The Involvement of Sigma Receptor Modulation in the Antidepressant Effects of Ketamine and the Neurotoxic Actions of Methamphetamine

Depression is estimated to affect at least 30% of the world\u27s population at some point during their lives. Currently marketed antidepressants require a period of at least 2 to 3 weeks to display any antidepressant effects in clinical populations and rates of clinical resistance to the antidepressant effects of these drugs are high. Ketamine is an N-methyl-D-aspartate (NMDA) antagonist and dissociative anesthetic that has been shown to display rapid acting and prolonged antidepressant activity in smallscale human clinical trials. Ketamine also binds to sigma receptors, which are believed to be protein targets for a potential new class of antidepressant medications. The purpose of this study was to determine the involvement of sigma receptors in the antidepressant-like actions of ketamine. Competition binding assays were performed to assess the affinity of ketamine for sigma-1 and sigma-2 receptors. The antidepressant-like effects of ketamine were assessed in vitro using a neurite outgrowth model and PC12 cells, and in vivo using the forced swim test. The sigma receptor antagonists, 4- methoxy-3-(2-phenylethoxy)-N,N-dipropylbenzeneethanamine hydrochloride (NE-100) and N-[2-(3,4- dichlorophenyl)ethyl]-N-methyl-2-(dimethylamino)ethylamine dihydrobromide (BD1047), were evaluated in conjunction with ketamine in these assays to determine the involvement of sigma receptors in the antidepressant-like effects of ketamine. Ketamine bound to both sigma-1 and sigma-2 receptors with iM affinities. Additionally, ketamine potentiated nerve growth factor (NGF)-induced neurite outgrowth in PC12 cells and this effect was attenuated in the presence of NE-100. Ketamine also displayed antidepressant-like effects in the forced swim test; however, these effects were not attenuated by pretreatment with NE-100 or BD1047. Taken together, these data suggest that sigma receptor-mediated neuronal remodeling may contribute to the antidepressant effects of ketamine

Transmission of ultraviolet, visible and near-infrared solar radiation to plants within a seasonal snow pack

Sunlight is strongly attenuated by the snowpack, causing irradiance to decrease exponentially with depth. The strength of attenuation is wavelength dependent across the spectrum. Changes in received irradiance and its spectral composition are used by plants as cues for the timing of phenology, and it is known that at shallow depths in the snowpack there is sufficient light for plants to photosynthesize if conditions are otherwise favourable. The spectral composition of solar radiation under snow in the visible region was already determined in the 1970s using scanning spectroradiometers, but spectral attenuation within the ultraviolet region (UV-B 280-315 nm, UV-A 315-400 nm) has not been well characterised because it is difficult to measure. We measured vertical transects of spectral irradiance (290-900 nm) transmitted through a settled seasonal snowpack. The peak transmission of radiation was in the UV-A region in the upper centimetres of the snowpack and transmittance generally declined at longer wavelengths. Given the known action spectra of plant photoreceptors, these results illustrate the possibility that changing UV-A:visible and red:far-red radiation ratios under the snowpack may serve as spectral cues for plants; potentially priming plants for the less stable environment they experience following snowmelt. Array spectrometers open opportunities for rapid and continuous measurement of irradiance in challenging environments, e.g. beneath the snowpack, and capturing changing light conditions for plants. Future research is needed to couple the spectral transmittance of snowpacks differing in their longevity and crystal structure with measurements of the perception and response to radiation by plants under snow.Peer reviewe

Sunfleck properties from time series of fluctuating light

Light in canopies is highly dynamic since the strength and composition of incoming radiation is determined by the wind and the Sun's trajectory and by canopy structure. For this highly dynamic environment, we mathematically defined sunflecks as periods of high irradiance relative to the background light environment. They can account for a large proportion of the light available for photosynthesis. Based on high-frequency irradiance measurements with a CCD array spectroradiometer, we investigated how the frequency of measurement affects what we define as sunflecks. Do different plant canopies produce sunflecks with different properties? How does the spectral composition and strength of irradiance in the shade vary during a sunfleck? Our results suggest that high-frequency measurements improved our description of light fluctuations and led to the detection of shorter, more frequent and intense sunflecks. We found that shorter wind-induced sunflecks contribute most of the irradiance attributable to sunflecks, contrary to previous reports from both forests and crops. Large variations in sunfleck properties related to canopy depth and species, including distinct spectral composition under shade and sunflecks, suggest that mapping canopy structural traits may help us model photosynthesis dynamically.Peer reviewe

Building subsidiary local responsiveness: (when) does the directionality of intrafirm knowledge transfers matter?

The present study focuses on effects of subsidiary internal knowledge-based activities—knowledge transfer and reverse knowledge transfer—and absorptive capacity on local responsiveness. We also examine whether absorptive capacity, shared values, and psychological safety, representing constituents of the motivation-opportunity-ability model of behavior, moderate relationships of subsidiary internal knowledge-based activities with responsiveness. Based on a sample of 173 Chinese subsidiaries, the results suggest knowledge transfer and absorptive capacity facilitate local responsiveness. Shared values moderates positively and absorptive capacity negatively, the relationship between knowledge transfer and responsiveness. Psychological safety strengthens the link between reverse knowledge transfer and local responsiveness

The contribution of PIP2-type aquaporins to photosynthetic response to increased vapour pressure deficit

