bluuebunny/crossref_metadata_2025 huggingface dataset:
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

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

Eicosanoid 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

Tregs 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.
Anabolic and Catabolic Regimens of Human Parathyroid Hormone 1–34 Elicit Bone- and Envelope-Specific Attenuation of Skeletal Effects in Sost-Deficient Mice
Authors: Robling Alexander G. , Kedlaya Rajendra , Ellis Shana N. , Childress Paul J. , Bidwell Joseph P. , Bellido Teresita , Turner Charles H.
Published: June 2011

PTH is a potent calcium-regulating factor that has skeletal anabolic effects when administered intermittently or catabolic effects when maintained at consistently high levels. Bone cells express PTH receptors, but the cellular responses to PTH in bone are incompletely understood. Wnt signaling has recently been implicated in the osteo-anabolic response to the hormone. Specifically, the Sost gene, a major antagonist of Wnt signaling, is down-regulated by PTH exposure. We investigated this mechanism by treating Sost-deficient mice and their wild-type littermates with anabolic and catabolic regimens of PTH and measuring the skeletal responses. Male Sost+/+ and Sost−/− mice were injected daily with human PTH 1–34 (0, 30, or 90 μg/kg) for 6 wk. Female Sost+/+ and Sost−/− mice were continuously infused with vehicle or high-dose PTH (40 μg/kg · d) for 3 wk. Dual energy x-ray absorptiometry-derived measures of intermittent PTH (iPTH)-induced bone gain were impaired in Sost−/− mice. Further probing revealed normal or enhanced iPTH-induced cortical bone formation rates but concomitant increases in cortical porosity among Sost−/− mice. Distal femur trabecular bone was highly responsive to iPTH in Sost−/− mice. Continuous PTH (cPTH) infusion resulted in equal bone loss in Sost+/+ and Sost−/− mice as measured by dual energy x-ray absorptiometry. However, distal femur trabecular bone, but not lumbar spine trabecular bone, was spared the bone-wasting effects of cPTH in Sost−/− mice. These results suggest that changes in Sost expression are not required for iPTH-induced anabolism. iPTH-induced resorption of cortical bone might be overstimulated in Sost-deficient environments. Furthermore, Sost deletion protects some trabecular compartments, but not cortical compartments, from bone loss induced by high-dose PTH infusion.
Sphingosine 1-phosphate regulates matrix metalloproteinase-9 expression and breast cell invasion through S1P3–Gαq coupling
Authors: Kim Eun-Sook , Kim Jong-Sook , Kim Sang Geon , Hwang Sejin , Lee Chang Ho , Moon Aree
Published: June 2011

Recent evidence suggests that inflammation is involved in malignant progression of breast cancer. Sphingosine 1-phosphate (S1P), acting on the G-protein-coupled receptors, is known as a potent inflammatory mediator. In this study, the effect of the inflammatory lipid S1P on the regulation of invasive/migratory phenotypes of MCF10A human breast epithelial cells was investigated to elucidate a causal relationship between inflammation and the control of invasiveness of breast cells. We show that S1P causes induction of matrix metalloproteinase-9 (MMP-9) in vitro and in vivo, and thus enhances invasion and migration. We also show that fos plays a crucial role in the transcriptional activation of MMP-9 by S1P. In addition, activation of extracellular-signal-regulated kinases 1 and 2 (ERK1/2), p38 and alpha serine/threonine-protein kinase (Akt) are involved in the process of S1P-mediated induction of MMP-9 expression and invasion. Activation of the S1P receptor S1P3 and Gαq are required for S1P-induced invasive/migratory responses, suggesting that the enhancement of S1P-mediated invasiveness is triggered by the specific coupling of S1P3 to the heterotrimeric Gαq subunit. Activation of phospholipase C-β4 and intracellular Ca2+ release are required for S1P-induced MMP-9 upregulation. Taken together, this study demonstrated that S1P regulates MMP-9 induction and invasiveness through coupling of S1P3 and Gαq in MCF10A cells, thus providing a molecular basis for the crucial role of S1P in promoting breast cell invasion.
Malin and laforin are essential components of a protein complex that protects cells from thermal stress
Authors: Sengupta Sonali , Badhwar Ishima , Upadhyay Mamta , Singh Sweta , Ganesh Subramaniam
Published: June 2011

