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The prognostic value of the systemic immune-inflammation index during induction (ISII) remains unclear in non-muscle-invasive bladder cancer (NMIBC) patients receiving Bacillus Calmette-Guérin (BCG). This study first found that ISII could independently predict the prognosis of NMIBC patients receiving BCG, which might help to select an optimal treatment schedule for patients with NMIBC. Background: The prognostic value of the systemic immune-inflammation index during induction (ISII) remains unclear in non-muscle-invasive bladder cancer (NMIBC) patients receiving Bacillus Calmette-Guérin (BCG). We aimed to determine and compare the prognostic value of the ISII, preoperative systemic immune-inflammation index (PSII) and their dynamic changes (PISII). Methods: This study respectively collected data from 362 NMIBC patients receiving BCG treatment in our institution. The prognostic values of PSII, ISII and PISII were analyzed by the Kaplan -Meier method and Cox proportional hazard regression models. The concordance index and receiver operating characteristic curve analysis were employed to compare the prognostic value of these 3 factors. Results: Our study enrolled 197 patients. These patients included 170 male patients, and the mean age was 64.17 years. During the follow-up time, 85 patients experienced recurrence and 55 patients found progression. According to the results of Cox multivariable analysis, PSII (P = .001) and ISII (P < .001) could independently predict the recurrence of NMIBC patients receiving BCG. Meanwhile, PSII (P = .025) and ISII (P < .001) were also independent prognostic factors of progression. Compared with PSII, ISII was associated with better accuracy for NMIBC patients receiving BCG. Conclusion: This study first found that ISII could independently predict the prognosis of NMIBC patients receiving BCG. Furthermore, we also identified that ISII was associated with higher prognostic value than PSII and PISII, which might help to select an optimal treatment schedule for patients with NMIBC. [ABSTRACT FROM AUTHOR]

• Les complications fœtales étaient plus fréquentes chez les nouveau-nés de mères atteintes de lupus érythémateux systémique ou de polyarthrite rhumatoïde. • Le risque de trouble du spectre autistique n'était pas élevé chez les enfants de mères atteintes de lupus érythémateux systémique ou de polyarthrite rhumatoïde. • Des facteurs de risque traditionnels, notamment âge maternel et score d'Apgar, ont été associés aux troubles du spectre autistique chez les nouveau-nés de mères atteintes de lupus érythémateux systémique ou de polyarthrite rhumatoïde. Déterminer si les nouveau-nés de mères taïwanaises atteintes de lupus érythémateux systémique ou de polyarthrite rhumatoïde ont plus de risques de présenter des troubles du spectre autistique. Nous avons identifié dans la base de données de l'assurance maladie nationale et le registre national des naissances une cohorte de toutes les naissances vivantes à Taïwan entre 2001 à 2012. Les enfants dont la mère était atteinte de lupus érythémateux systémique ou de polyarthrite rhumatoïde ont été identifiés et appariés à huit témoins selon l'âge maternel, le score d'Apgar à 1 minute, le score d'Apgar à 5 minutes, le type d'accouchement, le sexe de l'enfant, l'âge gestationnel, le poids de naissance et le lieu de résidence. Des modèles marginaux de régression de Cox ont été utilisés pour estimer le risque relatif (RR), avec un intervalle de confiance à 95 %, de TSA chez les nouveau-nés. Sur 1 893 244 nouveau-nés, 0,08 % (n = 1594) avaient une mère atteinte de lupus érythémateux systémique et 0,04 % (n = 673), une mère atteinte de polyarthrite rhumatoïde. Au total, 5 enfants de mère atteinte de polyarthrite rhumatoïde sur 673 (0,74 %), 7 enfants de mère atteinte de lupus érythémateux systémique sur 1594 (0,44 %) et 10 631 enfants de la cohorte totale de 1 893 244 (0,56 %) nouveau-nés présentaient des TSA. L'incidence des TSA (par 100 000 personnes-année) était de 140,39 (IC 95 % 45,58–327,62) dans le groupe polyarthrite rhumatoïde et de 76,19 (IC 95 % 30,63–156,97) dans le groupe lupus érythémateux systémique. Le risque de TSA n'était donc pas significativement plus élevé chez les nouveau-nés de mère atteinte de polyarthrite rhumatoïde (HR 1,42 ; IC 95 % 0,60–3,40) ou de lupus érythémateux systémique (HR 0,76 ; IC 95 % 0,36–1,59). Dans cette étude, les nouveau-nés dont la mère est atteinte de lupus érythémateux systémique ou de polyarthrite rhumatoïde n'ont pas plus de risques de présenter des troubles du spectre autistique. [ABSTRACT FROM AUTHOR]