The roles of different plasma membrane aquaporins (PIPs) in leaf-level gas exchange of Arabidopsis thaliana were examined using knockout mutants. Since multiple Arabidopsis PIPs are implicated in CO2 transport across cell membranes, we focused on identifying the effects of the knockout mutations on photosynthesis, and whether they are mediated through the control of stomatal conductance of water vapour (g(s)), mesophyll conductance of CO2 (g(m)), or both. We grew Arabidopsis plants in low and high humidity environments and found that the contribution of PIPs to g s was larger under low air humidity when the evaporative demand was high, whereas any effect of a lack of PIP function was minimal under higher humidity. The pip2;4 knockout mutant had 44% higher g(s) than wild-type plants under low humidity, which in turn resulted in an increased net photosynthetic rate (A(net)). We also observed a 23% increase in whole-plant transpiration (E) for this knockout mutant. The lack of functional plasma membrane aquaporin AtPIP2;5 did not affect g(s) or E, but resulted in homeostasis of g(m) despite changes in humidity, indicating a possible role in regulating CO2 membrane permeability. CO2 transport measurements in yeast expressing AtPIP2;5 confirmed that this aquaporin is indeed permeable to CO2.Peer reviewe

Contributions of cryptochromes and phototropins to stomatal opening through the day

The UV-A/blue photoreceptors phototropins and cryptochromes are both known to contribute to stomatal opening (∆gs) in blue light. However, their relative contributions to maintenance of gs in blue light through the whole photoperiod remains unknown. To elucidate this question, Arabidopsis phot1 phot2 and cry1 cry2 mutants (MTs) and their respective wild types (WTs) were irradiated with 200 μmol m-2 s-1 of blue-, green- or red-light (BL, GL or RL) throughout a 11-hour photoperiod. Stomatal conductance (gs) was higher under BL, than under RL or GL. Under RL, gs was not affected by either of the photoreceptor mutations, but under GL gs was slightly lower in cry1 cry2 than its WT. Under BL, the presence of phototropins was essential for rapid stomatal opening at the beginning of the photoperiod, while maximal stomatal opening beyond 3 h of irradiation required both phototropins and cryptochromes. Time courses of whole-plant net carbon assimilation rate (Anet) and the effective quantum yield of photosystem II photochemistry (ΦPSII) were consistent with an Anet-independent contribution of BL on gs both in phot1 phot2 and cry1 cry2 mutants. The changing roles of phototropins and cryptochromes through the day may allow more flexible coordination between gs and Anet.Peer reviewe

The benefits of informed management of sunlight in production greenhouses and polytunnels

Societal Impact Statement The effective management of light is beneficial for growers of plants in greenhouses, polytunnels and under cloches. The materials and structures used to construct these environments often create light-limited conditions for crops and change the spectral composition of sunlight they receive. Combining practical measures, drawn from knowledge of plant photobiology, allows growers to monitor, forecast and optimise conditions in their growing environment according to its geographical location and the crop grown. Improved management of light through these measures could be expected to improve food quality and yield, and potentially reduce use of energy, water and pesticides. Horticultural production in greenhouses and in polytunnels expands the viable geographic range of many crop species and extends their productive growing season. These semi-controlled growing environments buffer natural fluctuations in heat, cold and light and hold potential to improve food security with a low environmental footprint. Over the last decade, technological advances in cladding materials, smart filters, photo-electric cells for energy production and LED lighting have created opportunities to improve the light environment within these structures. In parallel, there have been large advances in plant photobiology, underpinned by progress in identifying the mechanisms of photomorphogenesis and photoprotection, mediated by plant photoreceptors and their interactions, across regions of the spectrum. However, there remains unexploited potential to synthesise and transfer knowledge from these fields to horticulture, particularly with respect to tailoring the use of sunlight to specific locations and production systems. Here, we systematically explain (1) the value of modelling and monitoring patterns of sunlight to allow for informed design of the growth environment; (2) the means of optimising light conditions through selection of materials and structures; (3) the requirements of different crop plants in terms of the amount and spectral composition of light that will benefit yield and food quality; (4) the potential to combine this knowledge for effective management of the sunlight; and, finally, (5) the additional benefits these actions may bring to growers and society at large, beyond the crops themselves, in terms of water use and energy efficiency.Peer reviewe

Longitudinally and circumferentially directed movements of the left ventricle studied by cardiovascular magnetic resonance phase contrast velocity mapping

OBJECTIVE: Using high resolution cardiovascular magnetic resonance (CMR), we aimed to detect new details of left ventricular (LV) systolic and diastolic function, to explain the twisting and longitudinal movements of the left ventricle. METHODS: Using CMR phase contrast velocity mapping (also called Tissue Phase Mapping) regional wall motion patterns and longitudinally and circumferentially directed movements of the left ventricle were studied using a high temporal resolution technique in healthy male subjects (n = 14, age 23 +/- 3 years). RESULTS: Previously undescribed systolic and diastolic motion patterns were obtained for left ventricular segments (based on the AHA segmental) and for basal, mid and apical segments. The summation of segmental motion results in a complex pattern of ventricular twisting and longitudinal motion in the normal human heart which underlies systolic and diastolic function. As viewed from the apex, the entire LV initially rotates in a counter-clockwise direction at the beginning of ventricular systole, followed by opposing clockwise rotation of the base and counter-clockwise rotation at the apex, resulting in ventricular torsion. Simultaneously, as the entire LV moves in an apical direction during systole, the base and apex move towards each other, with little net apical displacement. The reverse of these motion patterns occur in diastole. CONCLUSION: Left ventricular function may be a consequence of the relative orientations and moments of torque of the sub-epicardial relative to the sub-endocardial myocyte layers, with influence from tethering of the heart to adjacent structures and the directional forces associated with blood flow. Understanding the complex mechanics of the left ventricle is vital to enable these techniques to be used for the evaluation of cardiac pathology