Widespread translational control contributes to the regulation of Arabidopsis photomorphogenesis

Environmental light regulates and optimizes plant growth and development. Genomic profiling of polysome-associated mRNA reveals that light stimulates dramatic changes in translational regulation, which contribute more to light-induced gene expression changes than transcriptional regulation

Prevention and early management of carotid blowout syndrome for patients receiving head and neck salvage boron neutron capture therapy (BNCT)

Background/purpose The incidence rate of oral and pharyngeal cancers in Taiwan has increased gradually over the past few decades. The standard treatment strategy for oral and pharyngeal cancers includes surgery or radiotherapy, with concurrent chemotherapy in certain types of tumors. Unfortunately, in-field recurrence is sometimes inexorable. Furthermore, re-irradiation of the recurrence site may cause severe complications due to the tolerance of normal tissue to radiation therapy. One fatal complication is carotid blowout syndrome (CBS). Boron neutron capture therapy (BNCT) is a new modality of radiation therapy, which is also mentioned as targeted radiotherapy. It is a feasible treatment that has the potential to spare normal tissue from being damaged by irradiation while simultaneously treating the primary tumor. In this presentation, we will share our experience with BNCT in treating recurrent head and neck cancers, as well as the prevention and management of CBS. Materials and methods We evaluated 4 patients with head and neck cancers treated by BNCT in Taiwan. All patients had undergone surgery previously and had received postoperative concurrent chemoradiotherapy. Results The 4 patients in this study were diagnosed with head and neck malignancies. The median follow-up period after the first course of BNCT was 15.1 months. After BNCT, 2 patients developed impending CBS, and 1 of them died. The remaining 3 patients survived until the last date of follow-up. Conclusion Pre-BNCT carotid artery evaluation through computed tomography angiography and early intervention if necessary is crucial when treating patients with recurrent head and neck cancers by BNCT

An injectable non-cross-linked hyaluronic-acid gel containing therapeutic spheroids of human adipose-derived stem cells

For chronic wounds, the delivery of stem cells in spheroidal structures can enhance graft survival and stem cell potency. We describe an easy method for the 3D culture of adipose-derived stem/stromal cells (ASCs) to prepare a ready-to-use injectable. We transferred suspensions of monolayer-cultured ASCs to a syringe containing hyaluronic acid (HA) gel, and then incubated the syringe as a 3D culture vessel. Spheroids of cells formed after 12 h. We found that 6 × 106 ASCs/ml in 3% HA gel achieved the highest spheroid density with appropriate spheroid sizes (20–100 µm). Immunocytology revealed that the stem cell markers, NANOG, OCT3/4, SOX-2, and SSEA-3 were up-regulated in the ASC spheroids compared with those in nonadherent-dish spheroids or in monolayer cultured ASCs. In delayed wound healing mice models, diabetic ulcers treated with ASC spheroids demonstrated faster wound epithelialization with thicker dermis than those treated with vehicle alone or monolayer cultured ASCs. In irradiated skin ulcers in immunodeficient mice, ASC spheroids exhibited faster healing and outstanding angiogenic potential partly by direct differentiation into α-SMA+ pericytes. Our method of 3D in-syringe HA gel culture produced clinically relevant amounts of ready-to-inject human ASC microspheroids that exhibited superior stemness in vitro and therapeutic efficacy in pathological wound repair in vivo

Long-term results of intensity-modulated radiotherapy concomitant with chemotherapy for hypopharyngeal carcinoma aimed at laryngeal preservation

<p>Abstract</p> <p>Background</p> <p>The objective of this retrospective study is to investigate laryngeal preservation and long-term treatment results in hypopharyngeal carcinoma treated with intensity-modulated radiotherapy (IMRT) combined with chemotherapy.</p> <p>Methods</p> <p>Twenty-seven patients with hypopharyngeal carcinoma (stage II-IV) were enrolled and underwent concurrent chemoradiotherapy. The chemotherapy regimens were monthly cisplatin and 5-fluorouracil for six patients and weekly cisplatin for 19 patients. All patients were treated with IMRT with simultaneous integrated boost technique. Acute and late toxicities were recorded based on CTCAE 3.0 (Common Terminology Criteria for Adverse Events).</p> <p>Results</p> <p>The median follow-up time for survivors was 53.0 months (range 36-82 months). The initial complete response rate was 85.2%, with a laryngeal preservation rate of 63.0%. The 5-year functional laryngeal, local-regional control, disease-free and overall survival rates were 59.7%, 63.3%, 51.0% and 34.8%, respectively. The most common greater than or equal to grade 3 acute and late effects were dysphagia (63.0%, 17 of 27 patients) and laryngeal stricture (18.5%, 5 of 27 patients), respectively. Patients belonging to the high risk group showed significantly higher risk of tracheostomy compared to the low risk group (p = 0.014).</p> <p>Conclusions</p> <p>After long-term follow-up, our results confirmed that patients with hypopharyngeal carcinoma treated with IMRT concurrent with platinum-based chemotherapy attain high functional laryngeal and local-regional control survival rates. However, the late effect of laryngeal stricture remains a problem, particularly for high risk group patients.</p

