bluuebunny/crossref_metadata_2025 huggingface dataset:
Knockdown of lipocalin‐2 suppresses the growth and invasion of prostate cancer cells
Authors: Tung Min‐Che , Hsieh Shu‐Ching , Yang Shun‐Fa , Cheng Chun‐Wen , Tsai Rong‐Tzong , Wang Shao‐Chuan , Huang Min‐Hsien , Hsieh Yi‐Hsien
Published: June 2013

BACKGROUND

Lipocalin‐2 (LCN2) is a member of the lipocalin superfamily, and it has an important role in the regulation of cellular oncogenesis and apoptosis. However, the role for LCN2 in prostate cancer remains unclear.

METHOD

LCN2 expression has been determined by Western blotting, qRT‐PCR, and immunohistochemistry in the human prostate cell lines PC3, DU145, LNCaP, and 22Rv, and in human prostate tissue array. In this study, we identified shRNA‐LCN2 to determine the role of LCN2 in prostate‐cancer cell proliferation, migration, and invasion. Cell proliferative ability was measured by MTT, colony‐formation, and cell‐cycle analysis. The role of LCN2 in prostate‐cancer cell migration and invasion was analyzed by cell‐migration assay and Matrigel invasion assay. The effect of LCN2 knockdown on prostate tumor growth was assessed in a subcutaneous xenograft model.

RESULTS

LCN2 protein and mRNA expression are higher in PC3 and DU145 cells than in LNCaP and 22Rv cells, and prostate cancer tissue correlated significantly with tumor differentiation (P < 0.017) and Gleason's grade (P < 0.02). LCN2 knockdown in PC3 and DU145 cells decreased cell proliferation, colony formation, cell cycle arrest, migration, and invasion. Conversely, LCN2 overexpression in 22Rv cells produced the opposite effect. Subcutaneous xenografts in mice models showed decreased tumor growth in the LCN2‐knockdown mice.

CONCLUSIONS

Our results suggest that LCN2 might play an important role in regulation of proliferation and invasion of human prostate cancer, and that it can be a valuable marker of prostate cancer progression. Prostate 73:1281–1290. © 2013 Wiley Periodicals, Inc.
Androgen receptor enhances entosis, a non‐apoptotic cell death, through modulation of Rho/ROCK pathway in prostate cancer cells
Authors: Wen Simeng , Shang Zhiqun , Zhu Shimiao , Chang Chawnshang , Niu Yuanjie
Published: June 2013

BACKGROUND

Cell‐in‐cell phenomenon has been found for more than a century. Entosis, which is a newly found homogeneous cell‐in‐cell phenomenon and a non‐apoptosis cell death progress, has unclear function in prostate cancer progression. Here, we dissected mechanism of AR signaling related to entosis incidence in PCa progression.

METHODS

Two stable PCa cell lines, named LNCaP‐ARsi and C4‐2‐ARsi were established with stably transfected AR‐shRNA to knockdown AR mRNA expression in LNCaP and C4‐2 cells, respectively. PC3‐AR9 cell line was also established after stably transfecting full‐length AR‐cDNA into PC3 cells. All these cells were cultured in poly‐HEME‐coated plates to induce entosis, which is demonstrated via double staining.

RESULTS

Androgen‐DHT could enhance entosis in LNCaP, C4‐2 and PC3‐AR9 PCa cells in a dose dependent manner. Knock‐down of AR in LNCaP and C4‐2 significantly suppressed entosis as compared to LNCaP‐ARsc and C4‐2‐ARsc cells at both 1 and 10 nM DHT condition (P < 0.05). And suppression of Rho/ROCK expression resulted in interruption of AR‐mediated entosis. Human PCa samples surveys demonstrated that entosis was found only in CRPC but not in BPH and ADPC where AR was less expressed as compared to CRPC.

CONCLUSIONS

These results indicated that AR might play a negative role during PCa progression via influencing entosis by modulating Rho/ROCK pathway. This newly identified AR role of enhancing entosis might help us to better understand the multiple and opposite roles of AR, which could either promote or suppress PCa cell progression via different mechanisms. Prostate 73:1306–1315. © 2013 Wiley Periodicals, Inc.
Of mice and men‐warning: Intact versus castrated adult male mice as xenograft hosts are equivalent to hypogonadal versus abiraterone treated aging human males, respectively
Authors: Sedelaar J.P. Michiel , Dalrymple Susan S. , Isaacs John T.
Published: June 2013

BACKGROUND

Immune deficient male mice bearing human prostate cancer xenografts are used to evaluate therapeutic response to novel androgen ablation approaches and the results compared to surgical castration based upon assumption that testosterone microenvironment in intact and castrated adult male mice mimics eugonadal and castrated aging adult human males.

