Biomedical subjects

Yali Zhao

Publications and source records attributed to Yali Zhao.

18 recordsLinked to original sources

PubMed2025

Efficient site-specific integration of kilobase-length DNA fragments in plant cells via Kp03 recombinase.

Targeted insertion of large DNA sequences into plant genomes remains a major challenge in synthetic biology. Here, we evaluate the large serine recombinase Kp03 for site-specific integration of DNA fragments in rice and Arabidopsis. In transient protoplast assays, Kp03 mediates efficient insertion of donor DNA up to 27.3 kilobases (kb), with plasmid integration efficiencies reaching 99.1% for fragments up to 3.4 kb. Truncation experiments reveal that a minimal 15-bp attB sequence is necessary for integration. As a proof of concept, Kp03 successfully incorporates a 3.4-kb donor DNA into the rice genome at a locus containing this minimal attB sequence. Moreover, in rice callus, combining Kp03 with the NM-PE genome editing system to install a 26-bp attB site enables targeted integration of a 3.4-kb donor at the desired genomic locus. These findings establish Kp03 as a versatile tool for plant genome engineering, with broad applications for synthetic biology.

Oryza↗

PubMed2006

Adiponectin modulates carnitine palmitoyltransferase-1 through AMPK signaling cascade in rat cardiomyocytes.

Adiponectin, an adipocyte-derived polypeptide hormone, plays an important role in regulating fatty acid oxidation. beta-oxidation of fatty acids supplies most of the cardiac energy and carnitine palmitoyltransferase (CPT)-1 serves as a key regulator during this process. To characterize the potential effects of adiponectin on CPT-1, we incubated rat neonatal cardiomyocytes with globular adiponectin (gAd). Results showed that gAd promoted the activity and mRNA expression of CPT-1. The underlying signal pathway involved in this modulatory effect was further investigated. Inhibition of AMP-activated protein kinase (AMPK) with adenine 9-beta-d-arabinofuranoside (AraA) completely abrogated gAd-mediated AMPK and acetyl coenzyme A carboxylase (ACC) phosphorylation and suppressed the promotion of CPT-1 activity. gAd also induced the phosphorylation of p38 mitogen-activated protein kinase (MAPK) and peroxisome proliferator-activated receptor (PPAR)-alpha, which was inhibited by AraA. SB202190, a p38MAPK inhibitor, blocked gAd-stimulated PPAR-alpha phosphorylation. When AMPK and/or p38MAPK was inhibited, gAd-enhanced mRNA expression of CPT-1 was partially reduced. In conclusion, our study suggests that the activation of AMPK signaling cascade participates in the promotion effect of gAd on CPT-1.

AMP-Activated Protein Kinases↗

PubMed2006

Isoform specificity of PKC translocation in living Aplysia sensory neurons and a role for Ca2+-dependent PKC APL I in the induction of intermediate-term facilitation.

Protein kinase Cs (PKCs) are important effectors of synaptic plasticity. In Aplysia, there are two major phorbol ester-activated PKCs, Ca2+-activated PKC Apl I and Ca2+-independent PKC Apl II. Functional Apl II, but not Apl I, in sensory neurons is required for a form of short-term facilitation induced at sensorimotor synapses by the facilitatory transmitter serotonin (5-HT). Because PKCs are activated by translocating from the cytoplasm to the membrane, we used fluorescently tagged PKCs to determine the isoform and cell-type specificity of translocation in living Aplysia neurons. In Sf9 cells, low levels of diacylglycerol translocate Apl II, but not Apl I, which requires calcium for translocation at low concentrations of diacylglycerol. Accordingly, application of 5-HT to Aplysia sensory neurons in the absence of neuronal firing translocates Apl II, but not Apl I, consistent with the role of Apl II in short-term facilitation. This translocation is observed in sensory neurons, but not in motor neurons. Apl I translocates only if 5-HT is coupled to firing in the sensory neuron; firing alone is ineffective. Because combined 5-HT and firing are required for the induction of one type of intermediate-term facilitation at these synapses, we asked whether this form of synaptic plasticity involves activation of Apl I. We report here that dominant-negative Apl I, but not Apl II, blocks intermediate-term facilitation. Thus, different isoforms of PKC translocate under different conditions to mediate distinct types of synaptic plasticity: Ca2+-independent Apl II is involved in short-term facilitation, and Ca2+-dependent Apl I contributes to intermediate-term facilitation.

