The fission yeast MTREC complex targets CUTs and unspliced pre-mRNAs to the nuclear exosome

Cryptic unstable transcripts (CUTs) are rapidly degraded by the nuclear exosome. However, the mechanism by which they are recognized and targeted to the exosome is not fully understood. Here we report that the MTREC complex, which has recently been shown to promote degradation of meiotic mRNAs and regulatory ncRNAs, is also the major nuclear exosome targeting complex for CUTs and unspliced pre-mRNAs in Schizosaccharomyces pombe. The MTREC complex specifically binds to CUTs, meiotic mRNAs and unspliced pre-mRNA transcripts and targets these RNAs for degradation by the nuclear exosome, while the TRAMP complex has only a minor role in this process. The MTREC complex physically interacts with the nuclear exosome and with various RNA-binding and RNA-processing complexes, coupling RNA processing to the RNA degradation machinery. Our study reveals the central role of the evolutionarily conserved MTREC complex in RNA quality control, and in the recognition and elimination of CUTs

Fabrication of field-effect transistor device with higher fullerene, C₈₈

A fullerene field-effect transistor (FET) device has been fabricated with thin films of C88, and n-channel normally-on depletion-type FET properties have been found in this FET device. The C88 FET exhibited a high mobility, &#956;, of 2.5 x 10-3 cm2 V-1 s-1 at 300 K, in fullerene FETs. The carrier transport showed a thermally-activated hopping transport. The n-channel normally-on FET properties and the hopping transport reflect the small mobility gap and low carrier concentration in the channel region of C88 thin-films.</p

Safety and Complications of Medical Thoracoscopy

Objectives. To highlight the possible complications of medical thoracoscopy (MT) and how to avoid them. Methods. A retrospective and prospective analysis of 127 patients undergoing MT in Nagoya Medical Center (NMC) and Toyota Kosei Hospital. The data about complications was obtained from the patients, notes on the computer system, and radiographs. Results. The median age was 71.0 (range, 33.0–92.0) years and 101 (79.5%) were males. The median time with chest drain after procedure was 7.0 (range, 0.0–47.0) days and cases with talc poudrage were 30 (23.6%). Malignant histology was reported in 69 (54.3%), including primary lung cancer in 35 (27.5), mesothelioma in 18 (14.2), and metastasis in 16 (12.6). 58 (45.7%) revealed benign pleural diseases and TB was diagnosed in 15 (11.8%). 21 (16.5%) patients suffered from complications including lung laceration in 3 (2.4%), fever in 5 (3.9%) (due to hospital acquired infection (HAI) in 2, talc poudrage in 2, and malignancy in 1), HAI in 2 (1.6%), prolonged air-leak in 14 (11.0%), and subcutaneous emphysema in 1 (0.8%). Conclusions. MT is generally a safe procedure. Lung laceration is the most serious complication and should be managed well. HAI is of low risk and can be controlled by medical treatment

Hedgehog Promotes Neovascularization in Pancreatic Cancers by Regulating Ang-1 and IGF-1 Expression in Bone-Marrow Derived Pro-Angiogenic Cells

http://creativecommons.org/licenses/by/2.0/ PublisherBackground: The hedgehog (Hh) pathway has been implicated in the pathogenesis of cancer including pancreatic ductal adenocarcinoma (PDAC). Recent studies have suggested that the oncogenic function of Hh in PDAC involves signaling in the stromal cells rather than cell autonomous effects on the tumor cells. However, the origin and nature of the stromal cell type(s) that are responsive to Hh signaling remained unknown. Since Hh signaling plays a crucial role during embryonic and postnatal vasculogenesis, we speculated that Hh ligand may act on tumor vasculature specifically focusing on bone marrow (BM)-derived cells. Methodology/Principal Findings: Cyclopamine was utilized to inhibit the Hh pathway in human PDAC cell lines and their xenografts. BM transplants, co-culture systems of tumor cells and BM-derived pro-angiogenic cells (BMPCs) were employed to assess the role of tumor-derived Hh in regulating the BM compartment and the contribution of BM-derived cells to angiogenesis in PDAC. Cyclopamine administration attenuated Hh signaling in the stroma rather than in the cancer cells as reflected by decreased expression of full length Gli2 protein and Gli1 mRNA specifically in the compartment. Cyclopamine inhibited the growth of PDAC xenografts in association with regression of the tumor vasculature and reduced homing of BM-derived cells to the tumor. Host-derived Ang-1 and IGF-1 mRNA levels were downregulated by cyclopamine in the tumor xenografts. In vitro co-culture and matrigel plug assays demonstrated that PDAC cell-derived Shh induced Ang-1 and IGF-1 production in BMPCs, resulting in their enhanced migration and capillary morphogenesis activity. Conclusions/Significance: We identified the BMPCs as alternative stromal targets of Hh-ligand in PDAC suggesting that the tumor vasculature is an attractive therapeutic target of Hh blockade. Our data is consistent with the emerging concept that BM-derived cells make important contributions to epithelial tumorigenesis

A Robin sequence patient treated by the tongue-lip adhesion technique of modified Argamaso method

われわれは八戸赤十字病院小児科から, Robin sequenceの生後12週男児の呼吸障害の改善のための対診を依頼された。患者は下顎後退,上気道閉塞,軟口蓋裂,舌小帯強直症がみられた。当科を受診前に,何度か重度の呼吸障害がみられ,2か月以上気管内挿管による呼吸管理か行われていた。患者の咽頭部の閉塞は,内規鏡検査によるSheyの分類のType 1であったため,われわれは生後15週でArgamaso変法による舌固定術を行った。術後2年5か月経過するが,以来患者にチアノーセは見られず,舌固定術は同患者に有効な治療法と思われた。A 12-week-old boy with Robin sequence was referred to us for respiratory improvement by a pediatrician in Hachmohe Red Cross Hospital The patient had micrognathia, upper airway obstruction, incomplete cleft palate and ankyloglossia The patient had a history of repeated cyanotic episodes and had been under respiratory care with endotracheal intubation for more than 2 months Using flexible fiber optic nasopharyngoscopy, his pharyngeal obstruction was classified as Type 1 of Sher\u27s classification Thus, we performed glossopexy of modified Argamaso method at 15 weeks after birth The patient has had no cyanotic episodes at 2 years and 5 months postoperatively We conclude that the glossopexy was effective for this patien

Competition for Mitogens Regulates Spermatogenic Stem Cell Homeostasis in an Open Niche

In many tissues, homeostasis is maintained by physical contact between stem cells and an anatomically defined niche. However, how stem cell homeostasis is achieved in environments where cells are motile and dispersed among their progeny remains unknown. Using murine spermatogenesis as a model, we find that spermatogenic stem cell density is tightly regulated by the supply of fibroblast growth factors (FGFs) from lymphatic endothelial cells. We propose that stem cell homeostasis is achieved through competition for a limited supply of FGFs. We show that the quantitative dependence of stem cell density on FGF dosage, the biased localization of stem cells toward FGF sources, and stem cell dynamics during regeneration following injury can all be predicted and explained within the framework of a minimal theoretical model based on “mitogen competition.” We propose that this model provides a generic and robust mechanism to support stem cell homeostasis in open, or facultative, niche environments