Highlights • Time-resolved pump-probe system is used to monitoring the femtosecond laser annealing of indium tin oxide. • The transmittance variation detected by the probe beam gradually increases with increasing machining power. • The 400-nm probe beam is more sensitive than the 800-nm probe beam in measuring curve variation. Abstract In this study, a set of time-resolved pump-probe systems for the real-time monitoring of femtosecond (fs) laser annealing of ITO substrates is established. A pump beam is used as the light source for thermal annealing, and a probe beam is used to monitor the transmittance variation of ITO in real time. Measurement results show that with increasing machining energy, the transmittance variation detected by the probe beam gradually increases. When the laser energy is small, the transmittance changes arithmetically. When the laser energy is sufficient to complete the modification of ITO, the transmittance variation rises suddenly and sharply, indicating that the thermal annealing modification has been completed in the irradiated area. Then, the laser source is shut down to achieve real-time monitoring. Degenerate and non-degenerate pump-probe experimental results indicate that the 400-nm probe beam is more sensitive than the 800-nm probe beam in measuring curve variation because the variation in the ITO transmission spectrum in the 400-nm wave band is greater than that in the 800-nm wave band. Electron backscatter diffraction analysis indicates that the crystallographic directions of ITO after laser annealing are consistent. This shows that the ITO changed from non-crystallized to crystallized after being irradiated by the pump beam, confirming the thermal annealing modification. [ABSTRACT FROM AUTHOR]

Objectives: To determine whether offspring of Taiwanese mothers with systemic lupus erythematosus or rheumatoid arthritis have a higher risk of autism spectrum disorder.Methods: Using the National Health Insurance database and National Birth Registry, we identified a cohort of all live births in Taiwan between 2001 and 2012. Children born to mothers with systemic lupus erythematosus or rheumatoid arthritis were identified and matched with up to 8 controls by maternal age, 1-minute Apgar score, 5-minute Apgar score, mode of delivery, sex of the child, gestational age, birth weight and place of residence. Marginal Cox proportional hazard models were used to estimate relative risk (RR) with 95% confidence intervals (CI) for ASD in offspring.Results: Of 1,893,244 newborns, 0.08% (n=1594) were born to systemic lupus erythematosus mothers, and 0.04% (n=673) were born to rheumatoid arthritis mothers. Overall, 5 of 673 (0.74%) offspring of rheumatoid arthritis mothers, 7 of 1594 (0.44%) offspring of systemic lupus erythematosus mothers and 10,631 of 1,893,244 (0.56%) offspring of all mothers developed autism spectrum disorder. Autism spectrum disorder incidence (per 100,000 person-years) was 140.39 (95% CI, 45.58-327.62) for the rheumatoid arthritis group and 76.19 (95% CI, 30.63-156.97) for the systemic lupus erythematosus group. Autism spectrum disorder risk was not significantly higher for children born to mothers with rheumatoid arthritis (HR, 1.42; 95% CI, 0.60-3.40) or systemic lupus erythematosus (HR, 0.76; 95% CI, 0.36-1.59).Conclusions: Children born to women with systemic lupus erythematosus or rheumatoid arthritis do not have a higher risk of autism spectrum disorder. [ABSTRACT FROM AUTHOR]

