Specific configurations of electrical synapses filter sensory information to drive choices in behavior.

Synaptic configurations in precisely wired circuits underpin how sensory information is processed by the nervous system, and the emerging animal behavior. This is best understood for chemical synapses, but far less is known about how electrical synaptic configurations modulate, in vivo and in specific neurons, sensory information processing and context-specific behaviors. We discovered that INX-1, a gap junction protein that forms electrical synapses, is required to deploy context-specific behavioral strategies during C. elegans thermotaxis behavior. INX-1 couples two bilaterally symmetric interneurons, and this configuration is required for the integration of sensory information during migration of animals across temperature gradients. In inx-1 mutants, uncoupled interneurons display increased excitability and responses to subthreshold temperature stimuli, resulting in abnormally longer run durations and context-irrelevant tracking of isotherms. Our study uncovers a conserved configuration of electrical synapses that, by increasing neuronal capacitance, enables differential processing of sensory information and the deployment of context-specific behavioral strategies.

Exergaming delivery of a balance and fall prevention program for older adults: A feasibility study.

Objective: Older adults are at high risk of falls and this problem calls for efficient and scalable interventions. This study investigated whether a motion capture system paired with balance training exergaming software is a feasible strategy to deliver therapeutic exercise to older adults in an aged care facility. Methods: This study analyzed data from a quality improvement rehabilitation initiative. Two convenience samples of older adults were included: a usual care group (n = 12), admitted to a rehabilitation hospital and receiving standard in-patient therapy 5×/week and the Evolv group (n = 12), admitted to an aged care facility, prescribed exergaming 3×/week. All participants performed 30-minute exercise sessions based on a fall prevention program over 3 months. The Short Physical Performance Battery (SPPB) and Tinetti Performance Oriented Mobility Assessment test were administered pre- and post-treatment. Results: No adverse events were recorded during the interventions. Mean SPPB increase for Evolv participants was 2.25 ± 1.35 (p < .001, CI for mean = 1.39 to 3.11, d = 1.66), compared with a non-significant change in the usual care group (mean increase = 2.25 ± 3.82, p = .066, CI for mean = -0.18 to 4.68, d = 0.59). Tinetti improvement was significant for the individuals receiving usual care (3.83 ± 2.82, p = .012, CI for mean = 1.01 to 6.66, d = 0.86) but there were no significant between-group differences in outcomes. Conclusions: Exergaming with the Evolv system for balance and strength training may be a feasible strategy to improve physical function for older adults recovering in an aged care facility.

The Genomic and Phenotypic Landscape of Ichthyosis: An Analysis of 1000 Kindreds.

IMPORTANCE: Ichthyoses are clinically and genetically heterogeneous disorders characterized by scaly skin. Despite decades of investigation identifying pathogenic variants in more than 50 genes, clear genotype-phenotype associations have been difficult to establish. OBJECTIVE: To expand the genotypic and phenotypic spectra of ichthyosis and delineate genotype-phenotype associations. DESIGN, SETTING, AND PARTICIPANTS: This cohort study recruited an international group of individuals with ichthyosis and describes characteristic and distinguishing features of common genotypes, including genotype-phenotype associations, during a 10-year period from June 2011 to July 2021. Participants of all ages, races, and ethnicities were included and were enrolled worldwide from referral centers and patient advocacy groups. A questionnaire to assess clinical manifestations was completed by those with a genetic diagnosis. MAIN OUTCOMES AND MEASURES: Genetic analysis of saliva or blood DNA, a phenotyping questionnaire, and standardized clinical photographs. Descriptive statistics, such as frequency counts, were used to describe the cases in the cohort. Fisher exact tests identified significant genotype-phenotype associations. RESULTS: Results were reported for 1000 unrelated individuals enrolled from around the world (mean [SD] age, 50.0 [34.0] years; 524 [52.4%] were female, 427 [42.7%] were male, and 49 [4.9%] were not classified); 75% were from the US, 12% from Latin America, 4% from Canada, 3% from Europe, 3% from Asia, 2% from Africa, 1% from the Middle East, and 1% from Australia and New Zealand. A total of 266 novel disease-associated variants in 32 genes were identified among 869 kindreds. Of these, 241 (91%) pathogenic variants were found through multiplex amplicon sequencing and 25 (9%) through exome sequencing. Among the 869 participants with a genetic diagnosis, 304 participants (35%) completed the phenotyping questionnaire. Analysis of clinical manifestations in these 304 individuals revealed that pruritus, hypohydrosis, skin pain, eye problems, skin odor, and skin infections were the most prevalent self-reported features. Genotype-phenotype association analysis revealed that the presence of a collodion membrane at birth (odds ratio [OR], 6.7; 95% CI, 3.0-16.7; P < .001), skin odor (OR, 2.8; 95% CI, 1.1-6.8; P = .02), hearing problems (OR, 2.9; 95% CI, 1.6-5.5; P < .001), eye problems (OR, 3.0; 95% CI, 1.5-6.0; P < .001), and alopecia (OR, 4.6; 95% CI, 2.4-9.0; P < .001) were significantly associated with TGM1 variants compared with other ichthyosis genotypes studied. Skin pain (OR, 6.8; 95% CI, 1.6-61.2; P = .002), odor (OR, 5.7; 95% CI, 2.0-19.7; P < .001), and infections (OR, 3.1; 95% CI, 1.4-7.7; P = .03) were significantly associated with KRT10 pathogenic variants compared with disease-associated variants in other genes that cause ichthyosis. Pathogenic variants were identified in 869 (86.9%) participants. Most of the remaining individuals had unique phenotypes, enabling further genetic discovery. CONCLUSIONS AND RELEVANCE: This cohort study expands the genotypic and phenotypic spectrum of ichthyosis, establishing associations between clinical manifestations and genotypes. Collectively, the findings may help improve clinical assessment, assist with developing customized management plans, and improve clinical course prognostication.