Spontaneous emission from a two-level atom in anisotropic one-band photonic crystals: a fractional calculus approach

Spontaneous emission (SE) from a two-level atom in a photonic crystal (PC) with anisotropic one-band model is investigated using the fractional calculus. Analytically solving the kinetic equation in terms of the fractional exponential function, the dynamical discrepancy of SE between the anisotropic and isotropic systems is discussed on the basis of different photon density of states (DOS) and the existence of incoherent diffusion field that becomes even more clearly as the atomic transition frequency lies close to the band edge. With the same atom-field coupling strength and detuning in the forbidden gap, the photon-atom bound states in the isotropic system turn into the unbound ones in the anisotropic system that is consistent with the experimental observation in $Phys.$ $Rev.$ $Lett.$ \textbf{96}, 243902 (2006). Dynamics along different wavevectors with various curvatures of dispersion is also addressed with the changes of the photon DOS and the appearance of the diffusion fields.Comment: 16 pages, 4 figure

Intestinal Paneth cell differentiation relies on asymmetric regulation of Wnt signaling by Daam1/2

The mammalian intestine is one of the most rapidly self-renewing tissues, driven by stem cells residing at the crypt bottom. Paneth cells form a major element of the niche microenvironment providing various growth factors to orchestrate intestinal stem cell homeostasis, such as Wnt3. Different Wnt ligands can selectively activate β-catenin-dependent (canonical) or -independent (noncanonical) signaling. Here, we report that the Dishevelled-associated activator of morphogenesis 1 (Daam1) and its paralogue Daam2 asymmetrically regulate canonical and noncanonical Wnt (Wnt/PCP) signaling. Daam1/2 interacts with the Wnt inhibitor RNF43, and Daam1/2 double knockout stimulates canonical Wnt signaling by preventing RNF43-dependent degradation of the Wnt receptor, Frizzled (Fzd). Single-cell RNA sequencing analysis revealed that Paneth cell differentiation is impaired by Daam1/2 depletion because of defective Wnt/PCP signaling. Together, we identified Daam1/2 as an unexpected hub molecule coordinating both canonical and noncanonical Wnt, which is fundamental for specifying an adequate number of Paneth cells

Cancer and mTOR inhibitors in kidney transplantation recipients

Background Previous studies show that mTOR inhibitors decrease the risk of cancer development after kidney transplantation. However, the effect of cumulative doses of mTOR inhibitors on cancer after kidney transplantation is not well known. Methods In the current study, patients were registered into a national database in Taiwan. Between year 2000 and 2013, 4,563 patients received kidney transplantation. They were divided into two groups, according to mTOR inhibitors usage. The cumulative dose of mTOR inhibitors was recorded. Patients were followed-up until de novo cancer development, death, or the end of 2014. Results Patients were divided into two groups: mTOR inhibitors users (study group, n = 828) and mTOR inhibitors non-users (control group, n = 3,735). The median follow-up duration was 7.8 years. The risk of de novo cancer (hazards ratio (HR) 0.80, 95% CI [0.60–1.09], p = 0.16) and risk of death (HR 1.14, 95% CI [0.82–1.60], p = 0.43) was not different between mTOR inhibitor user and non-user groups. Neither high- nor low-dose exposure to mTOR inhibitors was associated with increased risk of cancer or mortality. Analysis of cancer subtypes showed no influence by mTOR inhibitors. In addition, the cause of mortality was not significantly different between the two groups. Discussion We could not find the association of mTOR inhibitors use and risk of de novo cancer development or mortality in patients with kidney transplantation in Chinese patients. Cumulative exposure to mTOR inhibitors did not change the results

Tracing oncogene-driven remodelling of the intestinal stem cell niche.

Interactions between tumour cells and the surrounding microenvironment contribute to tumour progression, metastasis and recurrence1-3. Although mosaic analyses in Drosophila have advanced our understanding of such interactions4,5, it has been difficult to engineer parallel approaches in vertebrates. Here we present an oncogene-associated, multicolour reporter mouse model-the Red2Onco system-that allows differential tracing of mutant and wild-type cells in the same tissue. By applying this system to the small intestine, we show that oncogene-expressing mutant crypts alter the cellular organization of neighbouring wild-type crypts, thereby driving accelerated clonal drift. Crypts that express oncogenic KRAS or PI3K secrete BMP ligands that suppress local stem cell activity, while changes in PDGFRloCD81+ stromal cells induced by crypts with oncogenic PI3K alter the WNT signalling environment. Together, these results show how oncogene-driven paracrine remodelling creates a niche environment that is detrimental to the maintenance of wild-type tissue, promoting field transformation dominated by oncogenic clones.Royal Societ