Migraine is a highly prevalent neurovascular disorder in the brain. An optimal therapy for migraine has not yet been developed. Gastrodin (Gas), the main effective constitute from Gastrodiae Rhizoma (Tianma in Chinese), has been indicated for migraine treatment and prophylaxis more than 30 years, with demonstrated safety. However, Gas is a phenolic glycoside, with relatively low concentrations and weak efficacy in the central nervous system. To develop more effective anti-migraine agents, we synthesized a novel Gas derivative (Gas-D). In the present study, comparative pharmacodynamic evaluations of Gas and Gas-D were performed in a model of nitroglycerin (NTG)-induced migraine in rats and the hot-plate test in mice. Following behavioral testing in this migraine model, external jugular vein blood and the trigeminal nucleus caudalis (TNC) were collected to analyze plasma nitric oxide (NO) and calcitonin gene-related peptide (CGRP) concentrations and c-Fos expression in the TNC. The acute oral toxicity of Gas and Gas-D was also examined. We found that Gas-D had potent anti-migraine effects, likely attributable to inhibition of both trigeminal nerve activation at central sites and the peripheral release of CGRP following NO scavenging. Additionally, Gas-D exerted significant anti-nociceptive effect in response to thermal pain compared with Gas. Furthermore, a single dose of 2.048 g/kg Gas or Gas-D presented no acute oral toxicity in mice. Altogether, the potent anti-migraine and anti-hyperalgesic effects of Gas-D suggest that it might be a potentially novel drug candidate for migraine treatment or prophylaxis. [ABSTRACT FROM AUTHOR]

Kruppel-like factors (KLFs) belong to a subclass of Cys2/His2 zinc-finger DNA-binding proteins, and act as important regulators with diverse roles in cell growth, proliferation, differentiation, apoptosis and tumorigenesis. Our previous research showed that PmKLF from Penaeus monodon is crucial for white spot syndrome virus (WSSV) infection, yet the mechanisms by which PmKLF influences WSSV infection remain unclear. This study cloned KLF from Litopenaeus vannamei (LvKLF), which had 93% similarity with PmKLF. LvKLF formed a dimer via the C-terminal zinc-finger motif. Knockdown of LvKLF expression by dsRNA injection in WSSV-challenged shrimps was found to significantly inhibit the transcription of two important immediate-early (IE) genes, IE1 and WSSV304, and also reduced WSSV copy numbers. Moreover, reporter assays revealed that the promoter activities of these two WSSV IE genes were substantially enhanced by LvKLF. Mutations introduced in the promoter sequences of IE1 and WSSV304 were shown to abolish LvKLF activation of promoter activities; and an electrophoretic mobility shift assay demonstrated that LvKLF binds to putative KLF-response elements (KRE) in the promoters. Taken together, these results indicate that LvKLF transcriptional regulation of key IE genes is critical to WSSV replication. [ABSTRACT FROM AUTHOR]

Cadherin junctions arise from the integrated action of cell adhesion, signaling, and the cytoskeleton. At the zonula adherens (ZA), a WAVE2-Arp2/3 actin nucleation apparatus is necessary for junctional tension and integrity. But how this is coordinated with cadherin adhesion is not known. We now identify cortactin as a key scaffold for actin regulation at the ZA, which localizes to the ZA through influences from both E-cadherin and N-WASP. Using cell-free protein expression and fluorescent single molecule coincidence assays, we demonstrate that cortactin binds directly to the cadherin cytoplasmic tail. However, its concentration with cadherin at the apical ZA also requires N-WASP. Cortactin is known to bind Arp2/3 directly (Weed, S. A., Karginov, A. V., Schafer, D. A., Weaver, A. M., Kinley, A.W., Cooper, J. A., and Parsons, J. T. (2000) J. Cell Biol. 151, 29-40). We further show that cortactin can directly bind WAVE2, as well as Arp2/3, and both these interactions are necessary for actin assembly at the ZA. We propose that cortactin serves as a platform that integrates regulators of junctional actin assembly at the ZA. [ABSTRACT FROM AUTHOR]