METHODS

To test these assumptions, serum total testosterone (TT) and free testosterone (FT) were determined longitudinally in groups (n > 20) of intact versus castrated adult male nude, NOG, and immune competent C57BL/6 mice.

RESULTS

In adult male mice, TT and FT varies by 30‐ to 100‐fold within the same animal providing a microenvironment that is only equivalent to hypogonadal, not eugonadal, adult human males (TT is 1.7 ± 1.2 ng/ml [5.8 ± 4.1 nM] in nude and 2.5 ± 1.3 ng/ml [8.7 ± 4.4 nM] in NOG mice versus >4.2 ng/ml [14.7 nM] in eugonadal humans). This was confirmed based upon enhanced growth of androgen dependent human prostate cancer xenografts inoculated into mice supplemented with exogenous testosterone to elevate and chronically maintain serum TT at a level (5 ng/ml [18 nM]) equivalent to a 50‐year‐old eugonadal human male. In castrated mice, TT and FT range from 2 to 20 pg/ml (7–70 pM) and <0.8 pg/ml (<2.6 pM), respectively, which is equivalent to castrate resistant prostate cancer (CRPC) patients treated with abiraterone. This was confirmed based upon the inability of another CYP17A1 inhibitor, ketoconazole, to inhibit the growth of CRPC xenografts in castrated mice.

CONCLUSIONS

Adult male mice supplemented with testosterone mimic eugonadal human males, while unsupplemented animals mimic standard androgen ablation and castrated animals mimic abiraterone treated patients. These studies confirm what is claimed in Robert Burns' poem “To a Mouse” that “The best laid schemes of mice and men/often go awry.” Prostate 73:1316–1325. © 2013 Wiley Periodicals, Inc.
Function of mutant and wild‐type plexinB1 in prostate cancer cells
Authors: Damola Adebiyi , Legendre Anne , Ball Stephen , Masters John R. , Williamson Magali
Published: June 2013

BACKGROUND

Semaphorins act as chemotactic cues for cell movement via their transmembrane receptors, plexins. Somatic missense mutations in the plexinB1 gene coupled with overexpression of the protein frequently occur in prostate tumors, indicating a role for plexinB1 in the pathogenesis of prostate cancer. However, the effect of semaphorin/plexin signaling is highly context dependent and whether plexinB1 acts as an inducer or inhibitor of prostate tumor progression in this context is not known.

METHODS

The response of prostate cancer cell lines to plexinB1 activation was assessed in migration, invasion, proliferation and protein phosphorylation assays. Expression was assessed by quantitative RTPCR and immunoblotting.

RESULTS

Different prostate cancer cell lines respond to Sema4D (the ligand for plexinB1) in diverse ways. Activation of endogenous plexinB1 enhances migration, invasion and anchorage‐independent growth of LNCaP prostate cancer cells via activation of ErbB2 and Akt. In contrast, Sema4D‐stimulation decreased the motility and proliferative capacity of PC3 cells. LNCaP has a missense mutation (Thr1697Ala) in the plexinB1 gene while LNCaP‐LN3, a derivative of LNCaP, expresses high levels of wild‐type plexinB1 only. Sema4D stimulation increases the motility and anchorage independent growth of both cell lines, showing that these responses are not dependent on the presence of the Thr1697Ala form of plexinB1. ErbB2 and plexinB1 are expressed in primary prostate epithelial cells.