The heat-shock response is a conserved cellular process characterized by the induction of a unique group of proteins known as heat-shock proteins. One of the primary triggers for this response, at least in mammals, is heat-shock factor 1 (HSF1) – a transcription factor that activates the transcription of heat-shock genes and confers protection against stress-induced cell death. In the present study, we investigated the role of the phosphatase laforin and the ubiquitin ligase malin in the HSF1-mediated heat-shock response. Laforin and malin are defective in Lafora disease (LD), a neurodegenerative disorder associated with epileptic seizures. Using cellular models, we demonstrate that these two proteins, as a functional complex with the co-chaperone CHIP, translocate to the nucleus upon heat shock and that all the three members of this complex are required for full protection against heat-shock-induced cell death. We show further that laforin and malin interact with HSF1 and contribute to its activation during stress by an unknown mechanism. HSF1 is also required for the heat-induced nuclear translocation of laforin and malin. This study demonstrates that laforin and malin are key regulators of HSF1 and that defects in the HSF1-mediated stress response pathway might underlie some of the pathological symptoms in LD.
Arginine methylation of G3BP1 in response to Wnt3a regulates β-catenin mRNA
Authors: Bikkavilli Rama Kamesh , Malbon Craig C.
Published: June 2011

Wnt/β-catenin signaling is essential for normal mammalian development. Wnt3a activates the Wnt/β-catenin pathway through stabilization of β-catenin; a process in which the phosphoprotein Dishevelled figures prominently. Protein arginine methylation in signaling complexes containing Dishevelled was investigated. Mass spectrometry of a prominent arginine-methylated, Dishevelled-associated protein identified the Ras GTPase activating protein-binding protein 1 G3BP1. Stimulation of totipotent mouse embryonic F9 cells with Wnt3a provoked increased methylation of G3BP1. We show that G3BP1 is a novel Ctnnb1 mRNA binding protein. Methylation of G3BP1 constitutes a molecular switch that regulates Ctnnb1 mRNA in response to Wnt3a. Thus, the protein arginine methylation that targets G3BP1 acts as a novel regulator of Ctnnb1 mRNA.
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

Because 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

Several 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

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.
Intermittent hypoxia conditioning prevents endothelial dysfunction and improves nitric oxide storage in spontaneously hypertensive rats
Authors: Manukhina Eugenia B , Jasti Dinesh , Vanin Anatoly F , Downey H Fred
Published: June 2011

Although intermittent hypoxia is often associated with hypertension, experimental and clinical studies have demonstrated definite antihypertensive effects of some intermittent hypoxia conditioning (IHC) regimens. Mechanisms of this antihypertensive response are unknown. Endothelial dysfunction related to disturbed synthesis and/or reduced availability of nitric oxide (NO) has been linked to hypertension. Thus, experiments were conducted to determine if IHC can improve endothelium-dependent relaxation and formation of releasable vascular NO stores of young (4–8-week-old) spontaneously hypertensive rats (SHR). Rats were subjected to either IHC (9.5–10% O2, 5–10 min, 5–8 times per day, 20 d) or to sham conditioning. Endothelium-dependent relaxation to acetylcholine was measured in norepinephrine-precontracted, isolated aortic rings, and the size of NO stores was evaluated by percent relaxation to N-acetylcysteine (NAC), which releases stored NO. The capacity of aortic rings for NO storage was evaluated by the relaxation to NAC after prior incubation with an NO donor. IHC significantly suppressed the development of hypertension in young SHR. Endothelial function decreased from 54.7 ± 4.6% to 28.1 ± 6.4% relaxation to acetylcholine after 20 d of sham IHC, whereas endothelial function was sustained (60.3 ± 6.0% relaxation) in IHC rats. IHC also induced formation of available NO stores and enhanced the capacity of aortic rings to store NO. Therefore, the antihypertensive effect of IHC in young SHR is associated with prevention of endothelial dysfunction and with increased accumulation of NO stores in vascular walls.
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.
Akathisia Induced by Gabapentin Withdrawal
Authors: See Sharon , Hendriks Erin , Hsiung Leslie
Published: June 2011

