Stimulus Direction Research Articles

How Does the Horizontal Position of Pictures and Text Affect Product Evaluation? Based on Left and Right Position Effect.

Due to the untouchability of online shopping environment, image and text description, as two main ways of product information display, are important indicators for consumers to evaluate products. However, few studies have discussed the synergistic effects of image and text information on consumers. In the present study, in conjunction with the left-right position effect, we examine the expectation that horizontal placement of visual stimuli in different directions has a strong influence on consumers’ product evaluation preferences. This implicit assumption is based on consumers’ unconscious psychological need for closure when processing information. The authors conducted three studies to investigate the relative effects of image information and text statements at different locations in online shopping pages on consumer product evaluations. The results show that: (1) when the evaluation object is a search product, compared with the display mode of left text-right image, the display mode of left image-right text plays a more significant role in consumer product evaluation. The results of experiential products were just the opposite. The way of presenting the text declaration on the left and image on the right has a stronger impact on consumers’ evaluation preference for experiential products (Study 1 and Study 3). (2) The difference in consumers’ evaluation mode of different presentation sequences based on product attributes is driven by their visual information processing fluency (Study 2). These preferences are robust, and it is worth noting that only the order of graphic presentation has no significant influence on consumer product evaluation preference.

A user study of directional tactile and auditory user interfaces for take-over requests in conditionally automated vehicles

General introduction of unconditionally and conditionally automated vehicles is expected to have a highly positive impact on the society, from increased accessibility to mobility and road traffic safety, to decreased environmental and economic negative impacts. However, there are several obstacles and risks slowing down the adoption of this technology, which are primarily related to the human–machine interaction (HMI) and exchange of control between the vehicle and the human driver. In this article, we present key takeaways for HMI design of take-over requests (TOR) that the vehicle issues to inform the driver to take over control of the vehicle. The key takeaways were developed based on the results of a user study, where directional tactile-ambient (visual) and auditory-ambient (visual) TOR user interfaces (UI) were evaluated with regards to commonly used take-over quality aspects (attention redirection, take-over time, correct interpretation of stimuli, off-road drive, brake application, lateral acceleration, minimal time-to-collision and occurrence of collision). 36 participants took part in the mixed design study, which was conducted in a driving simulator. The results showed that drivers’ attention was statistically significantly faster redirected with the auditory-ambient UI, however using the tactile-ambient UI resulted in less off-road driving and slightly less collisions. The results also revealed that drivers correctly interpreted the directional TOR stimuli more often than the non-directional one. Based on the study results, a list of key takeaways was developed and is presented in the conclusion of the paper. The results from this study are especially relevant to the TOR UI designers and the automotive industry, which tend to provide the most usable UI for ensuring safer end efficient human-vehicle interaction during the TOR task.

Inconsistent flanker congruency effects across stimulus types and age groups: A cautionary tale.

The flanker task is a common measure of selective attention and response competition across populations, age groups, and experiential contexts. Adapting it for different uses often involves changing methodological features that are rarely empirically compared with the previous design. This paper presents an example of how typical methodological changes can differentially elicit congruency effects across age groups. We compared two flanker tasks, using direction stimuli on a laptop versus color stimuli on a tablet, in young children (2-7 years; Experiment 1), older children (6-10 years; Experiment 2a), and adults (19-23 years; Experiment 2b). Young children showed the expected congruency effects in the direction task, and one year later a subset of the sample completed the color task, also showing congruency effects. Longitudinal comparisons showed no difference in the congruency effect across tasks, but nearly half of the sample was excluded due to high error rates. To avoid excluding children with few correct trials, we modified a new measure, signed residual time, to incorporate correctness and reaction time per trial. With the larger sample, this measure showed no difference in congruency effects across tasks. To compare these tasks when completed within the same session, we tested older children and young adults in both tasks and found congruency effects in the direction task but not the color task. These results raise concern that tasks adapted for young children may not perform comparably in other samples, and we caution researchers to anticipate this possibility when modifying cognitive tasks.