• Geometric dimension of molded part significantly depends on the V/P switchover point and holding condition. • This study proposes a simple least-squares regression-based approach for determining the V/P switchover point based on molded part quality requirement. • Multi-stage holding condition effectively minimizes the residual pressure difference between the near- and far-from-gate regions in the cavity at the end of the packing stage. • For the case investigated in this study (L/t ratio ≈ 141), the difference in width and thickness are greatly alleviated. Injection molding is widely used for the mass production of plastic components. However, an appropriate choice of the process parameters is essential to ensure the precision and uniformity of the molded parts. The flow length-to-wall thickness (L/t) ratio for most molded components lies in the range of 100∼200. For higher values of the L/t ratio, the flow resistance increases dramatically at the end of the molded part and the injection pressure propagates less easily through the mold cavity. Consequently, the geometric dimensions of the molded parts in the near-gate region are frequently different from those in the far-from-gate region as well as resulting in lower uniformity. In practice, the variation in the geometric dimensions is significantly dependent on the filling-to-holding (V/P) switchover point, injection speed, and holding condition. Accordingly, the present study commences by proposing a simple least-squares regression-based approach for determining the appropriate V/P switchover point based on the quality requirement for the geometric dimensions of the molded component. In addition, a multi-stage holding condition is used to improve the geometric uniformity of the molded component by minimizing the residual pressure difference between the near-gate and far-from-gate regions of the mold at the end of the packing stage. Finally, a deceleration strategy is considered for the injection screw at the end of the filling stage to further reduce the quality variation. The experimental results show that for molded components with a large L/t ratio, the V/P switchover point should be determined based on the quality requirement for the part in the far-from-gate region in order to avoid insufficient quality compensation in the early holding stage. Furthermore, compared with the single-stage holding condition, the multi-stage holding condition reduces the residual pressure difference between the near-gate and far-from-gate regions of the cavity by around 74.5% (from 48.7 to 12.5 MPa). As a result, the difference in width between the near-gate region of the molded component and the far-from-gate region is reduced by about 66.7% (0.09 to 0.03 mm), while the difference in thickness is reduced by approximately 32.1% (0.028 to 0.019 mm). The deceleration strategy for the injection screw has no noticeable effect on the quality uniformity of the molded part provided that the V/P switchover point and multi-stage holding pressure are appropriately designed. [ABSTRACT FROM AUTHOR]

Abstract: Introduction: Autophagy is a process for recycling intracellular organelles as a survival mechanism. Apoptosis has important biological roles in the pathogenesis of many diseases. This study elucidated the effect of simvastatin on autophagy/apoptosis in MC3T3E1 murine osteoblastic cells and also the significance of this action on the progression of induced rat apical periodontitis. Methods: We examined the H2O2-stimulated expression of LC3-II (an autophagy marker) and poly (adenosine phosphate ribose) polymerase (PARP) fragmentation (an apoptosis marker) in MC3T3E1 by Western analysis. In a rat model of induced apical periodontitis, the relation between disease progression and osteoblastic expression of Beclin-1 (an autophagy marker) and terminal deoxyuridine triphosphate nick end-labeling (an apoptosis marker) was studied by radiographic and immunohistochemistry analyses. Results: Western blot showed elevated levels of LC3-II and PARP cleavage after H2O2 treatment. An autophagy inhibitor 3-methyladenine promoted whereas rapamycin (an autophagy enhancer) diminished H2O2-induced PARP cleavage. Simvastatin enhanced H2O2-induced LC3-II formation and simultaneously decreased PARP fragmentation. Radiography and immunohistopathology demonstrated that simvastatin reduced the number of apoptotic osteoblasts and the extension of periapical lesions in rats. The number of Beclin-1–synthesizing osteoblasts also increased markedly after simvastatin treatment. Conclusions: We found a negative relation between autophagy and apoptosis in osteoblastic cells. In addition, simvastatin suppressed apoptosis and enhanced autophagy both in vitro and in vivo. Our data implied that simvastain might alleviate the progression of apical periodontitis by promoting autophagy to protect osteoblasts from turning apoptotic. [Copyright &y& Elsevier]

Abstract: Sp1-like proteins and Kruppel-like factors (KLFs) are highly related zinc-finger proteins that have crucial roles in transcription. One expressed sequence tag (EST, HPA-N-S01-EST0038) from shrimps is homologous to Sp1. This study reports the cloning and characteristics of a KLF from shrimp, Penaeus monodon (PmKLF). The full-length PmKLF cDNA is 1702bp, encoding a polypeptide of 360 amino acids. Sequence analysis revealed that the sequence of PmKLF is similar to that of KLF11 in humans, mice and zebrafish. RT-PCR analysis indicated that PmKLF mRNA is expressed in all examined tissues. Additionally, immunofluorescence analysis revealed that GFP–KLF fusion protein is located in the nucleus as dots in an insect cell line, Sf9. Localization of PmKLF in the nucleus is also observed in the hemolymph from white spot syndrome virus (WSSV)-infected and WSSV-uninfected Litopenaeus vannamei. Knockdown of the expression of PmKLF transcript in WSSV-infected shrimp resulted in delayed cumulative mortalities, suggesting that PmKLF is important to WSSV infection. Moreover, inhibition of PmKLF expression reduced the copy number of WSSV and ie1 expression, revealing that PmKLF affects WSSV infection via interfering with ie1 expression. [Copyright &y& Elsevier]

