Long noncoding RNA PVT1-214 enhances gastric cancer progression by upregulating TrkC expression in competitively sponging way.

The article "Long noncoding RNA PVT1-214 enhances gastric cancer progression by upregulating TrkC expression in competitively sponging way, by S. Zhao, N.-F. Fan, X.-H. Chen, C.-H. Zhuo, C.-W. Xu, R.-B. Lin, published in Eur Rev Med Pharmacol Sci 2019; 23(10): 4173-4184-DOI: 10.26355/eurrev_201905_17920-PMID: 31173288" has been withdrawn from the authors. The Publisher apologizes for any inconvenience this may cause. https://www.europeanreview.org/article/17920.

[Clinical and electrophysiological features and treatment of acrylamide-induced toxic peripheral neuropathy].

Objective: To investigate the clinical manifestations, electrophysiology results, treatment and prognosis of acrylamide-induced toxic peripheral neuropathy. Methods: The clinical data of 9 patients with acrylamide-induced toxic peripheral neuropathy, who were collected in Jinhua Municipal Central Hospital from January 2015 to August 2018, were retrospectively reviewed. Results: This disease was characterized by distal limb numbness, some patients with hypoalgesia or allergy, deep sense loss, reduction or disappearance of tendon reflexes, and peeling. One case had muscle weakening and another case had cerebellar ataxia. Examination of electromyography showed only one case had spontaneous potential. Examination of nerve conduction showed that the amplitude decreased by 34 (38.6%) and the velocity decreased by 2 (2.3%) , the percentage of amplitude decreased was significantly higher than that of velocity decreased. The amplitude of sensory nerve decreased by 30 (57.7%) and motor nerve decreased by 4 (11.1%) , the percentage of sensory nerve amplitude decreased was significantly higher than that of motor nerve. After the treatment of nutrition, circulation improvement, numbness relief, glucocorticoid and other drugs, the numbness of the patients was relieved, but it did not completely disappear. Poor recovery of pain, deep sensation and tendon reflex in all patients. The results of reexamination of electromyography in 3 cases were worse than before. Therefore, it is suggested that peripheral nerve damage is irreversible. Conclusion: This disease is characterized by distal limb numbness. Electrophysiological results suggest that the damage of sensory nerve axon is the main cause of the disease. Up to now, there is no effective drug to treat this disease, therefore, it is very important to do a good job of protection.

Effect of lncRNA GAS5 on the apoptosis of neurons via the notch1 signaling pathway in rats with cerebral infarction.

OBJECTIVE: To observe the effect of long non-coding ribonucleic acid (lncRNA) growth arrest specific 5 (GAS5) knockdown on the apoptosis of neurons in rats with cerebral infarction (CI), and to explore the potential mechanism of lncRNA GAS5 in the pathogenesis of CI. MATERIALS AND METHODS: A total of 60 adult male Sprague Dawley (SD) rats aged 12-14 weeks old and weighing (267.14±6.49) g were randomly divided into three groups: Sham operation group (Sham group, n=20), CI group (n=20) and CI + lncRNA GAS5 knockdown group [CI + GAS5 small interfering RNA (siRNA) group, n=20]. The rat model of focal CI was constructed by carotid artery embolization. After the CI model was successfully induced, a certain amount of lncRNA GAS5 siRNAs was injected into the rat lateral ventricle in a stereotactic manner. At 24 h after operation, triphenyl tetrazolium chloride (TTC) method was used to detect the infarction area in brain tissues of rats in each group. At the same time, the pathological changes of neurons in the hippocampus and prefrontal cortex of rats in each group were observed via hematoxylin and eosin (H&E) staining. The expressions of B-cell lymphoma 2 (Bcl-2) and Bcl-2-associated X protein (BAX) were detected via Western blotting. Terminal deoxynucleotidyl transferase dUTP nick end labeling (TUNEL) staining was adopted to detect the number of apoptotic neurons in brain tissues of rats in each group. Meanwhile, the expression level of Notch intracellular domain (NICD) proteins was measured using the Western blotting technique and immunohistochemical staining. RESULTS: Reverse transcription-polymerase chain reaction (RT-PCR) showed that the lncRNA GAS5 expression in brain tissues of rats in CI group was significantly higher than that of rats in Sham group (p<0.05). TTC staining results revealed that lncRNA GAS5 knockdown could remarkably reduce the CI area of rats in CI group (p<0.05). In addition, inhibiting lncRNA GAS5 could also significantly reduce the level of pro-apoptotic gene BAX and increase the expression level of anti-apoptotic gene Bcl-2 (p<0.05). In the meantime, the number of apoptotic neurons in CI + GAS5 siRNA group was also evidently decreased (p<0.05). Finally, it was found that lncRNA GAS5 knockdown notably inhibited the expression of NICD proteins (p<0.05). CONCLUSIONS: The inhibitory effect of lncRNA GAS5 knockdown on the apoptosis of neurons in CI rats may be related to the activation of the Notch1 signaling pathway. LncRNA GAS5 may be a new target for clinical treatment of CI.

