bluuebunny/crossref_metadata_2025_split huggingface dataset:
ER stress drives Lipocalin 2 upregulation in prostate cancer cells in an NF-κB-dependent manner
Authors: Mahadevan Navin R , Rodvold Jeffrey , Almanza Gonzalo , Pérez Antonio Fernández , Wheeler Matthew C , Zanetti Maurizio 
Published: June 2011

Abstract

Background
Tumor cells adapt to endoplasmic reticulum (ER) stress through a set of conserved intracellular pathways, as part of a process termed the unfolded protein response (UPR). The expression of UPR genes/proteins correlates with increasing progression and poor clinical outcome of several tumor types, including prostate cancer. UPR signaling can activate NF-κB, a master regulator of transcription of pro-inflammatory, tumorigenic cytokines. Previous studies have shown that Lipocalin 2 (Lcn2) is upregulated in several epithelial cancers, including prostate cancer, and recently Lcn2 was implicated as a key mediator of breast cancer progression. Here, we hypothesize that the tumor cell UPR regulates Lcn2 production.

Methods
We interrogated Lcn2 regulation in murine and human prostate cancer cells undergoing pharmacological and physiological ER stress, and tested UPR and NF-κB dependence by using pharmacological inhibitors of these signaling pathways.

Results
Induction of ER stress using thapsigargin (Tg), a canonical pharmacologic ER stress inducer, or via glucose deprivation, a physiologic ER stressor present in the tumor microenvironment, upregulates LCN2 production in murine and human prostate cancer cells. Inhibition of the UPR using 4-phenylbutyric acid (PBA) dramatically decreases Lcn2 transcription and translation. Inhibition of NF-κB in prostate cancer cells undergoing Tg-mediated ER stress by BAY 11-7082 abrogates Lcn2 upregulation.

Conclusions
We conclude that the UPR activates Lcn2 production in prostate cancer cells in an NF-κB-dependent manner. Our results imply that the observed upregulation of Lipocalin 2 in various types of cancer cells may be the direct consequence of concomitant UPR activation, and that the ER stress/Lipocalin 2 axis is a potential new target for intervention in cancer progression.
Renal denervation in an animal model of diabetes and hypertension: Impact on the autonomic nervous system and nephropathy
Authors: Dias Lucinara D , Casali Karina R , Leguisamo Natalia M , Azambuja Felipe , Souza Martina S , Okamoto Maristela , Machado Ubiratan F , Irigoyen Maria Cláudia , Schaan Beatriz D 
Published: June 2011

Abstract

Background
The effects of renal denervation on cardiovascular reflexes and markers of nephropathy in diabetic-hypertensive rats have not yet been explored.

Methods
Aim: To evaluate the effects of renal denervation on nephropathy development mechanisms (blood pressure, cardiovascular autonomic changes, renal GLUT2) in diabetic-hypertensive rats. Forty-one male spontaneously hypertensive rats (SHR) ~250 g were injected with STZ or not; 30 days later, surgical renal denervation (RD) or sham procedure was performed; 15 days later, glycemia and albuminuria (ELISA) were evaluated. Catheters were implanted into the femoral artery to evaluate arterial pressure (AP) and heart rate variability (spectral analysis) one day later in conscious animals. Animals were killed, kidneys removed, and cortical renal GLUT2 quantified (Western blotting).

Results
Higher glycemia (p < 0.05) and lower mean AP were observed in diabetics vs. nondiabetics (p < 0.05). Heart rate was higher in renal-denervated hypertensive and lower in diabetic-hypertensive rats (384.8 ± 37, 431.3 ± 36, 316.2 ± 5, 363.8 ± 12 bpm in SHR, RD-SHR, STZ-SHR and RD-STZ-SHR, respectively). Heart rate variability was higher in renal-denervated diabetic-hypertensive rats (55.75 ± 25.21, 73.40 ± 53.30, 148.4 ± 93 in RD-SHR, STZ-SHR- and RD-STZ-SHR, respectively, p < 0.05), as well as the LF component of AP variability (1.62 ± 0.9, 2.12 ± 0.9, 7.38 ± 6.5 in RD-SHR, STZ-SHR and RD-STZ-SHR, respectively, p < 0.05). GLUT2 renal content was higher in all groups vs. SHR.