Abstract: Based on the statistics of the features, dropping and leaking of well drilling, and the geophysical & logging data, the developing regulation of karst of buried hill in Renqiu oilfield was systematically studied. The results show that the period of the karst development is mainly in Tertiary, with spatial inhomogeneity. The inhomogeneity is mainly controlled by the geological construction in the horizontal direction. There are 3∼4 level karst developing zones in the profile section, which are mainly controlled by the intermittent subsidence of the earth’s crust started from Tertiary. The forming time of the lower karst zones is earlier than that of the upper ones. The horizontal karst zones are cut off by the latter faults. At present, the chief potential areas of residual oil of Renqiu oilfield are in the weak karst developing zones. [Copyright &y& Elsevier]

The purpose of this report was to present two cases of mandibular premolars with necrotic pulp and open apices treated with two different techniques. The first case was a 20-year-old female whose teeth 35 and 45 were diagnosed with pulpal necrosis and chronic apical periodontitis, possibly resulting from dens evaginatus. Traditional apexification with Ca(OH)2 was chosen; however, teeth 35 and 45 fractured after 2 and 9 months, respectively. The second case was an 11-year-old boy whose tooth 45 was diagnosed with necrotic pulp and a chronic apical abscess, possibly resulting from dens evaginatus. The mineral trioxide aggregate (MTA) barrier technique was performed after short-term Ca(OH)2 dressing, and the remaining space of the canal was fitted with light-cured composite resin. The tooth remained healthy and functional at 1-year follow-up. The apical barrier technique using MTA has the advantages of a reduced treatment time, lower chance of tooth fracture, and fewer visits to the dental office. This report demonstrates that the MTA barrier technique followed by light-cured composite resin filling can be a good alternative treatment to traditional apexification. [ABSTRACT FROM AUTHOR]

Abstract: This paper presents a computation scheme that generates optimized tool path for five-axis flank milling of ruled surface. Tool path planning is transformed into a matching problem between two point sets in 3D space, sampled from the boundary curves of the machined surface. Each connection in the matching corresponds to a possible tool position. Dynamic programming techniques are applied to obtain the optimal combination of tool positions with the objective function as machining error. The error estimation considers both the deviation induced by the cutter at discrete positions and the one between them. The path planning problem is thus solved in a systematic manner by formulizing it as a mathematical programming task. In addition, the scheme incorporates several optimization parameters that allow generating new patterns of tool motion. Implementation results obtained from simulation and experiment indicate that our method produces better machining quality. This work provides a concise but effective approach for machining error control in five-axis flank milling. [Copyright &y& Elsevier]

An excessive amount of matrix metalloproteinase-9 (MMP-9) has been well documented in inflammatory diseases, including chronic wounds and cancers. Secreted as a zymogen, proMMP-9 can be irreversibly converted to a mature form through cleavage of the N-terminal propeptide domain. Although the converting enzyme for proMMP-9 in human tissues is unknown, we previously found that tumor necrosis factor-α (TNF-α) promotes activation of proMMP-9 in human skin, and characterized the converting activities as tissue-associated chymotrypsin-like proteinases. On the other hand, the pathophysiologic inhibitor to prevent proMMP-9 maturation also remains elusive. In this regard, we observed the presence of the inhibitory property in burn blister fluid that abrogates the skin extract–mediated activation of proMMP-9. Then we determined that α-1-antichymotrypsin (α-ACT), an acute-phase factor abundantly present in the blister, effectively inhibited proMMP-9 activation in human and rodent skin. In contrast, the aminophenylmercuric acetate-induced “cysteine switch” and activation of proMMP-9 were not affected by α-ACT. TNF-α-induced activation of proMMP-9 by the explants of human skin was inhibited by α-ACT but not by related α-1-antitrypsin. α-ACT specifically attenuated maturation of proMMP-9 but not proMMP-2 or proMMP-13. Furthermore, short peptides that mimic the reactive center loop (RCL) of α-ACT were sufficient to inhibit the conversion. Mutation analysis demonstrated that a conserved leucine within the RCL was critical for α-ACT-exerted inhibition. In chronic wounds, a large amount of mature MMP-9 was associated with fragmentation and inactivation of α-ACT. Taken together, these results demonstrate that, to the best of our knowledge, α-ACT is a previously unreported pathophysiologic inhibitor that controls proMMP-9 activation in skin tissue.Journal of Investigative Dermatology (2008) 128, 2334–2342; doi:10.1038/jid.2008.77; published online 10 April 2008 [ABSTRACT FROM AUTHOR]

