Nodal signaling patterns the organizer

Development ◽  
2000 ◽  
Vol 127 (5) ◽  
pp. 921-932 ◽  
Author(s):  
K. Gritsman ◽  
W.S. Talbot ◽  
A.F. Schier

Spemann's organizer plays an essential role in patterning the vertebrate embryo. During gastrulation, organizer cells involute and form the prechordal plate anteriorly and the notochord more posteriorly. The fate mapping and gene expression analyses in zebrafish presented in this study reveal that this anteroposterior polarity is already initiated in the organizer before gastrulation. Prechordal plate progenitors reside close to the blastoderm margin and express the homeobox gene goosecoid, whereas notochord precursors are located further from the margin and express the homeobox gene floating head. The nodal-related genes cyclops and squint are expressed at the blastoderm margin and are required for prechordal plate and notochord formation. We show that differential activation of the Nodal signaling pathway is essential in establishing anteroposterior pattern in the organizer. First, overexpression of cyclops and squint at different doses leads to the induction of floating head at low doses and the induction of both goosecoid and floating head at higher doses. Second, decreasing Nodal signaling using different concentrations of the antagonist Antivin inhibits goosecoid expression at low doses and blocks expression of both goosecoid and floating head at higher doses. Third, attenuation of Nodal signaling in zygotic mutants for the EGF-CFC gene one-eyed pinhead, an essential cofactor for Nodal signaling, leads to the loss of goosecoid expression and expansion of floating head expression in the organizer. Concomitantly, cells normally fated to become prechordal plate are transformed into notochord progenitors. Finally, activation of Nodal signaling at different times suggests that prechordal plate specification requires sustained Nodal signaling, whereas transient signaling is sufficient for notochord development. Together, these results indicate that differential Nodal signaling patterns the organizer before gastrulation, with the highest level of activity required for anterior fates and lower activity essential for posterior fates.

1989 ◽  
Vol 61 (03) ◽  
pp. 463-467 ◽  
Author(s):  
G M Smith

SummaryIn this study, 5-hydroxytryptamine (5-HT) caused a dose- dependent fall in the circulating platelet count suggesting that 5-HT receptors are activated in rat platelets to cause platelet adhesion and aggregation. When low doses of adenosine diphosphate (ADP) were simultaneously injected with 5-HT, there was a significant potentiation of the responses to ADR Ketanserin significantly reduced the potentiated responses. When higher doses of ADP were infused with bolus injections of 5-HT there was no potentiation and ketanserin did not reduce these responses. Ketanserin did not inhibit the collagen-induced fall in circulating platelet count, but did significantly increase the rate of return to the basal platelet count compared with control. 5-HT did not cause a fall in platelet count in guinea-pigs


1984 ◽  
Vol 102 (3) ◽  
pp. 381-386 ◽  
Author(s):  
R. Gross ◽  
P. Mialhe

ABSTRACT To elucidate the hypolipacidaemic effect of insulin in ducks, its action on the uptake of free fatty acids (FFA) by duck hepatocytes was determined. At low doses (10 mu./l) insulin stimulated FFA uptake. This effect was not observed with higher doses of insulin (20, 30 and 50 mu./l). Growth hormone at physiological concentrations and corticosterone (14·4 nmol/l) decreased basal activity, probably by reducing glucose metabolism and consequently α-glycerophosphate (α-GP) supply. Insulin was able to reverse the inhibition induced by GH and corticosterone on both FFA uptake and α-GP production. These results therefore suggest that the hypolipacidaemic effect of insulin may be partly mediated by its action on hepatic FFA uptake. J. Endocr. (1984) 102, 381–386


2011 ◽  
Vol 26 (6) ◽  
pp. 508-513 ◽  
Author(s):  
Patrícia Gomes da Silva ◽  
Daniele Cristina Cataneo ◽  
Fernanda Leite ◽  
Erica Nishida Hasimoto ◽  
Guilherme Antonio Moreira de Barros

PURPOSE: To compare analgesia traditionally used for thoracic sympathectomy to intrapleural ropivacaine injection in two different doses. METHODS: Twenty-four patients were divided into three similar groups, and all of them received intravenous dipyrone. Group A received intravenous tramadol and intrapleural injection of saline solution. Group B received intrapleural injection of 0.33% ropivacaine, and Group C 0.5% ropivacaine. The following aspects were analyzed: inspiratory capacity, respiratory rate and pain. Pain was evaluated in the immediate postoperative period by means of the visual analog scale and over a one-week period. RESULTS: In Groups A and B, reduced inspiratory capacity was observed in the postoperative period. In the first postoperative 12 hours, only 12.5% of the patients in Groups B and C showed intense pain as compared to 25% in Group A. In the subsequent week, only one patient in Group A showed mild pain while the remainder reported intense pain. In Group B, half of the patients showed intense pain, and in Group C, only one presented intense pain. CONCLUSION: Intrapleural analgesia with ropivacaine resulted in less pain in the late postoperative period with better analgesic outcomes in higher doses, providing a better ventilatory pattern.


