bluuebunny/crossref_metadata_2025 huggingface dataset:
The potential role of HIF on tumour progression and dissemination
Authors: Unwith Sandeep , Zhao Hailin , Hennah Lindsay , Ma Daqing
Published: April 2014

Cancer is the second cause of mortality worldwide, primarily owing to failure to cure metastatic disease. The need to target the metastatic process to reduce mortality is clear and research over the past decade has shown hypoxia‐inducible factor‐1 (HIF‐1) to be one of the promising targets. In order for metastatic disease to be established, multiple steps need to be taken whereby the tumour cells escape into the bloodstream and survive, disseminate and then establish at a premetastatic niche. HIF‐1 mediates hypoxia‐induced proangiogenic factors such as vascular endothelial growth factor (VEGF) and platelet‐derived growth factor (PDGF), which promote extravasation and chemotaxis. The migration of tumour cells is mediated by loss of E‐cadherin, which results in a more invasive phenotype; dissemination of the tumour cells by increased vascular permeability and survival in the bloodstream through resistance to apoptosis as well as adhesion at the premetastatic niche are all controlled by factors under the influence of HIF‐1. The overexpression of HIF in many aggressive cancer types as well as its role in the establishment of metastatic disease and treatment resistance demonstrate its potential target in therapeutics. Taken together, the role of HIF‐1 in cancer and metastatic disease is clear and the need for better treatment targeting metastases is paramount; more aggressive phenotypes with less response to treatment are associated with HIF‐1 expression. Our research has shown promise but many questions still remain to be answered.
The sodium channel β1 subunit mediates outgrowth of neurite‐like processes on breast cancer cells and promotes tumour growth and metastasis
Authors: Nelson Michaela , Millican‐Slater Rebecca , Forrest Lorna C. , Brackenbury William J.
Published: April 2014

Voltage‐gated Na+ channels (VGSCs) are heteromeric proteins composed of pore‐forming α subunits and smaller β subunits. The β subunits are multifunctional channel modulators and are members of the immunoglobulin superfamily of cell adhesion molecules (CAMs). β1, encoded by SCN1B, is best characterized in the central nervous system (CNS), where it plays a critical role in regulating electrical excitability, neurite outgrowth and migration during development. β1 is also expressed in breast cancer (BCa) cell lines, where it regulates adhesion and migration in vitro. In the present study, we found that SCN1B mRNA/β1 protein were up‐regulated in BCa specimens, compared with normal breast tissue. β1 upregulation substantially increased tumour growth and metastasis in a xenograft model of BCa. β1 over‐expression also increased vascularization and reduced apoptosis in the primary tumours, and β1 over‐expressing tumour cells had an elongate morphology. In vitro, β1 potentiated outgrowth of processes from BCa cells co‐cultured with fibroblasts, via trans‐homophilic adhesion. β1‐mediated process outgrowth in BCa cells required the presence and activity of fyn kinase, and Na+ current, thus replicating the mechanism by which β1 regulates neurite outgrowth in CNS neurons. We conclude that when present in breast tumours, β1 enhances pathological growth and cellular dissemination. This study is the first demonstration of a functional role for β1 in tumour growth and metastasis in vivo. We propose that β1 warrants further study as a potential biomarker and targeting β1‐mediated adhesion interactions may have value as a novel anti‐cancer therapy.
Lack of Absent in Melanoma 2 (AIM2) expression in tumor cells is closely associated with poor survival in colorectal cancer patients
Authors: Dihlmann Susanne , Tao Sha , Echterdiek Fabian , Herpel Esther , Jansen Lina , Chang‐Claude Jenny , Brenner Hermann , Hoffmeister Michael , Kloor Matthias
Published: April 2014

Functional studies on colorectal cancer cells indicated a protective role of the interferon‐inducible dsDNA sensor Absent in Melanoma 2 (AIM2) in cancer progression. Given that a high mutation rate and lack of AIM2 expression was previously detected in a subset of colorectal cancers, we here investigated the association of AIM2 expression in tumor cells and patient prognosis (5‐year follow‐up). A tissue microarray analysis of 476 matched tissue pairs (colorectal tumor and adjacent normal colon epithelium) was performed by two independent observers. Samples from 62 patients were excluded because of missing follow‐up information or due to neo‐adjuvant therapy before tissue sampling. Out of the remaining 414 tissue pairs, 279 (67.4%) displayed reduced AIM2 expression in cancer cells when compared to epithelial cells of their normal counterpart. Thirty‐eight patients (9.18%) had completely lost AIM2 expression in tumor cells. After adjustment for sex, age, cancer stage, tumor site, tumor grade and chemotherapy, complete lack of AIM2 expression was associated with an up to 3‐fold increase in overall mortality (HR = 2.40; 95% CI = 1.44–3.99) and disease specific mortality (HR = 3.14; 95% CI = 1.75–5.65) in comparison to AIM2‐positive tumor samples. Our results demonstrate that lack of AIM2 expression is closely associated with poor outcome in colorectal cancer. The data thus strongly substantiate a protective role of AIM2 against progression of colorectal tumors. Further studies are required to assess whether lack of AIM2 expression may be used as a biomarker for the identification of colorectal cancer patients with poor prognosis.
Multiple effects of the special AT‐rich binding protein 1 (SATB1) in colon carcinoma
Authors: Frömberg Anja , Rabe Michael , Aigner Achim
Published: April 2014

