The segmentation motor activity of the gut that facilitates absorption of nutrients was first described in the late 19th century, but the fundamental mechanisms underlying it remain poorly ...understood. The dominant theory suggests alternate excitation and inhibition from the enteric nervous system. Here we demonstrate that typical segmentation can occur after total nerve blockade. The segmentation motor pattern emerges when the amplitude of the dominant pacemaker, the slow wave generated by interstitial cells of Cajal associated with the myenteric plexus (ICC-MP), is modulated by the phase of induced lower frequency rhythmic transient depolarizations, generated by ICC associated with the deep muscular plexus (ICC-DMP), resulting in a waxing and waning of the amplitude of the slow wave and a rhythmic checkered pattern of segmentation motor activity. Phase-amplitude modulation of the slow waves points to an underlying system of coupled nonlinear oscillators originating in the networks of ICC.
Better understanding of intrinsic control mechanisms of colonic motility will lead to better treatment options for colonic dysmotility. The aim was to investigate neurogenic and myogenic control ...mechanisms underlying pan-colonic motor patterns.
Analysis of in vitro video recordings of whole rat colon motility was used to explore motor patterns and their spatiotemporal organizations and to identify mechanisms of neurogenic and myogenic control using pharmacological tools.
Study of the pan-colonic spatiotemporal organization of motor patterns revealed: fluid-induced or spontaneous rhythmic propulsive long distance contractions (LDCs, 0.4-1.5/min, involving the whole colon), rhythmic propulsive motor complexes (RPMCs) (0.8-2.5/min, dominant in distal colon), ripples (10-14/min, dominant in proximal colon), segmentation and retrograde contractions (0.1-0.8/min, prominent in distal and mid colon). Spontaneous rhythmic LDCs were the dominant pattern, blocked by tetrodotoxin, lidocaine or blockers of cholinergic, nitrergic or serotonergic pathways. Change from propulsion to segmentation and distal retrograde contractions was most prominent after blocking 5-HT3 receptors. In the presence of all neural blockers, bethanechol consistently evoked rhythmic LDC-like propulsive contractions in the same frequency range as the LDCs, indicating the existence of myogenic mechanisms of initiation and propulsion.
Neurogenic and myogenic control systems orchestrate distinct and variable motor patterns at different regions of the pan-colon. Cholinergic, nitrergic and serotonergic pathways are essential for rhythmic LDCs to develop. Rhythmic motor patterns in presence of neural blockade indicate the involvement of myogenic control systems and suggest a role for the networks of interstitial cells of Cajal as pacemakers.
Abstract
Background
Interstitial cells of Cajal associated with the submuscular plexus (
ICC
‐
SMP
) generate omnipresent slow‐wave activity in the colon and are associated with prominent motor ...patterns. Our aim was to investigate colon motor dysfunction in
W/W
v
mice in which the
ICC
are reportedly reduced.
Methods
Whole organ colon motility was studied using spatio‐temporal mapping; immunohistochemical staining was carried out for c‐Kit and Ano1; calcium imaging was applied to
ICC
‐
SMP
.
Key Results
Discrepancies between Ano1 and c‐Kit staining were found in both wild‐type and
W/W
v
colon.
ICC
‐
SMP
were reduced to ~50% in the
W/W
v
mouse colon according to c‐Kit immunohistochemistry, but Ano1 staining indicated a normal network of
ICC
‐
SMP
. The latter was consistent with rhythmic calcium transients occurring at the submucosal border of the colon in
W/W
v
mice, similar to the rhythmic transients in wild‐type
ICC
‐
SMP
. Furthermore, the motor pattern associated with
ICC
‐
SMP
pacemaking, the so‐called ‘ripples’ were normal in the
W/W
v
colon.
Conclusions & Inferences
c‐Kit is not a reliable marker for quantifying
ICC
‐
SMP
in the mouse colon. Ano1 staining revealed a normal network of
ICC
‐
SMP
consistent with the presence of a normal ‘ripples’ motor pattern. We detected a class of Ano1 positive c‐Kit negative cells that do not depend on Kit expression for maintenance, a feature shared with
ICC
progenitors.
Background
Interstitial cells of Cajal associated with the submuscular plexus (ICC‐SMP) generate omnipresent slow‐wave activity in the colon and are associated with prominent motor patterns. Our aim ...was to investigate colon motor dysfunction in W/Wv mice in which the ICC are reportedly reduced.
Methods
Whole organ colon motility was studied using spatio‐temporal mapping; immunohistochemical staining was carried out for c‐Kit and Ano1; calcium imaging was applied to ICC‐SMP.
Key Results
Discrepancies between Ano1 and c‐Kit staining were found in both wild‐type and W/Wv colon. ICC‐SMP were reduced to ~50% in the W/Wv mouse colon according to c‐Kit immunohistochemistry, but Ano1 staining indicated a normal network of ICC‐SMP. The latter was consistent with rhythmic calcium transients occurring at the submucosal border of the colon in W/Wv mice, similar to the rhythmic transients in wild‐type ICC‐SMP. Furthermore, the motor pattern associated with ICC‐SMP pacemaking, the so‐called ‘ripples’ were normal in the W/Wv colon.