Conclusions
Renal denervation in diabetic-hypertensive rats improved previously reduced heart rate variability. The GLUT2 equally overexpressed by diabetes and renal denervation may represent a maximal derangement effect of each condition.
Identification of maturation and protein synthesis related proteins from porcine oocytes during in vitro maturation
Authors: Kim Jumi , Kim Ji-Su , Jeon Young-Joo , Kim Dong-Wook , Yang Tae-Ho , Soh Yunjo , Lee Hak Kyo , Choi Nag-Jin , Park Soo-Bong , Seo Kang Seok , Chung Hyung Min , Lee Dong-Seok , Chae Jung-Il 
Published: June 2011

Abstract

Background
In vitro maturation (IVM) of mammalian oocytes is divided into the GV (germinal vesicle stage), MI (metaphase I stage) and MII (metaphase II stage) stages, and only fully mature oocytes have acquired the ability to be fertilized and initiate zygotic development. These observations have been mostly based on morphological evaluations, but the molecular events governing these processes are not fully understood.
The aim of the present study was to better understand the processes involved in the molecular regulation of IVM using 2-DE analysis followed by mass spectrometry to identify proteins that are differentially expressed during oocyte IVM.

Result
A total of 16 up-regulated and 12 down-regulated proteins were identified. To investigate the IVM process, we specifically focused on the proteins that were up-regulated during the MII stage when compared with the GV stage, which included PRDX 2, GST, SPSY, myomegalin, PED4D, PRKAB 1, and DTNA. These up-regulated proteins were functionally involved in redox regulation and the cAMP-dependent pathway, which are essential for the intracellular signaling involved in oocyte maturation. Interestingly, the PDE4D and its partner, myomegalin, during the MII stage was consistently confirmed up-regulation by western blot analyses.

Conclusion
These results could be used to better understand some aspects of the molecular mechanisms underlying porcine oocyte maturation. This study identified some regulatory proteins that may have important roles in the molecular events involved in porcine oocyte maturation, particularly with respect to the regulation of oocyte meiotic resumption, MII arrest and oocyte activation. In addition, this study may have beneficial applications not only to basic science with respect to the improvement of oocyte culture conditions but also to mammalian reproductive biotechnology with potential implications.
Porous anodic alumina on galvanically grown PtSi layer for application in template-assisted Si nanowire growth
Authors: Michelakaki Irini , Nassiopoulou Androula G , Stavrinidou Eleni , Breza Katerina , Frangis Nikos 
Published: June 2011

AbstractWe report on the fabrication and morphology/structural characterization of a porous anodic alumina (PAA)/PtSi nano-template for use as matrix in template-assisted Si nanowire growth on a Si substrate. The PtSi layer was formed by electroless deposition from an aqueous solution containing the metal salt and HF, while the PAA membrane by anodizing an Al film deposited on the PtSi layer. The morphology and structure of the PtSi layer and of the alumina membrane on top were studied by Scanning and High Resolution Transmission Electron Microscopies (SEM, HRTEM). Cross sectional HRTEM images combined with electron diffraction (ED) were used to characterize the different interfaces between Si, PtSi and porous anodic alumina.
Liao ning virus in China
Authors: Lu Zhi , Liu Hong , Fu Shihong , Lu Xinjun , Dong Qiang , Zhang Song , Tong Suxiang , Li Minghua , Li Wenjuan , Tang Qing , Liang Guodong 
Published: June 2011

Abstract

Background
Liao ning virus is in the genus Seadornavirus within the family Reoviridae and has a genome composed of 12 segments of double-stranded RNA (dsRNA). It is transmitted by mosquitoes and only isolated in China to date and it is the only species within the genus Seadornavirus which was reported to have been propagated in mammalian cell lines. In the study, we report 41 new isolates from northern and southern Xinjiang Uygur autonomous region in China and describe the phylogenetic relationships among all 46 Chinese LNV isolates.

Findings
The phylogenetic analysis indicated that all the isolates evaluated in this study can be divided into 3 different groups that appear to be related to geographic origin based on partial nucleotide sequence of the 10th segment which is predicted to encode outer coat proteins of LNV. Bayesian coalescent analysis estimated the date of the most recent common ancestor for the current Chinese LNV isolates to be 318 (with a 95% confidence interval of 30-719) and the estimated evolutionary rates is 1.993 × 10-3 substitutions per site per year.

