A circadian and an ultradian rhythm are both evident in root growth of rice

This paper presents evidence for the existence of both a circadian and an ultradian rhythm in the elongation growth of rice roots. Root elongation of rice (Oryza sativa) was recorded under dim green light by using a CCD camera connected to a computer. Four treatment conditions were set-up to investigate the existence of endogenous rhythms: 28 °C constant temperature and continuous dark (28 DD); 28 °C constant temperature and alternating light and dark (28 LD); 33 °C constant temperature and continuous dark (33 DD); and diurnal temperature change and alternating light and dark (DT-LD). The resulting spectral densities suggested the existence of periodicities of 20.4-25.2 h (circadian cycles) and 2.0-6.0 h (ultradian cycles) in each of the 4 treatments. The shorter ultradian cycles can be attributed to circumnutational growth of roots and/or to mucilage exudation. The average values across all the replicate data showed that the highest power spectral densities (PSDs) corresponded to root growth rhythms with periods of 22.9, 23.7, and 2.1 h for the 28 DD, 28 LD, and 33 DD treatments, respectively. Accumulation of PSD for each data set indicated that the periodicity was similar in both the 28 DD and 33 DD treatments. We conclude that a 23-h circadian and a 2-h ultradian rhythmicity exist in rice root elongation. Moreover, root elongation rates during the day were 1.08 and 1.44 times faster than those during the night for the 28 LD and DT-LD treatments, respectively.     

In situ hybridization analysis of the temporospatial expression of the midkine/pleiotrophin family in rat embryonic pituitary gland

Pituitary gland development is controlled by numerous signaling molecules, which are produced in the oral ectoderm and diencephalon. A newly described family of heparin-binding growth factors, namely midkine (MK)/pleiotrophin (PTN), is involved in regulating the growth and differentiation of many tissues and organs. Using in situ hybridization with digoxigenin-labeled cRNA probes, we detected cells expressing MK and PTN in the developing rat pituitary gland. At embryonic day 12.5 (E12.5), MK expression was localized in Rathke’s pouch (derived from the oral ectoderm) and in the neurohypophyseal bud (derived from the diencephalon). From E12.5 to E19.5, MK mRNA was expressed in the developing neurohypophysis, and expression gradually decreased in the developing adenohypophysis. To characterize MK-expressing cells, we performed double-staining of MK mRNA and anterior pituitary hormones. At E19.5, no MK-expressing cells were stained with any hormone. In contrast, PTN was expressed only in the neurohypophysis primordium during all embryonic stages. In situ hybridization clearly showed that MK was expressed in primitive (immature/undifferentiated) adenohypophyseal cells and neurohypophyseal cells, whereas PTN was expressed only in neurohypophyseal cells. Thus, MK and PTN might play roles as signaling molecules during pituitary development.     

Interleukin-1 Receptor-associated Kinase-4 (IRAK4) Promotes Inflammatory Osteolysis by Activating Osteoclasts and Inhibiting Formation of Foreign Body Giant Cells

Formation of foreign body giant cells (FBGCs) occurs following implantation of medical devices such as artificial joints and is implicated in implant failure associated with inflammation or microbial infection. Two major macrophage subpopulations, M1 and M2, play different roles in inflammation and wound healing, respectively. Therefore, M1/M2 polarization is crucial for the development of various inflammation-related diseases. Here, we show that FBGCs do not resorb bone but rather express M2 macrophage-like wound healing and inflammation-terminating molecules in vitro. We also found that FBGC formation was significantly inhibited by inflammatory cytokines or infection mimetics in vitro. Interleukin-1 receptor-associated kinase-4 (IRAK4) deficiency did not alter osteoclast formation in vitro, and IRAK4-deficient mice showed normal bone mineral density in vivo. However, IRAK4-deficient mice were protected from excessive osteoclastogenesis induced by IL-1β in vitro or by LPS, an infection mimetic of Gram-negative bacteria, in vivo. Furthermore, IRAK4 deficiency restored FBGC formation and expression of M2 macrophage markers inhibited by inflammatory cytokines in vitro or by LPS in vivo. Our results demonstrate that osteoclasts and FBGCs are reciprocally regulated and identify IRAK4 as a potential therapeutic target to inhibit stimulated osteoclastogenesis and rescue inhibited FBGC formation under inflammatory and infectious conditions without altering physiological bone resorption.     

