Two entry tunnels in mouse TAAR9 suggest the possibility of multi-entry tunnels in olfactory receptors.

Orthosteric binding sites of olfactory receptors have been well understood for ligand-receptor interactions. However, a lack of explanation for subtle differences in ligand profile of olfactory receptors even with similar orthosteric binding sites promotes more exploration into the entry tunnels of the receptors. An important question regarding entry tunnels is the number of entry tunnels, which was previously believed to be one. Here, we used TAAR9 that recognizes important biogenic amines such as cadaverine, spermine, and spermidine as a model for entry tunnel study. We identified two entry tunnels in TAAR9 and described the residues that form the tunnels. In addition, we found two vestibular binding pockets, each located in one tunnel. We further confirmed the function of two tunnels through site-directed mutagenesis. Our study challenged the existing views regarding the number of entry tunnels in the subfamily of olfactory receptors and demonstrated the possible mechanism how the entry tunnels function in odorant recognition.

Evolution of Brain-Expressed Biogenic Amine Receptors into Olfactory Trace Amine-Associated Receptors.

The family of trace amine-associated receptors (TAARs) is distantly related to G protein-coupled biogenic aminergic receptors. TAARs are found in the brain as well as in the olfactory epithelium where they detect biogenic amines. However, the functional relationship of receptors from distinct TAAR subfamilies and in different species is still uncertain. Here, we perform a thorough phylogenetic analysis of 702 TAAR-like (TARL) and TAAR sequences from 48 species. We show that a clade of Tarl genes has greatly expanded in lampreys, whereas the other Tarl clade consists of only one or two orthologs in jawed vertebrates and is lost in amniotes. We also identify two small clades of Taar genes in sharks related to the remaining Taar genes in bony vertebrates, which are divided into four major clades. We further identify ligands for 61 orphan TARLs and TAARs from sea lamprey, shark, ray-finned fishes, and mammals, as well as novel ligands for two 5-hydroxytryptamine receptor 4 orthologs, a serotonin receptor subtype closely related to TAARs. Our results reveal a pattern of functional convergence and segregation: TARLs from sea lamprey and bony vertebrate olfactory TAARs underwent independent expansions to function as chemosensory receptors, whereas TARLs from jawed vertebrates retain ancestral response profiles and may have similar functions to TAAR1 in the brain. Overall, our data provide a comprehensive understanding of the evolution and ligand recognition profiles of TAARs and TARLs.

Convergent olfactory trace amine-associated receptors detect biogenic polyamines with distinct motifs via a conserved binding site.

Biogenic amines activate G-protein-coupled receptors (GPCRs) in the central nervous system in vertebrate animals. Several biogenic amines, when excreted, stimulate trace amine-associated receptors (TAARs), a group of GPCRs in the main olfactory epithelium, and elicit innate behaviors. How TAARs recognize amines with varying numbers of amino groups is largely unknown. We reasoned that a comparison between lamprey and mammalian olfactory TAARs, which are thought to have evolved independently but show convergent responses to polyamines, may reveal structural determinants of amine recognition. Here, we demonstrate that sea lamprey TAAR365 (sTAAR365) responds strongly to biogenic polyamines cadaverine, putrescine, and spermine, and shares a similar response profile as a mammalian TAAR (mTAAR9). Docking and site-directed mutagenesis analyses show that both sTAAR365 and mTAAR9 recognize the two amino groups of cadaverine with the conserved Asp3.32 and Tyr6.51 residues. sTAAR365, which has remarkable sensitivity for cadaverine (EC50 = 4 nM), uses an extra residue, Thr7.42, to stabilize ligand binding. These cadaverine recognition sites also interact with amines with four and three amino groups (spermine and spermidine, respectively). Glu7.36 of sTAAR365 cooperates with Asp3.32 and Thr7.42 to recognize spermine, whereas mTAAR9 recognizes spermidine through an additional aromatic residue, Tyr7.43. These results suggest a conserved mechanism whereby independently evolved TAAR receptors recognize amines with two, three, or four amino groups using the same recognition sites, at which sTAAR365 and mTAAR9 evolved distinct motifs. These motifs interact directly with the amino groups of the polyamines, a class of potent and ecologically important odorants, mediating olfactory signaling.

Multi-wavelength photoplethysmography method for skin arterial pulse extraction.

