Dorsal motor nucleus of the vagus: a site for evoking simultaneous changes in crural diaphragm activity, lower esophageal sphincter pressure, and fundus tone

The sphincter mechanism at the esophagogastric junction includes smooth muscle of the lower esophagus and skeletal muscle of the crural diaphragm (CD). Smooth muscle is known to be under the control of the dorsal motor nucleus of the vagus (DMV), while central nervous system (CNS) control of the CD is unknown. The main purposes of our study were to determine the CNS site that controls the CD and whether simultaneous changes in lower esophageal sphincter (LES) pressure and CD activity occur when this site is activated. Experiments were performed on anesthetized male ferrets whose LES pressure, CD activity, and fundus tone were monitored. To activate DMV neurons, L-glutamate was microinjected unilaterally into the DMV at three areas: intermediate, rostral, and caudal. Stimulation of the intermediate DMV decreased CD activity (-4.8 +/- 0.1 bursts/min and -0.3 +/- 0.01 mV) and LES pressure (-13.2 +/- 2.0 mmHg; n = 9). Stimulation of this brain site also produced an increase in fundus tone. Stimulation of the rostral DMV elicited increases in the activity of all three target organs (n = 5). Stimulation of the caudal DMV had no effect on the CD but did decrease both LES pressure and fundus tone (n = 5). All changes in LES pressure, fundus tone, and some DMV-induced changes in CD activity (i.e., bursts/min) were prevented by ipsilateral vagotomy. Our data indicate that simultaneous changes in activity of esophagogastric sphincters and fundus tone occur from rostral and intermediate areas of the DMV and that these changes are largely mediated by efferent vagus nerves.     

Characterization of noradrenergic transmission at the dorsal motor nucleus of the vagus involved in reflex control of fundus tone

Quantitative analysis of innervation to dorsal motor nucleus of the vagus (DMV) fundus-projecting neurons indicates that approximately 17% of input neurons are noradrenergic. To determine whether this small percentage of neurons innervating DMV output to the stomach is physiologically relevant, we evaluated the role of norepinephrine at the DMV in mediating a vagovagal reflex controlling the fundus. A strain gauge was sutured onto the fundus of isoflurane-anesthetized rats to monitor changes in tone evoked by esophageal distension (ED). ED produced a decrease in fundus tone of 0.31 +/- 0.02 g (P < 0.05), which could be reproduced after a 30-min interval between distensions. Bilateral cervical vagotomy and/or pretreatment with intravenous atropine methylbromide prevented the reflex-induced fundus relaxation. In contrast, intravenous N(G)-nitro-L-arginine methyl ester had no effect. Bilateral microinjection of alpha2-adrenoreceptor antagonists (yohimbine and RS-79948) into the DMV also prevented the response. Before microinjection of alpha2-adrenoreceptor antagonists, ED decreased fundus tone by 0.33 +/- 0.05 g (P < 0.05). After antagonist microinjection, ED decreased fundus tone by only 0.05 +/- 0.06 g (P > 0.05). Bilateral microinjection of prazosin into the DMV had no effect on the response. Microinjection of norepinephrine into the DMV mimicked the effect of ED and was also prevented by prior microinjection of an alpha2-adrenoreceptor antagonist. Our results indicate that noradrenergic innervation of DMV fundus-projecting neurons is physiologically important and suggest that norepinephrine released at the DMV acts on alpha2-adrenoreceptors to inhibit activity in a cholinergic-cholinergic excitatory pathway to the fundus.     

CAR T-cells for cancer therapy

Chimeric antigen receptor (CAR) T-cells are redirected T-cells that can recognize cancer antigens in a major histocompatibility complex (MHC)-independent fashion. A typical CAR is comprised of two main functional domains: an extracellular antigen recognition domain, called a single-chain variable fragment (scFv), and an intracellular signaling domain. Based on the number of intracellular signaling molecules, CARs are categorized into four generations. CAR T-cell therapy has become a promising treatment for hematologic malignancies. However, results of its clinical trials on solid tumors have not been encouraging. Here, we described the structure of CARs and summarized the clinical trials of CD19-targeted CAR T-cells. The side effects, safety management, challenges, and future prospects of CAR T-cells for the treatment of cancer, particularly for solid tumors, were also discussed.     