Influence of lncRNA ANRIL on neuronal apoptosis in rats with cerebral infarction by regulating the NF-κB signaling pathway.

OBJECTIVE: The aim of this study was to evaluate the influence of long non-coding ribonucleic acid (lncRNA) antisense non-coding RNA in the INK4 locus (ANRIL) on neuronal apoptosis in rats with cerebral infarction (CI), and to further explore the underlying mechanism of lncRNA ANRIL in the occurrence and development of CI. MATERIALS AND METHODS: A total of 60 adult male Wistar rats were randomly divided into three groups using a random number table, including sham group (n=20), CI group (n=20) and CI + lncRNA ANRIL knockdown group [CI + lncRNA ANRIL small-interfering RNA (siRNA) group, n=20]. Focal CI was constructed by suture occlusion. After successful modeling, lncRNA ANRIL siRNA was stereotactically injected into the lateral ventricle of the rats. 24 h after operation, the neurological function of the rats in each group was evaluated by the modified neurological severity score (mNSS). Meanwhile, the infarction area of brain tissues was evaluated using the triphenyl tetrazolium chloride (TTC) method. The protein expression levels of apoptosis-related genes, including B-cell lymphoma-2 (Bcl-2) and Bcl-2 associated X protein (Bax), were detected via Western blotting. Subsequently, immunofluorescence staining was performed to detect the expression and location of Caspase-3 in brain tissues. Moreover, the apoptosis level of rats in each group was detected by terminal deoxynucleotidyl transferase-mediated dUTP nick end labeling (TUNEL) assay. Furthermore, the expressions of nuclear factor-κB (NF-κB) signaling pathway-related proteins were detected via Western blotting. RESULTS: Polymerase Chain Reaction (PCR) results revealed that the expression level of lncRNA ANRIL in the CI group was significantly increased when compared with that of the sham group (p<0.05). The results of mNSS and TTC staining manifested that knockdown of lncRNA ANRIL could significantly reduce CI-induced neurological deficits and CI area (p<0.05). At the same time, knockdown of lncRNA ANRIL markedly decreased the level of Bax, whereas increased the expression of Bcl-2 (p<0.05). Besides, the number of apoptotic cells in the CI + lncRNA ANRIL siRNA group was remarkably decreased (p<0.05). In addition, lncRNA ANRIL down-regulation remarkably inhibited the phosphorylation of p65 (p<0.05). CONCLUSIONS: The inhibitory effect of lncRNA ANRIL knockdown on neuronal apoptosis in CI rats may be probably related to its inhibition of the NF-κB signaling pathway. Furthermore, lncRNA ANRIL inhibitor is expected to become a targeted drug in the clinical treatment of CI.

Long noncoding RNA PVT1-214 enhances gastric cancer progression by upregulating TrkC expression in competitively sponging way.