Synthesis and characterization of radioiodinated 3-phenethyl-2-indolinone derivatives for SPECT imaging of survivin in tumors

Survivin, overexpressed in most cancers, is associated with poor prognosis and resistance to radiation therapy and chemotherapy. Herein, we report the synthesis of three 3-phenethyl-2-indolinone derivatives and their application as in vivo imaging agents for survivin. Of these, 3-(2-(benzo[d][1,3]dioxol-5-yl)-2-oxoethyl)-3-hydroxy-5- iodoindolin-2-one (IPI-1) showed the highest binding affinity (K_d?=?68.3?nM) to recombinant human survivin, as determined by quartz crystal microbalance (QCM). In vitro studies demonstrated that the [¹²⁵I]IPI-1 binding in survivin-positive MDA-MB-231 cells was significantly higher than that in survivin-negative MCF-10A cells. In addition, uptake of [¹²⁵I]IPI-1 by MDA-MB-231 cells decreased in a dose-dependent manner in the presence of the high-affinity survivin ligand S12; this is indicative of specific binding of [¹²⁵I]IPI-1 to cellular survivin protein in vitro. Biodistribution studies in MDA-MB-231 tumor-bearing mice demonstrated the moderate uptake of [¹²⁵I]IPI-1 in the tumor tissue (1.37%?ID/g) at 30?min that decreased to 0.32%?ID/g at 180?min. Co-injection of S12 (2.5?mg/kg) slightly reduced tumor uptake and the tumor/muscle ratio of [¹²⁵I]IPI-1. Although further structural modifications are necessary to improve pharmacokinetic properties, our results indicate that PI derivatives may be useful as tumor-imaging probes targeting survivin.     

Two types of X-ray-induced radioresistance in mice: Presence of 4 dose ranges with distinct biological effects

Preirradiation with 0.05 Gy of X rays 2 months before a second exposure to a mid-lethal dose significantly enhanced the survival rate in both female and male ICR strain mice. The radioresistance was observed between 2–2.5 months after exposure to 0.05 Gy. It did not appear within 1.5 months, and disappeared after 3 months. This radioresistance was induced only by whole-body preirradiation (not by partial irradiation of the head or the trunk). On the other hand, preirradiation with 0.30 Gy as well as 0.50 Gy resulted in radioresistance 2 weeks later, but not 2 months later. The radioresistance was induced by whole-body preirradiation or partial preirradiation of the trunk. No radioresistance was evident after exposure of intermediate preirradiation doses of 0.15 and 0.20 Gy administered before 2 months and 2–5 weeks, respectively. The present and previous results show that the biological effects of ionizing radiation may be distinguished with the following four radiation dose ranges; (1) below 0.025 Gy: no radioresistance after 2 months; (2) 0.05–0.10 Gy: significant radioresistance after 2–2.5 months; (3) 0.20 Gy: no radioresistance after 2–5 weeks; and (4) 0.30–0.50 Gy or more: significant radioresistance after 2 weeks. These results conflict with previous findings of the biological effects of ionizing radiation in which the radiation hazard increases in relation to increasing accumulated doses. Some stimulation, in addition to adaptation, by low dose irradiation may have occurred.     