Conclusions
The results indicated that LNV may be an emerging virus at a stage that evaluated rapidly and has been widely distributed in the north part of China.
Ionizing radiation and inhibition of angiogenesis in a spontaneous mammary carcinoma and in a syngenic heterotopic allograft tumor model: a comparative study
Authors: Riesterer Oliver , Oehler-Jänne Christoph , Jochum Wolfram , Broggini-Tenzer Angela , Vuong Van , Pruschy Martin 
Published: June 2011

Abstract

Background
The combined treatment modality of ionizing radiation (IR) with inhibitors of angiogenesis (IoA) is a promising treatment modality based on preclinical in vivo studies using heterotopic xeno- and allograft tumor models. Nevertheless reservations still exist to translate this combined treatment modality into clinical trials, and more advanced, spontaneous orthotopic tumor models are required for validation to study the efficacy and safety of this treatment modality.

Findings
We therefore investigated the combined treatment modality of IR in combination with the clinically relevant VEGF receptor (VEGFR) tyrosine kinase inhibitor PTK787 in the MMTV/c-neu induced mammary carcinoma model and a syngenic allograft tumor model using athymic nude mice. Mice were treated with fractionated IR, the VEGFR-inhibitor PTK787/ZK222584 (PTK787), or in combination, and efficacy and mechanistic-related endpoints were probed in both tumor models. Overall the treatment response to the IoA was comparable in both tumor models, demonstrating minimal tumor growth delay in response to PTK787 and PTK787-induced tumor hypoxia. Interestingly spontaneously growing tumors were more radiosensitive than the allograft tumors. More important combined treatment of irradiation with PTK787 resulted in a supraadditive tumor response in both tumor models with a comparable enhancement factor, namely 1.5 and 1.4 in the allograft and in the spontaneous tumor model, respectively.

Conclusions
These results demonstrate that IR in combination with VEGF-receptor tyrosine kinase inhibitors is a valid, promising treatment modality, and that the treatment responses in spontaneous mammary carcinomas and syngenic allografts tumor models are comparable.
Specificity of eicosanoid production depends on the TLR-4-stimulated macrophage phenotype
Authors: Norris Paul C , Reichart Donna , Dumlao Darren S , Glass Christopher K , Dennis Edward A 
Published: June 2011

ABSTRACTEicosanoid metabolism differs in profile and quantity between macrophages of different tissue origin and method of elicitation, as well as between primary and immortalized macrophages after activation with inflammatory stimuli. Using a lipidomic approach, we comprehensively analyzed the eicosanoids made by murine RPMs, TGEMs, BMDM, and the macrophage-like cell line RAW after stimulation with the TLR-4-specific agonist KLA. Direct correlation among total COX metabolites, COX side-products (11-HETE, 15-HETE), COX-2 mRNA, and protein at 8 h was found when comparing each cell type. Comprehensive qPCR analysis was used to compare relative transcript levels between the terminal prostanoid synthases themselves as well as between each cell type. Levels of PGE2, PGD2, and TxB2 generally correlated with enzyme transcript expression of PGES, PGDS, and TBXS, providing evidence of comparable enzyme activities. PGIS transcript was expressed only in RPM and TGEM macrophages and at an exceptionally low level, despite high metabolite production compared with other synthases. Presence of PGIS in RPM and TGEM also lowered the production of PGE2 versus PGD2 by approximately tenfold relative to BMDM and RAW cells, which lacked this enzyme. Our results demonstrate that delayed PG production depends on the maximal level of COX-2 expression in different macrophages after TLR-4 stimulation. Also, the same enzymes in each cell largely dictate the profile of eicosanoids produced depending on the ratios of expression between them, with the exception of PGIS, which appears to have much greater synthetic capacity and competes selectively with mPGES-1.
Technical Advance: Soluble OX40 molecule mimics regulatory T cell modulatory activity on FcɛRI-dependent mast cell degranulation
Authors: Sibilano Riccardo , Gri Giorgia , Frossi Barbara , Tripodo Claudio , Suzuki Ryo , Rivera Juan , MacDonald Andrew S , Pucillo Carlo E 
Published: June 2011