Abnormal wound healing encompasses a wide spectrum, from chronic wounds to hypertrophic scars. Both conditions are associated with an abnormal cytokine profile in the wound bed. In this study, we sought to understand the dynamic relationships between myofibroblast differentiation and mechanical performance of the collagen matrix under tissue growth factor–β (TGF-β) and tumor necrosis factor–α (TNF-α) stimulation. We found TGF-β increased α-smooth muscle actin (α-SMA) and TNF-α alone decreased the basal α-SMA expression. When TGF-β1 and TNF-α were both added, the α-SMA expression was suppressed below the baseline. Real-time PCR showed that TNF-α suppresses TGF-β1-induced myofibroblast (fibroproliferative) phenotypic genes, for example, α-SMA, collagen type 1A, and fibronectin at the mRNA level. TNF-α suppresses TGF-β1-induced gene expression by affecting its mRNA stability. Our results further showed that TNF-α inhibits TGF-β1-induced Smad-3 phosphorylation via Jun N-terminal kinase signaling. Mechanical testing showed that TNF-α decreases the stiffness and contraction of the lattices after 5 days in culture. We proposed that changes in α-SMA, collagen, and fibronectin expression result in decreased contraction and stiffness of collagen matrices. Therefore, the balance of cytokines in a wound defines the mechanical properties of the extracellular matrix and optimal wound healing.Journal of Investigative Dermatology (2007) 127, 2645–2655; doi:10.1038/sj.jid.5700890; published online 31 May 2007 [ABSTRACT FROM AUTHOR]

Hepatic stellate cells (HSCs) undergo myofibroblastic transdifferentiation in liver fibrogenesis. We previously showed that dual stimulation with three-dimensional type-I collagen and interleukin-1 (IL-1) synergistically induces HSC trans-differentiation in a manner dependent on the activation of matrix metallopreinase-9 (MMP-9). The present study is aimed to determine the mechanism of MMP-9 activation in this model. The pro-MMP-9-converting activities expressed by trans-differentiating HSCs are characterized as secreted factors that are sensitive to MMP inhibitor and have apparent molecular masses of 50 and 25 kDa. This is in sharp contrast to the pro-MMP-9 activator from mouse and human skin, which is a chymotrypsin-like proteinase. Among multiple MMPs induced in HSCs by the dual stimulation, MMP-13 is most conspicuously up-regulated and meets all criteria as the pro-MMP-9 activator. HSC cultured in three-dimensional type-I collagen, but not in Matrigel, IL-1 induces expression of MMP-13 and its matured form at 50 and 25 kDa, respectively. In vitro reconstitution experiment proves that MMP-13, but not its zymogen, activates pro-MMP-9. Further, short hairpin RNA targeting MMP-13 abolishes pro-MMP-9 activation and HSC trans-differentiation. We further demonstrate that pro-MMP-13 activation is facilitated with a membrane-associated factor, inhibited with tissue inhibitor of metalloproteinase-2, and abolished with short hairpin RNA against MMP-14. Moreover, pro-MMP-13 is also activated by a secreted factor, which is absorbed by gelatin-Sepharose and reconstituted with MMP-9. Thus, IL-1-induced trans-differentiation of HSCs in three-dimensional extracellular matrix is facilitated by an MMP activation cascade (MMP-14 > MMP-13 > MMP-9) and a positive feedback loop of MMP-9 > MMP-13, suggesting their critical roles in liver injury and repair. [ABSTRACT FROM AUTHOR]