SATB1 (special AT‐rich binding protein 1) is a global chromatin organizer regulating the expression of a large number of genes. Overexpression has been found in various solid tumors and positively correlated with prognostic and clinicopathological properties. In colorectal cancer (CRC), SATB1 overexpression and its correlation with poor differentiation, invasive depth, TNM (tumor, nodes, metastases) stage and prognosis have been demonstrated. However, more detailed studies on the SATB1 functions in CRC are warranted. In this article, we comprehensively analyze the cellular and molecular role of SATB1 in CRC cell lines with different SATB1 expression levels by using RNAi‐mediated knockdown. Using siRNAs with different knockdown efficacies, we demonstrate antiproliferative, cell cycle‐inhibitory and proapoptotic effects of SATB1 knockdown in a SATB1 gene dose‐dependent manner. Tumor growth inhibition is confirmed in vivo in a subcutaneous tumor xenograft mouse model using stable knockdown cells. The in‐depth analysis of cellular effects reveals increased activities of caspases‐3, ‐7, ‐8, ‐9 and other mediators of apoptotic pathways. Similarly, the analysis of E‐ and N‐cadherin, slug, twist, β‐catenin and MMP7 indicates SATB1 effects on epithelial–mesenchymal transition (EMT) and matrix breakdown. Our results also establish SATB1 effects on receptor tyrosine kinases and (proto‐)oncogenes such as HER receptors and Pim‐1. Taken together, this suggests a more complex molecular interplay between tumor‐promoting and possible inhibitory effects in CRC by affecting multiple pathways and molecules involved in proliferation, cell cycle, EMT, invasion and cell survival.
Reinforcer magnitude and resistance to disruption of forgetting functions and response rates
Authors: Berry Meredith S. , Odum Amy L.
Published: April 2014

The present experiment investigated the effects of reinforcer magnitude on resistance to disruption of remembering and response rates. Pigeons were exposed to a variable‐interval (VI), delayed‐matching‐to‐sample (DMTS) procedure with two components (rich and lean, distinguished by differing discriminative stimuli and hopper presentation duration). Completion of a VI 20 s schedule resulted in DMTS trials. In a DMTS trial, a choice of one of two comparison stimuli resulted in food if the choice matched the color of the previously presented sample stimulus. Separable aspects of the forgetting functions (initial discrimination and rate of forgetting) were examined by determining accuracy across a range of delays. Response rates and accuracy were higher in the rich relative to the lean component during baseline, and were more persistent during disruptors (extinction and prefeeding). During DMTS trials, extinction decreased initial discrimination more in the lean than the rich component, but had no systematic effect on rate of forgetting. During prefeeding, the rate of forgetting increased more in the lean than the rich component, but initial discrimination was not systematically affected. These results show persistence of response rates and remembering are positively related to reinforcer magnitude. The type of disruptor also influences the way in which remembering is disrupted.
The impact of filtering self‐organizing maps: a case study with Australian pressure and rainfall
Authors: Huva Robert , Dargaville Roger , Rayner Peter
Published: April 2014

This study presents a semi‐objective set of criteria for filtering the time series of a self‐organizing map (SOM, a method for collapsing a complex data set onto a series of typical instances/nodes). The purpose of the filter (or selection process) is to avoid the problem of associating anomalous time steps with SOM nodes that do not adequately describe that time step. The filter is based on measures of the match of the original field to the nearest SOM node. We demonstrate the method by using 21 years of MSLP reanalysis data for the Australian region from the European Centre for Medium Range Weather Forecasting product, ERA‐Interim. We show that there are instances in which the SOM is incapable of describing the original data and that these instances can be removed using a set of criteria. We then show that this filtering/removal process improves both the quantitative and qualitative matching of the SOM to the MSLP data. Finally, we show that SOM‐associated precipitation at three Australian cities (Melbourne, Sydney and Perth) is significantly influenced by the MSLP distributions that do not relate to the SOM and were removed by the filtering. The results show that care is required when interpreting trends inferred from data sorted into SOM nodes.
The importance of systemic therapy in minimizing local recurrence after breast‐conserving surgery: The NSABP experience
Authors: Mamounas Eleftherios P. , Tang Gong , Liu Qing
Published: April 2014

Adjuvant systemic therapy significantly reduces rates of distant recurrence and death. The effect of systemic therapy is not limited to reducing distant recurrences but also extends to reducing loco‐regional recurrences, and rates of loco‐regional recurrence have steadily declined over the past 25 years. This review focuses on the effect of adjuvant systemic therapy on rates of ipsilateral breast tumor recurrence following lumpectomy plus breast irradiation in several pivotal NSABP trials in early‐stage breast cancer. J. Surg. Oncol. 2014 110:45–50. © 2014 Wiley Periodicals, Inc.
Graphene oxide coated capillary for the analysis of endocrine‐disrupting chemicals by open‐tubular capillary electrochromatography with amperometric detection
Authors: Jiang Xiaoying , Jiang Yuehuang , Shi Guoyue , Zhou Tianshu
Published: April 2014

A graphene oxide‐coated capillary was fabricated by using 3‐aminopropyltriethoxysilane as the cross‐linking agent. It was used for the separation and detection of three endocrine‐disrupting chemicals, including bisphenol A, 4‐nonylphenol, and 4‐octylphenol by capillary electrochromatography. Due to the hydrophobicity, hydrogen bonding, and π–π interaction between graphene oxide and the analytes, the three analytes could be well separated in pH = 11.0, 20 mmol/L Na2B4O7‐NaOH/methanol mobile phase (50:50, v/v) within 950 s. After preconcentration, the detection limits were 6.7 × 10−10, 3.3 × 10−9, and 6.7 × 10−10 mol/L (S/N = 3) for bisphenol A, nonylphenol, and octylphenol, respectively. The developed method was successfully applied to the determination of the above analytes in water samples. The satisfactory result demonstrated that the graphene oxide coated capillary used in capillary electrochromatography with amperometric detection was convenient to prepare, highly stable, and had good reproducibility.
Incidence of second metachronous head and neck cancers: Population‐based outcomes over 25 years
Authors: Tiwana Manpreet S. , Hay John , Wu Jonn , Wong Frances , Cheung Winson , Olson Robert A.
Published: April 2014

Objectives/Hypothesis

The primary objective was to determine the incidence of second metachronous head and neck cancers (HNC) following an index HNC and estimate their overall survival.

