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Cell–cell communications in multicellular organisms generally involve secreted ligand–receptor (LR) interactions, which is vital for various biological phenomena. Recent advancements in single-cell RNA sequencing (scRNA-seq) have effectively resolved cellular phenotypic heterogeneity and the cell-type composition of complex tissues, facilitating the systematic investigation of cell–cell communications at single-cell resolution. However, assessment of chemical-signal-dependent cell–cell communication through scRNA-seq relies heavily on prior knowledge of LR interaction pairs. We constructed CellTalkDB (http://tcm.zju.edu.cn/celltalkdb), a manually curated comprehensive database of LR interaction pairs in humans and mice comprising 3398 human LR pairs and 2033 mouse LR pairs, through text mining and manual verification of known protein–protein interactions using the STRING database, with literature-supported evidence for each pair. Compared with SingleCellSignalR, the largest LR-pair resource, CellTalkDB includes not only 2033 mouse LR pairs but also 377 additional human LR pairs. In conclusion, the data on human and mouse LR pairs contained in CellTalkDB could help to further the inference and understanding of the LR-interaction-based cell–cell communications, which might provide new insights into the mechanism underlying biological processes.
Repetitive correlated spiking can induce long-term potentiation (LTP) and long-term depression (LTD) of many excitatory synapses on glutamatergic neurons, in a manner that depends on the timing of presynaptic and postsynaptic spiking. However, it is mostly unknown whether and how such spike-timing-dependent plasticity (STDP) operates at neocortical excitatory synapses on inhibitory interneurons, which have diverse physiological and morphological characteristics. In this study, we found that these synapses exhibit target-celldependent STDP. In layer 2/3 of the somatosensory cortex, the pyramidal cell (PC) forms divergent synapses on fast spiking (FS) and low-threshold spiking (LTS) interneurons that exhibit short-term synaptic depression and facilitation in response to high-frequency stimulation, respectively. At PC-LTS synapses, repetitive correlated spiking induced LTP or LTD, depending on the timing of presynaptic and postsynaptic spiking. However, regardless of the timing and frequency of spiking, correlated activity induced only LTD at PC-FS synapses. This target-cell-specific STDP was not caused by the difference in the short-term plasticity between these two types of synapses. Activation of postsynaptic NMDA subtype of glutamate receptors (NMDARs) was required for LTP induction at PC-LTS synapses, whereas activation of metabotropic glutamate receptors was required for LTD induction at both PC-LTS and PC-FS synapses. Additional analysis of synaptic currents suggests that LTP and LTD of PC-LTS synapses, but not LTD of PC-FS synapses, involves presynaptic modifications. Such dependence of both the induction and expression of STDP on the type of postsynaptic interneurons may contribute to differential processing and storage of information in cortical local circuits.
Lateral and medial parts of entorhinal cortex (EC) convey nonspatial 'what' and spatial 'where' information, respectively, into hippocampal CA1, via both the indirect EC layer 2→ hippocampal dentate gyrus→CA3→CA1 and the direct EC layer 3→CA1 paths. However, it remains elusive how the direct path transfers distinct information and contributes to hippocampal learning functions. Here we report that lateral EC projection neurons selectively form direct excitatory synapses onto a subpopulation of morphologically complex, calbindin-expressing pyramidal cells (PCs) in the dorsal CA1 (dCA1), while medial EC neurons uniformly innervate all dCA1 PCs. Optogenetically inactivating the distinct lateral EC-dCA1 connections or the postsynaptic dCA1 calbindin-expressing PC activity slows olfactory associative learning. Moreover, optetrode recordings reveal that dCA1 calbindin-expressing PCs develop more selective spiking responses to odor cues during learning. Thus, our results identify a direct lateral EC→dCA1 circuit that is required for olfactory associative learning.
The human nose serves vital physiological functions, including warming, filtration, humidification, and olfaction. These functions are based on transport phenomena that depend on nasal airflow patterns and turbulence. Accurate prediction of these airflow properties requires careful selection of computational fluid dynamics models and rigorous validation. The validation studies in the past have been limited by poor representations of the complex nasal geometry, lack of detailed airflow comparisons, and restricted ranges of flow rate. The objective of this study is to validate various numerical methods based on an anatomically accurate nasal model against published experimentally measured data under breathing flow rates from 180 to 1100 ml/s. The numerical results of velocity profiles and turbulence intensities were obtained using the laminar model, four widely used Reynolds-averaged Navier-Stokes (RANS) turbulence models (i.e., k- , standard k- Shear Stress Transport k- , and Reynolds Stress Model), large eddy simulation (LES) model, and direct numerical simulation (DNS). It was found that, despite certain irregularity in the flow field, the laminar model achieved good agreement with experimental results under restful breathing condition (180 ml/s) and performed better than the RANS models. As the breathing flow rate increased, the RANS models achieved more accurate predictions but still performed worse than LES and DNS. As expected, LES and DNS can provide accurate predictions of the nasal airflow under all flow conditions but have an approximately 100-fold higher computational cost. Among all the RANS models tested, the standard k- model agrees most closely with the experimental values in terms of velocity profile and turbulence intensity.
Objective The precise pathogenesis of empty nose syndrome (ENS) remains unclear. Various factors such as nasal aerodynamics and sensorineural dysfunction have been suspected, yet, evidence is limited. This study reported the first examination of both nasal aerodynamics and trigeminal sensory factors in actual ENS patients. Study Design Prospective case control. Methods We enrolled 6 patients diagnosed with ENS. Three patients had pre- and post-inferior turbinate (IT) reduction computed tomography (CT) scans, which allowed comparison of their nasal aerodynamics changes through Computational Fluid Dynamic (CFD) simulation. Their symptoms were confirmed through SNOT-22, ENS6Q, acoustic rhinometry and rhinomanometry findings. Nasal trigeminal sensitivity that potentially mediates their perception of airflow, was assessed via menthol lateralization detection thresholds (LDT) and compared with 14 healthy controls. Results Post-surgical reductions in nasal resistance were observed and significantly lower than normal (p<0.05). CFD analysis showed that, paradoxically for all ENS patients, IT reduction did not draw more airflow to the airway surrounding the ITs, but rather resulted in nasal airflow forming into a narrow jet towards the middle meatus region, leaving the airway surrounding the inferior turbinate with significantly reduced airflow intensity and air-mucosal interactions (inferior region flow percentage reduced from 35.7%±15.9% to post-surgery 17.7%±15.7, p<0.05; inferior wall-shear-stress, reduced from 7.5±4.2×10−2 Pa to 3.4±3.1×10−2 Pa, p<0.01). ENS patients also had significantly impaired menthol LDT compared to healthy controls (p<0.005). Conclusion The results indicated that a combinatory of factors, including paradoxically distorted nasal aerodynamic, impaired sensorineural sensitivity, and potential pre-disposing conditions, may contribute to the development of ENS.
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