Re-Evaluation of Florigen Transport Kinetics with Separation of Functions by Mutations That Uncouple Flowering Initiation and Long-Distance Transport.

In many plants, timing of flowering is regulated by day length. In Arabidopsis, florigen, FLOWERING LOCUS T (FT) protein, is synthesized in leaf phloem companion cells in response to long days and is transported to the shoot apical meristem (SAM) through the phloem. The temporal aspects of florigen transportation have been studied in various plants by physiological experiments. Nevertheless, little is known about how FT protein transportation is regulated in Arabidopsis. In this study, we performed heat shock-based transient FT induction in a single leaf blade and detected the FT protein in the shoot apex by 2D-PAGE. We demonstrated that detectable amounts of FT were transported from the leaf to the shoot apex within 8 h, and subsequent FT-induced target gene expression was detected within 8-12 h. Furthermore, we identified three amino acid residues (V70, S76 and R83) where missense mutations led to reduced mobility. Interestingly, these FT variants lost only their transportation ability, but retained their flowering promotion capacity, suggesting that discrete amino acids are involved in flowering regulation and transport regulation. Since the interaction with FT-INTERACTING PROTEIN 1 (FTIP1) was not affected in these FT variants, we hypothesize that the three amino acid residues are not involved in the FTIP1-mediated pathway of uploading, but rather in the subsequent step(s) of FT transport.

Author Correction: Oral immunotherapy combined with omalizumab for high-risk cow's milk allergy: a randomized controlled trial.

A correction to this article has been published and is linked from the HTML and PDF versions of this paper. The error has not been fixed in the paper.

Oral immunotherapy combined with omalizumab for high-risk cow's milk allergy: a randomized controlled trial.

We evaluated the efficacy and safety of oral immunotherapy (OIT) combined with 24 weeks of omalizumab (OMB) at inducing desensitization in children with cow's milk allergy (CM) compared with an untreated group. The present study was a prospective randomized controlled trial. Sixteen patients (age, 6-14 years) with high IgE levels to CM were enrolled in the present study. Patients were randomized 1:1 to receive OMB-OIT group or untreated group. The primary outcome was the induction of desensitization at 8 weeks after OMB was discontinued in OMB-OIT treated group and at 32 weeks after study entry. None of the 6 children in the untreated group developed desensitization to CM while all of the 10 children in the OIT-OMB treated group achieved desensitization (P < 0.001). A significantly decreased wheal diameter in response to a skin prick test using CM was found in the OMB-OIT treated group (P < 0.05). These data suggest that OIT combined with OMB using microwave heated CM may help to induce desensitization for children with high-risk CM allergy. This prospective randomized controlled trial was intended for 50 participants but was prematurely discontinued due to overwhelming superiority of OMB combined with microwave heated OIT over CM avoidance.

Sensitivity of pressor responses to central hypertonic saline is greatly enhanced even in pre-hypertensive spontaneously hypertensive rats.

It has been suggested that intracerebroventricular injection of hypertonic saline mimics the effects of a high salt diet in spontaneously hypertensive rats (SHR), a genetic model of hypertension. Intracerebroventricular injection of hypertonic saline produces an increase in blood pressure and the pressor response to hypertonic saline is enhanced in adult hypertensive SHR. In this study, we examined whether the intracerebroventricular hypertonic saline-induced pressor response is enhanced even in pre-hypertensive SHR. The basal mean blood pressure was almost the same in 4-week-old SHR and age-matched Wistar Kyoto rats (WKY), whereas it was greater in 15-16-week-old SHR than in age-matched WKY. Intracerebroventricular injection of hypertonic saline (10 microl of 230 mM NaCl) produced an increase in blood pressure in both 4-week-old and 15-16-week-old SHR, whereas it did not affect blood pressure in both age-matched WKY. Intracerebroventricular injection of hypertonic saline (10 microl of 260 mM NaCl) produced an increase in blood pressure in all rats but the pressor response was greater in both 4-week-old and 15-16-week-old SHR than in respective age-matched WKY. Intracerebroventricular injection of Phe-Met-Arg-Phe amide (FMRF), an FMRF-inducible sodium channel activator, produced an increase in blood pressure in all rats but the pressor response was greater in SHR than in WKY at both ages. These findings indicate that the sensitivities of pressor responses to intracerebroventricular hypertonic saline and FMRF are enhanced not only in hypertensive but also in pre-hypertensive SHR.

Central injection of hypertonic saline activates angiotensin II-sensitive neurons in the anterior hypothalamic area of rats.

We have previously reported that microinjection of angiotensin II into the anterior hypothalamic area (AHA) produces pressor responses and that angiotensin II-sensitive neurons in the AHA are tonically activated by endogenous angiotensins in rats. Central injection of hypertonic saline causes pressor responses via release of angiotensins in brain. In this study, we examined whether angiotensin II-sensitive neurons in the AHA are responsive to intracerebroventricular injection of hypertonic saline and whether endogenous angiotensins in the AHA are involved in the central hypertonic saline-induced pressor response. Male Wistar rats were anesthetized and artificially ventilated. Extracellular potentials were recorded from single neurons in the AHA. Intraventricular injection of hypertonic saline increased the neural activity of angiotensin II-sensitive neurons, whereas pressure application of hypertonic saline onto angiotensin II-sensitive neurons themselves did not affect their neural activities. The intraventricular hypertonic saline-induced increase of unit activity of AHA neurons was inhibited by pressure application of the angiotensin AT1 receptor antagonist losartan onto the same neurons. The hypertonic saline-induced increase of unit firing was also blocked by intraventricular injection of the amiloride-sensitive sodium channel blocker benzamil. In conscious rats, intraventricular injection of hypertonic saline produced pressor responses, and the hypertonic saline-induced pressor response was inhibited by bilateral microinjection of losartan into the AHA. Repeated intraventricular injection of hypertonic saline caused an increase in the release of angiotensins in the AHA of anesthetized rats. These findings indicate that intracerebroventricular injection of hypertonic saline increases neural activity of angiotensin II-sensitive neurons trans-synaptically via endogenous angiotensins in the AHA. In addition, these findings also indicate that the intracerebroventricular injection of hypertonic saline produces a pressor response at least partly via release of angiotensins in the AHA.