ABSTRACTTregs play a central role in modulating FcɛRI-dependent MC effector functions in the course of the allergic response. Cellular interaction depends on the constitutive expression of OX40 on Tregs and the OX40L counterpart on MCs. Study of OX40L signaling on MCs is hampered by the need of a highly purified molecule, which triggers OX40L specifically. We now report that sOX40 mimics the physiological activity of Treg interaction by binding to activated MCs. When treated with sOX40, activated MCs showed decreased degranulation and Ca++ influx, whereas PLC-γ2 phosphorylation remained unaffected. Once injected into experimental animals, sOX40 not only located within the endothelium but also in parenchyma, where it could be found in close proximity and apparently bound to MCs. This soluble molecule triggers MC-OX40L without the requirement of Tregs, thus allowing study of OX40L signaling pathways in MCs and in other OX40L-expressing cell populations. Importantly, as sOX40 inhibits MC degranulation, it may provide an in vivo therapeutic tool in allergic disease.
Physiological adaptation of an Antarctic Na+/K+-ATPase to the cold
Authors: Galarza-Muñoz Gaddiel , Soto-Morales Sonia I. , Holmgren Miguel , Rosenthal Joshua J. C. 
Published: June 2011

SUMMARYBecause enzymatic activity is strongly suppressed by the cold, polar poikilotherms face significant adaptive challenges. For example, at 0°C the catalytic activity of a typical enzyme from a temperate organism is reduced by more than 90%. Enzymes embedded in the plasma membrane, such as the Na+/K+-ATPase, may be even more susceptible to the cold because of thermal effects on the lipid bilayer. Accordingly, adaptive changes in response to the cold may include adjustments to the enzyme or the surrounding lipid environment, or synergistic changes to both. To assess the contribution of the enzyme itself, we cloned orthologous Na+/K+-ATPase α-subunits from an Antarctic (Pareledone sp.; –1.8°C) and a temperate octopus (Octopus bimaculatus; ∼18°C), and compared their turnover rates and temperature sensitivities in a heterologous expression system. The primary sequences of the two pumps were found to be highly similar (97% identity), with most differences being conservative changes involving hydrophobic residues. The physiology of the pumps was studied using an electrophysiological approach in intact Xenopus oocytes. The voltage dependence of the pumps was equivalent. However, at room temperature the maximum turnover rate of the Antarctic pump was found to be 25% higher than that of the temperate pump. In addition, the Antarctic pump exhibited a lower temperature sensitivity, leading to significantly higher relative activity at lower temperatures. Orthologous Na+/K+ pumps were then isolated from two tropical and two Arctic octopus. The temperature sensitivities of these pumps closely matched those of the temperate and Antarctic pumps, respectively. Thus, reduced thermal sensitivity appears to be a common mechanism driving cold adaptation in the Na+/K+-ATPase.
Characteristics of vortex formation and thrust performance in drag-based paddling propulsion
Authors: Kim Daegyoum , Gharib Morteza 
Published: June 2011

SUMMARYSeveral characteristics of drag-based paddling propulsion are studied with a simple mechanical model and a measurement technique for mapping three-dimensional flow fields. In drag-based propulsion, the temporal change of the vortex strength is an important parameter in the relationship between vortex formation and thrust generation. Our results indicate that spanwise flow behind the paddling propulsor significantly affects tip vortex development and thrust generation. The distribution of spanwise flow is dependent on the propulsor shape and the Reynolds number. A delta-shaped propulsor generates strong spanwise flow compared with a rectangular propulsor. For the low Reynolds number case, spanwise flow is not as strong as that for the high Reynolds number case. Without sacrificing total impulse, the flexible propulsor can smooth out thrust peaks during sudden stroke motions, which is favorable for avoiding structural failures and stabilizing body motion. We also explored the role of stopping vortex shedding in efficient thrust generation by determining the relationship between stroke angles and total impulses generated by paddling propulsors.
In ovo thyroxine exposure alters later UVS cone loss in juvenile rainbow trout
Authors: Raine Jason C. , Coffin Allison B. , Hawryshyn Craig W. 
Published: June 2011