OBJECTIVE: Long noncoding RNA plasmacytoma variant translocation 1 (lncRNA PVT1) is aberrantly expressed and involved in the promotion of various cancers. However, the vital epigenetic function of PVT1-214, a transcript isoform of PVT1, in gastric cancer (GC) remains unknown. We aimed to investigate the dysregulation and detailed mechanism underlying the involvement of lncRNA PVT1-214 in GC. PATIENTS AND METHODS: The expression of PVT1-214 in GC tissues and cell lines was detected by qRT-PCR. The relationship between increased PVT1-214 levels and the advanced clinicopathological features of tumor tissues was analyzed using a Chi-square test. The influence of PVT1-214 on the survival rate of GC cell lines was evaluated by the log-rank test. Cell lines were used to explore the carcinogenic effects of PVT1-214 in vitro and in vivo, and specific tests included cell apoptosis determined by flow cytometry, cell proliferation assayed by Cell Counting Kit-8 (CCK-8) and colony formation, and the use of these cells for mice xenograft models. Direct complementary binding was predicted by bioinformatics and verified by dual luciferase reporter assay, RNA transfection, quantitative polymerase chain reaction (qPCR), and Western blotting. Spearman's correlation coefficient was adopted to evaluate the correlation between miR-128 and PVT1-214 levels. RESULTS: PVT1-214 expression in GC tissues and cell lines is markedly elevated. In GC patients, high expression of PVT1-214 is associated with late tumor stage, increased tumor size, and poor survival. PVT1-214 silencing represses cell proliferation and enhances apoptosis of GC cells both in vivo and in vitro. Additionally, PVT1-214 functions as a competing endogenous RNA (ceRNA) by binding to miR-128. Inhibition of miR-128 releases Tropomyosin receptor kinase C (TrkC) from the complementary binding complex, subsequently increasing the protein level of TrkC in GC cells. CONCLUSIONS: PVT1-214-induced miR-128 repression regulates TrkC to further the progression of GC, indicating that this process will provide a promising therapeutic target in GC.

[Diffusion tensor imaging and visual evoked potentials in pediatric patients with sellar region lesions].

Objiective: To evaluate the prognosis of visual function and the impact of surgery in pediatric patients with sellar mass lesions, as evidenced by diffusion tensor imaging (DTI) and visual evoked potentials. Methods: Twenty patients with sellar mass lesions were included in the study. DTI and visual evoked potentials were obtained before and after surgery. Fractional anisotropy (FA) and apparent diffusion coefficient (ADC) values were calculated for both optic nerves. DTI parameters and visual evoked potential amplitudes were compared for all patients to assess the correlation between DTI parameters and visual function. Results: The 20 patients were divided into two groups according the relationship between the lesions and the optic chiasm. The FA values increased significantly after operation, while the ADC values decreased (P<0.05). And the average amplitude of visual evoked potentials after operation was significantly higher than before operation (P<0.05). Conclusions: DTI assessments of the affected sides, with the resulting FA and ADC values, may help to estimate the visual improvement produced by surgical therapy in the early postoperative period. Surgical removal can improve visual function dramatically.

[The application of stereo-electroencephalography guided radiofrequency thermocoagulation in refractory temporal epilepsy].

Objective: To investigate the clinical value of stereo-electroencephalography guided radiofrequency thermos-coagulation (RFTC) in drug resistant temporal epilepsy. Methods: The clinical data of 12 patients with refractory temporal epilepsy who underwent implantation of SEEG electrodes and radiofrequency thermos-coagulation from July 2016 to November 2017 were analysed retrospectively. Results: The mean follow-up time was 6.4±4.6 months after thermos-coagulation, and 10.2±3.5 months after resection. Engel Ⅰa was observed in 9 cases, with Ⅱa, Ⅲa and Ⅳa 1 cases respectively. Nine patients experienced a ≥50% decrease of seizure frequency after RFTC (R+ , 75%), of whom one had got a sustained seizure free for 15 months and the other with decrease of seizure frequency by over 90% for 14 months. There was a statistical significance in seizure frequency between pre- and post-thermo-coagulation (P=0.008). Ten cases underwent open surgery following SEEG-guided RFTC, of them 8 cases got seizure free. RFTC was effective in 6 of 8 cases. In our group, all patients have not suffered from any neurologic and cognitive deficiency, and even several patients have some improvements on memory quotient. Conclusions: Although it is less effective than resective surgery, SEEG-guided RFTC can be a relatively safe, effective treatment because of its precision and minimal invasion for patients with complex drug resistant temporal epilepsy, especially for impossible any cortical resection. In addition, its effect may be a predictor of outcome after conventional cortectomy.

