that eM magnitude rolls off faster than membrane voltage (28), and now we show that this rolloff corresponds to sensor charge activity (Fig. 4 B). It is possible that eM is not the main player and that OHC voltage-dependent stiffness, for which there is a wealth of evidence (63?5), is important. On the other hand, we have found that the low-pass kinetic features of prestin can have high-frequency effects that could influence its ability to interact with basilar membrane/cochlear partition mechanics. Notably, we recently found a frequency-dependent phase lag in eM (re voltage) that is chloride dependent and is attributable to prestin’s multistate kinetic features (28). Interestingly, phase lags are also predicted based on an electrodiffusion model of prestin (66), order AZD3759 although the group that made that prediction suggested through additional modeling that power-law viscoelastic properties of the membrane could counter the effects of such lags (67). Whether such unusual viscoelastic properties characterize prestin’s membrane environment is not known; however, our measured eM phase behavior in OHCs suggests no countering effects of viscoelasticity in the frequency range we studied. We propose that an accumulating phase lag at the molecular level could have a significant influence on the OHC’s ability to inject power intothe cochlear partition, despite an associated magnitude rolloff dictated by low-pass sensor charge movement. SUPPORTING MATERIALSupporting Materials and Methods and three figures are available at http:// www.biophysj.org/biophysj/supplemental/S0006-3495(16)30278-8.AUTHOR CONTRIBUTIONSJ.S.S. designed and performed CEP-37440 web experiments, analyzed data, and wrote the article. LS performed experiments.ACKNOWLEDGMENTSThis research was supported by National Institutes of Health National Institute on Deafness and Other Communication Disorders grants DC00273 and DC008130 to J.S.S.
www.nature.com/scientificreportsOPENReceived: 21 April 2016 Accepted: 06 July 2016 Published: 01 AugustRotation is visualisation, 3D is 2D: using a novel measure to investigate the genetics of spatial abilityNicholas G. Shakeshaft1, Kaili Rimfeld1, Kerry L. Schofield1, Saskia Selzam1, Margherita Malanchini2, Maja Rodic3, Yulia Kovas2,4 Robert PlominSpatial abilities efined broadly as the capacity to manipulate mental representations of objects and the relations between them ave been studied widely, but with little agreement reached concerning their nature or structure. Two major putative spatial abilities are “mental rotation” (rotating mental models) and “visualisation” (complex manipulations, such as identifying objects from incomplete information), but inconsistent findings have been presented regarding their relationship to one another. Similarly inconsistent findings have been reported for the relationship between two- and three-dimensional stimuli. Behavioural genetic methods offer a largely untapped means to investigate such relationships. 1,265 twin pairs from the Twins Early Development Study completed the novel “Bricks” test battery, designed to tap these abilities in isol.An basilar motion, based on the cell’s RC time constant. This problem has been addressed by many investigators, and many ostensible resolutions to the RC time-constant problem have been proposed (15,25,59?2). However, we must now consider the slow kinetics of prestin at physiological chloride levels that we have uncovered. This can only make matters worse. To be sure, we have recently found that eM magnitude rolls off faster than membrane voltage (28), and now we show that this rolloff corresponds to sensor charge activity (Fig. 4 B). It is possible that eM is not the main player and that OHC voltage-dependent stiffness, for which there is a wealth of evidence (63?5), is important. On the other hand, we have found that the low-pass kinetic features of prestin can have high-frequency effects that could influence its ability to interact with basilar membrane/cochlear partition mechanics. Notably, we recently found a frequency-dependent phase lag in eM (re voltage) that is chloride dependent and is attributable to prestin’s multistate kinetic features (28). Interestingly, phase lags are also predicted based on an electrodiffusion model of prestin (66), although the group that made that prediction suggested through additional modeling that power-law viscoelastic properties of the membrane could counter the effects of such lags (67). Whether such unusual viscoelastic properties characterize prestin’s membrane environment is not known; however, our measured eM phase behavior in OHCs suggests no countering effects of viscoelasticity in the frequency range we studied. We propose that an accumulating phase lag at the molecular level could have a significant influence on the OHC’s ability to inject power intothe cochlear partition, despite an associated magnitude rolloff dictated by low-pass sensor charge movement. SUPPORTING MATERIALSupporting Materials and Methods and three figures are available at http:// www.biophysj.org/biophysj/supplemental/S0006-3495(16)30278-8.AUTHOR CONTRIBUTIONSJ.S.S. designed and performed experiments, analyzed data, and wrote the article. LS performed experiments.ACKNOWLEDGMENTSThis research was supported by National Institutes of Health National Institute on Deafness and Other Communication Disorders grants DC00273 and DC008130 to J.S.S.
www.nature.com/scientificreportsOPENReceived: 21 April 2016 Accepted: 06 July 2016 Published: 01 AugustRotation is visualisation, 3D is 2D: using a novel measure to investigate the genetics of spatial abilityNicholas G. Shakeshaft1, Kaili Rimfeld1, Kerry L. Schofield1, Saskia Selzam1, Margherita Malanchini2, Maja Rodic3, Yulia Kovas2,4 Robert PlominSpatial abilities efined broadly as the capacity to manipulate mental representations of objects and the relations between them ave been studied widely, but with little agreement reached concerning their nature or structure. Two major putative spatial abilities are “mental rotation” (rotating mental models) and “visualisation” (complex manipulations, such as identifying objects from incomplete information), but inconsistent findings have been presented regarding their relationship to one another. Similarly inconsistent findings have been reported for the relationship between two- and three-dimensional stimuli. Behavioural genetic methods offer a largely untapped means to investigate such relationships. 1,265 twin pairs from the Twins Early Development Study completed the novel “Bricks” test battery, designed to tap these abilities in isol.