OBJECTIVE:

To report a case of akathisia in a patient with type 2 diabetes after abrupt discontinuation of gabapentin.

CASE SUMMARY:

A 76-year-old female with type 2 diabetes was admitted for change in mental status, agitation, and restless limb movements. She had been taking gabapentin 3600 mg daily for approximately 1 month for diabetic neuropathy. Her other home medications were glyburide 10 mg twice daily, oxycodone/acetaminophen 5 mg/325 mg every 6 hours as needed for leg pain, and zolpidem 5 mg at bedtime. She had taken none of these drugs for 4 days prior to admission because she was unable to have the prescriptions refilled. Subsequently, the patient exhibited repeated arm and leg motions in response to an inner restlessness. Upon admission to the emergency department, she was agitated and restless; all vital signs and results of laboratory studies were within normal limits. Gabapentin was restarted at the original dosage and the symptoms resolved within 8 hours. Because the patient developed lethargy, the gabapentin dosage was reduced and titrated to the original level over 2 days. After 3 days, the patient was well oriented and experienced no further symptoms. She was discharged on the original dosage of gabapentin.

DISCUSSION:

To our knowledge, this is the first reported cases of akathisia induced by gabapentin withdrawal. Available case reports suggest that gabapentin withdrawal can occur at doses ranging from 400-8000 mg/day. Patients experienced symptoms similar to those that develop with benzodiazepine withdrawal and were taking gabapentin for as little as 3 weeks to as long as 5 years. This is the first case report to describe akathisia induced by gabapentin withdrawal. The Naranjo probability scale revealed a probable relationship between akathisia and gabapentin withdrawal.

CONCLUSIONS:

If gabapentin discontinuation is desired, it is prudent to gradually taper the dose to avoid withdrawal symptoms, which may occur after as little as 1 month of treatment. Should the patient experience withdrawal symptoms, the optimal treatment is to restart gabapentin.
Application of instrumental neutron activation analysis for the examination of oil pigments
Authors: Chung Y.-S. , Kim S.-H. , Sun G.-M. , Lim J.-M. , Moon J.-H. , Kim Y.-J. , Lim S.-J. , Song Y.-N. , Kim K.
Published: June 2011

This study is to investigate the applicability of instrumental neutron activation analysis (INAA) as a non-destructive examination tool for the quantitative chemical composition analysis associated with authentication, restoration and conservation of art objects in the field of cultural heritage. The quantitative analysis of major, minor and trace elements in Rembrandt´s® oil pigments recently collected at the Korean market as one of the art objects was carried out using INAA facilities of the HANARO research reactor at the Korea Atomic Energy Research Institute in collaboration with the National Museum of Contemporary Art in Korea. Analytical quality control was implemented using NIST SRM 2709, certified reference materials and metal standards. The analytical results for seventeen characteristic elements of thirty-one measured elements were statistically treated to identify the characteristic correlations and patterns between color and source of oil pigment and similarity degree of constituents using a cluster and discriminate analysis.
Adsorption interaction of astatine species with quartz and gold surfaces
Authors: Serov A. , Aksenov N. V. , Bozhikov G. A. , Eichler R. , Dressler R. , Lebedev V. Ya. , Petrushkin O. , Piguet D. , Shishkin S. , Tereshatov E. , Türler A. , et al.
Published: June 2011