Study Design

Retrospective cohort study.

Methods

A total of 1,658 consecutive primary HNC patients diagnosed in 1986 to 1990 were identified through the prospectively maintained provincial BC Cancer Registry database. They were followed up for a period of 25 years. Survival analysis and second cancer estimates were performed with standard Kaplan‐Meier & Cox regression analysis.

Results

Out of a total of 443 (27%) second cancers, 89 (5%) second HNC occurred in 1,658 HNC patients, with an actuarial metachronous HNC incidence rate at 5, 10, 15, 20, and 25 years that was 3.9%, 8.1%, 10.4%, 13.2%, and 14.5%, respectively. Second primary cancer (SPC) in lung and esophagus occurred in 155 (9%) and 32 (2%) patients, respectively. The median follow‐up time for all patients and alive patients was 4.05 years (range, 0.2–25.0 years) and 23.2 years (range, 20.76–25.0 years), respectively. Of second HNC, 83 (93%) were metachronous. Oral cavity (P < 0.001) and oropharyngeal (P < 0.002) index cancers were more likely to develop a metachronous HNC. The overall survival rate for the metachronous HNC patients at 5 years is 15%. SPCs in esophagus and lung had lower overall survival compared to second HNC (P < 0.001).

Conclusion

Oral cavity and oropharyngeal cancers carry the highest risk of a subsequent metachronous HNC. Given the incidence and prognosis of second HNC, future research should address the frequency and duration of screening the head and neck region for a second cancer.

Level of Evidence

2b. Laryngoscope 124:2287–2291, 2014
Management Efficiency in Football: An Empirical Analysis of Two Extreme Cases
Authors: Jara Miguel , Paolini Dimitri , de Dios Tena Horrillo Juan
Published: April 2014

Analysis of managerial efficiency in sport economics typically focuses on evaluating coach decisions instead of assessing the organization as a whole. This paper studies the relative importance of variables related to power and managerial decisions by estimating stochastic production frontiers models for the Chilean and Italian football leagues. We find that historical and geographical variables intended to capture market size play their expected roles in both Italy and Chile. However, the degree of technical inefficiency is lower magnitude in Chile. This difference could be due to a smaller market size and/or to financial constraints faced by small clubs in this country. Copyright © 2014 John Wiley & Sons, Ltd.
A flow‐dependent quadratic steiner tree problem in the Euclidean plane
Authors: Brazil Marcus N. , Ras Charl J. , Thomas Doreen A.
Published: April 2014

We introduce a flow‐dependent version of the quadratic Steiner tree problem in the plane. An instance of the problem on a set of embedded sources and a sink asks for a directed tree T spanning of these nodes and a bounded number of Steiner points, such that is a minimum, where f(e) is the flow on edge e. The edges are uncapacitated and the flows are determined additively, that is, the flow on an edge leaving a node u will be the sum of the flows on all edges entering u. Our motivation for studying this problem is its utility as a model for relay augmentation of wireless sensor networks. In these scenarios, one seeks to optimize power consumption—which is predominantly due to communication and, in free space, is proportional to the square of transmission distance—in the network by introducing additional relays. We prove several geometric and combinatorial results on the structure of optimal and locally optimal solution‐trees (under various strategies for bounding the number of Steiner points) and describe a geometric linear‐time algorithm for constructing such trees with known topologies. © 2014 Wiley Periodicals, Inc. NETWORKS, Vol. 64(1), 18–28 2014
Organizational Climate and Hospital Nurses' Caring Practices: A Mixed‐Methods Study
Authors: Roch Geneviève , Dubois Carl‐Ardy , Clarke Sean P.
Published: April 2014

Organizational climate in healthcare settings influences patient outcomes, but its effect on nursing care delivery remains poorly understood. In this mixed‐methods study, nurse surveys (N = 292) were combined with a qualitative case study of 15 direct‐care registered nurses (RNs), nursing personnel, and managers. Organizational climate explained 11% of the variation in RNs' reported frequency of caring practices. Qualitative data suggested that caring practices were affected by the interplay of organizational climate dimensions with patients and nurses characteristics. Workload intensity and role ambiguity led RNs to leave many caring practices to practical nurses and assistive personnel. Systemic interventions are needed to improve organizational climate and to support RNs' involvement in a full range of caring practices. © 2014 Wiley Periodicals, Inc.
Proteomic analysis of hypoxia‐induced U373MG glioma secretome reveals novel hypoxia‐dependent migration factors
Authors: Yoon Jong Hyuk , Kim Jaeyoon , Kim Kyung Lock , Kim Do‐Hyeon , Jung Sun‐Ju , Lee Hyeongjoo , Ghim Jaewang , Kim Dayea , Park Jong Bae , Ryu Sung Ho , Lee Taehoon G.
Published: April 2014