CONCLUSIONS

PlexinB1 signals via ErbB2 to increase the invasive phenotype of prostate cancer cells. Both wild‐type and mutant forms of plexinB1 are potential targets for anti‐cancer therapy in prostate tumors that express ErbB2. Prostate 73:1326–1335, 2013. © 2013 The Authors. The Prostate published by Wiley Periodicals, Inc.
A study of caloric restriction versus standard diet in overweight men with newly diagnosed prostate cancer: A randomized controlled trial
Authors: Wright Jonathan L. , Plymate Stephen , D'Oria‐Cameron Andrea , Bain Carolyn , Haugk Kathy , Xiao Liren , Lin Daniel W. , Stanford Janet L. , McTiernan Anne
Published: June 2013

INTRODUCTION

Obese men have an increased risk of prostate cancer (PCa)‐specific mortality. Potential mechanisms include insulin and related proteins. We investigate whether a short‐term caloric restriction diet in overweight/obese men with newly diagnosed PCa can lead to measurable changes in patient anthropometrics and insulin‐related proteins.

METHODS

Overweight and obese PCa patients choosing active surveillance or radical prostatectomy were randomized to a 6‐week, caloric‐restricted diet or to continue their current diet. Changes from baseline to end of study in anthropometrics, dietary constituents and serum proteins (insulin, c‐peptide, IGF‐1, adiponectin, IGF‐BP3) were compared between the intervention and control groups using a Generalized Estimating Equation model.

RESULTS

Nineteen patients were randomized to the intervention (N = 10) or control (N = 9) group. Men in the intervention group had a 1.7% (3.7 lbs) mean decline in weight versus 1.0% (2.0 lbs) in controls (P < 0.05), and a reduced intake of calories, total and saturated fat, protein and starch (all P < 0.1 compared to controls). There was a significant difference (P = 0.002) in mean serum IGFBP‐3 between the intervention (+2.8%) and control group (−6.9%). Other biomarkers changed with the diet intervention to a degree similar to previous weight loss studies but were not statistically significant compared with controls.

CONCLUSION

In this small pilot study, a 6‐week caloric restricted diet in men with newly diagnosed PCa produced changes in weight, diet and serum proteins possibly related to prognosis. These results support larger‐scale trials testing longer‐term weight loss effects on potential PCa progression biomarkers. Prostate 73:1345–1351, 2013. © 2013 Wiley Periodicals, Inc.
Tests of marginal homogeneity and special cases
Authors: Dunnigan Keith
Published: June 2013

The analysis of two‐way contingency tables is common in clinical studies. In addition to summary counts and percentages, statistical tests or summary measures are often desired. If the data can be viewed as two categorical measurements on the same experimental unit (matched pair data) then a test of marginal homogeneity may be appropriate. The most common clinical example is the so called ‘shift table’ whereby a quantity is tested for change between two time points. The two principal marginal homogeneity tests are the Stuart Maxwell and Bhapkar tests. At present, SAS software does not compute either test directly (for tables with more than two categories) and a programmatic solution is required. Two examples of programmatic SAS code are found in the current literature. Although accurate in most instances, they fail to produce output for certain tables (‘special cases’). After summarizing the mathematics behind the two tests, a SAS macro is presented, which produces correct output for all tables. Finally, several examples are coded and presented with resultant output. Copyright © 2013 John Wiley & Sons, Ltd.
Analysis of hypoglycemic events using negative binomial models
Authors: Luo Junxiang , Qu Yongming
Published: June 2013

Negative binomial regression is a standard model to analyze hypoglycemic events in diabetes clinical trials. Adjusting for baseline covariates could potentially increase the estimation efficiency of negative binomial regression. However, adjusting for covariates raises concerns about model misspecification, in which the negative binomial regression is not robust because of its requirement for strong model assumptions. In some literature, it was suggested to correct the standard error of the maximum likelihood estimator through introducing overdispersion, which can be estimated by the Deviance or Pearson Chi‐square. We proposed to conduct the negative binomial regression using Sandwich estimation to calculate the covariance matrix of the parameter estimates together with Pearson overdispersion correction (denoted by NBSP). In this research, we compared several commonly used negative binomial model options with our proposed NBSP. Simulations and real data analyses showed that NBSP is the most robust to model misspecification, and the estimation efficiency will be improved by adjusting for baseline hypoglycemia. Copyright © 2013 John Wiley & Sons, Ltd.
A Controlled Study of a Lecithinized Delivery System of Curcumin (Meriva®) to Alleviate the Adverse Effects of Cancer Treatment
Authors: Belcaro Gianni , Hosoi Morio , Pellegrini Luciano , Appendino Giovanni , Ippolito Edmondo , Ricci Andrea , Ledda Andrea , Dugall Mark , Cesarone Maria Rosaria , Maione Claudia , Ciammaichella Giovanna , Genovesi Domenico , Togni Stefano
Published: June 2013