The adsorption interaction of various astatine species with quartz and gold surfaces was investigated by gas chromatography methods. Due to variations of the redox potential of the carrier gas elemental astatine, astatine oxide and hypo-astatic acid have been produced. The identification of the astatine compounds is based on the analogy assumption to the gas phase chemistry of the closest homologues in group 17 of the periodic table, iodine and bromine. The deposition temperatures as well as enthalpies of adsorption have been determined for the astatine species. The enhancement of the metallic character within group 17 towards higher Z is clearly confirmed. Macroscopic properties (sublimation enthalpy) of previously unstudied AtO2 and HAtO were estimated. The determined data for elemental astatine were compared to available literature data. Based on the obtained experimental results possible designs of experiments for studying of chemical properties of the recently discovered element 117 can be suggested.
Y-box binding protein-1 promotes castration-resistant prostate cancer growth via androgen receptor expression
Authors: Shiota Masaki , Takeuchi Ario , Song YooHyun , Yokomizo Akira , Kashiwagi Eiji , Uchiumi Takeshi , Kuroiwa Kentaro , Tatsugami Katsunori , Fujimoto Naohiro , Oda Yoshinao , Naito Seiji
Published: June 2011

The androgen receptor (AR) is well known to play a central role in the pathogenesis of prostate cancer (PCa). In several studies, AR was overexpressed in castration-resistant PCa (CRPC). However, the mechanism of AR overexpression in CRPC is not fully elucidated. Y-box binding protein-1 (YB-1) is a pleiotropic transcription factor that is upregulated in CPRC. We aimed to elucidate the role of YB-1 in castration resistance of PCa and identify therapeutic potential of targeting YB-1. Using immunohistochemistry, we found that nuclear YB-1 expression significantly correlated with the Gleason score and AR expression in PCa tissues. In PCa cells, YB-1 regulated AR expression at the transcriptional level. Furthermore, YB-1 expression and nuclear localization were upregulated in CRPC cells. Overexpression of AR, as well as YB-1, conferred castration-resistant growth in LNCaP and 22Rv1 cells. Conversely, knocking down YB-1 resulted in suppressed cell growth and induced apoptosis, which was more efficient than knocking down AR in LNCaP cells. In other types of PCa cells, such as CRPC cells, knocking down YB-1 resulted in a significant reduction of cell growth. In conclusion, these findings suggested that YB-1 induces castration resistance in androgen-dependent PCa cells via AR expression. Thus, YB-1 may be a promising therapeutic target for PCa, as well as CRPC.
Chromatoid body and small RNAs in male germ cells
Authors: Meikar Oliver , Da Ros Matteo , Korhonen Hanna , Kotaja Noora
Published: June 2011

The chromatoid body (CB) is a germ granule in the cytoplasm of postmeiotic haploid round spermatids that is loaded with RNA and RNA-binding proteins. Following the discovery of small non-coding RNA-mediated gene regulation and the identification of PIWI-interacting RNAs (piRNAs) that have crucial roles in germ line development, the function of the CB has slowly begun to be revealed. Male germ cells utilise small RNAs to control the complex and specialised process of sperm production. Several microRNAs have been identified during spermatogenesis. In addition, a high number of piRNAs are present both in embryonic and postnatal male germ cells, with their expression being impressively induced in late meiotic cells and haploid round spermatids. At postmeiotic stage of germ cell differentiation, the CB accumulates piRNAs and proteins of piRNA machinery, as well as several other proteins involved in distinct RNA regulation pathways. All existing evidence suggests a role for the CB in mRNA regulation and small RNA-mediated gene control, but the mechanisms remain uncharacterised. In this review, we summarise the current knowledge of the CB and its association with small RNA pathways.
Novel Genetic Selection System for Quantitative Trait Loci of Quality Protein Maize
Authors: Wu Yongrui , Messing Joachim
Published: June 2011