Differences in drought tolerance between cultivars of field bean and field pea. Morphological characteristics, germination and seedling growth

Different responses among legume species were observed, but the morphological and physiological differences that confer drought resistance or susceptibility are not well explained. The objective of this study was the determination of variation of morphological characteristics within 7 field bean and 4 field pea cultivars as related to drought tolerance. Also differences in the effect of drought on seed germination and seedling growth in 2 field bean and 2 field pea cultivars of different drought tolerances were investigated. The examined cultivars were characterized by variation of certain morphological characteristics regarded as xeromorphic features associated with the ability of plant to survive under drought. The drought resistant cultivars (field bean Gobo and field pea Solara) in comparison with the sensitive ones (field bean Victor and field pea Bareness) were characterized by more favourable relations between the size of the above—ground parts and the size of root, as well as the frequency and size of stomata. Moreover, in the resistant cultivars there was observed, a smaller influence of simulated drought (ψ=−0.6 MPa) on the increase of dry matter of the above-ground parts and of the roots. Also there was smaller influence on the height of seedlings and on the length of lateral roots. The correlation coefficients between the measured characteristics and the values of the drought susceptibility index (DSI) were in most cases statistically not significant, although, on the whole, they were very high. This may be an indication of a relatively high participation of the measured characteristics in the total variation of the drought tolerance in the cultivars. In cultivars regarded as belonging to the group of sensitive ones, a more disadvantageous effect of simulated drought (ψ=−0.6 MPa) on seed germination was observed, especially in the determination of the promptness index (PI).     

Differences in drought tolerance between cultivars of field bean and field pea. A comparison of drought-resistant and drought-sensitive cultivars

Relatively little research has been conducted to determine different responses to drought among cultivars of the legume species. The objective of this study was to identify differences in seedlings growth, water relations and leaf conductances resulting from drought imposed on two field bean and two field pea cultivars that had been observed to differ in their drought tolerances, and special emphasis was placed on the root system development. Distinct differences between resistant and sensitive cultivars of field bean and field pea became evident in measurements of the characteristics of the lateral root. The drought treatment induced statistically significant decrease in the number of the developed laterals, their total length and dry matter. In the drought resistant cultivars (field bean Gobo and field pea Solara) this reduction was smaller in comparison with sensitive ones (field bean Victor and field pea Bareness). The effect of drought on growth of tap root in the drought resistant and drought sensitive cultivars was smaller and statistically not significant. The results showed that drought resistant cultivars when compared with drought sensitive one would demonstrate less abundance in the above-ground part and greater dimensions of the root system. The measurements of leaf water potential and stomata diffusive resistance measurements indicate that the physiological reasons for the different reactions to drought between the resistant and the sensitive field bean and field pea cultivars may be due to a more effective protection of the level of tissue hydration and due to increase stomata diffusive resistance in the resistant cultivars. During recovery period it has been also demonstrated that in the drought resistant cultivars a tendency exists for a more complete return to the level of the control plants.     

Selective Estrogen Receptor Modulators Suppress Hif1α Protein Accumulation in Mouse Osteoclasts

Anti-bone resorptive drugs such as bisphosphonates, the anti-RANKL antibody (denosumab), or selective estrogen receptor modulators (SERMs) have been developed to treat osteoporosis. Mechanisms underlying activity of bisphosphonates or denosumab in this context are understood, while it is less clear how SERMs like tamoxifen, raloxifene, or bazedoxifene inhibit bone resorption. Recently, accumulation of hypoxia inducible factor 1 alpha (Hif1α) in osteoclasts was shown to be suppressed by estrogen in normal cells. In addition, osteoclast activation and decreased bone mass seen in estrogen-deficient conditions was found to require Hif1α. Here, we used western blot analysis of cultured osteoclast precursor cells to show that tamoxifen, raloxifene, or bazedoxifene all suppress Hif1α protein accumulation. The effects of each SERM on osteoclast differentiation differed in vitro. Our results suggest that interventions such as the SERMs evaluated here could be useful to inhibit Hif1α and osteoclast activity under estrogen-deficient conditions.