Action Potentials↗

PubMed2006

Synapse formation and mRNA localization in cultured Aplysia neurons.

mRNA localization and regulated translation provide a means of spatially restricting gene expression within neurons during axon guidance and long-term synaptic plasticity. Here we show that synapse formation specifically alters the localization of the mRNA encoding sensorin, a peptide neurotransmitter with neurotrophin-like properties. In isolated Aplysia sensory neurons, which do not form chemical synapses, sensorin mRNA is diffusely distributed throughout distal neurites. Upon contact with a target motor neuron, sensorin mRNA rapidly concentrates at synapses. This redistribution only occurs in the presence of a target motor neuron and parallels the distribution of sensorin protein. Reduction of sensorin mRNA, but not protein, with dsRNA inhibits synapse formation. Our results indicate that synapse formation can alter mRNA localization within individual neurons. They further suggest that translation of a specific localized mRNA, encoding the neuropeptide sensorin, is required for synapse formation between sensory and motor neurons.

Analysis of Variance↗

PubMed2005

Clinical and molecular analysis of a four-generation Chinese family with aminoglycoside-induced and nonsyndromic hearing loss associated with the mitochondrial 12S rRNA C1494T mutation.

We report here the clinical, genetic, and molecular characterization of a four-generation Chinese family with aminoglycoside-induced and nonsyndromic hearing loss. Five of nine matrilineal relatives had aminoglycoside-induced hearing loss. These matrilineal relatives exhibited variable severity and audiometric configuration of hearing impairment, despite sharing some common features: being bilateral and having sensorineural hearing impairment. Sequence analysis of mitochondrial DNA (mtDNA) in the pedigree identified 16 variants and the homoplasmic 12S rRNA C1494T mutation, which was associated with hearing loss in the other large Chinese family. In fact, the occurrence of the C1494T mutation in these genetically unrelated pedigrees affected by hearing impairment strongly indicated that this mutation is involved in the pathogenesis of aminoglycoside-induced and nonsyndromic hearing loss. However, incomplete penetrance of hearing loss indicated that the C1494T mutation itself is not sufficient to produce a clinical phenotype but requires the involvement of modifier factors for the phenotypic expression. Those mtDNA variants, showing no evolutional conservation, may not have a potential modifying role in the pathogenesis of the C1494T mutation. However, nuclear background seems to contribute to the phenotypic variability of matrilineal relatives in this family. Furthermore, aminoglycosides modulate the expressivity and penetrance of deafness associated with the C1494T mutation in this family.

Adolescent↗

PubMed2005

Assessing the quality of RCTs on the effect of beta-elemene, one ingredient of a Chinese herb, against malignant tumors.

OBJECTIVE: To evaluate the quality of randomized controlled trials (RCTs) for Elemene injections, one ingredient of Chinese herb Curcuma wenyujin, for malignant tumors widely used in clinical practice in China. METHODS: We used a systematic sample of 127 reports of RCTs that used Elemene injections as an intervention. The quality of each report was assessed using the number of Consolidated Standards for Reporting of Trials (CONSORT) checklist items included, the frequency of allocation concealment and a 5-point quality assessment instrument (Jadad). RESULTS: 69.44% of the CONSORT checklist items was included in the reports. Only 2 (1.57%) RCTs reported allocation concealment by sealed envelopes. 123 (96.85%) reports described baseline demographic and clinical characteristics of each group. But only 5 (3.94%) of 127 RCTs reported statistics analysis results of baseline data. None of the reports stated in the methods section that intention-to-treat (ITT) analysis was used, although 111 (87.40%) reports described the number of participants (denominator) in each group included in each analysis. Information regarding adverse events was reported in 83.46% of the RCTs. However the quality of reports were low as assessed by the Jadad scale. CONCLUSIONS: The methodological quality of RCTs of Elemene injection against malignant tumors was low. Therefore, the effect of Elemene injection being used in clinical settings needs to be confirmed by further RCTs. Meanwhile, there is a need to supervise and urge researchers in China to conform to Good Clinical Practice (GCP) and CONSORT guidelines when reporting.

Antineoplastic Agents↗

PubMed2005

Role of Ras/PKCzeta/MEK/ERK1/2 signaling pathway in angiotensin II-induced vascular smooth muscle cell proliferation.