TRIM59 is a key regulator of growth and migration inrenal cell carcinoma.

Renal cell carcinoma (RCC) is the most common renal neoplasms and metastatic is common. Previous data have shown that the tripartite motif (TRIM) family proteinswere implicated in human tumoriogenesis. In this study, we aimed to investigate the role of TRIM59 in the cell growth and migration in RCC. The expression of TRIM59 in human RCC tissues was initially examined by qRT-PCR. Alentivirus-based shRNA against TRIM59 (Lv-shTRIM59) was constructed. The effects of TRIM59 knockdown on cell proliferation were examined by in vitro MTT assay, colony formation assay and in vivo a mouse xenograft model of RCC. Cell migration and invasion after knockdown of TRIM59 were also examined by transwell assay. Our data showed that the mRNA level of TRIM59 in cancerous tissues was 2-fold increased as compared with non-cancerous tissues. Knockdown of TRIM59 in a RCC cell line 786-O significantly slowed down cell proliferative rate and decreased both the colony number and sizes. In the mouse model, knockdown of TRIM59 consistently inhibited tumor growth in vivo. Moreover, it was shown that cell migration and invasion were suppressed by 68% and 50%, respectively in TRIM59-depleted 786-O cells. Our data suggest that TRIM59 may serve as a pro-oncogenic protein in promoting the progression of RCC. Knockdown of TRIM59 may be a promising strategy concerning the early detection and treatment of RCC.

Expression and prognostic roles of magnesium-dependent phosphatase-1 in gastric cancer.

OBJECTIVE: Gastric cancer is a leading cause of cancer deaths and has a poor prognosis after diagnosis. Previous studies showed that Magnesium-Dependent Phosphatase-1 (MDP-1) might be a key component for glycosylation in human protein repair, and an alteration of its function has been involved in some aspects of cellular metabolic networks linked to either normal or pathological processe. In this study, we investigate the MDP-1 status in patients with gastric carcinoma, and determine the potential relationship between MDP-1 and clinical outcome. PATIENTS AND METHODS: One hundred and seventy-one consecutive patients with stage I-III gastric carcinoma who had received a D2 gastrectomy were recruited. The MDP-1 expression was determined by immunohistochemistry (IHC). Disease-free survival (DFS) and overall survival (OS) were evaluated. RESULTS: We generate an IHC score on a continuous scale of 0-7. The IHC cutoff point generated by ROC analysis and the threshold IHC score was 2. Low MDP-1 expression was scored for 61 (35.7%) and high MDP-1 expression for 110 (64.3%) patients. We saw a significant down-regulation of MDP-1 expression in G3-4 and stage III tumor tissue compared with G1-2 and stage I-II tumors, p=0.023 and p=0.047. In univariate survival analysis, high expression of MDP-1 predicted a significantly better DFS (56.0 months vs. 25.0 months, p=0.029) and OS (59.0 months vs. 41.0 months, p=0.043) compared with low expression. In a multivariate analysis, the tumor stage was a significant predictor for DFS and OS even after adjustment for all other covariates. The MDP-1 status was a joint predictor for DFS and OS with a multivariate HR 0.728, 95% CI 0.530-0.999, p=0.049 and a multivariate HR 0.745, 95% CI 0.543-1.022, p=0.068, respectively. CONCLUSIONS: We showed that down-regulation of MDP-1 expression was correlated with poorly differentiated carcinoma and later tumor stage, and it predicted a significantly poorer DFS and OS. Down-regulation of MDP-1 expression was a predictor of a poor prognosis for gastric cancer patients, and it may refer to tumor cells that have lost a protective enzymatic system.

[Clinicopathologic features and expression of OCT4 protein in testicular diffuse large B cell lymphoma].