High‐grade gliomas are one of the most common brain tumors and notorious for poor prognosis due to their malignant nature. Gliomas have an extensive area of hypoxia, which is critical for glioma progression by inducing aggressiveness and activating the angiogenesis process in the tumor microenvironment. To resolve the factors responsible for the highly malignant nature of gliomas, we comprehensively profiled the U373MG glioma cell secretome—exosome and soluble fraction under hypoxic and normoxic conditions. A total of 239 proteins were identified from the exosome and soluble fractions. Vascular endothelial growth factor, stanniocalcin 1 (STC1) and stanniocalcin 2, and insulin‐like growth factor binding protein 3 and 6, enriched in the soluble fraction, and lysyl oxidase homolog 2 enriched in the exosomal fraction were identified as upregulated proteins by hypoxia based on a label‐free quantitative analysis. STCs and insulin‐like growth factor binding proteins, which were identified as secretory proteins under hypoxic conditions, were highly correlated with glioma grade in human patients by microarray analysis. An in vitro scratch wound assay revealed that STC1 and 2 have important functions in the induction of cell migration in a hypoxia‐dependent manner, suggesting that they are hypoxia‐dependent migration factors.
Targeting ribosomal S6 kinases/Y‐box binding protein‐1 signaling improves cellular sensitivity to taxane in prostate cancer
Authors: Shiota Masaki , Itsumi Momoe , Yokomizo Akira , Takeuchi Ario , Imada Kenjiro , Kashiwagi Eiji , Inokuchi Junichi , Tatsugami Katsunori , Uchiumi Takeshi , Naito Seiji
Published: April 2014

BACKGROUND

Taxanes are the only cytotoxic chemotherapeutic agents proved to prolong the survival in patients with castration‐resistant prostate cancer. However, because of intrinsic and acquired resistances to taxanes, their therapeutical efficiencies are modest, bringing only a few months of survival benefit. Y‐box binding protein‐1 (YB‐1) promotes cancer cell resistance to various anticancer treatments, including taxanes. Here, we aimed to elucidate the mechanism of taxane resistance by YB‐1 and examined overcoming resistance by targeting YB‐1 signaling.

METHODS

Gene and protein expression levels were evaluated by quantitative real‐time polymerase chain reaction and Western blot analysis, respectively. We evaluated the sensitivity of prostate cancer cells to taxanes using cytotoxicity assays.

RESULTS

Natural taxane paclitaxel from Taxus brevifolia activated the Raf‐1/extracellular signal‐regulated kinase (ERK) pathway, leading to an activation of ribosomal S6 kinases (RSK)/YB‐1 signaling. Activated Raf‐1/ERK pathway was blunted by YB‐1 knockdown in prostate cancer cells, indicating regulation between Raf‐1/ERK signaling and YB‐1. In addition, ERK or RSK was activated in taxane‐resistant prostate cancer cells, resulting in YB‐1 activation. YB‐1 knockdown as well as RSK inhibition using RSK‐specific siRNA or the small molecule inhibitor SL0101 successfully blocked activation of YB‐1, leading to suppression of prostate cancer growth and sensitization to paclitaxel.

CONCLUSIONS

Taken together, these findings indicate that RSK/YB‐1 signaling contributes to taxane resistance, and implicate the therapeutics targeting RSK/YB‐1 signaling such as RSK inhibitor as a promising novel therapy against prostate cancer, especially in combination with taxane. Prostate 74:829–838, 2014. © 2014 Wiley Periodicals, Inc.
NEDD9 crucially regulates TGF‐β‐triggered epithelial–mesenchymal transition and cell invasion in prostate cancer cells: Involvement in cancer progressiveness
Authors: Morimoto Kazuya , Tanaka Tomoaki , Nitta Yujiro , Ohnishi Keiko , Kawashima Hidenori , Nakatani Tatsuya
Published: April 2014

BACKGROUND

NEDD9 is one of the Crk‐associated substrate (Cas) family proteins that mediate downstream signaling processes including cytoskeletal organization, cell‐cycle and tumorigenesis. While NEDD9 plays a crucial role in epithelial–mesenchymal transition (EMT), the functional mechanism underlying NEDD9‐mediated EMT in prostate cancer (PCa) remains uncertain.

METHODS

The expression levels of NEDD9 and its downstream molecules in PC‐3, LNCaP, and VCaP cells exposed to transforming growth factor‐β (TGF‐β) were determined by western blotting. The invasion of these cells with ectopic overexpression of NEDD9 or silencing of NEDD9 expression was measured by transwell invasion assay. Human tissue samples comprising 45 PCa specimens and ten specimens of normal prostatic tissue were used for immunohistochemical (IHC) analysis of NEDD9 expression.

RESULTS

Both NEDD9 and its downstream signaling molecules associated with EMT were strongly induced by TGF‐β in PCa cells. PC‐3 cells with stable overexpression of NEDD9 had a mesenchymal phenotype and significantly enhanced cell invasion, despite their decreased cell proliferation. Knockdown of endogenous NEDD9 expression completely diminished TGF‐β‐triggered tumor invasion in several PCa cell lines. The IHC data revealed a significant positive correlation between the NEDD9 staining score and tumor aggressiveness (e.g., Gleason grade, serum PSA level). The NEDD9 staining score in primary PCa with bone metastasis was significantly higher than that in PCa without metastasis.