The role of protein kinase C (PKC) and its cross talk with extracellular signal-regulated kinase (ERK) cascade in angiotensin II (AngII)-elicited vascular smooth muscle cell (VSMC) proliferation are still unclear. In this study, the PKC pathway of AngII to activate ERK1/2 and induce cell proliferation was investigated in rat aortic smooth muscle cells. The proliferation of VSMCs was tested by [3H]-thymidine incorporation assay. Phosphorylated and non-phosphorylated PKCzeta, ERK1/2, Elk-1, and mitogen-activated ERK-activating kinase (MEK) were estimated by Western blot analysis. The interactions of signal molecules were examined by immunoprecipitation. AngII-induced VSMC proliferation and activation of ERK1/2 and nuclear transcription factor Elk-1 were all down-regulated by PKC non-specific inhibitor (staurosporine) and PKCzeta pseudosubstrate inhibitor (PS-PKCzeta). Dominant negative Ras transfection into VSMCs decreased AngII-induced PKCzeta and ERK1/2 phosphorylation. AngII stimulated the association of PKCzeta with Ras. AngII-induced MEK phosphorylation was inhibited by PKCzeta pseudosubstrate inhibitor and the PKCzeta-MEK complex was detected by immunoprecipitation. These results suggest that PKCzeta isoform is involved in VSMC proliferation and Elk-1 activation. AngII can activate ERK1/2 by Ras/PKCzeta/MEK pathway, which may be one of the important signal transduction pathways in AngII-induced VSMC proliferation.

Angiotensin II↗

PubMed2005

Diagnosis and follow-up study of carotid cavernous fistulas with color Doppler ultrasonography: analysis of 33 cases.

OBJECTIVE: The purpose of this study was to observe image characteristics and hemodynamic changes of carotid-cavernous sinus fistulas (CCFs) and to evaluate the efficacy of interventional treatment for CCFs by color Doppler ultrasonography (CDUS). METHODS: Thirty-three patients with suspected CCFs were studied with CDUS. Forty-six volunteers took part in this study as controls. Scanning was performed through temporal, orbital, and occipital windows to measure the blood flow parameters of the internal carotid artery (ICA) and related vessels. All results were confirmed by cerebral angiography. Nineteen patients were followed after interventional treatment. RESULTS: Thirty-two patients (97%) were found to have CCFs by CDUS. Irregular mosaic flashes were observed in the cavernous sinus region, the cross-section areas of which were significantly larger than those of the normal intracranial ICA (1.7-5.2 versus 0.2-0.5 cm(2); P < .01). A lower resistive index of the ICA in the affected side was revealed with spectral analysis of relevant vessels. The peak velocity of vessels distal to the fistula was significantly lower than that of the healthy side and control group (P < .05). Superior ophthalmic veins had a reversed arterialized flow pattern with a mean velocity of 34.5 cm/s and an average resistive index +/- SD of 0.31 +/- 0.08. In follow-up study, the mosaic flashes and turbulence flow disappeared in 14 patients and remained in 5 after the interventional operation. CONCLUSIONS: Combined with the direct sign of an irregular mosaic flash in the cavernous sinus region, hemodynamic changes in relevant branch vessels, and a reversed arterialized flow pattern in superior ophthalmic veins, CDUS has great value in confirming diagnosis and follow-up study of CCFs.

Adult↗

PubMed2004

Synapse to nucleus signaling during long-term synaptic plasticity; a role for the classical active nuclear import pathway.

The requirement for transcription during long-lasting plasticity indicates that signals generated at the synapse must be transported to the nucleus. We have investigated whether the classical active nuclear import pathway mediates intracellular retrograde signal transport in Aplysia sensory neurons and rodent hippocampal neurons. We found that importins localize to distal neuronal processes, including synaptic compartments, where they are well positioned to mediate synapse to nucleus signaling. In Aplysia, stimuli known to produce long-lasting but not short-lasting facilitation triggered importin nuclear translocation. In hippocampal neurons, NMDA receptor activation but not depolarization induced importin nuclear translocation. We further showed that LTP-inducing stimuli recruited active nuclear import in hippocampal slices. Together with our finding that long-term facilitation of Aplysia sensory-motor synapses required active nuclear import, our results indicate that regulation of the active nuclear import pathway plays a critical role in transporting synaptically generated signals into the nucleus during learning-related forms of plasticity.