Vaccination failure is one of the major constraints to disease control in poultry. To investigate Infectious bursa disease (IBD)-vaccination failures (frequently/globally reported), batches of the Nigerian live-vaccine were tested for viral units before vaccinating following chick-groups: 16 doses (65,536 units), 8 doses (32,768 units), 4 doses (6,384 units), 2 doses (8,192 units), 1 dose (4,096 units), 1:2 dose (2,048 units), 1:4 dose (1,024 units), 1:8 dose (512 units), 1:16 dose (256 units) and control. Each batch gave 4,096 viral units. Mean bursa weight/body weight ratios (immune stimulation) and mean antibody titres of the chick-groups were 47.40 ±5.45 and 51.20 ±7.83; 44.25 ±7.28 & 48.00 ±9.24; 45.25 ± 4.28 and 64.00 ± 0.00; 43.00 ±7.58 and 101.60 ± 35.05; 44.60 ± 5.51 and 128.00 ± 0.00; 42.60 ± 6.23 and 268.80 ± 16.00; 40.50 ± 1.76 and 80.00 ±16.00; 31.40 ± 3.80 and 80.00 ± 27.71; 37.18 ± 4.07 and 89.60 ± 15.68 and 26.20 ± 3.31 and 19.20 ± 5.99, respectively. Half (2,048 units) of the recommended 1-dose gave optimal antibody-titre. The higher doses gave lower antibody-titres like the lower doses but immune stimulation continued to increase as doses/units increased. Both over-stimulating the immune system (too high vaccine-doses/viral-units/viral-virulence) and under-stimulation cause vaccination failure.


Author(s):  
Sudipta Dakua ◽  
Rakesh Gawaly ◽  
Pratyush Jain ◽  
Alok Pal Jain

The present study was designed to authenticate the anti-anxiety activity (by using elevated plus maze model) of methanolic extract of the leaves of Gentiana diffusa. by authors Swiss Albino mice were treated with different doses of the leaf extracts (200 mg / kg p.o.) and Diazepam (2mg/ kg, p.o) was used as a positive control. Results of study show that methanolic extract in higher doses (200 mg/kg) possesses marked anti-anxiety activity and was comparable to the effect produced by diazepam. The plant can be developed as a commercial source of anxiolytic agent. Further studies are in process to isolate the active constituent responsible for this activity and mechanism of action. Keywords: Leaves, Methanol, Anxiety, Diazepam


2018 ◽  
Vol 29 (3) ◽  
pp. 241-246 ◽  
Author(s):  
Augusto P.I. Gargiulo ◽  
María P. Gargiulo De Aranda ◽  
Mercedes M.L. Gargiulo ◽  
Angel J.M. Gargiulo ◽  
Andres Acuña ◽  
...  

AbstractBackground:In previous studies, we have observed that specificN-methyl-d-aspartic acid (NMDA) antagonists and non-NMDA antagonists injected within the nucleus accumbens septi (NAS) induced an anxiolytic-like effect in the plus maze test in rats. In the present study, the effect of intracanalicular blockade of NMDA receptors using dizocilpine in the plus maze was studied in male rats bilaterally cannulated NAS.Methods:Rats were divided into five groups that received either 1 μL injections of saline or dizocilpine (MK-801, [5R,10S]-[+]-5-methyl-10,11-dihydro-5H-dibenzo [a,d] cyclohepten-5,10-imine) in different doses (0.5, 1, 2, or 4 μg) 15 min before testing.Results:Time spent in the open arm increased under dizocilpine treatment with the two higher doses (2 and 4 μg, p<0.05), extreme arrivals were increased by the three higher doses (1 μg, p<0.05; 2 and 4 μg, p<0.01), and open arm entries by the three higher doses (1, 2, and 4 μg, p<0.05). A dose-effect relationship was observed in all cases.Conclusions:We conclude that dizocilpine-glutamatergic blockade in the accumbens lead to an anxiolytic-like effect and a behavioral disinhibition related to an increase in some motoric parameters, showing specific behavioral patterns.