CONCLUSIONS

NEDD9 may be a key mediator involved in TGF‐β‐mediated EMT and cell motility in PCa cells and a novel target in the treatment of metastatic PCa and prevention of spread of localized PCa cells to other organs. Prostate 74:901–910, 2014. © 2014 Wiley Periodicals, Inc.
Detection of methemoglobin in whole blood based on confocal micro‐raman spectroscopy and multivariate statistical techniques
Authors: Zhu M. F. , Ye X. P. , Huang Y. Y. , Guo Z. Y. , Zhuang Z. F. , Liu S. H.
Published: April 2014

Raman spectroscopy has been shown to have the potential for revealing oxygenated and spin ability of hemoglobin. In this study, confocal micro‐Raman spectroscopy is developed to monitor the effect of sodium nitrite on oxyhemoglobin (HbO2) in whole blood. We observe that the band at 1,638 cm−1which is sensitive to the oxidation state decreases dramatically, while the 1,586 cm−1(low‐spin state band) reduces both in methemoglobin (MetHb) and poisoning blood. Our results show that adding in sodium nitrite lead to the transition from HbO2(Fe2+) to MetHb (Fe3+) in whole blood, and the iron atom converts from the low spin state to the high spin state with a delocalization from porphyrin plane. Moreover, multivariate statistical techniques, including principal components analysis (PCA) and linear discriminant analysis (LDA) are employed to develop effective diagnostic algorithms for classification of spectra between pure blood and poisoning blood. The diagnostic algorithms based on PCA–LDA yield a diagnostic sensitivity of 100% and specificity of 100% for separating poisoning blood from normal blood. Receiver operating characteristic (ROC) curve further confirms the effectiveness of the diagnostic algorithm based on PCA–LDA technique. The results from this study demonstrate that Raman spectroscopy combined with PCA–LDA algorithms has tremendous potential for the non‐invasive detection of nitrite poisoning blood. SCANNING 36:471–478, 2014. © 2014 Wiley Periodicals, Inc.
Relationship Between Oil Uptake and Water Content During Deep‐Fat Frying of Potato Particulates Under Isothermal Temperature
Authors: Huang Pay‐Yau , Fu Yi‐Chung
Published: April 2014

The purpose of this study is to correlate water content and oil uptake with the structural changes of potato particulates during deep‐fat frying. Raw potato particulates were sliced to form cylinders of 0.006 m diameter × 0.006 m length and subjected to deep‐fat frying at isothermal oil temperatures of 160, 190 and 220 °C. The microstructure properties were assessed using a field emission scanning electron microscope (FESEM). Previous results showed that a simultaneous two first‐order kinetic model adequately predicted water loss of potato particulates during isothermal frying. In this study, a simple rational model with two parameters in which regression squared (Rsqr) reaches 0.983 shows that oil uptake can be expressed by water content. The cross‐sectional structure of potato particulates observed using FESEM is different from the surface structure. Regardless of the frying temperature, pores not only become larger but also increase in number after the transition time. The observations of structural changes at the surface and inner section of potato particulates through the pictures of FESEM are critical. This physical evidence supports our previous assumption that the mechanisms of water loss (two‐stage rate processes) before and after transition time are different.
Posterior spinal fusion to sacrum in non-ambulatory hypotonic neuromuscular patients: Sacral rod/bone graft onlay method
Authors: Bui Theresa , Shapiro Frederic
Published: April 2014

Purpose

A retrospective study involving 65 non-ambulatory patients with hypotonic neuromuscular scoliosis has assessed the effectiveness of a sacral rod/bone onlay technique for extending spinal fusion to the sacrum.

Methods

To extend posterior spinal fusion to the sacrum, we used either 1 Harrington rod and 1 Luque L rod with sublaminar wires in 14 patients (Group 1) or two rods with sublaminar wires in 51 patients (Group 2) along with abundant autograft and allograft bone covering the ends of the rods.

Results

Diagnoses were Duchenne muscular dystrophy 53, spinal muscular atrophy 4, myopathy 3, limb girdle muscular dystrophy 2, infantile FSH muscular dystrophy 1, cerebral palsy 1, and Friedreich ataxia 1. Mean age at surgery was 14.3 years (±2.2, range 10.9–25.2). Radiographic follow-up (2 years post-surgery or greater) was 6.4 years (±4.4, range 2–25.3). Using the onlay technique, all patients fused with no rod breakage or pseudarthrosis. For the entire series, the mean pre-operative scoliosis was 54.7° (±31.1, range 0°–120°) with post-operative correction to 21.8° (±21.7, range 0°–91°) and long-term follow-up 24° (±22.9, range 0°–94°). For pelvic obliquity, pre-operative deformity was 17.3° (±11.3, range 0°–51°) with post-operative correction to 8.9° (±7.8, range 0°–35°) and long-term follow-up 10.1° (±8.1, range 0°–27°). Five required revision at a mean of 3.3 years post-original surgery involving rod shortening at the distal end. One of these had associated infection.

Conclusion

Lumbosacral stability and long-term sitting comfort have been achieved in all patients. Problems can be minimized by positioning the rods firmly against the sacrum at the time of surgery with a relatively short extension beyond the L5–S1 junction. The procedure is valuable in hypotonic non-ambulatory neuromuscular patients whose immobility enhances the success rate for fusion due to diminished stress at the lumbosacral junction. It is particularly warranted for those with osteoporosis and a small, deformed pelvis. Considerable weight loss and lengthy rods not closely apposed to the sacrum at the time of surgery played a major role in patients needing revision.
Wild type p53 reactivation: From lab bench to clinic
Authors: Selivanova Galina
Published: April 2014

The p53 tumor suppressor is the most frequently inactivated gene in cancer. Several mouse models have demonstrated that the reconstitution of the p53 function suppresses the growth of established tumors. These facts, taken together, promote the idea of p53 reactivation as a strategy to combat cancer. This review will focus on recent advances in the development of small molecules which restore the function of wild type p53 by blocking its inhibitors Mdm2 and MdmX or their upstream regulators and discuss the impact of different p53 functions for tumor prevention and tumor eradication. Finally, the recent progress in p53 research will be analyzed concerning the role of p53 cofactors and cellular environment in the biological response upon p53 reactivation and how this can be applied in clinic.
Weak pulling forces exerted on Nin‐orientated transmembrane segments during co‐translational insertion into the inner membrane of Escherichia coli
Authors: Cymer Florian , Ismail Nurzian , von Heijne Gunnar
Published: April 2014