Active Transport, Cell Nucleus↗

PubMed2004

ApTrkl, a Trk-like receptor, mediates serotonin- dependent ERK activation and long-term facilitation in Aplysia sensory neurons.

The Trk family of receptor tyrosine kinases plays a role in synaptic plasticity and in behavioral memory in mammals. Here, we report the discovery of a Trk-like receptor, ApTrkl, in Aplysia. We show that it is expressed in the sensory neurons, the locus for synaptic facilitation, which is a cellular model for memory formation. Serotonin, the facilitatory neurotransmitter, activates ApTrkl, which, in turn, leads to activation of ERK. Finally, inhibiting the activation of ApTrkl with the Trk inhibitor K252a or using dsRNA to inhibit ApTrkl blocks the serotonin-mediated activation of ERK in the cell body, as well as the cell-wide long-term facilitation induced by 5-HT application to the cell body. Thus, transactivation of the receptor tyrosine kinase ApTrkl by serotonin is an essential step in the biochemical events leading to long-term facilitation in Aplysia.

Amino Acid Sequence↗

PubMed2003

Changes in the readily releasable pool of transmitter and in efficacy of release induced by high-frequency firing at Aplysia sensorimotor synapses in culture.

Synaptic transmission at the sensory neuron-motor neuron synapses of Aplysia, like transmission at many synapses of both vertebrates and invertebrates, is increased after a short burst of high-frequency stimulation (HFS), a phenomenon known as posttetanic potentiation (PTP). PTP is generally attributable to an increase in transmitter release from presynaptic neurons. We investigated whether changes in the readily releasable pool of transmitter (RRP) contribute to the potentiation that follows HFS. We compared the changes in excitatory postsynaptic potentials (EPSPs) evoked with action potentials to changes in the RRP as estimated from the asynchronous transmitter release elicited by a hypertonic solution. The changes in the EPSP were correlated with changes in the RRP, but the changes matched quantitatively only at connections whose initial synaptic strength was greater than the median for all experiments. At weaker connections, the increase in the RRP was insufficient to account for PTP. Weaker connections initially released a smaller fraction of the RRP with each EPSP than stronger ones, and this fraction increased at weaker connections after HFS. Moreover, the initial transmitter release in response to the hypertonic solution was accelerated after HFS, indicating that the increase in the efficacy of release was not restricted to excitation-secretion coupling. Modulation of the RRP and of the efficacy of release thus both contribute to the enhancement of transmitter release by HFS.

Action Potentials↗

PubMed2003

The ubiquitin proteasome system functions as an inhibitory constraint on synaptic strengthening.

BACKGROUND: Long-lasting forms of synaptic plasticity have been shown to depend on changes in gene expression. Although many studies have focused on the regulation of transcription and translation during learning-related synaptic plasticity, regulated protein degradation provides another common means of altering the macromolecular composition of cells. RESULTS: We have investigated the role of the ubiquitin proteasome system in long-lasting forms of learning-related plasticity in Aplysia sensory-motor synapses. We find that inhibition of the proteasome produces a long-lasting (24 hr) increase in synaptic strength between sensory and motor neurons and that it dramatically enhances serotonin-induced long-term facilitation. The increase in synaptic strength produced by proteasome inhibitors is dependent on translation but not transcription. In addition to the increase in synaptic strength, proteasome inhibition leads to an increase in the number of synaptic contacts formed between the sensory and motor neurons. Blockade of the proteasome in isolated postsynaptic motor neurons produces an increase in the glutamate-evoked postsynaptic potential, and blockade of the proteasome in the isolated presynaptic sensory cells produces increases in neurite length and branching. CONCLUSIONS: We conclude that both pre- and postsynaptic substrates of the ubiquitin proteasome function constitutively to regulate synaptic strength and growth and that the ubiquitin proteasome pathway functions in mature neurons as an inhibitory constraint on synaptic strengthening.

Analysis of Variance↗

PubMed2003

Activation of peroxisome proliferator-activated receptor alpha in human endothelial cells increases plasminogen activator inhibitor type-1 expression.