A proprietary lecithin delivery system of curcumin (Meriva) was evaluated in a controlled study to assess its efficacy in alleviating the side effects of cancer chemo‐ and radiotherapy in 160 patients undergoing these treatments. In both cases, a semi‐quantitative evaluation of the side effects was carried out using a visual analogue scale, assessing also the plasma free radical status in all patients. Results showed that lecithinized curcumin might alleviate the burden of side effects associated to chemo‐ and radiotherapy, suggesting that the anecdotal use of various preparations of curcumin as a supportive agent for cancer treatment is well worth a systematic investigation in larger scale clinical trials. The capacity of curcumin to upregulate anti‐oxidative responses and downregulate inflammatory pathways could explain its beneficial effect in tempering the prolonged and systemic oxidative and inflammatory effects of cancer treatment, and the beneficial effects observed in the plasma oxidative status in all patients of the treatment group support this view. © 2013 The Authors. Phytotherapy Research published by John Wiley & Sons, Ltd.
Pycnogenol® in Chronic Venous Insufficiency and Related Venous Disorders
Authors: Gulati Om P.
Published: June 2013

The present review provides an update of the biological profile of Pycnogenol in the light of its use in the treatment of chronic venous insufficiency (CVI) and related venous disorders such as deep vein thrombosis (DVT), post‐thrombotic syndrome, long haul air‐travel‐related leg oedema, venous ulcers and acute haemorrhoids. Pycnogenol is a French maritime pine bark extract produced from the outer bark of Pinus pinaster Ait. subsp. atlantica. Its strong antioxidant, anti‐inflammatory and vasodilator activities, antithrombotic effects and collagen stabilizing properties make it uniquely able to target the multi facet pathophysiology of CVI and related venous disorders. Clinical studies have shown that it can reduce oedema of the legs in CVI, reduce the incidence of deep venous thrombosis during long haul flights and enhance the healing of venous ulcers and haemorrhoidal episodes by topical application and/or oral administration. This review highlights clinical research findings on the safety, compliance and efficacy of Pycnogenol, including its use in combination products. Copyright © 2013 John Wiley & Sons, Ltd.
Detecting pygmy rabbits (Brachylagus idahoensis) using DNA extracted from fecal pellets of mixed‐species groups
Authors: Torstrom Shannon M. , Adams Jennifer R. , Waits Lisette P.
Published: June 2013

Noninvasive genetic sampling is an essential tool for studying elusive and endangered species. However, the DNA from noninvasive genetic sampling tends to be low in quantity and quality, which leads to poor DNA amplification. Using fecal pellets of pygmy rabbits (Brachylagus idahoensis) collected in February, March, and November 2011, we tested a possible solution of increasing the amount of sample by combining multiple pellet groups during DNA extraction. One potential drawback of this approach is accidental mixing of samples from multiple species. This study evaluates the mitochondrial DNA (mtDNA) species identification success rate for pygmy rabbit (PY) fecal DNA when mixed with eastern cottontail (Sylvilagus floridanus; EC) fecal pellet DNA at lower frequencies (1PY:3EC and 2PY:6EC) and eastern cottontail or mountain cottontail (S. nuttalli) pellet samples at an equal frequency (4:4). We found that successful detection of pygmy rabbit DNA using a species‐specific mtDNA polymerase chain reaction (PCR) test varies from 0% to 95% depending on the competing species and PCR protocol. From these results, we conclude that if samples are unintentionally mixed, the species with a greater number of pellets within the sample will be more likely to be detected. Also, if pellet piles are intentionally mixed to reduce sampling cost, the protocol should be optimized to maximize DNA amplification for the focal species; however, there will be reduced detection rates depending on the quality and quantity of the focal species DNA within the sample. © 2013 The Wildlife Society.
Beliefs, attitudes, and intentions for allowing elephants in group ranches around amboseli national park, Kenya
Authors: Browne‐Nuñez Christine , Jacobson Susan K. , Vaske Jerry J.
Published: June 2013