Local and systemic transcriptomic responses from acute exercise induced muscle damage of the human knee extensors.

Skeletal muscle is adaptable to a direct stimulus of exercise-induced muscle damage (EIMD). Local muscle gene networks and systemic circulatory factors respond to EIMD within days, mediating anti-inflammation and cellular proliferation. Here we show in humans that local EIMD of one muscle group is associated with a systemic response of gene networks that regulate muscle structure and cellular development in nonlocal homologous muscle not directly altered by EIMD. In the nondominant knee extensors of seven males, EIMD was induced through voluntary contractions against an electric motor that lengthened muscles. Neuromuscular assessments, vastus lateralis muscle biopsies, and blood draws occurred 2 days prior and 1 and 2 days after the EIMD intervention. From the muscle and blood plasma samples, RNA-Seq measured transcriptome changes of differential expression using bioinformatic analyses. Relative to the time of the EIMD intervention, local muscle that was mechanically damaged had 475 genes differentially expressed, as compared with 33 genes in the nonlocal homologous muscle. Gene and network analysis showed that activity of the local muscle was related to structural maintenance, repair, and energetic processes, whereas gene and network activities of the nonlocal muscle (that was not directly modified by the EIMD) were related to muscle cell development, stress response, and structural maintenance. Altered expression of two novel miRNAs related to the EIMD response supported that systemic factors were active. Together, these results indicate that the expression of genes and gene networks that control muscle contractile structure can be modified in response to nonlocal EIMD in humans.

Development of the horizontal optocollic reflex in juvenile barn owls (Tyto furcata pratincola)

Adult barn owls and primates possess an almost symmetric monocular rotational horizontal optocollic reflex. In primates, the reflex is initially asymmetric and becomes symmetric with time after birth. The condition in barn owls has not been studied so far. Here, we present data on the development of this reflex in this bird. We tested juvenile barn owls from the time before they open their eyes after hatching to the time they reach adult feather length. Wide-field visual patterns served as stimuli. They were presented at different rotational speeds in binocular and monocular settings. The binocular horizontal optocollic responses of juvenile barn owls were symmetric and adult-like on the first day that the birds responded to the stimulus. The monocular responses showed different rates of development in respect to stimulus velocity and stimulus direction. For velocities up to 20 deg/s, the monocular reflex was also adult-like on the first day that the birds responded to the stimulus. An initially higher asymmetry for 30 deg/s compared to adults disappeared within about two weeks. The development at even higher velocities remained unclear.

Sinusoidal Vibration Source Localization in Two-Dimensional Space Around the Hand.

There are use cases where presenting spatial information via the tactile sense is useful (e.g., situations where visual and audio senses are not available). Conventional methods that directly attach a vibrotactile array to a user's body present spatial information such as direction by having users localize the vibration source from among the sources in the array. These methods suffer from problems such as heat generation of the actuator or the installation cost of the actuators in a limited space. A promising method of coping with these problems is to place the vibrotactile array at a distance from the body, instead of directly attaching it to the body, with the aim of presenting spatial information in the same way as the conventional method. The present study investigates the method's effectiveness by means of a psychophysical experiment. Specifically, we presented users with sinusoidal vibrations from remote vibrotactile arrays in the space around the hand and asked them to localize the source of the vibration. We conducted an experiment to investigate the localization ability by using two vibration frequencies (30 Hz as a low frequency and 230 Hz as a high frequency). We chose these two frequencies since they effectively activate two distinctive vibrotactile channels: the rapidly adapting afferent channel and the Pacinian channel. The experimental results showed that humans can recognize the direction of the vibration source, but not the distance, regardless of the source frequency. The accuracy of the direction recognition varied slightly according to the vibration source direction, and also according to the vibration frequency. This suggests that the calibration of stimulus direction is required in the case of both high and low frequencies for presenting direction accurately as intended. In addition, the accuracy variance of direction recognition increased as the source became farther away, and the degree of increase was especially large with the low-frequency source. This suggests that a high frequency is recommended for presenting accurate direction with low variance.