OBJECTIVE: To investigate the effect of peroxisome proliferator-activated receptors (PPARs) activators on plasminogen activator inhibitor 1 (PAI-1) expression in human umbilical vein endothelial cells and elucidate a possible mechanism. METHODS: Human umbilical vein endothelial cells (HUVECs) were obtained from normal fetus, and cultured conventionally. Then the HUVEC were exposed to fatty acids and prostaglandin J(2) in varying concentrations with fresh media. RT-PCR and ELISA were used to determine the expression of PPAR and PAI-1 in HUVECs. Transient co-transfection of PAI-1 promoter and PPARalpha gene or PPARgamma gene to ECV304 was performed. RESULTS: PPARalpha, PPARdelta and PPARgamma mRNA in HUVECs were detected by RT-PCR. Treatment of HUVECs with PPARalpha and PPARgamma activators-linolenic acid, linoleic acid, oleic acid and prostaglandin J(2), but not with stearic acid could augment PAI-I mRNA expression and protein secretion in a concentration-dependent manner. Proportional induction of PAI-1 promoter activity was observed through increasing amounts of PPARalpha DNA in HUVECs through a transient gene transfection assay, although the mRNA expression of the 3 subtypes of PPAR with their activators were not changed compared with controls. CONCLUSIONS: HUVECs express PPARs. PPARs activators may increase PAI-1 expression in endothelial cells (EC). Although PPARs expression was not enhanced after being stimulated by their activators in EC, the functionally active PPARalpha is probably involved in regulating PAI-1 expression in EC.

Cells, Cultured↗

PubMed2002

Modulation of the readily releasable pool of transmitter and of excitation-secretion coupling by activity and by serotonin at Aplysia sensorimotor synapses in culture.

Short-term homosynaptic depression and heterosynaptic facilitation of transmitter release from mechanoreceptor sensory neurons of Aplysia are involved in habituation and sensitization, respectively, of defensive withdrawal reflexes. We investigated whether synaptic transmission is regulated in these forms of plasticity by means of changes in the size of the pool of transmitter available for immediate release [the readily releasable pool (RRP)] or in the efficacy of release from an unchanging pool. Using sensorimotor synapses formed in cell culture, we estimated the number of transmitter quanta in the RRP from the asynchronous release of neurotransmitter caused by application of a hypertonic bathing solution. Our experiments indicate that the transmitter released by action potentials and by hypertonic solution comes from the same pool. The RRP was reduced after homosynaptic depression of the EPSP by low-frequency stimulation and increased after facilitation of the EPSP by application of the endogenous facilitatory transmitter serotonin (5-HT) after homosynaptic depression. However, although the fractional changes in the RRP and in the EPSP were similar for both synaptic depression and facilitation when depression was induced by repeated hypertonic stimulation, the changes in the EPSP were significantly greater than the changes in the RRP when depression was induced by repeated electrical stimulation. These observations indicate that homosynaptic depression and restoration of depressed transmission by 5-HT are caused by changes in both the amount of transmitter available for immediate release and in processes involved in the coupling of the action potential to transmitter release.

Animals↗

PubMed2002

Enhanced transdermal transport by electroporation using anionic lipids.

Transdermal drug delivery is an attractive approach for either local or systemic treatment in medicine. In the last decade, different active transdermal delivery methods have been further investigated such as cationic liposomal delivery and electroporation-enhanced delivery. In light of gaining a synergistic effect of lipid and electroporation, a new method of using anionic lipids to enhance the transdermal transport of molecules under electroporation is reported here. Heat-stripped porcine epidermis was used for measurement of transdermal transport using an in vitro vertical diffusion apparatus. Lipid vesicles were prepared using a 1:1 mole ratio mixture of 1,2-dioleoyl-3-phosphatidylglycerol (DOPG) and 1,2-dioleoyl-3-phosphatidylcholine (DOPC). When the lipids were mixed with (but not encapsulating) the transport target molecule, the electroporation-induced transport through porcine epidermis was increased as compared to that without the lipids. The enhancement in transport was dependent upon the size and the charge of the transported molecule. Methylene blue (MB), protoporphyrin IX (PpIX) and dimethyl-protoporphyrin IX (DM-PpIX) were used as small target molecules, and FITC-dextrans (4 to 155 kDa) were used as large target molecules in our studies. Enhancement of transport, to varying degree, was observed for all three small molecules (molecular weights <1 kDa), in the presence of DOPG:DOPC vesicles. In the case of large molecules, lipid-enhanced transport was only observed for the 4 kDa dextran, and not for the larger ones (M(w)>10 kDa). Neutral or cationic lipids alone did not enhance the transdermal transport under the electroporation conditions we used.