Are Cystic Fibrosis <Emphasis Type="Italic">Aspergillus fumigatus</Emphasis> Isolates Different? Intermicrobial Interactions with <Emphasis Type="Italic">Pseudomonas</Emphasis>

Pseudomonas aeruginosa and Aspergillus fumigatus are the leading bacterial and fungal pathogens in cystic fibrosis (CF). We have shown that Af biofilms are susceptible to Pseudomonas, particularly CF phenotypes. Those studies were performed with a reference virulent non-CF Aspergillus. Pseudomonas resident in CF airways undergo profound genetic and phenotypic adaptations to the abnormal environment. Studies have also indicated Aspergillus from CF patients have unexpected profiles of antifungal susceptibility. This would suggest that Aspergillus isolates from CF patients may be different or altered from other clinical isolates. It is important to know whether Aspergillus may also be altered, as a result of that CF environment, in susceptibility to Pseudomonas. CF Aspergillus proved not different in that susceptibility.     

Glucose does not activate nonadrenergic, noncholinergic inhibitory neurons in the rat stomach

We reported previously that intravenously administered d-glucose acts in the central nervous system to inhibit gastric motility induced by hypoglycemia in anesthetized rats. The purpose of this study was to determine whether this effect is due to inhibition of dorsal motor nucleus of the vagus (DMV) cholinergic motoneurons, which synapse with postganglionic cholinergic neurons, or to excitation of DMV cholinergic neurons, which synapse with postganglionic nonadrenergic, noncholinergic (NANC) neurons, particularly nitrergic neurons. Three approaches were employed: 1) assessment of the efficacy of d-glucose-induced inhibition of gastric motility in hypoglycemic rats with and without inhibition of nitric oxide synthase [10 mg/kg iv nitro-l-arginine methyl ester (l-NAME)], 2) assessment of the efficacy of intravenous bethanechol (30 mug.kg(-1).min(-1)) to stimulate gastric motility in hypoglycemic rats during the time of d-glucose-induced inhibition of gastric motility, and 3) determination of c-Fos expression in DMV neurons after intravenous d-glucose was administered to normoglycemic rats. Results obtained demonstrated that l-NAME treatment had no effect on d-glucose-induced inhibition of gastric motility; there was no reduction in the efficacy of intravenous bethanechol to increase gastric motility, and c-Fos expression was not induced by d-glucose in DMV neurons that project to the stomach. These findings indicate that excitation of DMV cholinergic motoneurons that synapse with postganglionic NANC neurons is not a significant contributing component of d-glucose-induced inhibition of gastric motility.     

Relationship between blood pressure,sleep K-complexes,and muscle sympathetic nerve activity in humans

Stage 2 sleep is characterized by the EEG appearance of "K-complexes" and blood pressure oscillations. K-complexes may be directly related to blood pressure changes or they may reflect central sympathetic activation. We analyzed the temporal relationship among K-complexes, heart rate (HR), blood pressure (BP), and muscle sympathetic nerve activity (MSNA) during sleep in eight healthy volunteers (3 men and 5 women, age 22-41 yr). Most K-complexes presented as single large complexes (56 +/- 20%), followed by single small complexes (15 +/- 14%) and as couplets or triplets (13 +/- 6%). Single large K-complexes were preceded by a baroreflex-mediated increase of MSNA in approximately one-half (55%) of the cases. Detailed analysis of HR, BP, and MSNA was possible in 63 (45%) large single K-complexes not disturbed by preceding baroreflex-related changes. Systolic and diastolic BP and MSNA increased significantly after single events (22.5 +/- 13, 5.2 +/- 2.1, and 6.5 +/- 3.0%). Mean sympathetic baroreflex latency was similar after the single large K-complexes compared with the mean value during stage 2 sleep (1,290 +/- 126 vs. 1,279 +/- 61 ms). The area under the burst was significantly increased after single large K-complexes (median 3.9 vs. 9.0 arbitrary units, P < 0.03). The results support the hypothesis that K-complexes express cortical activation leading to temporary facilitation of sympathetic outflow in a graded fashion. Their functional effects appear to be independent of baroreflex modulation of MSNA in approximately 50% of the cases.     