Quality protein maize combines a high-lysine trait with kernel hardness, for which a new, simpler genetic selection was designed.
First step of tracing the effects of family constellation – A follow-up study on family constellation
Authors: Zseni Annamária , Varga S. Katalin , Angster Mária , Béleczki Nikolett , Füzér Gábor , Néveri Emese , Joó Mária Nóra , Nagy Zoltán , Lőrik Dóra
Published: June 2011

Kutatásunkban a családállítás közép- és hosszú távú hatásait kívántuk vizsgálni. Az utánkövetéses vizsgálatot 209 személlyel, saját szerkesztésű kérdőívvel végeztük. A kérdőívek adatait az SPSS 10.0 statisztikai programcsomag felhasználásával elemeztük. Kimutattuk, hogy a hazánkban is egyre népszerűbb módszer tényleges hatással rendelkezik. A családállítást követően megélt közép- és hosszú távú változás mértéke szignifikáns. Ez mind a saját hipotézisünknek, mind a hasonló céllal végzett nemzetközi vizsgálatok eredményeinek megfelel.
Hypnosis, pain, assuaging of pain
Authors: Gyulaházi Judit , Varga Katalin
Published: June 2011

A hipnoterápiát régóta használják fájdalomcsillapító eljárásként, mégis meglehetősen ismeretlen a betegek és a gyógyítók előtt is. Hipnóziskutatók kitartó munkájának eredményeként jelentős ismereteket szerezhetünk a módszer neurofiziológiai hátteréről, hatásmechanizmusairól. Célunk az, hogy eredményeiket beillesztve napjaink fájdalomkutatásának perspektívájába a gyógyítók szélesebb rétege számára tegyük megismerhetővé. Az utolsó 15 évben az agyi képalkotó technikák ugrásszerű fejlődése lehetővé tette a kutatók számára, hogy tanulmányozzák a fájdalom élményének kialakulásában részt vevő agyterületeket, amelyeket közösen fájdalomhálózatnak vagy a fájdalom neuron-mátrixának nevezünk. Bemutatjuk a pszichoterápiák fájdalomcsillapító hatásának alapmechanizmusaiként értelmezhető kognitív szabályozási folyamatokat, a figyelem, az előzetes elvárások és az újraértékelés, valamint a hangulat moduláló szerepét. A fájdalom neuron-mátrixa aktiválódhat a testet ért fizikai inger hatására, de e nélkül is, a mediális rész elsődleges aktiválódása útján. Mindez hozzásegíthet a krónikus fájdalomállapotok keletkezési mechanizmusának a jobb megértéséhez. A hipnózisban végzett fájdalomcsillapítási vizsgálatok eredményei részben a módosult tudatállapot, részben a fájdalomcsillapítás idegrendszeri hátteréről is tájékoztatnak.
Clinical significance and the first identification of human parechoviruses in Hungary
Authors: Reuter Gábor , Új Mária , Pankovics Péter , Kolozsi Tímea , Mihály Ilona , Liptai Zoltán , Boros Ákos
Published: June 2011