Social Interactions Increase Activation of Vasopressin-Responsive Neurons in the Dorsal Raphe

Social interactions play an important role in our daily lives and can profoundly impact our health for better and worse. To better understand the neural circuitry underlying social behavior, we focused on neural circuits involving vasopressin neurons of the bed nucleus of the stria terminalis (BNST) and serotonin neurons of the dorsal raphe (DR). Previous research shows that BNST vasopressin neurons are activated in male mice by interaction with a female and that vasopressin indirectly excites serotonin neurons. In our studies, we tested the hypothesis that specific social interactions would also activate neurons in the DR, specifically vasopressin 1A receptor (Avpr1a)-expressing neurons, which may be direct targets of the BNST vasopressin neurons. Using in separate experiments immunohistochemistry and in situ hybridization, we found that male and female subjects exposed to a female conspecific show activation in the DR, and the activated neurons include populations of Avpr1a-expressing and other non-serotonergic, non-Avpr1a neurons in roughly equal numbers. Avpr1a neurons in the DR constitute a largely undocumented neuron population. Electrophysiological data suggest that most DR Avpr1a neurons behave like fast spiking interneurons found in other brain regions. Examination of RNAseq and in situ hybridization data suggests that there are glutamatergic, GABAergic, and serotonergic subtypes of Avpr1a neurons in the DR. Together our data support a model in which a subset of vasopressin-responsive interneurons in the DR may relay stimulus specific social signals from the forebrain BNST to the serotonergic DR system, which could help direct prosocial stimulus specific behavioral responses.

Estimating How Sounds Modulate Orientation Representation in the Primary Visual Cortex Using Shallow Neural Networks.

Audiovisual perception results from the interaction between visual and auditory processing. Hence, presenting auditory and visual inputs simultaneously usually improves the accuracy of the unimodal percepts, but can also lead to audiovisual illusions. Cross-talks between visual and auditory inputs during sensory processing were recently shown to occur as early as in the primary visual cortex (V1). In a previous study, we demonstrated that sounds improve the representation of the orientation of visual stimuli in the naïve mouse V1 by promoting the recruitment of neurons better tuned to the orientation and direction of the visual stimulus. However, we did not test if this type of modulation was still present when the auditory and visual stimuli were both behaviorally relevant. To determine the effect of sounds on active visual processing, we performed calcium imaging in V1 while mice were performing an audiovisual task. We then compared the representations of the task stimuli orientations in the unimodal visual and audiovisual context using shallow neural networks (SNNs). SNNs were chosen because of the biological plausibility of their computational structure and the possibility of identifying post hoc the biological neurons having the strongest influence on the classification decision. We first showed that SNNs can categorize the activity of V1 neurons evoked by drifting gratings of 12 different orientations. Then, we demonstrated using the connection weight approach that SNN training assigns the largest computational weight to the V1 neurons having the best orientation and direction selectivity. Finally, we showed that it is possible to use SNNs to determine how V1 neurons represent the orientations of stimuli that do not belong to the set of orientations used for SNN training. Once the SNN approach was established, we replicated the previous finding that sounds improve orientation representation in the V1 of naïve mice. Then, we showed that, in mice performing an audiovisual detection task, task tones improve the representation of the visual cues associated with the reward while deteriorating the representation of non-rewarded cues. Altogether, our results suggest that the direction of sound modulation in V1 depends on the behavioral relevance of the visual cue.