Efficiency of different types of biochars to mitigate Cd stress and growth of sunflower (Helianthus; L.) in wastewater irrigated agricultural soil

Cadmium contamination in croplands is recognized one of the major threat, seriously affecting soil health and sustainable agriculture around the globe. Cd mobility in wastewater irrigated soils can be curtailed through eco-friendly and cost effective organic soil amendments (biochars) that eventually minimizes its translocation from soil to plant. This study explored the possible effects of various types of plants straw biochar as soil amendments on cadmium (Cd) phytoavailability in wastewater degraded soil and its subsequent accumulation in sunflower tissues. The studied biochars including rice straw (RS), wheat straw (WS), acacia (AC) and sugarcane bagasse (SB) to wastewater irrigated soil containing Cd. Sunflower plant was grown as a test plant and Cd accumulation was recorded in its tissues, antioxidant enzymatic activity chlorophyll contents, plant biomass, yield and soil properties (pH, NPK, OM and Soluble Cd) were also examined. Results revealed that addition of biochar significantly minimized Cd mobility in soil by 53.4%, 44%, 41% and 36% when RS, WS, AC and SB were added at 2% over control. Comparing the control soil, biochar amended soil effectively reduced Cd uptake via plants shoots by 71.7%, 60.6%, 59% and 36.6%, when RS, WS, AC and SB. Among all the biochar, rice husk induced biochar significantly reduced oxidative stress and reduced SOD, POD and CAT activity by 49%, 40.5% and 46.5% respectively over control. In addition, NPK were significantly increased among all the added biochars in soil–plant system as well as improved chlorophyll contents relative to non-bioachar amended soil. Thus, among all the amendments, rice husk and wheat straw biochar performed well and might be considered the suitable approach for sunflower growth in polluted soil.     

Synchronization of Boron application methods and rates is environmentally friendly approach to improve quality attributes of Mangifera indica L. On sustainable basis

Micronutrient deficiency in the soil is one of the major causes of mango fruit and yield's poor quality. Besides, the consumption of such a diet also causes a deficiency of micronutrients in humans. Boron deficiency adversely affects the flowering and pollen tube formation, thus decreasing mango yield and quality attributes. Soil and foliar application of B are considered a productive method to alleviate boron deficiency. A field experiment was conducted to explore the Boron most suitable method and application rate in mango under the current climatic scenario. There were nine treatments applied in three replications. The results showed that application of T8 = RD + Borax (75 g plant ^-1 as a basal application) + H₃ BO₃ (0.8% as a foliar spray) and T9 = RD + Borax (150 g plant ^-1 as a basal application) + H₃ BO₃ (0.8% as a foliar spray) significantly enhanced the nitrogen, potassium, proteins, ash, fats, fiber, and total soluble solids in mango as compared to the control. A significant decrease in sodium, total phenolics contents, antioxidant activity, and acidity as citric acid also validated the effective functioning of T8 = RD + Borax (75 g plant ^-1 as a basal application) + H₃ BO₃ (0.8% as a foliar spray) and T9 = RD + Borax (150 g plant ^-1 as a basal application) + H₃ BO₃ (0.8% as a foliar spray) as compared to control. In conclusion, T8 = RD + Borax (75 g plant ^-1 as a basal application) + H₃ BO₃ (0.8% as a foliar spray) and T9 = RD + Borax (150 g plant ^-1 as a basal application) + H₃ BO₃ (0.8% as a foliar spray) is a potent strategy to improve the quality attributes of mango under the changing climatic situation.