Objective: To evaluate the expression of OCT4 and SALL4 in testicular diffuse large B-cell lymphoma (DLBCL), and the utility of an immunohistochemical (IHC) panel of OCT4, SALL4 and CD20 in the differential diagnosis of DLBCL and GCT of the testis. Methods: Eighteen cases of testicular DLBCL were selected.IHC method was used to detect the protein expression of CD20, CD3, CD5, CD10, bcl-6, MUM1, Ki-67, bcl-2, c-MYC, OCT4 and SALL4. Results: Among the 18 cases, CD20 and PAX5 were strongly and diffusely expressed in all cases, while CD21, CD3, cyclinD1, SALL4, CD117 and PLAP were all negative. CD5, bcl-2 and c-myc were expressed in 3, 16 and 8 cases, respectively. Ki-67 proliferation index ranged from 40%-95%. Bcl-2 and c-MYC were co-expressed in seven cases. Four cases were GCB-DLBCL and the remaining 14 cases were non-GCB-DLBCL, according to Hans algorithm. Nuclear OCT4 expression was present in two cases, which demonstrated moderate expression in >50% of neoplastic cells. Univariate analysis showed that clinical stage, CD5 and OCT4 expression were relevant to prognosis. Multivariate Cox regression analysis further confirmed that clinical stage, CD5 and OCT4 were independent prognostic factors in patients with testicular DLBCL. Conclusions: Care should be exercised in using OCT4 as the sole marker of germ cell differentiation in the testis. The association of OCT4 and CD5, bcl-2 co-expression raises the question of whether OCT4 expression in DLBCL may reflect more aggressive biology.

miR-760 mediates chemoresistance through inhibition of epithelial mesenchymal transition in breast cancer cells.

OBJECTIVE: Therapeutic resistance has been a great obstacle for successful treatment of breast cancer. Our study aimed to explore the role of microRNA-760 (miR-760) in chemoresistant breast cancer cells. MATERIALS AND METHODS: Real-time PCR was performed to measure the mRNA expression of miR-760 and Nanog. Western blot was used to determine the protein expression of Nanog and mesenchymal and epithelial markers. Cell viability was measured by the CCK-8 assay. RESULTS: Our results showed that the expression of miR-760 was significantly reduced the doxorubicin (DOX)-resistant MCF-7/DOX cells and chemoresistant breast cancer tissues. Moreover, up-regulation of miR-760 sensitized breast cancer cells to the anti-cancer agents. The MCF-7/DOX cells exhibited increased expression of Snail, a mesenchymal marker, and decreased levels of E-Cadherin, an epithelial marker. In addition, overexpression of miR-760 suppressed the expression of Nanog, a transcriptional factor involved in chemoresistance, and resulted in the reversal of EMT in breast cancer cells. CONCLUSIONS: Our study demonstrated that miR-760 modulated chemoresistance through the epithelial-mesenchymal transition in breast cancer cells, providing a potential therapeutic target for treatment of drug-resistant breast cancer.

[Expression of PDGFRA and CMYC in extranodal NK/T-cell lymphoma and their prognostic implications].

Objective: To investigate the relationship between expression of PDGFRA/CMYC and clinicopathologic features of extranodal NK/T-cell lymphoma. Methods: Fifty-four cases of extranodal NK/T-cell lymphoma were included in the study.Immunohistochemistry was used to detect the expression of CD20, CD2, CD3, CD56, TIA1, GrB, Ki-67, PDGFRA and CMYC.In situ hybridization was performed to detect the presence of EBV encoded small RNA (EBER). Fifty cases of nasopharyngeal mucosal lymphoid tissue hyperplasia were used as normal control. Results: Among 54 cases of ENKTL, CD2, CD3, GrB, and TIA1 were expressed in all the tumors. CD56 was expressed in 47 cases (81.0%) and CD20 was not detectable in any cases. Ki-67 proliferative index expression of > 60% was found in 45 cases (83.3%). In situ hybridization for EBER was positive in all cases (100%). The positive expression rates of PDGFRA and CMYC in extranodal NK/T-cell lymphomas were 51.9%(28/54) and 53.7%(29/54), respectively, much higher than those in nasopharyngeal mucosal lymphoid tissue hyperplasia (0, P<0.05). There was a positive correlation between PDGFRA and CMYC (r=0.295, P<0.05). The expression of CMYC was correlated with clinical efficacy (P<0.05), but not with gender, age, Ann Arbor stage, B symptoms and therapeutic regimen (all P>0.05). The expression of PDGFRA was correlated with B symptoms (P<0.05), while not with gender, age, Ann Arbor stage, therapeutic regimen and clinical efficacy (all P>0.05). The co-expression of PDGFRA and CMYC was not correlated with gender, age, Ann Arbor stage, B symptoms, therapeutic regimen and clinical efficacy (P>0.05). Univariate analysis showed that the stage, clinical efficacy, CMYC protein and the co-expression of PDGFRA and CMYC were significantly correlated with the prognosis. The overall survival of the patients with CMYC positive expression was shorter than of that of the patients with negative expression (P<0.05). Multivariable Cox regression analysis further confirmed that clinical stage, CMYC protein expression, and the co-expression of PDGFRA and CMYC were independent prognostic factors in patients with extranodal NK/T-cell lymphoma. Conclusion: CMYC protein, and the co-expression of PDGFRA and CMYC can be as an independent prognostic factor in patients with extranodal NK/T-cell lymphoma and influence the prognosis of patients.