Individualism versus collective movement during travel

Collective movement may emerge if coordinating one’s movement with others produces a greater benefit to oneself than can be achieved alone. Experimentally, the capacity to manoeuvre simulated groups in the wild could enable powerful tests of the impact of collective movement on individual decisions. Yet such experiments are currently lacking due to the inherent difficulty of controlling whole collectives. Here we used a novel technique of experimentally simulating the movement of collectives of social hermit crabs (Coenobita compressus) in the wild. Using large architectural arrays of shells dragged across the beach, we generated synchronous collective movement and systematically varied the simulated collective’s travel direction as well as the context (i.e., danger level). With drone video from above, we then tested whether focal individuals were biased in their movement by the collective. We found that, despite considerable engagement with the collective, individuals’ direction was not significantly biased. Instead, individuals expressed substantial variability across all stimulus directions and contexts. Notably, individuals typically achieved shorter displacements in the presence of the collective versus in the presence of the control stimulus, suggesting an impact of traffic. The absence of a directional bias in individual movement due to the collective suggests that social hermit crabs are individualists, which move with a high level of opportunistic independence, likely thanks to the personal architecture and armour they carry in the form of a protective shell. Future studies can manipulate this level of armour to test its role in autonomy of movement, including the consequences of shell architecture for social decisions. Our novel experimental approach can be used to ask many further questions about how and why collective and individual movement interact.

Don’t Go Chasing Windfalls: California’s 2021-2022 Budget

Amidst a global pandemic, a gubernatorial recall election, and a shaky economy, California had one of its best budget years in recent memory. Flush with cash, the state was able to make unprecedented investments in education, health, and social welfare programs, provide direct stimulus payments to many California residents, and still set aside money in its rainy-day fund. Governor Newsom handily defeated the recall effort, and the budget outlook for 2022 looks bright. 2021 was a tumultuous year, but California is proving that it’s once again the “Golden State”.

Identification of 1,3‐(Dimethyl / Propyl)‐8‐Susbtituted (Cinnamic acid/Furan) Xanthine Derivatives with Anti‐bronchospasmodic Activity Using in silico and in vivo Techniques

AbstractAsthma is a chronic obstructive pulmonary disease which affects the bronchi airways and results in the inflammation of bronchioles along with the hyper‐responsiveness to some direct or indirect stimuli which leads to bronchoconstriction. Substituted xanthines have provided several lead compounds for the development of antiasthmatic agents over the decades. In this present paper, a series of 42 xanthine based derivatives (17 a–g; 18 a–g; 19 a–g; 20 a–g; 28 a–g and 29 a–g) were designed and synthesized. Chemical structures were elucidated by spectroscopic methods. All target compounds were evaluated for their in silico anti‐bronchospasmodic potential using PASS software. Compounds with >95 % potential (18 c–f; 28 a and 29 a–g) in comparison to the standard drug were selected for in vivo bronchospasmodic activity using histamine chamber model. In silico and in vivo activity revealed that the compounds substituted with furan spacer were more active than the cinnamic acid. Substitution with propyl functionality at 1‐and 3‐position of xanthine moiety is also accounted for the enhanced activity of furan derivatives (29 a–g). In conclusion, the synthesized new xanthine derivatives stands out as promising anti‐bronchospasmodic agents for future development.

In Situ Effects of Doxycycline on Neuromuscular Junction in Mice.

The antibacterial mechanism of doxycycline is known, but its effects on the nerve-muscle system are still not unclear. The aim of the study was to combine molecular targets of the neuromuscular machinery using the in situ neuronal blocker effect of doxycycline, a semisynthetic second-generation tetracycline derivative, on mice neuromuscular preparations. The effects of doxycycline were assessed on presynaptic, synaptic cleft, and postsynaptic neurotransmission, along with the muscle fiber, using the traditional myographic technique. Precisely, the effects of doxycycline were categorized into "all" or "nothing" effects depending on the concentration of doxycycline used; "all" was obtained with 4 μM doxycycline, and "nothing" was obtained with 1-3 μM doxycycline. The rationale of this study was to apply known pharmacological tools against the blocker effect of 4 μM doxycycline, such as F55-6 (Casearia sylvestris), CaCl2 (or Ca2+), atropine, neostigmine, polyethylene glycol (PEG 400), and d-Tubocurarine. The evaluation of cholinesterase enzyme activity and the diaphragm muscle histology were performed, and protocols on the neuromuscular preparation submitted to indirect or direct stimuli were complementary. Doxycycline does not affect cholinesterase activity nor causes damage to skeletal muscle diaphragm; it acts on ryanodine receptor, sarcolemmal membrane, and neuronal sodium channel with a postjunctional consequence due to the decreased availability of muscle nicotinic acetylcholine receptors. In conclusion, in addition to the neuronal blocker effect of doxycycline, we showed that doxycycline acts on multiple targets. It is antagonized by F55-6, a neuronal Na+-channel agonist, and Ca2+, but not by neostigmine.

