A pathway of signals regulating effector and initiator caspases in the developing Drosophila eye

Regulated cell death and survival play important roles in neural development. Extracellular signals are presumed to regulate seven apparent caspases to determine the final structure of the nervous system. In the eye, the EGF receptor, Notch, and intact primary pigment and cone cells have been implicated in survival or death signals. An antibody raised against a peptide from human caspase 3 was used to investigate how extracellular signals controlled spatial patterning of cell death. The antibody crossreacted specifically with dying Drosophila cells and labelled the activated effector caspase Drice. It was found that the initiator caspase Dronc and the proapoptotic gene head involution defective were important for activation in vivo. Dronc may play roles in dying cells in addition to activating downstream effector caspases. Epistasis experiments ordered EGF receptor, Notch, and primary pigment and cone cells into a single pathway that affected caspase activity in pupal retina through hid and Inhibitor of Apoptosis Proteins. None of these extracellular signals appeared to act by initiating caspase activation independently of hid. Taken together, these findings indicate that in eye development spatial regulation of cell death and survival is integrated through a single intracellular pathway

Syk/Src Pathway-Targeted Inhibition of Skin Inflammatory Responses by Carnosic Acid

Carnosic acid (CA) is a diterpene compound exhibiting antioxidative, anticancer, anti-angiogenic, anti-inflammatory, anti-metabolic disorder, and hepatoprotective and neuroprotective activities. In this study, the effect of CA on various skin inflammatory responses and its inhibitory mechanism were examined. CA strongly suppressed the production of IL-6, IL-8, and MCP-1 from keratinocyte HaCaT cells stimulated with sodium lauryl sulfate (SLS) and retinoic acid (RA). In addition, CA blocked the release of nitric oxide (NO), tumor necrosis factor (TNF)-α, and prostaglandin E2 (PGE2) from RAW264.7 cells activated by the toll-like receptor (TLR)-2 ligands, Gram-positive bacterium-derived peptidoglycan (PGN) and pam3CSK, and the TLR4 ligand, Gram-negative bacterium-derived lipopolysaccharide (LPS). CA arrested the growth of dermatitis-inducing Gram-positive and Gram-negative microorganisms such Propionibacterium acnes, Pseudomonas aeruginosa, and Staphylococcus aureus. CA also blocked the nuclear translocation of nuclear factor (NF)-κB and its upstream signaling including Syk/Src, phosphoinositide 3-kinase (PI3K), Akt, inhibitor of κBα (IκBα) kinase (IKK), and IκBα for NF-κB activation. Kinase assays revealed that Syk could be direct enzymatic target of CA in its anti-inflammatory action. Therefore, our data strongly suggest the potential of CA as an anti-inflammatory drug against skin inflammatory responses with Src/NF-κB inhibitory properties

Subsidence and Nonunion after Anterior Cervical Interbody Fusion Using a Stand-Alone Polyetheretherketone (PEEK) Cage

Background: The purposes of the present study are to evaluate the subsidence and nonunion that occurred after anterior cervical discectomy and fusion using a stand-alone intervertebral cage and to analyze the risk factors for the complications.Methods: Thirty-eight patients (47 segments) who underwent anterior cervical fusion using a stand-alone polyetheretherketone (PEEK) cage and an autologous cancellous iliac bone graft from June 2003 to August 2008 were enrolled in this study. The anterior and posterior segmental heights and the distance from the anterior edge of the upper vertebra to the anterior margin of the cage were measured on the plain radiographs. Subsidence was defined as ≥ a 2 mm (minor) or 3 mm (major) decrease of the segmental height at the final follow-up compared to that measured at the immediate postoperative period. Nonunion was evaluated accordingto the instability being ≥ 2 mm in the interspinous distance on the flexion-extension lateral radiographs.Results: The anterior and posterior segmental heights decreased from the immediate postoperative period to the final follow-up at 1.33 ± 1.46 mm and 0.81 ± 1.27 mm, respectively. Subsidence ≥ 2 mm and 3 mm were observed in 12 segments (25.5%) and 7 segments (14.9%), respectively. Among the expected risk factors for subsidence, a smaller anteroposterior (AP) diameter (14 mm vs. 12 mm) of cages (p = 0.034; odds ratio [OR], 0.017) and larger intraoperative distraction (p = 0.041; OR, 3.988) had a significantlyhigher risk of subsidence. Intervertebral nonunion was observed in 7 segments (7/47, 14.9%). Compared with the union group, the nonunion group had a significantly higher ratio of two-level fusion to one-level fusions (p = 0.001).Conclusions: Anterior cervical fusion using a stand-alone cage with a large AP diameter while preventing anterior intraoperative over-distraction will be helpful to prevent the subsidence of cages. Two-level cervical fusion might require more careful attention for avoiding nonunion.Keywords: Anterior cervical fusion, PEEK cage, Subsidence, NonunionOAIID:oai:osos.snu.ac.kr:snu2011-01/102/0000004226/3SEQ:3PERF_CD:SNU2011-01EVAL_ITEM_CD:102USER_ID:0000004226EMP_ID:A076317DEPT_CD:801FILENAME:E031T_CiOS-2011_Yang_Subsidence and nonunion after anterior cervical.pdfDEPT_NM:의학과EMAIL:[email protected]_YN:NCONFIRM:

The Expression of Estrogen Receptors in Hepatocellular Carcinoma in Korean Patients

Expression of estrogen receptors (ER)-α and -β, as well as androgen receptor (AR), in hepatocellular carcinoma (HCC) is thought to be correlated with prognosis, survival, and male prevalence of HCC. These hypotheses are based on investigations of European patients; however the expression patterns of these receptors in Asian patients are largely unknown. In this study, we collected liver carcinoma and peritumor tissues from 32 patients (9 females and 23 males) in South Korea. The expression of ERs and ARs was studied using RT-PCR. Wild-type ER-α and AR were expressed in all of the samples investigated, and their expression was independent of the causal virus or patient sex. Expression of the ER-α variant was independent of sex (100% female vs. 91.3% male) and HCV and HBV status (91.3% vs. 100%). Wild-type ER-β was expressed more often in HCV patients than in HBV patients (95.7% vs. 44.4%; p < 0.05). In conclusion, the stronger ER-α variant expression in HCC tissues implies that this variant has an important role in HCC development. However, at least in Korean patients, expression of the ER-α variant (vER-α) is not related to male HCC prevalence. In addition, the predominant expression of ER-β in HCV patients suggests that it plays an important role in HCV-induced liver disease

Functional analysis of the zinc finger and activation domains of Glis3 and mutant Glis3(NDH1)

The Krüppel-like zinc finger protein Gli-similar 3 (Glis3) plays a critical role in pancreatic development and has been implicated in a syndrome with neonatal diabetes and hypothyroidism (NDH). In this study, we examine three steps critical in the mechanism of the transcriptional regulation by Glis3: its translocation to the nucleus, DNA binding and transcriptional activity. We demonstrate that the putative bipartite nuclear localization signal is not required, but the tetrahedral configuration of the fourth zinc finger is essential for the nuclear localization of Glis3. We identify (G/C)TGGGGGGT(A/C) as the consensus sequence of the optimal, high-affinity Glis3 DNA-binding site (Glis-BS). All five zinc finger motifs are critical for efficient binding of Glis3 to Glis-BS. We show that Glis3 functions as a potent inducer of (Glis-BS)-dependent transcription and contains a transactivation function at its C-terminus. A mutation in Glis3 observed in NDH1 patients results in a frameshift mutation and a C-terminal truncated Glis3. We demonstrate that this truncation does not effect the nuclear localization but results in the loss of Glis3 transactivating activity. The loss in Glis3 transactivating function may be responsible for the abnormalities observed in NDH1

Genome-wide comparative analysis of the Brassica rapa gene space reveals genome shrinkage and differential loss of duplicated genes after whole genome triplication

Euchromatic regions of the Brassica rapa genome were sequenced and mapped onto the corresponding regions in the Arabidopsis thaliana genome

Cancer associated fibroblasts: the architects of stroma remodelling

Fibroblasts have exceptional phenotypic plasticity and capability to secrete vast amount of soluble factors, ECM components and extracellular vesicles. While in physiological conditions this makes fibroblasts master regulators of tissue homeostasis and healing of injured tissues, in solid tumours cancer-associated fibroblasts (CAFs) co-evolve with the disease, and alter the biochemical and physical structure of the tumour microenvironment, as well as the behaviour of the surrounding stromal and cancer cells. Thus CAFs are fundamental regulators of tumour progression and influence response to therapeutic treatments. Increasing efforts are devoted to better understand the biology of CAFs to bring insights to develop complementary strategies to target this cell type in cancer. Here we highlight components of the tumour microenvironment that play key roles in cancer progression and invasion, and provide an extensive overview of past and emerging understanding of CAF biology as well as the contribution that mass spectrometry (MS)-based proteomics has made to this field