The N-terminal regulatory region of the high affinity cAMP-specific phosphodiesterase, PDE7A1, contains two copies of the cAMP-dependent kinase (PKA) pseudosubstrate site RRGAI. In βTC3 insulinoma cells, PDE7A1 co-localizes with PKA II in the Golgi-centrosome region. The roles PDE7A1 and its regulatory region play in cAMP signaling were examined by studying interactions with PKA subunits. PDE7A1 associates with the dissociated C subunit of PKA (C), but does not bind tetrameric PKA holoenzyme. High affinity binding of C by PDE7A1 inhibits kinase activity in vitro (IC50 = 0.5 nM). The domain containing PKA pseudosubstrate sites at the N terminus of PDE7A1 mediates complex formation with C. The PDE7A1 N-terminal repeat region inhibits C activity in CHO-K1 cells and also suppresses C dependent, cAMP-independent, physiological responses in yeast. Thus, PDE7A1 possesses a non-catalytic activity that can contribute to the termination of cAMP signals via direct inhibition of C. This study identifies a novel inhibitor of PKA and a non-catalytic affect of a cyclic nucleotide phosphodiesterase. [ABSTRACT FROM AUTHOR]

Located within the perisinusoidal space and surrounded by extracellular matrix, hepatic stellate cells (HSC) undergo phenotypic trans-differentiation called "myofibroblastic activation" in liver fibrogenesis. This study investigated the regulation of interleukin-1 (IL1α) on expression of matrix metalloproteinases (MMPs) by HSC grown in three-dimensional extracellular matrix and the role of MMPs in HSC activation. To recapitulate the in vivo "quiescent" state of HSC, the isolated rat HSC were grown in three-dimensional Matrigel or type I collagen. Stimulation with IL-1α caused robust induction of pro-MMP-9 (the precursor of matrix metalloproteinase-9) when HSC were cultured in these matrices. IL-1α induced a conversion of the pro-MMP-9 to the active form only when the cells were in type I collagen. In collagen lattices, IL-1α provoked activation of HSC with induction of MMP-13, MMP-3, and breakdown of the matrix. The HSC activation was completely prevented by a treatment of the cells with tissue inhibitor of metalloproteinase-1 or deprivation of MMP-9. Once fully activated, HSC failed to express MMP-9 and showed attenuated induction of MMP-13 and MMP-3. Further, we demonstrated colocalization of α-smooth muscle actin and MMP-9 in a subpopulation of HSC in human fibrotic liver tissues. Thus, this study provides a novel model to enlighten the role of MMPs, particularly that of MMP-9, in HSC activation regulated by a specific cytokine in liver fibrogenesis. [ABSTRACT FROM AUTHOR]

Earlier reports on resonance Raman scattering in ZnO suggests that the electron phonon coupling in ZnO usually increase with nanoparticle size or decline with the doping concentration. We investigated the effect of combination of the concentration of dopant and the variation of size of nanorods over the electron phonon interaction in Cd doped ZnO nanorod array fabricated by a simple, low temperature (90 °C) growth process. The resonant Raman measurement revealed minor decrease in the electron phonon coupling strength as defined by the intensity ratio (I 2LO /I 1LO) at low doping concentration (20 mol %) and increase at high Cd concentration (>20 mol %) confirming a strong dependence of electron phonon coupling strength on the concentration of dopant. The enhancement in the electron phonon coupling strength at high doping concentration was due to the increase in the diameter of the nanorod rather than the concentration of dopants explaining the competitive effect of dopant and size over the electron phonon interaction in a range of doping concentration. The Cd doping led to the decrease in the band gap and the increase (decrease) in the intensity of the excitonic emission (visible luminescence) as observed by the photoluminescence property. X-ray, Fourier transform infrared (FTIR) analysis confirmed low temperature doping of Cd at the tetrahedral coordination site of the ZnO lattice Although, the Cd concentration in the growth solution was systematically varied from 1 mol % to 80 mol %, the maximum Cd doping varied from 3 at. % (80 mol %) at the surface to 0.2 at % - 0.6 at. % in the bulk after surface cleaning by Ar ion etching. • Investigation of the electron phonon interaction in Cd doped ZnO nanorod array. • Competitive effect of dopant and size of the nanorod over the electron phonon coupling strength. • Dopant induced enhancement in the near band edge excitonic emission. • Gradation of Cd doping concentration from surface (3 at. %) to bulk (0.6 at. %). • Simple, low temperature (90 °C) growth of Cd doped ZnO nanorods and a detailed analysis. [ABSTRACT FROM AUTHOR]