Topography of Thalamic Projections Requires Attractive and Repulsive Functions of Netrin-1 in the Ventral Telencephalon

Recent studies have demonstrated that the topography of thalamocortical (TC) axon projections is initiated before they reach the cortex, in the ventral telencephalon (VTel). However, at this point, the molecular mechanisms patterning the topography of TC projections in the VTel remains poorly understood. Here, we show that a long-range, high-rostral to low-caudal gradient of Netrin-1 in the VTel is required in vivo for the topographic sorting of TC axons to distinct cortical domains. We demonstrate that Netrin-1 is a chemoattractant for rostral thalamic axons but functions as a chemorepulsive cue for caudal thalamic axons. In accordance with this model, DCC is expressed in a high-rostromedial to low-caudolateral gradient in the dorsal thalamus (DTh), whereas three Unc5 receptors (Unc5A–C) show graded expression in the reverse orientation. Finally, we show that DCC is required for the attraction of rostromedial thalamic axons to the Netrin-1–rich, anterior part of the VTel, whereas DCC and Unc5A/C receptors are required for the repulsion of caudolateral TC axons from the same Netrin-1–rich region of the VTel. Our results demonstrate that a long-range gradient of Netrin-1 acts as a counteracting force from ephrin-A5 to control the topography of TC projections before they enter the cortex

Modes of Action of Microbially-Produced Phytotoxins

Some of the most potent phytotoxins are synthesized by microbes. A few of these share molecular target sites with some synthetic herbicides, but many microbial toxins have unique target sites with potential for exploitation by the herbicide industry. Compounds from both non-pathogenic and pathogenic microbes are discussed. Microbial phytotoxins with modes of action the same as those of commercial herbicides and those with novel modes of action of action are covered. Examples of the compounds discussed are tentoxin, AAL-toxin, auscaulitoxin aglycone, hydantocidin, thaxtomin, and tabtoxin

Sildenafil added to sitaxsentan in overcirculation-induced pulmonary arterial hypertension.

Experimental left-to-right shunt-induced pulmonary arterial hypertension (PAH) can be partially prevented by the endothelin-A receptor blocker sitaxsentan or by the phosphodiesterase-5 inhibitor sildenafil. We hypothesized that the combined administration of these drugs would completely prevent shunt-induced PAH, arguing in favor of a major role of endothelial dysfunction in the initiation of the disease. Twenty-four 3-wk-old piglets were randomized to a sham operation or to placebo, sitaxsentan therapy, or sitaxsentan combined with sildenafil after the anastomosis of the left subclavian artery to the pulmonary arterial trunk. Three months later, the animals underwent a hemodynamic evaluation, followed by pulmonary tissue sampling for morphometry and quantitative real-time PCR for endothelin-1, angiopoietin-1, and bone morphogenetic protein receptor (BMPR) signaling molecules. Three months of left-to-right shunting induced an increase in pulmonary vascular resistance (PVR) and medial thickness, an overexpression of endothelin-1, and angiopoietin-1 and decreased expressions of BMPR-2 and BMPR-1A. Sitaxsentan partially prevented a shunt-induced increase in PVR, medial thickness, and associated biological disturbances. Sildenafil combined with sitaxsentan normalized PVR, medial thickness, and the expression of endothelin-1. However, the expression of angiopoietin-1 remained increased, and the expressions of BMPR-1A and BMPR-2 were incompletely returned to normal. The coupling of right ventricular end-systolic to arterial elastances was maintained in all circumstances. Sitaxsentan combined with sildenafil prevents shunt-induced PAH more effectively than sitaxsentan alone, suggesting a major role for the targeted signaling pathways in the initiation of the disease. Sitaxsentan alone or combined with sildenafil did not affect right ventricular function.Journal ArticleResearch Support, Non-U.S. Gov'tSCOPUS: ar.jinfo:eu-repo/semantics/publishe

INTERMEDIATE INFORMATION, LOSS AVERSION, AND EFFORT: EMPIRICAL EVIDENCE

Schneemann S, Deutscher C. INTERMEDIATE INFORMATION, LOSS AVERSION, AND EFFORT: EMPIRICAL EVIDENCE. Economic Inquiry. 2017;55(4):1759-1770

Influence of a selective guanylate cyclase inhibitor, and of the contraction level, on nitrergic relaxations in the gastric fundus

1. The influence of the soluble guanylate cyclase inhibitor 1H-[1,2,4]oxadiazolo[4,3,-a]quinoxalin-1-one (ODQ) on non-adrenergic non-cholinergic (NANC) relaxations and the possible role of a nerve-derived hyperpolarizing factor in NANC relaxation were investigated in the rat gastric fundus. 2. ODQ (10(−6) and 10(−5) M) concentration-dependently inhibited the short-lasting relaxations by NO (2×10(−6) M–10(−4) M) administered as a bolus without influencing the relaxation by 3×10(−8) M isoprenaline. The relaxation by an infusion of NO was reduced to the same extent by 10(−6) and 10(−5) M ODQ. 3. The electrically induced short-lasting and sustained relaxations (40 V, 1 ms, 0.5–16 Hz, 10 s trains at 2 min interval or cumulative increase in the frequency every 2 min) in NANC conditions were inhibited to a similar extent by 10(−6) and 10(−5) M ODQ, and by the NO synthase inhibitor N(G)-nitro-L-arginine methyl ester (L-NAME; 3×10(−4) M). 4. ODQ (10(−6) M) and L-NAME (3×10(−4) M), administered after 5, 10 or 20 min of long-term stimulation, reversed the relaxation to a similar extent (approximately 50% at 2 Hz and 20% at 8 Hz). 5. When the tissues were contracted to 40% of maximum by adapting the concentration of prostaglandin F(2α) (PGF(2α)), the inhibitory effect of 3×10(−4) M L-NAME on relaxations induced by train and cumulative stimulation was the same as when tissues were contracted with 3×10(−7) M PGF(2α). 6. The findings of this study illustrate that the relaxation by exogenous and endogenous NO in the rat gastric fundus is due to activation of soluble guanylate cyclase. During long-term electrical stimulation, the partial contribution of NO to NANC relaxation is maintained but it is small at higher frequencies of stimulation. Evidence for the contribution of a nerve-derived hyperpolarizing factor to NANC relaxation was not obtained