Wildlife authorities and conservationists are working to improve attitudes toward elephants (Loxodonta africana) among residents of the Greater Amboseli Ecosystem in southern Kenya; yet information on existing attitudes and their antecedents is lacking. In 2005, we conducted a survey of 569 randomly selected residents of group ranches—communally held lands around Amboseli National Park—to 1) identify intentions to allow elephants in group ranches, 2) examine attitudes toward this behavior, 3) explore underlying beliefs that influence attitudes, and 4) identify socio‐demographic predictors of residents for and against elephants in group ranches. A slight majority (53%) supported elephants in the group ranches and 47% were opposed. Residents who favored elephants in group ranches were more likely to believe that allowing elephants would increase opportunities to see elephants and attract more tourists to visit group ranches. Those opposed believed that it would cause conflict between people, increase dangerous human–elephant interactions, and increase costs to local people. Both groups believed allowing elephants in the group ranches would cause elephants to increase in number, but those in favor gave this outcome a positive evaluation, whereas those opposed felt this was a negative outcome. Women were less positive than men toward allowing elephants outside the park. Information on beliefs and evaluations of outcomes associated with allowing elephants in group ranches can assist stakeholder groups in addressing concerns of local people and developing interventions to facilitate the continued coexistence of people and elephants. © 2013 The Wildlife Society.
Movements of female exurban white‐tailed deer in response to controlled hunts
Authors: Rhoads Craig L. , Bowman Jacob L. , Eyler Brian
Published: June 2013

White‐tailed deer (Odocoileus virginianus) thrive in exurban habitats, which results in increased occurrences of deer–human conflicts. Controlled hunts are one method currently used by managers to deal with increasing exurban deer populations. To develop successful controlled hunts, managers must understand how deer respond to hunting pressure during controlled hunts. Previous research has documented a varied response of deer to harvest pressure and this response could affect the efficacy of a controlled hunt. We investigated deer responses to controlled hunts by examining an exurban deer population residing on Fair Hill Natural Resource Management Area in Cecil County, Maryland, USA. During controlled hunts in 2005 and 2006, we collected locations on 74 collared adult female deer. The percentage of deer available for harvest decreased 20–25% from before to after the hunt, because deer moved to refuges. Deer in refuges had similar movement rates before, during, and after the hunt, and these movement rates were similar to deer in non‐refuge areas before the hunt. Deer in non‐refuge areas increased their movement rates 12.6–15.6 m/hour during the hunt and returned to before‐hunt levels after the hunt. Our results suggest that refuges may provide sanctuary to a substantial portion of exurban deer during controlled hunts. To maximize deer harvests during controlled hunts, managers should identify and attempt to eliminate as many refuge areas as possible and plan multiple short‐duration hunts to reduce the impact of deer moving into refuge areas. © 2013 The Wildlife Society.
The use of bio‐metal concentrations correlated with clinical prognostic factors to assess human breast tissues
Authors: Al‐Ebraheem Alia , Geraki Kalotina , Leek Russell , Harris Adrian L , Farquharson Michael J
Published: June 2013

Worldwide, breast cancer is the most frequently diagnosed cancer in women and the leading cause of cancer death among women. The concentrations of bio‐metals are crucial for the homeostasis of human health and are being shown to have significantly different concentrations when comparing human cancer tissue and normal tissue. This is the first study that correlates the findings of the differences in the levels of certain elements between individual tumours, to the clinical prognostic factors such as oestrogen receptor (ER) status, lymph node status, tumour size, grade, menopause status, human epidermal growth factor receptor 2 status, epidermal growth factor receptor status, relapsed status and survival status. Micro probe synchrotron radiation X‐ray fluorescence techniques have been used to determine the localization and the relative concentrations of Zn, Cu, Fe and Ca in 128 formalin‐fixed paraffin‐embedded invasive ductal breast cancer (IDC) samples and normal surrounding breast tissue. The statistical analysis reveals a significant increase in the levels of Ca, Fe, Cu and Zn concentrations by 85%, 20%, 23% and 117%, respectively, in IDC tissue when compared to the normal breast tissue. Our study shows that increased relative expressions of Zn, Fe and Ca are all associated with ER positive breast cancers and also indicates that the imbalance in iron concentration (deficiency) should be viewed as an important risk factor that is associated with aggressive features of the cancer. Characterisation of the difference of bio‐metals in tumour to normal regions will help in selecting treatment for breast cancer with novel agents that chelate iron or zinc. Copyright © 2013 John Wiley & Sons, Ltd.
Determination of Zn distribution and speciation in basic oxygen furnace sludge by synchrotron radiation induced μ‐XRF and μ‐XANES microspectroscopy
Authors: Wang Lihua , Lu Xiaoming , Huang Yuying
Published: June 2013

