Molecular and cellular mechanisms of teneurin signaling in synaptic partner matching.

In developing brains, axons exhibit remarkable precision in selecting synaptic partners among many non-partner cells. Evolutionarily conserved teneurins are transmembrane proteins that instruct synaptic partner matching. However, how intracellular signaling pathways execute teneurins' functions is unclear. Here, we use in situ proximity labeling to obtain the intracellular interactome of a teneurin (Ten-m) in the Drosophila brain. Genetic interaction studies using quantitative partner matching assays in both olfactory receptor neurons (ORNs) and projection neurons (PNs) reveal a common pathway: Ten-m binds to and negatively regulates a RhoGAP, thus activating the Rac1 small GTPases to promote synaptic partner matching. Developmental analyses with single-axon resolution identify the cellular mechanism of synaptic partner matching: Ten-m signaling promotes local F-actin levels and stabilizes ORN axon branches that contact partner PN dendrites. Combining spatial proteomics and high-resolution phenotypic analyses, this study advanced our understanding of both cellular and molecular mechanisms of synaptic partner matching.

Molecular mechanisms of proteoglycan-mediated semaphorin signaling in axon guidance.

The precise assembly of a functional nervous system relies on axon guidance cues. Beyond engaging their cognate receptors and initiating signaling cascades that modulate cytoskeletal dynamics, guidance cues also bind components of the extracellular matrix, notably proteoglycans, yet the role and mechanisms of these interactions remain poorly understood. We found that Drosophila secreted semaphorins bind specifically to glycosaminoglycan (GAG) chains of proteoglycans, showing a preference based on the degree of sulfation. Structural analysis of Sema2b unveiled multiple GAG-binding sites positioned outside canonical plexin-binding site, with the highest affinity binding site located at the C-terminal tail, characterized by a lysine-rich helical arrangement that appears to be conserved across secreted semaphorins. In vivo studies revealed a crucial role of the Sema2b C-terminal tail in specifying the trajectory of olfactory receptor neurons. We propose that secreted semaphorins tether to the cell surface through interactions with GAG chains of proteoglycans, facilitating their presentation to cognate receptors on passing axons.

Discriminative Grandparental Investment in China : Evidence from an Undergraduate Questionnaire Study.

Many studies in Western societies show a pattern of discriminative grandparental investment as follows: maternal grandmothers (MGMs) > maternal grandfathers (MGFs) > paternal grandmothers (PGMs) > paternal grandfathers (PGFs). This pattern is in line with the expectation from evolutionary reasoning. Yet whether or not this pattern applies in China is in question. The present study was based on a questionnaire survey at a university in Central China (N = 1,195). Results show that (1) when grandparent-grandchild residential distance during grandchildren's childhood is controlled, in the case of grandsons and granddaughters as a whole and granddaughters only, both grandparental caregiving and grandchildren's emotional closeness to grandparents display a rank order of MGM > MGF > PGM > PGF, but in the case of grandsons only, this order is not statistically significant. (2) There are stable relationships between grandparental caregiving/grandchildren's emotional closeness and residential distance/similarity in appearance. (3) The effects of residential distance on either PGFs' or PGMs' caregiving exceed those on either MGFs' or MGMs'. (4) The PGF and PGM prefer grandsons to granddaughters in their caregiving, whereas the MGF and MGM do not have a sex preference, and (5) the fact that the PGF and PGM invest more in grandsons than in granddaughters does not depend on grandsons' duration of living in a rural area. Our results suggest that (1) in general, the Chinese display a pattern of differential grandparental investment predicted by an evolutionary perspective, (2) the evolutionary perspective that combines the two factors of paternal uncertainty and sex-specific reproductive strategies is applicable to grandparental investment in China, and (3) the traditional son-preference culture also plays some role in affecting grandparental investment in China, though the roles of culture and urban-rural cultural difference should not be exaggerated.

Analysis of the Current Status of Nurses' Knowledge of Pressure Injuries and Factors Influencing It in Shaanxi Province, China: A Cross-Sectional Study.