Human parechoviruses (HPeV) belonging to the family Picornaviridae are widespread enteric pathogens and are associated with various clinical syndromes in human. At present, 16 HPeV genotypes (HPeV1–16) are known. There is no report on the detection of HPeVs in Central Europe. Aims: The aim of the retrospective study was to detect and characterize HPeVs using molecular methods in cell cultures with “enterovirus-like” cytophatic effect (CPE) archived between 1990 and 2004, in two virology laboratories, in Hungary. Materials and methods: In Laboratory I, fecal samples from children with symptoms of gastroenteritis under the age of 10 years were cultured as a previous routine diagnostic laboratory protocol for “enterovirus”. Cell cultures indicating CPE were archived between 1990 and 2000. In Laboratory II, 2 fecal samples, a liquor and a nasopharyngeal aspirate were re-tested which contained an “enterovirus-like” virus in cell cultures and were positive by HPeV1 neutralization immunosera between 2000 and 2004. Specimens were tested retrospectively for HPeV by reverse transcription–PCR (RT-PCR) method using 5’UTR conserved primers. Specific primers were designed to determine the HPeV structural region (VP0-VP3-VP1). Results: 9 of the 66 archived samples (9.1%) from Laboratory I and all the 4 samples from Laboratory II were found to be HPeV-positive. 10 samples were identified as HPeV1, 2 were HPeV4 and 1 could not be determined. 3 HPeV1 clusters were identified in Laboratory I according to the isolation date originated from years 1990/1991, 1992/1995 and 1998. HPeV1 was detected in clinical syndromes: gastroenteritis (in a 24-years-old adult), recurrent stomatitis aphtosa (in a 42-years-old adult), encephalitis and ataxia cerebellaris acuta in infants and children in Laboratory II. Conclusions: This is the first detection of HPeVs in Central Europe. Detection and genetic characterization of HPeV in available historical samples infected with previously unidentifiable agents with “enterovirus-like” cytopathogenic effect may help to understand the clinical importance and spectrum of the infections and the genetic diversity and evolution of these viruses. Orv. Hetil., 2011, 152, 1007–1012.
Functional vascular alterations associated with aortic valve stenosis
Authors: Nemes Attila , Forster Tamás
Published: June 2011

Degenerative changes, atherosclerotic process and calcification of valvular leaflets are mostly responsible for valvular aortic valve stenosis, but congenital bicuspid aortic valve and rheumatic fever in history are also known predisposing factors. Aortic valve stenosis is frequently associated with different functional vascular alterations. The aim of this review is to demonstrate these vascular alterations evaluated by non-invasive methods and underlying physiologic and pathophysiologic processes. Orv. Hetil., 2011, 152,993–999.
A Pig Model for the Histomorphometric Evaluation of Hard Tissue Around Dental Implants
Authors: Erdogan Özgür , Üstün Yakup , Tatli Ufuk , Damlar Ibrahim , Daglıoglu Kenan
Published: June 2011

This study aimed to evaluate the frontal bone of Swiss Domestic pigs as an animal model for the histologic-histomorphometric examination of bony tissue around dental implants. We inserted SLA surface implants 4.1 mm in diameter and 10 mm in length into the frontal bones of 9 Swiss-Domestic pigs. Histologic and histomorphometric studies were conducted on the undecalcified sections. Histologic examinations showed that the specimens contain a sufficient amount of bone to provide homogenous bone coverage for standard diameter dental implant placement. The mean bone to implant contact was 61.9% ± 8.7%. Other histomorphometric parameters revealed the regular trabecular architecture at this site. Pigs' frontal bone appears to be a suitable animal model in short-term dental implant studies because it provides a sufficient amount of bone and favorable bone microarchitecture.
Determinants of species abundance in the Quaternary vertebrate fossil record
Authors: Turvey Samuel T. , Blackburn Tim M.
Published: June 2011

Species abundance data are of vital importance in paleontology, but fossil accumulations invariably represent a biased subset of original source communities. Efforts to quantify taphonomic biases are typically prevented by a lack of independent data on the ecological composition of prehistoric faunas. However, analysis of the continental Holocene record can provide a rare opportunity for independent calibration of fossil abundance patterns. We analyzed a comprehensive data set available for the Holocene avifauna of Sweden to investigate the relationship between species abundance in the recent fossil and zooarchaeological records and in prehistoric source communities, and to characterize the importance of different ecological factors in determining terrestrial vertebrate fossil abundances. The number of assemblages in which species occurred was compared with modern-day species abundance, annual residence, body mass, and ecological realm. Modern-day abundance is only one of several significant predictors of fossil abundance; the strongest predictor is body mass, and Holocene species abundance can be interpreted as a measure of species abundance in source communities for a given size class only. Our study represents one of the only direct attempts to quantify species abundance biases between fossil faunas and source communities, and has general applicability for a wide range of terrestrial vertebrate faunas.
Comparing the differential filling of morphospace and allometric space through time: the morphological and developmental dynamics of Early Jurassic ammonoids
Authors: Gerber Sylvain
Published: June 2011