SUMMARY
Thyroid hormones (THs) play a vital role in vertebrate neural development, and, together with the beta isoform of the thyroid hormone receptor (TRβ), the development and differentiation of cone photoreceptors in the vertebrate retina. Rainbow trout undergo a natural process of cone cell degeneration during development and this change in photoreceptor distribution is regulated by thyroxine (T4; a thyroid hormone). In an effort to further understand the role of T4 in photoreceptor ontogeny and later developmental changes in photoreceptor subtype distribution, the influence of enhanced in ovo T4 content on the onset of opsin expression and cone development was examined. Juvenile trout reared from the initial in ovo-treated embryos were challenged with exogenous T4 at the parr stage of development to determine if altered embryonic exposure to yolk THs would affect later T4-induced short-wavelength-sensitive (SWS1) opsin transcript downregulation and ultraviolet-sensitive (UVS) cone loss. In ovo TH manipulation led to upregulation of both SWS1 and long-wavelength-sensitive (LWS) opsin transcripts in the pre-hatch rainbow trout retina and to changes in the relative expression of TRβ. After 7 days of exposure to T4, juveniles that were also treated with T4 in ovo had greatly reduced SWS1 expression levels and premature loss of UVS cones relative to T4-treated juveniles raised from untreated eggs. These results suggest that changes in egg TH levels can have significant consequences much later in development, particularly in the retina.
A practical assessment of the short-term in vitro stability of troponin I at the 99th percentile
Authors: Peake Roy W A , Deans Kevin A , Croal Bernard L 
Published: June 2011

Background Serial troponin measurement is important for the diagnosis of myocardial infarction. As troponin concentrations approach the cut-off for detectable myocardial necrosis, smaller changes in troponin as a result of decreased in vitro stability may be sufficient to generate changes of apparent clinical significance. This is particularly relevant regarding retrospective ‘add-on’ testing on samples several hours after venepuncture. We investigated the stability of troponin I (cTnI) at values close to the 99th percentile limit. Methods Serum samples with baseline cTnI concentrations in the range 0.04–0.15 μg/L were analysed routinely using the Siemens TnI-Ultra assay. Follow-up analysis was carried out at 6, 9, 12, 24 and 48 h post-venepuncture after storage at room temperature and in the cold room. Results There was a significant decrease in cTnI concentration after 6 h post-venepuncture compared with baseline levels ( P < 0.001). The maximum percentage change was −17.1% observed after 48 h storage at room temperature. Of samples with baseline cTnI concentration 0.040 μg/L, 80% had a cTnI concentration below 0.040 μg/L on re-analysis after 6 h. Conclusions Requests for retrospective addition of troponin measurement on samples several hours after venepuncture is commonplace in many laboratories. Analysis of samples drawn >6 h previously may produce values below the cut-off for myocardial necrosis (0.040 μg/L) that would have been detectable if measured earlier as a result of decreased in vitro stability. Significant percentage decreases in cTnI concentration following storage may also have implications in lowering the threshold for an apparently clinically significant change to occur.
Nebulized Antibiotics for the Treatment of Refractory Bacterial Chronic Rhinosinusitis
Authors: Woodhouse Brittany Mae , Cleveland Kevin W 
Published: June 2011

OBJECTIVE: To review the safety and efficacy of nebulized antibiotics for refractory bacterial chronic rhinosinusitis (CRS) in adults. DATA SOURCES: PubMed (up to February 2011) and The Cochrane Library (up to February 2011) were searched using the terms nebulizer, nebulized, antibiotics, and chronic sinusitis. STUDY SELECTION AND DATA EXTRACTION: All English-language articles reporting clinical trials in adults were evaluated; 4 relevant studies were identified. DATA SYNTHESIS: Conventional therapy for CRS, including pharmacologic treatments (eg, oral antibiotics, corticosteroids, antihistamines) and surgery, are not effective for all patients, which has led to experimentation with nebulized antibiotics. The 4 trials analyzing the effectiveness of nebulized antibiotics for refractory CRS in adults identified in our literature search were diverse in their methods, and different antibiotics were used in each trial. Furthermore, all of the trials had small sample sizes, with the largest comprising 42 patients. Two of the studies compared nebulized antibiotics to nebulized saline, and even though rhinosinusitis symptoms improved, nebulized antibiotics were found to offer no additional benefit over saline. The 2 other trials had no control groups and found that nebulized antibiotics led to an improvement in symptoms. In 1 trial, antibiotics were selected based on the results of sinus cultures, which led to infection resolution in 38 of 50 (76%) treatment courses. Nebulized antibiotics were well tolerated, with only minor adverse effects noted. CONCLUSIONS: Based on current studies, use of nebulized antibiotics for refractory CRS cannot be recommended at this time. Although supportive evidence is limited, nebulized antibiotics appear to improve rhinosinusitis symptoms in some patients with minimal adverse effects. With further studies, culture-directed nebulized antibiotic therapy may be a treatment option in patients with CRS refractory to conventional treatments.