Animals↗

PubMed2002

Mammalian suppressor of Sec4 modulates the inhibitory effect of Rab15 during early endocytosis.

Rab15 is a novel endocytic Rab that counters the stimulatory effect of Rab5-GTP on early endocytic trafficking. Rab15 may interfere with Rab5 function directly by sequestering Rab5 effectors or indirectly through novel sets of effector interactions. To distinguish between these possibilities, we examined the effector binding properties of Rab15. Rab15 does not interact directly with the Rab5 effectors rabex-5 and rabaptin-5 in a yeast two-hybrid binding assay. Rather mammalian suppressor of Sec4 (Mss4) was identified as a binding partner for Rab15. Mss4 preferentially binds GDP-bound (T22N) and nucleotide-free (N121I) Rab15, consistent with the proposed role of Mss4 as a chaperone that stabilizes target Rabs in their nucleotide-free form. Mutational analysis of Rab15 indicates that lysine at position 48 (K48Q) is important for the binding of Rab15-GDP to Mss4. Moreover, the mutation K48Q counters the inhibitory phenotype of wild type Rab15 on receptor-mediated endocytosis in HeLa cells and homotypic endosome fusion in vitro without altering the relative amount of cell surface-associated transferrin receptor. Together, these data indicate a novel role for Mss4 as an effector for Rab15 in early endocytic trafficking.

Amino Acid Sequence↗

PubMed2002

The increase in plasminogen activator inhibitor type-1 expression by stimulation of activators for peroxisome proliferator-activated receptors in human endothelial cells.

OBJECTIVE: [corrected] To investigate the effect of peroxisome proliferator-activated receptors (PPARs) activators on plasminogen activator inhibitor type-1 (PAI-1) expression in human umbilical vein endothelial cells and the possible mechanism. METHODS: Human umbilical vein endothelial cells (HUVECs) were obtained from normal fetus, and cultured conventionally. Then the HUVECs were exposed to test agents (linolenic acid, linoleic acid, oleic acid, stearic acid and prostaglandin J2 respectively) in varying concentrations with fresh media. RT-PCR and ELISA were applied to determine the expression of PPARs and PAI-1 in HUVECs. RESULTS: PPAR alpha, PPAR beta and PPAR gamma mRNA were detected by using RT-PCR in HUVECs. Treatment of HUVECs with PPARalpha and PPAR gamma activators--linolenic acid, linoleic acid, oleic acid and prostaglandin J2 respectively, but not with stearic acid could augment PAI-1 mRNA expression and protein secretion in a concentration-dependent manner. However, the mRNA expressions of 3 subclasses of PPAR with their activators in HUVECs were not changed compared with controls. CONCLUSION: HUVECs express PPARs. PPARs activators may increase PAI-1 expression in ECs, but the underlying mechanism remains unclear. Although PPARs expression was not enhanced after stimulated by their activators in ECs, the role of functionally active PPARs in regulating PAI-1 expression in ECs needs to be further investigated by using transient gene transfection assay.

Cells, Cultured↗

PubMed2000

[Cloning and Expression of Various Deletants of Gsalpha Gene in Escherichia Coli]

Gsalpha gene mutation has been discovered in some human tumors. In our previous studies, three novel deletants of Gsalpha gene, Gsalpha L-1(500 bp), Gsalpha L-2(300 bp), and Gsalpha L-3(200 bp), and wild type Gsalpha-4(1 200 bp) were found in human leukemia cell lines and detected in leukemic cells from patients with acute leukemia. To investigate the construction, function and biological significance of the deletants, the plasmids of Gsalpha L-1, Gsalpha L-2 and wild Gsalpha-4 were transformed into E. coli DH5, amplified by PCR, and cloned in expression vector pET22b(+), and then transformed into E. coli, respectively. As a result, higher levels of expression of three recombinants were obtained in form of inclusion bodies. The results suggested that these Gsalpha isoforms have an open reading frame of gene and can be expressed in vitro. The data lay a foundation to study the relation of Gsalpha gene to leukemogenesis.

Journal Article↗