Conclusions & Inferences
c‐Kit is not a reliable marker for quantifying ICC‐SMP in the mouse colon. Ano1 staining revealed a normal network of ICC‐SMP consistent with the presence of a normal ‘ripples’ motor pattern. We detected a class of Ano1 positive c‐Kit negative cells that do not depend on Kit expression for maintenance, a feature shared with ICC progenitors.
c‐Kit is not a reliable marker for quantifying ICC‐SMP in the mouse colon. Ano1 staining revealed a normal network of ICC‐SMP consistent with the presence of a normal ‘ripples’ motor pattern. We detected a class of Ano1 positive c‐Kit negative cells that do not depend on Kit expression for maintenance, a feature shared with ICC progenitors.
Background: Chinese university freshmen receive 4-weeks military training that involved moderate to intense physical exercise. Studies have demonstrated heterogeneous effects of exercise on the ...autonomic nervous system.
Objective: To evaluate the effects of training on the autonomic nervous system noninvasively using electrogastrograms, heart rate variability (HRV), pulse rate, and the sympathetic skin response (SSR).
Methods: Twenty freshmen received all assessments in the fasting state and after a standard meal: (1) one week before the training, (2) at the end of the second week of the training, and (3) one week after the training.
Results: (1) The training had a significant effect on meal-induced gastric pacemaker activity. Before the training, a standard meal did not increase the dominant frequency of gastric slow waves, but the frequency increased during and after the training; (2) The preprandial high frequency (HF), low frequency (LF), and very low frequency (VLF) components of heart rate variability decreased significantly after the training. The ratio of the LF and HF (LF/HF) of the heart rate variability (HRV) did not significantly change after a meal or training condition. The basal pulse rate did not change. The latencies of the sympathetic skin response (SSR), as measured in the arm muscle, increased in response to the training.
Conclusion: Military training affects meal-induced changes in gastric pacemaker activity, causes a marked reduction of the vagal tone to the heart with maintenance of the vagal-sympathetic balance, and its effects on SSR may reflect a reduction in sympathetic tone.
Oat is an annual gramineous forage grass with the remarkable ability to survive under various stressful environments. However, understanding the effects of high altitude stresses on oats is poor. ...Therefore, the physiological and the transcriptomic changes were analyzed at two sites with different altitudes, low (ca. 2,080 m) or high (ca. 2,918 m), respectively. Higher levels of antioxidant enzyme activity, reactive oxygen and major reductions in photosynthesis-related markers were suggested for oats at high altitudes. Furthermore, oat yields were severely suppressed at the high altitude. RNA-seq results showed that 11,639 differentially expressed genes were detected at both the low and the high altitudes in which 5,203 up-regulated and 6,436 down-regulated. Gene Ontology and Kyoto Encyclopedia of Genes and Genomes pathway enrichment tests were conducted and a group of major high altitude-responsive pigment metabolism genes, photosynthesis, hormone signaling, and cutin, suberine and wax biosynthesis were excavated. Using quantitative real-time polymerase chain response, we also confirmed expression levels of 20 DEGs (qRT-PCR). In summary, our study generated genome-wide transcript profile and may be useful for understanding the molecular mechanisms of
Avena sativa
L. in response to high altitude stress. These new findings contribute to our deeper relevant researches on high altitude stresses and further exploring new candidategenes for adapting plateau environment oat molecular breeding.
Land use change obviously changes the plant community composition and soil properties of grasslands and thus affects multiple functions and services of grassland ecosystems. However, the response ...mechanisms of soil microorganisms, key drivers of the nutrient cycle and other soil functions during changes in grassland use type and associated vegetation are not well understood. In this study, Illumina high-throughput sequencing was used to analyze the changes in the soil microbial community structure of four grassland use types: exclosure (EL), mowed land (ML), grazed land (GL), and farmland (FL) in the Songnen Plain of Northeast China. The results showed that the FL and EL had significantly higher soil total nitrogen (TN) and lower soil electrical conductivity (EC) and pH than GL and ML. In contrast, the GL and ML had higher soil bulk density (BD) and organic matter, respectively, than the other land use types. In addition, the values of the Shannon diversity and Pielou’s evenness indexes were highest in the EL of all the land use types. Based on the high-throughput sequencing results, we observed high levels of α diversity in the FL for both bacteria and fungi. A structural equation model (SEM) revealed that pH and EC had a direct and positive effect on the bacterial community structure and composition. In addition, plant taxonomic diversity (according to the Shannon diversity and Pielou’s evenness indexes) indirectly affected the bacterial community composition via soil pH and EC. Notably, fungal composition was directly and positively correlated with soil nutrients and the value of Pielou’s evenness index changed with land use type. In conclusion, soil properties and/or plant diversity might drive the changes in the soil microbial community structure and composition in different grassland use types.