Development ◽  
1993 ◽  
Vol 118 (2) ◽  
pp. 499-507 ◽  
Author(s):  
H. Steinbeisser ◽  
E.M. De Robertis ◽  
M. Ku ◽  
D.S. Kessler ◽  
D.A. Melton

In this study, we compare the effects of three mRNAs-goosecoid, activin and Xwnt-8- that are able to induce partial or complete secondary axes when injected into Xenopus embryos. Xwnt-8 injection produces complete secondary axes including head structures whereas activin and goosecoid injection produce partial secondary axes at high frequency that lack head structures anterior to the auditory vesicle and often lack notochord. Xwnt-8 can activate goosecoid only in the deep marginal zone, i.e., in the region in which this organizer-specific homeobox gene is normally expressed on the dorsal side. Activin B mRNA, however, can turn on goosecoid in all regions of the embryo. We also tested the capacity of these gene products to restore axis formation in embryos in which the cortical rotation was blocked by UV irradiation. Whereas Xwnt-8 gives complete rescue of anterior structures, both goosecoid and activin give partial rescue. Rescued axes including hindbrain structures up to level of the auditory vesicle can be obtained at high frequency even in the absence of notochord structures. The possible functions of Wnt-like and activin-like signals and of the goosecoid homeobox gene, and their order of action in the formation of Spemann's organizer are discussed.


Development ◽  
2002 ◽  
Vol 129 (13) ◽  
pp. 3055-3065 ◽  
Author(s):  
Juliette Mathieu ◽  
Anukampa Barth ◽  
Frederic M. Rosa ◽  
Stephen W. Wilson ◽  
Nadine Peyriéras

Despite its evolutionary conservation and functional importance, little is known of the signaling pathways that underlie development of the hypothalamus. Although mutations affecting Nodal and Hedgehog signaling disrupt hypothalamic development, the time and site of action and the exact roles of these pathways remain very poorly understood. Unexpectedly, we show here that cell-autonomous reception of Nodal signals is neither required for the migration of hypothalamic precursors within the neural plate, nor for further development of the anterior-dorsal hypothalamus. Nodal signaling is, however, cell-autonomously required for establishment of the posterior-ventral hypothalamus. Conversely, Hedgehog signaling antagonizes the development of posterior-ventral hypothalamus, while promoting anterior-dorsal hypothalamic fates. Besides their distinct roles in the regionalization of the diencephalon, we reveal cooperation between Nodal and Hedgehog pathways in the maintenance of the anterior-dorsal hypothalamus. Finally we show that it is the prechordal plate and not the head endoderm that provides the early signals essential for establishment of the hypothalamus.


Author(s):  
Joshua Bodie

This chapter summarizes the results of a landmark trial comparing different doses of oral sildenafil versus placebo to treat erectile dysfunction. Patients received either an identical placebo or 25- mg, 50-mg, or 100-mg tablets of sildenafil to be taken approximately one hour before planned sexual activity (but not more than once daily) for 24 weeks. Higher doses of sildenafil resulted in higher mean score for frequency of penetration and maintenance of erection, which were also consistently better than placebo. The most common side effects were headaches, flushing, dyspepsia, rhinitis, and visual disturbances. This study established sildenafil as an effective, reasonably well-tolerated treatment for men with erectile dysfunction of varying etiologies.


1966 ◽  
Vol 52 (3) ◽  
pp. 177-185
Author(s):  
Aurelio Di Marco ◽  
Rosella Silvestrini ◽  
Emidio Calendi

The possibility that the «in vivo» treatment with heterologous albumin coupled with diazotized acriflavine may affect the sensitivity of lymphoid cells to the action of acriflavine was studied. Albino mice CFW strain were treated subcutanceusly with the coupled albumin in the presence of complete Freund adjuvant. Lymph nodes from control and immunized animals, fifteen days after the treament, were cultured «in vitro» in the presence of different doses of acriflavine (from 0.5 to 4 μg/ml). The action of acriflavine was evaluated as the growth of cultures, the percent of lymphoid cells in the different phases of differentiation and the percent of proliferating cells after incubation for 24 hours in the presence of 3H thymidine. Results show that lymphoid cells of immunized mice are less sensitive to the citotoxic activity of acriflavine than those of the controls. Acriflavine, at low doses, reduces the growth of normal cultures and the proliferative activity of immature elements. At the highest doses the proliferation area is almost completely absent and the elements still present are strongly degenerated. Acriflavine, at the concentration able to reduce or to inhibit the growth of control cultures, is ineffective in altering the ratio of immature elements in cultures of immunized animals. The ability of these elements to incorporate 3H thymidine is also unchanged.


Sign in / Sign up

Export Citation Format

Share Document