The maternal cytoplasmic environment may be involved in the viability selection of gametes and zygotes.

Segregation distortion is the phenomenon whereby the observed genotypic frequencies of a locus fall outside the expected Mendelian segregation ratio, and it is increasingly recognised as a potentially powerful evolutionary force. The main reason for segregation distortion is a difference in the viability of gametes and zygotes caused by viability loci in the segregating progeny. However, the maternal cytoplasm may also be involved in the viability selection of gametes and zygotes. The objectives of this study were to map the segregation distortion loci (SDL) in maize and to test the hypothesis that the viability of gametes and zygotes may also be associated with the maternal cytoplasmic environment. In the present study, a reciprocal mating design was conducted to generate an F2-segregating population. A linkage map was constructed with 126 microsatellite markers. A whole-genome scan was performed to detect the SDL in segregating populations with different maternal cytoplasm environments. Altogether, 14 SDL with strong LOD (logarithm (base 10) of odds) supports were identified in the specifically designed F2 populations. Interestingly, we found dramatic changes in the genotypic frequencies of the SDL in the two maternal cytoplasmic backgrounds, which indicated a change in the viability of gametes and zygotes in different cytoplasmic environments. Furthermore, in the JB cytoplasmic background, most of the detected SDL and complete distortion markers exhibited similar bias patterns favouring the Y53 alleles. These results suggested that selfish cytoplasmic elements may have an important role in shaping the patterns of segregation distortion in F2 populations through selective viability of gametes and zygotes.

Genetic variation in thrombin-activatable fibrinolysis inhibitor is associated with the risk of diabetic nephropathy.

Diabetic nephropathy is a kidney disease or damage that results as a complication of diabetes, especially Type 2 diabetes, while albuminuria is an early marker for diabetic nephropathy as it can predict cardiovascular events and mortality in diabetic patients. A potent inhibitor of fibrinolysis, the thrombin-activatable fibrinolysis inhibitor (TAFI) has been isolated and characterized from human plasma. We investigated the associations of the activity-related variants in the TAFI coding gene (505A/G,1040C/T) with the risk of diabetic nephropathy by examining 297samples including 140 health controls and 157 confirmed diabetic nephropathy patients. Diabetic nephropathy grades were further categorized by the urine albumin excretion (UAE)-to-creatinine ratios (ACR). We found little difference that was statistically significant in terms of 505A/G among patients and controls. While at 1040C/T, the detected frequency for the T allele in the group of diabetic nephropathy patients was significantly smaller than that of the control group (15.6% vs 25.7%, respectively; p<0.05). This was due to the relative decrease of T/T homozygotes in the patients (p<0.05, 95% odds ratio 0.28, confidence interval 0.11-0.70). Surprisingly, the difference was only observed with initial diabetic nephropathy stages. This study clearly indicates that, at 1040C/T, the frequency for the T allele is strongly associated with increased risk for diabetic nephropathy in a subset of the general population, implying that the T allele confers protection against the onset of diabetic nephropathy only in homozygosity and may function as a recessive trait.

Diode-pumped femtosecond Yb:CaNb2O6 laser.