How do China’s lockdown and post-COVID-19 stimuli impact carbon emissions and economic output? Retrospective estimates and prospective trajectories

SummaryThis paper develops a multi-sector and multi-factor structural gravity model that allows an analytical and quantitative decomposition of the emission and output changes into composition and technique effects. We find that the negative production shock of China’s containment policy propagates globally via supply chains, with the carbon-intensive sectors experiencing the greatest carbon emission shocks. We further reveal that China’s current stimulus package in 2021–2025 is consistent with China’s emission intensity-reduction goals for 2025, but further efforts are required to meet China’s carbon emissions-peaking target in 2030 and Cancun 2°C goal. Short-term changes in carbon emissions resulting from lockdowns and initial fiscal stimuli in “economic rescue” period have minor long-term effects, whereas the transitional direction of future fiscal stimulus exerts more predominant impact on long-term carbon emissions. The efficiency improvement effects are more important than the sectoral structure effects of the fiscal stimulus in achieving greener economic growth.

Simultaneous learning of directional and non-directional stimulus relations in baboons (Papio papio)

SummaryWhile humans exposed to a sequential stimulus pairing A-B are commonly assumed to form a bidirectional mental relation between A and B, evidence that non-human animals can do so is limited. Careful examination of the animal literature suggests possible improvements in the test procedures used to probe such effects, notably measuring transfer effects on the learning of B-A pairings, rather than direct recall of A upon cuing with B. We developed such an experimental design and tested 20 Guinea baboons (Papio papio). Two pairings of visual shapes were trained (A1-B1, A2-B2) and testing was conducted in a reversed order, either with conserved pairings (B1-A1, B2-A2) or broken ones (B1-A2, B2-A1). We found baboons’ immediate test performance to be above chance level for conserved pairings and below chance level for broken ones. Moreover, baboons needed less trials to learn conserved pairings compared to broken ones. These effects were apparent for both pairings on average, and separately for the best learned pairing. Baboons’ responding on B-A trials was thus influenced by their previous A-B training. Performance level at the onset of testing, however, suggests that baboons did not respond in full accordance with the hypothesis of bidirectionality. To account for these data, we suggest that two competing types of relations were concomitantly encoded: a directional relation between A and B, which retains the sequential order experienced, and a non-directional relation, which retains only the co-occurrence of events, not their temporal order.

A Pre-Post Study on the Cardiorespiratory Response to Different Protocols of Exposure on a Vibratory Platform in Young Healthy Individuals.

This study aimed to investigate the acute specific physiological effects of 15 min of whole-body vibration (WBV) exposure at six different types of vibrations on cardiorespiratory function in 26 healthy young subjects (sex ratio, 1:1; mean age, 20.73 years). The protocols included six variants of a combination of mechanical stimuli with different frequencies (15, 25, and 35 Hz) and direction of stimuli (vertical or diagonal). The investigated cardiorespiratory parameters were heart rate (HR), arterial oxygen saturation (SaO2), respiratory rate (RR), and spirometric indicators: tidal volume (TV), vital capacity (VC), forced vital capacity (FVC), forced expiratory volume at 1 s (FEV1), and maximum voluntary ventilation for 12 s (MVV). The data series were statistically processed by using descriptive and inferential statistical methods: the Shapiro–Wilk test, the two-way ANOVA with repeated measures, and post hoc analysis. We obtained significantly higher values for HR, TV, VC, FVC, FEV1, and MVV after the WBV exposure. These parameters are significantly influenced by both the frequency and direction of stimuli, and certain protocols of WBV are noticeable for their distinct effects. Our results offer a new perspective on the possibility of using preferential variants of vibratory stimulation to obtain maximum cardiorespiratory physiological effects.