Contagious yawning is not a signal of empathy: no evidence of familiarity, gender or prosociality biases in dogs.

Contagious yawning has been suggested to be a potential signal of empathy in non-human animals. However, few studies have been able to robustly test this claim. Here, we ran a Bayesian multilevel reanalysis of six studies of contagious yawning in dogs. This provided robust support for claims that contagious yawning is present in dogs, but found no evidence that dogs display either a familiarity or gender bias in contagious yawning, two predictions made by the contagious yawning-empathy hypothesis. Furthermore, in an experiment testing the prosociality bias, a novel prediction of the contagious yawning-empathy hypothesis, dogs did not yawn more in response to a prosocial demonstrator than to an antisocial demonstrator. As such, these strands of evidence suggest that contagious yawning, although present in dogs, is not mediated by empathetic mechanisms. This calls into question claims that contagious yawning is a signal of empathy in mammals.

Integration of Plasticity Mechanisms within a Single Sensory Neuron of C. elegans Actuates a Memory.

Neural plasticity, the ability of neurons to change their properties in response to experiences, underpins the nervous system's capacity to form memories and actuate behaviors. How different plasticity mechanisms act together in vivo and at a cellular level to transform sensory information into behavior is not well understood. We show that in Caenorhabditis elegans two plasticity mechanisms-sensory adaptation and presynaptic plasticity-act within a single cell to encode thermosensory information and actuate a temperature preference memory. Sensory adaptation adjusts the temperature range of the sensory neuron (called AFD) to optimize detection of temperature fluctuations associated with migration. Presynaptic plasticity in AFD is regulated by the conserved kinase nPKCε and transforms thermosensory information into a behavioral preference. Bypassing AFD presynaptic plasticity predictably changes learned behavioral preferences without affecting sensory responses. Our findings indicate that two distinct neuroplasticity mechanisms function together through a single-cell logic system to enact thermotactic behavior. VIDEO ABSTRACT.

Establishing and Validating an Ichthyosis Severity Index.

We designed and validated a Visual Index for Ichthyosis Severity for scale and erythema that provides (1) written descriptions of the features characteristic of each level of severity, (2) visual standards for four body sites, and (3) two distinct standards to account for different types of scale. We tested the Visual Index for Ichthyosis Severity for reliability and reproducibility using two different settings: one that utilized scoring of 60 test photographs by 10 dermatologists, and one with in-person evaluations on 85 subjects by 12 dermatologists at the Foundation for Ichthyosis and Related Skin Types conference. The validation process revealed high reliability and reproducibility for both scale and erythema. The interrater and intrarater intraclass correlation coefficients for scale were consistently near or greater than 0.7 in both settings. By contrast, the interrater reliability for erythema was higher during in-person validation compared with validation on test photographs. Our analysis indicates that the Visual Index for Ichthyosis Severity performs better in person than with photographs, an important consideration in the design of clinical trials. Power analysis predicts that a 1-point difference on this 5-step scale would be detectable with 12 subjects in each of two defined groups. This index provides a tool for clinical phenotyping and assessment of therapeutic response for many disorders of keratinization.