The evolutionary history of shell geometry of Early Jurassic ammonoids during the Pliensbachian–Toarcian second-order mass extinction is explored at both adult and ontogenetic levels. The ontogenetic approach builds on the concept of allometric space to get insights into the developmental aspects of morphological evolution. Investigation of the deployment of taxa in adult morphospace and allometric space allows the appraisal of the temporal evolution of morphological and allometric disparities. Curves of taxonomic diversity, adult morphological disparity, allometric disparity, and average adult size are contrasted. Results show that during the Pliensbachian–Toarcian interval, ammonoids underwent two successive and drastic declines in taxonomic diversity. Patterns of morphospace and allometric space occupancy suggest nonselective extinction at both morphological and developmental levels. Another measure of allometric disparity suggests the occurrence of two heterochronic trends, a peramorphocline followed by a paedomorphocline, during the Toarcian. These trends are concomitant with changes in average adult size that compensate for the heterochronic effects and explain the striking stability of morphological disparity despite changes in diversity. The results also emphasize the existence of two contrasted evolutionary dynamics in Pliensbachian and Toarcian ammonoids. Methodologically, the allometric disparity approach appears to be a fruitful tool to analyze the rather understudied clade-wide ontogenetic aspects of morphological evolution. Combining multiple approaches to describe clade morphological dynamics leads to a better characterization and understanding of the diversity-disparities relationships and a better distinction of the potential processes driving these macroevolutionary patterns.
A geographic test of species selection using planktonic foraminifera during the Cretaceous/Paleogene mass extinction
Authors: Powell Matthew G. , MacGregor Johnryan
Published: June 2011

Species selection has received a great deal of theoretical attention but it has rarely been empirically tested. It is important to determine the level of selection that operated during a particular extinction event because it can help distinguish between traits that were actually responsible for extinction and those that were merely correlated with it. Here, we present a test that can help distinguish between organismal and species-level selection, which we demonstrate using the high-resolution fossil record of planktonic foraminifera species recorded in deep-sea sediment cores. Our test examines the fate of survivors and victims during the Cretaceous/Paleogene (K/Pg) mass extinction within single geographic regions, where all individuals experience the same selection pressures. Selection at the organismal level implies that individual members of surviving species are more fit than those of victimized species, and therefore should be more likely to survive in affected areas; conversely, selection at the species level implies individuals will suffer equally within an affected area. We find that survivors of the mass extinction suffered very high extirpation rates in cores where the overall extinction rate was high, indicating that individual members of the surviving species were generally no more fit than individual members of extinct species. Rather, these species were able to survive because they possessed advantageous species-level traits, such as larger geographic ranges and greater abundances than victimized species. This geographic pattern of extirpation suggests that selection operated at the species, rather than organismal, level during the K/Pg mass extinction of planktonic foraminifera.
Reinforcement of timber beams with carbon fibers reinforced plastics
Authors: Gugutsidze G. , Draškovič F.
Published: June 2011