ASPP2 reduction attenuates HBV induced chronic liver damage: A hybrid mouse model study

Background & AimP53 Apoptosis Stimulating Protein 2 (ASPP2) is confirmed to participate in cellular activities including apoptosis, proliferation, autophagy, injury and so on. However, the role of ASPP2 in Hepatitis B virus (HBV) infection has not been reported in detail. The study explored the role of ASPP2 in HBV induced chronic liver damage. MethodsTranscriptome profiling of ASPP2-konckdown mouse liver were analyzed by RNA-sequencing. HBV-ASPP2-knockdown mice was the hybrid offspring of HBV transgenic mice and ASPP2 knockdown mice. Liver tissues were taken for the experiments such as western Blot (WB), PCR, Hematoxylin and Eosin (HE), Immunohistochemistry and high throughput sequencing of transcriptome. ResultsPathological and transcriptomic analysis of liver tissue from ASPP2 knockdown vs con mice showed that after ASPP2 knockdown, the pathological changes in the liver tissue of mice were not significant, but transcriptomics showed obvious changes in immune system process, and response to stimulus, metabolism, Human Diseases and other directions etc.In the HBV-ASPP2-knockdown mice, liver tissue HE staining found less cell swelling and necrosis foci; F4/80 and MPO staining showed less inflammatory cell infiltration; serum ALT and AST decreased than the HBV-ASPP2-con mice. Transcriptome results showed significantly changed in HBV-ASPP2-knockdown mice including immune system process, inflammatory response, and innate immune response etc. Further comparison of the two transcriptomes yielded 9 identical pathways related to inflammatory and cell injury. The PPAR pathway was verified, and found that the increase of PPARγ caused by the reduction of ASPP2 is likely to be the reason for the reduction of HBV-related liver injury. The expression of PPARγ was then analyzed by transcriptome and PCR, it was found that in the absence of HBV, ASPP2 knockdown resulted in a mild decrease in PPARγ, and in the presence of HBV infection, ASPP2 knockdown resulted in a marked increase in PPARγ.In addition, this study found that high expression of ASPP2 had opposite effects on HCC (HBV-none) and HCC (HBV-yes). ConclusionThis study demonstrated that reduction of ASPP2 reduces HBV-induced hepatocyte damage during chronic HBV infection. This phenomenon is related to the different regulation of PPARγ by ASPP2 in the presence or absence of HBV stimulation.

P 56 Deep learning derived quantitative Video-NystagmoGraphy using smartphone cameras: DeepVNG