Background: Pressure injuries are present in all healthcare environments and not only pose a significant health risk to individuals but also impose a heavy economic burden on society and families. Nurses, as the primary caregivers responsible for the prevention and management of pressure injuries, have knowledge that directly determines the incidence of pressure injuries. Aim: To understand the current status of nurses' knowledge of pressure injuries in Shaanxi Province and the factors influencing it. Design: A cross-sectional survey. Methods: In April - May 2022, 16,599 nurses from hospitals at all levels in Shaanxi Province were selected as survey subjects by convenience sampling method. They were surveyed using the general information questionnaire and the Pieper-Zulkowski pressure injury Knowledge Questionnaire through the Questionnaire Star platform. Results: 16,599 nurses had a pressure injury knowledge score of (44.32±10.11). Wound description and pressure ulcer staging dimensions were less than 60% correct. Comparison of pressure injury knowledge scores of nursing staff with different genders, hospital levels, titles, education, whether they were specialized nurses in wound stoma when they last attended a lecture on pressure ulcers, when they last read literature or books on pressure ulcers, and whether they ever looked for information about pressure ulcers on the Internet showed that the differences were statistically significant (P < 0.05), which were the influencing factors of the knowledge scores of the nursing staff in Shaanxi Province. Conclusion: Clinical nurses' awareness of stress-related injuries still needs to be improved, and nursing administrators can improve the quality of pressure-related injury care by increasing nursing staff's awareness through continuing education, tiered training, and other measures.

Embryonically active piriform cortex neurons promote intracortical recurrent connectivity during development.

Neuronal activity plays a critical role in the maturation of circuits that propagate sensory information into the brain. How widely does early activity regulate circuit maturation across the developing brain? Here, we used targeted recombination in active populations (TRAP) to perform a brain-wide survey for prenatally active neurons in mice and identified the piriform cortex as an abundantly TRAPed region. Whole-cell recordings in neonatal slices revealed preferential interconnectivity within embryonically TRAPed piriform neurons and their enhanced synaptic connectivity with other piriform neurons. In vivo Neuropixels recordings in neonates demonstrated that embryonically TRAPed piriform neurons exhibit broad functional connectivity within piriform and lead spontaneous synchronized population activity during a transient neonatal period, when recurrent connectivity is strengthening. Selectively activating or silencing these neurons in neonates enhanced or suppressed recurrent synaptic strength, respectively. Thus, embryonically TRAPed piriform neurons represent an interconnected hub-like population whose activity promotes recurrent connectivity in early development.

Embryonically Active Piriform Cortex Neurons Promote Intracortical Recurrent Connectivity during Development.

Neuronal activity plays a critical role in the maturation of circuits that propagate sensory information into the brain. How widely does early activity regulate circuit maturation across the developing brain? Here, we used Targeted Recombination in Active Populations (TRAP) to perform a brain-wide survey for prenatally active neurons in mice and identified the piriform cortex as an abundantly TRAPed region. Whole-cell recordings in neonatal slices revealed preferential interconnectivity within embryonically TRAPed piriform neurons and their enhanced synaptic connectivity with other piriform neurons. In vivo Neuropixels recordings in neonates demonstrated that embryonically TRAPed piriform neurons exhibit broad functional connectivity within piriform and lead spontaneous synchronized population activity during a transient neonatal period, when recurrent connectivity is strengthening. Selectively activating or silencing of these neurons in neonates enhanced or suppressed recurrent synaptic strength, respectively. Thus, embryonically TRAPed piriform neurons represent an interconnected hub-like population whose activity promotes recurrent connectivity in early development.

A cerebellar granule cell-climbing fiber computation to learn to track long time intervals.

In classical cerebellar learning, Purkinje cells (PkCs) associate climbing fiber (CF) error signals with predictive granule cells (GrCs) that were active just prior (∼150 ms). The cerebellum also contributes to behaviors characterized by longer timescales. To investigate how GrC-CF-PkC circuits might learn seconds-long predictions, we imaged simultaneous GrC-CF activity over days of forelimb operant conditioning for delayed water reward. As mice learned reward timing, numerous GrCs developed anticipatory activity ramping at different rates until reward delivery, followed by widespread time-locked CF spiking. Relearning longer delays further lengthened GrC activations. We computed CF-dependent GrC→PkC plasticity rules, demonstrating that reward-evoked CF spikes sufficed to grade many GrC synapses by anticipatory timing. We predicted and confirmed that PkCs could thereby continuously ramp across seconds-long intervals from movement to reward. Learning thus leads to new GrC temporal bases linking predictors to remote CF reward signals-a strategy well suited for learning to track the long intervals common in cognitive domains.