Transmembrane helices (TMHs) in membrane proteins can be orientated with their N‐terminus towards the cytoplasm (Nin), or facing the non‐cytoplasmic side (Nout). Most membrane proteins are inserted co‐translationally into membranes, aided by Sec‐type translocons. Since the final orientation of Nin‐ and Nout‐orientated TMHs differs, they could also interact differently with the translocon and the surrounding membrane during insertion. We measured pulling forces exerted on Nin‐orientated TMHs during co‐translational insertion into the inner membrane of Escherichia coli. Our results demonstrate that Nin‐orientated TMHs experience a weaker pulling force but retain the overall biphasic force profile seen previously for Nout‐orientated TMHs (Ismail et al., 2012 [1]).
Arginine methylation of the cellular nucleic acid binding protein does not affect its subcellular localization but impedes RNA binding
Authors: Wei Hung-Ming , Hu Huan-Hsuan , Chang Gia-Yun , Lee Yu-Jen , Li Yi-Chen , Chang Hong-How , Li Chuan
Published: April 2014

CNBP
physically interacts with
PRMT1
by anti tag coimmunoprecipitation (View interaction)
The cytochrome c peroxidase and cytochrome c encounter complex: The other side of the story
Authors: Schilder Jesika , Löhr Frank , Schwalbe Harald , Ubbink Marcellus
Published: April 2014

Formation of an encounter complex is important for efficient protein complex formation. The encounter state consists of an ensemble of orientations of two proteins in the complex. Experimental description of such ensembles inherently suffers from insufficient data availability. We have measured paramagnetic relaxation enhancements (PRE) on cytochrome c peroxidase (CcP) caused by its partner cytochrome c (Cc) carrying a spin label. The data complement earlier PRE data of spin labelled CcP, identifying several new interactions. This work demonstrates the need of obtaining as many independent data sets as possible to achieve the most accurate description of an encounter complex.
Recent applications of fluorescence correlation spectroscopy in live systems
Authors: Macháň Radek , Wohland Thorsten
Published: April 2014

Fluorescence correlation spectroscopy (FCS) is a widely used technique in biophysics and has helped address many questions in the life sciences. It provides important advantages compared to other fluorescence and biophysical methods. Its single molecule sensitivity allows measuring proteins within biological samples at physiological concentrations without the need of overexpression. It provides quantitative data on concentrations, diffusion coefficients, molecular transport and interactions even in live organisms. And its reliance on simple fluorescence intensity and its fluctuations makes it widely applicable. In this review we focus on applications of FCS in live samples, with an emphasis on work in the last 5 years, in the hope to provide an overview of the present capabilities of FCS to address biologically relevant questions.
MIR146A inhibits JMJD3 expression and osteogenic differentiation in human mesenchymal stem cells
Authors: Huszar Jessica M. , Payne Christopher J.
Published: April 2014

Chromatin remodeling is important for cell differentiation. Histone methyltransferase EZH2 and histone demethylase JMJD3 (KDM6B) modulate levels of histone H3 lysine 27 trimethylation (H3K27me3). Interplay between the two modulators influence lineage specification in stem cells. Here, we identified microRNA MIR146A to be a negative regulator of JMJD3. In the osteogenic differentiation of human mesenchymal stem cells (hMSCs), we observed an upregulation of JMJD3 and a downregulation of MIR146A. Blocking JMJD3 activity in differentiating hMSCs reduced transcript levels of osteogenic gene RUNX2. H3K27me3 levels decreased at the RUNX2 promoter during cell differentiation. Modulation of MIR146A levels in hMSCs altered JMJD3 and RUNX2 expression and affected osteogenic differentiation. We conclude that JMJD3 promotes osteogenesis in differentiating hMSCs, with MIR146A regulating JMJD3.
Molecular insights into NF2/Merlin tumor suppressor function
Authors: Cooper Jonathan , Giancotti Filippo G.
Published: April 2014

The FERM domain protein Merlin, encoded by the NF2 tumor suppressor gene, regulates cell proliferation in response to adhesive signaling. The growth inhibitory function of Merlin is induced by intercellular adhesion and inactivated by joint integrin/receptor tyrosine kinase signaling. Merlin contributes to the formation of cell junctions in polarized tissues, activates anti‐mitogenic signaling at tight‐junctions, and inhibits oncogenic gene expression. Thus, inactivation of Merlin causes uncontrolled mitogenic signaling and tumorigenesis. Merlin's predominant tumor suppressive functions are attributable to its control of oncogenic gene expression through regulation of Hippo signaling. Notably, Merlin translocates to the nucleus where it directly inhibits the CRL4DCAF1 E3 ubiquitin ligase, thereby suppressing inhibition of the Lats kinases. A dichotomy in NF2 function has emerged whereby Merlin acts at the cell cortex to organize cell junctions and propagate anti‐mitogenic signaling, whereas it inhibits oncogenic gene expression through the inhibition of CRL4DCAF1 and activation of Hippo signaling. The biochemical events underlying Merlin's normal function and tumor suppressive activity will be discussed in this Review, with emphasis on recent discoveries that have greatly influenced our understanding of Merlin biology.
The Inoperative Iphigenia: Race, Law, and Emancipation in Michi Barall'sRescue Me
Authors: Chambers-Letson Joshua
Published: April 2014

José Esteban Muñoz once described the problem of minoritarian knowledge and cultural production within a majoritarian sphere thus:

Within majoritarian institutions the production of minoritarian knowledge is a project set up to fail. Mechanisms ensure that the production of such knowledge “misfires” insofar as it is misheard, misunderstood, and devalued. Politics are only possible when we acknowledge that dynamic.
Seed-mediated synthesis of bimetallic ruthenium–platinum nanoparticles efficient in cinnamaldehyde selective hydrogenation
Authors: Qi Xueqiang , Axet M. Rosa , Philippot Karine , Lecante Pierre , Serp Philippe
Published: April 2014

The two-step synthesis of small ruthenium–platinum nanoparticles leads to the formation of a core–shell structure. The catalytic results provide supplementary evidence of the core–shell structure.
Diverse mutational pathways converge on saturable chloroquine transport via the malaria parasite’s chloroquine resistance transporter
Authors: Summers Robert L. , Dave Anurag , Dolstra Tegan J. , Bellanca Sebastiano , Marchetti Rosa V. , Nash Megan N. , Richards Sashika N. , Goh Valerie , Schenk Robyn L. , Stein Wilfred D. , Kirk Kiaran , Sanchez Cecilia P. , Lanzer Michael , Martin Rowena E.
Published: April 2014

Significance

This study provides detailed insights into the workings of a protein that is a key determinant of drug resistance in the malaria parasite. We found that two main lineages of mutational routes lead to chloroquine transport via the chloroquine resistance transporter (PfCRT) and that a low level of chloroquine transport is conferred by as few as two mutations. However, the attainment of full transport activity is a rigid process that requires the mutations be added in a specific order to avoid decreases in chloroquine transport. Our finding that diverse forms of mutant PfCRT are all limited in their capacity to transport chloroquine indicates that resistance should be overcome by reoptimizing the chloroquine dosage.
Codon Optimization OnLine (COOL): a web-based multi-objective optimization platform for synthetic gene design
Authors: Chin Ju Xin , Chung Bevan Kai-Sheng , Lee Dong-Yup
Published: April 2014

Summary: Codon optimization has been widely used for designing synthetic genes to improve their expression in heterologous host organisms. However, most of the existing codon optimization tools consider a single design criterion and/or implement a rather rigid user interface to yield only one optimal sequence, which may not be the best solution. Hence, we have developed Codon Optimization OnLine (COOL), which is the first web tool that provides the multi-objective codon optimization functionality to aid systematic synthetic gene design. COOL supports a simple and flexible interface for customizing various codon optimization parameters such as codon adaptation index, individual codon usage and codon pairing. In addition, users can visualize and compare the optimal synthetic sequences with respect to various fitness measures. User-defined DNA sequences can also be compared against the COOL optimized sequences to show the extent by which the user’s sequences can be further improved.

Availability and implementation: COOL is free to academic and non-commercial users and licensed to others for a fee by the National University of Singapore. Accessible at http://bioinfo.bti.a-star.edu.sg/COOL/

Contact:  cheld@nus.edu.sg

Supplementary information:  Supplementary data are available at Bioinformatics online
Integrating stochastic age-structured population dynamics into
complex fisheries economic models for management evaluations: the North Sea
saithe fishery as a case study
Authors: Simons Sarah Laura , Bartelings Heleen , Hamon Katell Gaelle , Kempf Alexander Johannes , Döring Ralf , Temming Axel
Published: April 2014

There is growing interest in bioeconomic models as tools for understanding pathways of fishery behaviour in order to assess the impact of alternative policies on natural resources. A model system is presented that combines stochastic age-structured population dynamics with complex fisheries economics. Explicitly, the economic response of fleet segments to changes in stock development is analysed by applying observed values and stochastic recruitment. The optimization of net profits determines the fishing effort and the investment and disinvestment behaviour of fleet segments, which, in turn, affect the level of catch rates and discards. This tool was applied to the North Sea saithe fishery, where ICES re-evaluated the existing EU–Norway management plan, focusing on biological reference points only. Two scenarios were tested with alternative harvest control rules and then contrasted with one unregulated scenario with no quotas and driven by optimizing the net profit of the whole fleet. The model showed the success of both harvest control rules in rebuilding the stock and the associated costs to the fleets in terms of maximal 21% reduction in net profits, 21% reduction in crew wages and 11% reduction in fleet size in the midterm (2007–2015). In the long term (2022), successful stock recovery coincided with net profits almost equalling that of the unrestricted fishery. The model is highly sensitive to the parameter values but can be used strategically, providing a qualitative understanding of the anticipated relative changes.
Spleen Stiffness Measurement by Transient Elastography to Diagnose Portal Hypertension in Children
Authors: Goldschmidt Imeke , Brauch Catharina , Poynard Thierry , Baumann Ulrich
Published: April 2014

Background:

The development of esophageal varices is a late complication of chronic liver disease (LD) in children. The diagnosis is presently limited to invasive procedures such as endoscopy. Noninvasive tools to diagnose the presence and degree of esophageal varices would alter management decisions and support indications for invasive procedures in affected children. The aim of the study was to test the feasibility of spleen stiffness measurement (SSM) by transient elastography (TE; FibroScan) in children and compare data on its diagnostic use with established markers of liver fibrosis and parameters of portal hypertension.

Methods:

A total of 99 children (62 with chronic LD, 6 after liver transplantation, 31 controls) underwent SSM by TE. Fibrotest was determined in 37 children, 45 children had an additional liver stiffness measurement, and 19 underwent upper endoscopy.