Reinforcement of timber beams with carbon fibers reinforced plastics

Wood is a polymeric material with many valuable features and which also lacks some negative features. In order to keep up with high construction rates and the minimization of negative effects, wood has become one of the most valuable materials in modern engineering. But the use of timber material economically is also an actual problem in order to protect the environment and improve natural surroundings. A panel of scientists is interested in solving these problems and in creating rational structures, where timber can be used efficiently. These constructions are as follows: glue-laminated (gluelam), composed and reinforced wooden constructions. Composed and reinforced wooden constructions are examined less, but according to researches already carried out, it is clear that significant work can be accomplished in creating rational, highly effective and economic timber constructions. The paper deals with research on the formation of composed fiber-reinforced beams (CFRP) made of timber and provide evidence of their effectiveness. The aim of the paper is to investigate cross-bending of CFRP-reinforced gluelaminated timber beams. According to the results we were able to determine the additional effectiveness of reinforcement with CFRP (which depends on the CFRP material's quality, quantity and module of elasticity) on the mechanical features of timber and a whole beam.
Special dynamic soilstructure analysis procedures demonstrated for two tower-like structures
Authors: Koleková Y. , Petronijević M. , Schmid G.
Published: June 2011

Special dynamic soilstructure analysis procedures demonstrated for two tower-like structures

Many problems in Earthquake Engineering require the modeling of the structure as a dynamic system including the sub-grade. A structural engineer is usually familiar with the Finite Element Method but has a problem modeling the sub-grade when its infinite extension and wave propagation are the essential features. If the dynamic equation of a soil-structure system is written in a frequency domain and the variables of the system are total displacements, then the governing equations are given as in statics. The dynamic stiffness matrix of the system is obtained as the sum of the stiffnesses of the structure and sub-grade sub-structures. To illustrate the influence of the sub-grade on the dynamic behavior of the structure, the frequency response of two tower-like structures excited by a seismic harmonic wave field is shown. The sub-grade is modeled as an elastic homogeneous half-space. The structure is modeled as a finite beam element with lumped masses
Wall Crossing and M-Theory
Authors: Aganagic Mina , Ooguri Hirosi , Vafa Cumrun , Yamazaki Masahito
Published: June 2011

We study BPS bound states of D0 and D2 branes on a single D6 brane wrapping a Calabi-Yau 3-fold

X

. When

X

has no compact 4-cyles, the BPS bound states are organized into a free field Fock space, whose generators correspond to BPS states of spinning M2 branes in M-theory compactified down to 5 dimensions by a Calabi-Yau 3-fold

X

. The generating function of the D-brane bound states is expressed as a reduction of the square of the topological string partition function, in all chambers of the Kähler moduli space.
Conceptual Invention
Authors: Bontea Adriana
Published: June 2011

By taking into account those operations of modernity initiated by Stendhal and Cézanne, Manet and Proust, which were continued by Merleau-Ponty and Lévi-Strauss, this paper considers Claude Imbert's writings from the perspective of the formative role that literature and painting had and still have in mapping a new rationality. The aim is to show how the philosopher reintegrates such priceless experiences, captured by peculiar literary forms, syntagms, and juxtaposition of genres or pictorial manners, into a conceptual and stylistic invention affecting the very core of philosophical activity.
Manière du départ: Beauvoir, Merleau-Ponty and Lévi-Strauss Take their Leave
Authors: Deutscher Penelope
Published: June 2011

Claude Imbert's responses to Beauvoir, Merleau-Ponty and Lévi-Strauss characteristically interpret their work as philosophical departures and emigrations. Less interested in definitively abandoned conceptual models, Imbert focuses on incomplete, ‘vexed’, ‘active’ leaving: a text which is ‘out of synchronicity with its own philosophical time’; which is ‘in advance of oneself’; or uses a philosophical mode whose limitations and fracture points are concurrently revealed. Beauvoir's project in The Second Sex is interpreted as sustained by, and productive in, its own cul-de-sacs, while Merleau-Ponty is interpreted as engaged in an ongoing emigration from phenomenology and transcendentalism. Whereas Derrida's Lévi-Strauss reinstates a Rousseauist vision, Imbert's Lévi-Strauss is a figure perpetually departing from his own resources. In their irony, his reinstatements of nostalgia take leave of themselves. Imbert is described as a critic who has brought her acuity to such philosophical departures.