In this work, we present a multi-wavelength (MW) PPG method exploiting the wavelength dependence of light penetration in skin tissue to provide depth resolution of skin blood pulsation. The MW PPG system requires two to three light sources in different wavelengths and extracts the arterial blood pulsation through a multi-wavelength multi-layer light-skin interaction model, which removes the capillary pulsation (determined from the short-wavelength PPG signal) from the long-wavelength PPG signal using absorption weighting factors that are quasi-analytically calibrated. The extracted pulsations are used to calculate blood pressure (BP) through pulse transit time (PTT), and the results are compared with those obtained from the single wavelength PPG method. The comparative study is clinically performed on 20 subjects including 10 patients diagnosed with cardiovascular diseases and 10 healthy subjects. The result demonstrates that the MW PPG method significantly improves the measurement accuracy of systolic BP (SBP), reducing the mean absolute difference between the reference and the estimated SBP values from 5.7 mmHg (for single-wavelength PPG) to 2.9 mmHg (for three-wavelength PPG).

The well-designed hierarchical structure of Musa basjoo for supercapacitors.

Application of biological structure is one of the hottest topics in the field of science and technology. The unimaginable and excellent architectures of living beings supporting their vital activities have attracted the interests of worldwide researchers. An intriguing example is Musa basjoo which belongs to the herb, while appears like a tree. The profound mystery of structure and potential application of Musa basjoo have not been probed. Here we show the finding of the hierarchical structure of Musa basjoo and the outstanding electrochemical performance of the super-capacitors fabricated through the simple carbonization of Musa basjoo followed by KOH activation. Musa basjoo has three layers of structure: nanometer-level, micrometer-level and millimeter-level. The nanometer-level structure constructs the micrometer-level structure, while the micrometer-level structure constructs the millimeter-level structure. Based on this hierarchical structure, Musa basjoo reduces the unnecessary weight and therefore supports its huge body. The super-capacitors derived from Musa basjoo display a high specific capacitance and a good cycling stability. This enlightening work opens a window for the applications of the natural structure and we hope that more and more people could pay attention to the bio-inspired materials.

Continuous Cuffless Blood Pressure Estimation Using Pulse Transit Time and Photoplethysmogram Intensity Ratio.

Pulse transit time (PTT) has attracted much interest for cuffless blood pressure (BP) measurement. However, its limited accuracy is one of the main problems preventing its widespread acceptance. Arterial BP oscillates mainly at high frequency (HF) because of respiratory activity, and at low frequency (LF) because of vasomotor tone. Prior studies suggested that PTT can track BP variation in HF range, but was inadequate to follow the LF variation, which is probably the main reason for its unsatisfactory accuracy. This paper presents a new indicator, the photoplethysmogram intensity ratio (PIR), which can be affected by changes in the arterial diameter, and, thus, trace the LF variation of BP. Spectral analysis of BP, PTT, PIR, and respiratory signal confirmed that PTT was related to BP in HF at the respiratory frequency, while PIR was associated with BP in LF range. We, therefore, develop a novel BP estimation algorithm by using both PTT and PIR. The proposed algorithm was validated on 27 healthy subjects with continuous Finapres BP as reference. The results showed that the mean ± standard deviation (SD) for the estimated systolic, diastolic, and mean BP with the proposed method against reference were -0.37 ±5.21, -0.08 ±4.06, -0.18 ±4.13 mmHg, and mean absolute difference (MAD) were 4.09, 3.18, 3.18 mmHg, respectively. Furthermore, the proposed method outperformed the two most cited PTT algorithms for about 2 mmHg in SD and MAD. These results demonstrated that the proposed BP model using PIR and PTT can estimate continuous BP with improved accuracy.

Effects of cuff inflation and deflation on pulse transit time measured from ECG and multi-wavelength PPG.

Pulse transit time (PTT), which refers to the time it takes a pulse wave to travel between two arterial sites is a promising index for cuff-less blood pressure (BP) estimation, as well as non-invasive assessment of arterial functions. However, it has not been investigated whether PTTs measured from ECG and different wavelength PPG are equally affected by the arterial status. Furthermore, comparison between the changes of different PTTs can provide enlightenment on the hardware implementation of the PTT-based BP estimation method. This work mainly studied the changes of PTTs calculated from electrocardiogram (ECG) and multi-wavelength photoplethysmogram (PPG) after exerting cuff pressure on the upper arm. A four-channel PPG acquisition system was developed to collect the multi-wavelength PPG signals of red, yellow, green and blue light at the fingertip simultaneously. Ten subjects participated in the experiment and their PTTs measured from different PPG and ECG signals before and after exerting cuff pressure were compared. This study found that within one minute after the four-minute cuff inflation and deflation process, the PTT measured from ECG and yellow PPG experienced a significant increase (p<;0.05) while the PTT from ECG and blue PPG had no statistical difference (p>0.9) compared with that before exerting cuff pressure. This indicates that PTTs calculated from different wavelength PPG have different recoverability from smooth muscle relaxation. Another interesting finding is that the PTT calculated from ECG and yellow PPG had a strong correlation (|r|>0.7) with the time difference between yellow PPG and other PPG signals, which implies the potential of the time difference between yellow PPG and other PPGs as a complementary to PTT-based model for blood pressure estimation.