The rapid urbanization in China has already put heavy pressures on imperfect infrastructure, especially for fundamental urban functions such as power and water supply, traffic, education, and ...healthcare. The emergence of smart cities can help cope with the rapidly expanding demands on urban infrastructure. However, the development of smart cities in China is just in its infancy, and there is still a lack of clear understanding of the development path of smart cities. This article focuses on the development of smart cities in China. It aims to (a) judge whether there is spatial autoregression in the construction of smart cities in 83 Chinese cities and (b) identify key influencing factors in the development of smart cities in China through a spatial econometric model developed by GeoDa software. The results show that there exists spatial autoregression in the development of smart cities in China. Four key influencing factors (governmental support, innovative level, economic development, and human capital) are identified. Based on these findings, suggestions for future promoting development of smart cities in China are put forward. This research can deepen the understanding of the spatial effects of smart cities and provide valuable decision-making references for policy makers.
Type H vessels have recently been identified to modulate osteogenesis. Epoxyeicostrioleic acids (EETs) have an essential contribution to vascular homeostasis. However, whether increased EETs with ...soluble epoxide hydrolase (sEH) inhibitor TPPU enhance the coupling of angiogenesis and osteogenesis remains largely unknown. The effects of TPPU on cross‐talk between co‐cultured human umbilical vein endothelial cells (HUVECs) and human dental pulp stem cells (hDPSCs), and on long bone growth and calvarial defect repair in mice were investigated in vitro and in vivo. TPPU enhanced osteogenic differentiation of co‐cultured HUVECs and hDPSCs in vitro and increased type H vessels, and long bone growth and bone repair of calvarial defect. Mechanistically, TPPU promoted cell proliferation and angiogenesis, reclined cell apoptosis, and significantly increased CD31hiEMCNhi endothelial cells (ECs) and SLIT3 and HIF‐1α expression levels in co‐cultured HUVECs and hDPSCs. Knockdown of Slit3 in hDPSCs or Hif‐1α in HUVECs impaired the formation of CD31hiEMCNhi ECs and reversed TPPU‐induced osteogenesis. We defined a previously unidentified effect of TPPU coupling angiogenesis and osteogenesis. TPPU induced type H vessels by upregulating the expression of hDPSCs‐derived SLIT3, which resulted in the activation of ROBO1/YAP1/HIF‐1α signalling pathway in ECs. Targeting metabolic pathways of EETs represents a new strategy to couple osteogenesis and angiogenesis, sEH is a promising therapeutic target for bone regeneration and repair.
TPPU increases endogenous epoxyeicostrioleic acids (EETs) by inhibiting soluble epoxide hydrolase (sEH). Then, the increased EETs upregulate the expression of SLIT3 in mesenchymal stem cells (MSCs), which results in the activation of ROBO1/YAP1/HIF‐1α signalling pathway in endothelial cells (ECs) and induces type H vessels with high specific expression of CD31 and endomucin (EMCN). Type H vessels promote the cross‐talk between ECs and MSCs and modulate osteogenesis. Thus, targeting metabolic pathways of EETs represents a new strategy to couple osteogenesis and angiogenesis, sEH is a potential therapeutic target for bone repair and regeneration.
CC chemokine receptor 9 (CCR9), an organ-specific chemokine receptor, interacts with its exclusive ligand CCL25 to promote tumor proliferation and metastasis. However, the effect of CCR9 on salivary ...adenoid cystic carcinoma (SACC) malignant behavior remains unknown. This study aimed to investigate the specific molecular mechanism by which CCR9/CCL25 modulates malignant progression in SACC.
Immunohistochemistry staining and RT-qPCR analyses were performed to detect the correlation of CCR9 expression and tumor progression-associated markers in SACC.
, SACC cell proliferation and apoptosis were evaluated using Cell Counting Kit-8 and colon formation, and cell migration and invasion were detected by wound healing and transwell assays. Vercirnon was used as an inhibitor of CCR9, and LY294002 was used as an inhibitor of the PI3K/AKT pathway in this study. Western blot and RT-qPCR assays were carried out to measure the downstream factors of the interaction of CCL25 and CCR9. The effect of CCL25 on the development of SACC
was examined by a xenograft tumor model in nude mice following CCL25, Vercirnon and LY294002 treatment.
CCR9 was highly expressed in SACC compared with adjacent salivary gland tissues, and its level was associated with tumor proliferation and metastases. CCL25 enhanced cell proliferation, migration, and invasion through its interaction with CCR9 and exerted an antiapoptotic effect on SACC cells. Targeting CCR9
Vercirnon significantly reduced the phosphorylation level of AKT induced by CCL25. CCL25/CCR9 could activate its downstream factors through the PI3K/AKT signaling pathway, such as cyclin D1, BCL2 and SLUG, thus promoting SACC cell proliferation, antiapoptosis, invasion and metastasis. The
data from the xenograft mouse models further proved that CCL25 administration promoted malignant tumor progression by activating the PI3K/AKT pathway.
The interaction of CCL25 and CCR9 promotes tumor growth and metastasis in SACC by activating the PI3K/AKT signaling pathway, offering a promising strategy for SACC treatment.
PDF