We report to our knowledge a diode-pumped passively mode-locked Yb:CaNb(2)O(6) (Yb:CN) laser for the first time. Both CW and passive mode-locking operation of the laser are experimentally investigated. A maximum CW output power of 1.4 W with a slope efficiency of 20% is obtained on a 7 mm long 1.5 at.% Yb:CN crystal, while stable passive mode-locking with a commercial semiconductor saturable absorption mirror (SESAM) was achieved on a 3 mm long 3 at.% Yb:CN crystal. The mode-locked pulses have pulse width of 251 fs and an average output power of 44 mW at 1038 nm.

Evidence of dissipative solitons in Yb³âº:CaYAlO4.

Operation of an end-pumped Yb³âº:CaYAlO4 laser operating in the positive dispersion regime is experimentally investigated. The laser emitted strongly chirped pulses with extremely steep spectral edges, resembling the characteristics of dissipative solitons observed in fiber lasers. The results show that dissipative soliton emission constitutes another operating regime for mode locked Yb³âº-doped solid state lasers, which can be explored for the generation of stable large energy femtosecond pulses.

Femtosecond and continuous-wave laser performance of a diode-pumped Yb3+:CaYAlO4 laser.

The cw and femtosecond laser operations of Yb(3+):CaYAlO(4) (Yb:CYA) are demonstrated. The laser emitted a maximum cw power of 1.94 W with a slope efficiency (η(slope)) of 71% and an optical-to-optical efficiency (η(opt)) of 51%. Under mode-locking operation, the laser emitted near transform-limited pulses with 156 fs pulse width, 8.1 nJ pulse energy and 0.74 W average power. The η(slope) and η(opt) of the mode-locked laser were 37% and 20%, respectively.

Cell growth suppression by thanatos-associated protein 11(THAP11) is mediated by transcriptional downregulation of c-Myc.

Thanatos-associated proteins (THAPs) are zinc-dependent, sequence-specific DNA-binding factors involved in cell proliferation, apoptosis, cell cycle, chromatin modification and transcriptional regulation. THAP11 is the most recently described member of this human protein family. In this study, we show that THAP11 is ubiquitously expressed in normal tissues and frequently downregulated in several human tumor tissues. Overexpression of THAP11 markedly inhibits growth of a number of different cells, including cancer cells and non-transformed cells. Silencing of THAP11 by RNA interference in HepG2 cells results in loss of cell growth repression. These results suggest that human THAP11 may be an endogenous physiologic regulator of cell proliferation. We also provide evidence that the function of THAP11 is mediated by its ability to repress transcription of c-Myc. Promoter reporter assays indicate a DNA binding-dependent c-Myc transcriptional repression. Chromatin immunoprecipitations and EMSA assay suggest that THAP11 directly binds to the c-Myc promoter. The findings that expression of c-Myc rescues significantly cells from THAP11-mediated cell growth suppression and that THAP11 expression only slightly inhibits c-Myc null fibroblasts cells growth reveal that THAP11 inhibits cell growth through downregulation of c-Myc expression. Taken together, these suggest that THAP11 functions as a cell growth suppressor by negatively regulating the expression of c-Myc.

Overexpression of a hematopoietic transcriptional regulator EDAG induces myelopoiesis and suppresses lymphopoiesis in transgenic mice.

Erythroid differentiation-associated gene (EDAG) is a hematopoietic tissue-specific gene that is highly expressed in the earliest CD34+ lin- bone marrow (BM) cells and involved in the proliferation and differentiation of hematopoietic cells. To investigate the role of EDAG in hematopoiesis, we established an EDAG transgenic mouse model driven by human CD11a promoter. The transgenic mice showed increased mortality with severe organ infiltration by neutrophils, and the homeostasis of hematopoiesis was broken. The myelopoiesis was enhanced with expansion of myeloid cells in BM, increased peripheral granulocytes and extramedullary myelopoiesis in spleen. In contrast to myeloid cells, the lymphoid commitment was severely impaired with the B lymphopoiesis blocked at the transition from pro/pre-B I to pre-B II stage in BM and T thymocytes development blocked at the most immature stage (DN I). Moreover, we showed that EDAG was a transcriptional regulator which had transactivation activity and regulated the expression of several key transcription factors such as PU.1 and Pax5 in transgenic hematopoietic stem cells. These data suggested that EDAG was a key transcriptional regulator in maintaining the homeostasis of hematopoietic lineage commitment.