Background: The assessment of eye movements is commonly considered a “ window into the brain ”. However, sole clinical observation is limited to semiquantitative findings. Recent advances in quantitative oculomotor phenotyping using video-oculography (VOG) promise additional diagnostic and prognostic value. However, methodological complexity and limited availability have hampered broad use of VOG in clinical and outpatient settings. Here, a novel approach for binocular video-nystagmography (VNG), capitalizing on recently deployed artificial intelligence frameworks for markerless pose estimation, is validated. Methods: Standardized 2D-optokinetic stimuli were presented on a smartphone screen and elicited nystagmus was recorded with two methods: first, using a conventional smartphone camera (1920x1080 px, 30 frames per second) mounted frontoparallely on a tripod and second, using gold standard infrared VOG goggles (EyeSeeCam, 188x120 px, 220 frames per second). Using the open-source software DeepLabCut , a recurrent neural network (RCNN) architecture was fine-tuned for tracking of pupils and facial anatomical landmarks. For subsequent comparisons, kinematic parameters (e. g. slow phase velocity (SPV)) of nystagmus were calculated from RCNN- and VOG-derived time series datasets using an instantaneous gradient algorithm. Precision of methods was compared using ANOVA and modified T-statistics, namely two one-sided T-testing (TOST) and one-sample T-tests. Results: In monocular analyses of RCNN-derived data, neither eye nor stimulus direction exerted significant influence on SPV (F (1, 5) = 1.33, p= [DZ1] .30 and F (3, 15) = 0.66, p = .59). Furthermore, method did not significantly influence omnidirectional SPV measurements (F (1, 5) = 0.009, p = .78). Finally, TOST results demonstrated equivalence in both horizontal (upper bound T(5) = -3.45, p = .009; lower bound (T(5) = 5.0, p= .002) and vertical (T(5) = -3.06, p = .01; T(5) = 3.35, p = .01) stimulus planes. Conclusions: This proof-of-concept study shows that a deep learning based tool (DeepVNG) can extract characteristics of nystagmus from smartphone video recordings of eye movements elicited by standardized optokinetic stimuli with comparable precision to gold standard VOG. These results may lay the groundwork for broadly available “ vestibular event monitors ” assisting both caregivers and patients in detection and quantification of nystagmus and may open an avenue for more granular analyses of nystagmus expected to improve its diagnostic value.

Unveiling the abstract format of mnemonic representations

Working memory (WM) enables information storage for future use, bridging the gap between perception and behavior. We hypothesize that WM representations are abstractions of low-level perceptual features. However, the neural nature of these putative abstract representations has thus far remained impenetrable. Here, we demonstrate that distinct visual stimuli (oriented gratings and moving dots) are flexibly recoded into the same WM format in visual and parietal cortices when that representation is useful for memory-guided behavior. Specifically, the behaviorally relevant features of the stimuli (orientation and direction) were extracted and recoded into a shared mnemonic format that takes the form of an abstract line-like pattern. We conclude that mnemonic representations are abstractions of percepts that are more efficient than and proximal to the behaviors they guide.

Photophobia as a Presenting Feature in Adie’s Tonic Pupil

A 34 years old female presented with complains of photophobia since 6-7 months. On examination, she had anisocoria of 4 mm in room light which increased in bright light. The left pupil was dilated and unresponsive to direct and indirect light stimuli. It did however, constrict slowly on near fixation followed by slow re-dilatation on distance fixation. A diagnosis of Adie’s tonic pupil was made since left pupil constricted with instillation of dilute pilocarpine 0.1%. Her symptoms of photophobia and blurred vision immediately resolved. Photochromatic glasses and dilute pilocarpine 0.1% three times a day were prescribed. Prompt symptomatic relief of photophobia and blurred vision was observed.

An optogenetic tool to recruit individual PKC isozymes to the cell surface and promote specific phosphorylation of membrane proteins

The PKC family consists of several closely related kinases. These enzymes regulate the function of proteins through the phosphorylation of hydroxyl groups on serines and/or threonines. The selective activation of individual PKC isozymes has proven challenging because of a lack of specific activator molecules. Here, we developed an optogenetic blue light–activated PKC isozyme that harnesses a plant-based dimerization system between the photosensitive cryptochrome-2 (CRY2) and the N terminus of the transcription factor calcium and integrin-binding protein 1 (CIB1) (N-terminal region of the CRY2-binding domain of CIB1). We show that tagging CRY2 with the catalytic domain of PKC isozymes can efficiently promote its translocation to the cell surface upon blue light exposure. We demonstrate this system using PKCε and show that this leads to robust activation of a K+ channel (G protein–gated inwardly rectifying K+ channels 1 and 4), previously shown to be activated by PKCε. We anticipate that this approach can be utilized for other PKC isoforms to provide a reliable and direct stimulus for targeted membrane protein phosphorylation by the relevant PKCs.