Results:

SSM by FibroScan is feasible. Spleen size significantly determined success rate (90.5% in patients with splenomegaly vs 70.2% in patients without, P = 0.02). Spleen stiffness was significantly higher in patients with splenomegaly (62.96 vs 18.4 kPa, P < 0.001), in patients with varices (75 vs 24 kPa, P < 0.01), and in patients with a history of variceal hemorrhage (75 vs 50.25 kPa, P < 0.05). Variceal hemorrhage did not occur in patients with SSM results <60 kPa. Spleen stiffness decreased after liver transplantation, but remained elevated compared with controls (27.5 vs 16.3 kPa). Liver stiffness measurements and Fibrotest did not reflect the presence or degree of esophageal varices.

Conclusions:

SSM by TE is feasible in children and the results reflect the degree and occurrence of complications. A prospective follow‐up study with larger patient numbers and performance of screening endoscopies appears justified and desirable.
Microbacterium kyungheense sp. nov. and Microbacterium jejuense sp. nov., isolated from salty soil
Authors: Kook MooChang , Son Heung-Min , Yi Tae-Hoo
Published: April 2014

Two novel strains, THG-C26T and THG-C31T, were characterized using a polyphasic approach to determine their taxonomic positions. These two isolates were aerobic, Gram-stain-positive, non-motile, non-spore-forming and rod-shaped. 16S rRNA gene sequences and phenotypic features including chemotaxonomic characteristics indicated that the two isolates clearly represented members of the genus

Microbacterium

. The quinone systems of strains THG-C26T and THG-C31T contained MK-12/MK-13 as major menaquinones. The diamino acid in cell-wall hydrolysates of the two strains was ornithine. The major fatty acids were iso-C16 : 0, anteiso-C15 : 0 and anteiso-C17 : 0. The polyamine pattern had spermidine as the predominant component. The major polar lipids were phosphatidylglycerol, diphosphatidylglycerol and unidentified glycolipids. Phenotypic characteristics supported the affiliation of strains THG-C26T and THG-C31T to the genus

Microbacterium

. Chemotaxonomic data and DNA–DNA relatedness values allowed differentiation of these strains from other species of the genus

Microbacterium

with validly published names. Strains THG-C26T and THG-C31T showed highest 16S rRNA gene sequence similarities with

Microbacterium resistens

DMMZ 1710T (98.5 %) and

Microbacterium trichothecenolyticum

IFO 15077T (98.8 %), respectively, and the 16S rRNA gene sequence similarity between them was 99.0 %. DNA–DNA hybridization values between the novel isolates and strains of other species of the genus

Microbacterium

with validly published names were 4–25 %. Therefore, strains THG-C26T and THG-C31T are considered to represent two novel species of the genus

Microbacterium

, for which the names Microbacterium kyungheense sp. nov. [type strain THG-C26T ( = KACC 17124T = JCM 18735T)] and Microbacterium jejuense sp. nov. [type strain THG-C31T ( = KACC 17123T = JCM 18734T)] are proposed.
A new tubRZ operon involved in the maintenance of the Bacillus sphaericus mosquitocidal plasmid pBsph
Authors: Ge Yong , Hu Xiaomin , Zhao Ni , Shi Tingyu , Cai Quanxin , Yuan Zhiming
Published: April 2014

pBsph is a mosquitocidal plasmid first identified from Bacillus sphaericus, encoding binary toxins (Bin toxins) that are highly toxic to mosquito larvae. This plasmid plays an important role in the maintenance and evolution of the bin genes in B. sphaericus. However, little is known about its replication and partitioning. Here, we identified a 2.4 kb minimal replicon of pBsph plasmid that contained an operon encoding TubR-Bs and TubZ-Bs, each of which was shown to be required for plasmid replication. TubR-Bs was shown to be a transcriptional repressor of tubRZ-Bs genes and could bind cooperatively to the replication origin of eleven 12 bp degenerate repeats in three blocks, and this binding was essential for plasmid replication. TubZ-Bs exhibited GTPase activities and interacted with TubR-Bs : DNA complex to form a ternary nucleoprotein apparatus. Electron and fluorescence microscopy revealed that TubZ-Bs assembled filaments both in vitro and in vivo, and two point mutations in TubZ-Bs (T114A and Y260A) that severely impaired the GTPase and polymerization activities were found to be defective for plasmid maintenance. Further investigation demonstrated that overproduction of TubZ-Bs-GFP or its mutant forms significantly reduced the stability of pBsph. Taken together, these results suggested that TubR-Bs and TubZ-Bs are involved in the replication and probably in the partitioning of pBsph plasmid, increasing our understanding of the genetic particularity of TubZ systems.
Genetic diversity of feline morbilliviruses isolated in Japan
Authors: Sakaguchi Shoichi , Nakagawa So , Yoshikawa Rokusuke , Kuwahara Chieko , Hagiwara Hiroko , Asai Ken-ichi , Kawakami Kazuo , Yamamoto Yu , Ogawa Makoto , Miyazawa Takayuki
Published: April 2014

Feline morbillivirus (FmoPV) is an emerging virus in domestic cats and considered to be associated with tubulointerstitial nephritis. Although FmoPV was first described in China in 2012, there has been no report of the isolation of this virus in other countries. In this report, we describe the isolation and characterization of FmoPV from domestic cats in Japan. By using reverse transcription (RT)-PCR, we found that three of 13 urine samples from cats brought to veterinary hospitals were positive for FmoPV. FmoPV strains SS1 to SS3 were isolated from the RT-PCR-positive urine samples. Crandell-Rees feline kidney (CRFK) cells exposed to FmoPV showed cytopathic effects with syncytia formation, and FmoPV N protein was detected by indirect immunofluorescence assays. In addition, pleomorphic virus particles with apparent glycoprotein envelope spikes were observed by electron microscopy. By sequence analysis of FmoPV H and L genes, we found that FmoPVs showed genetic diversity; however, signatures of positive selection were not identified.