Basic oxygen furnace off gas (BOF OG) sludge is one important type of metallurgical residues in steelmaking industry. The presence of zinc element is one key factor that constrains the practical use of such metallurgical residues. Information about the chemical association of zinc in BOF OG sludge is fundamental for understanding its behavior during the formation and further treatments. In this paper, the spatial distribution and the chemical forms of zinc in accumulated particles of BOF OG sludge have been investigated using synchrotron radiation induced μ‐X‐ray fluorescence and μ‐X‐ray absorption near edge spectroscopy microspectroscopy. Results of μ‐X‐ray fluorescence analysis showed that zinc distributed in two ways. One was shared with iron, and its distribution showed a positive correlation with that of iron. The other was accumulated in some well‐defined hot spots with high amount and its distribution showed negative correlation with that of iron. And results of μ‐X‐ray absorption near edge spectroscopy microspectroscopy indicated that ZnFe2O4 was the main constituent in some well‐defined hot spots, whereas in other cases, zinc was mainly in the form of zinc carbonate. Copyright © 2013 John Wiley & Sons, Ltd.
Three-point correlators of twist-2 operators in N=4 SYM at Born approximation
Authors: Kazakov Vladimir , Sobko Evgeny
Published: June 2013

Abstract

We calculate two different types of 3-point correlators involving twist-2 operators in the leading weak coupling approximation and all orders in N

c
in N=4 SYM theory. Each of three operators in the first correlator can be any component of twist-2 supermultiplet, though the explicit calculation was done for a particular component which is an SU(4) singlet. It is calculated in the leading, Born approximation for arbitrary spins j
1
, j
2
, j
3. The result significantly simplifies when at least one of the spins is large or equal to zero and the coordinates are restricted to the 2d plane spanned by two light-rays. The second correlator involves two twist-2 operators Tr(X∇
j1
X) + . . ., Tr(Z∇
j2
Z) + . . . and one Konishi operator
$ \mathrm{Tr}{{\left[ {\overline{Z},\overline{X}} \right]}^2} $
. It vanishes in the lowest g
0 order and is computed at the leading g
2 approximation.
Evaluation of a Heredofamilial Cancer Unit in Increasing Family History Collection and Genetic Counseling Referrals Among Spanish Oncologists at a University Hospital
Authors: Márquez‐Rodas Iván , López‐Tarruella Sara , Jerez Yolanda , Cavanagh Mercedes , Custodio Sara , López‐Trabada Daniel , Moya Beatriz , Pérez Sara , Rupérez Ana B. , Martín Miguel
Published: June 2013

A comprehensive family history is essential to identify patients at risk for hereditary cancer who could benefit from genetic counseling (GC). In a previous study, we observed a low occurrence of family history record (FHR) collection rate and GC referral among oncologists at our institution. The present work analyzes whether the implementation of a heredofamilial cancer unit (HFCU) would improve these parameters. We retrospectively compared the FHR rate in clinical records, National Cancer Institute (NCI) general criteria for hereditary cancer suspicion, GC referrals and FHR quality in two cohorts: cohort 1 (patients diagnosed before HFCU creation) and cohort 2 (after HFCU creation). Of 1,175 patients (590 cohort 1 and 585 cohort 2), FHRs were consigned in 27.3 % and 52.5 % of patients, respectively (p < 0.001). The GC referral of patients with any NCI criterion was 13.6 % xin cohort 1 vs. 40.5 % in cohort 2 (p < 0.001). FHR quality improved in terms of the total number of relatives (164 vs. 314, p = 0.1, N.S.) and number of healthy relatives consigned (80 vs. 191, p < 0.01). Nine mutations (6 BRCA, 1 MEN1, 2 Lynch), 4 unknown significance variants (all in BRCA) and 2 with no mutation were identified among patients referred from cohort 2. We conclude that the creation of a heredofamilial cancer unit has changed both FHR and GC referrals among oncologists at our institution, although continuous educational efforts are required.
Typhoon-dominated influence on wood debris distribution and transportation in a high gradient headwater catchment
Authors: Chen Su-Chin , Chao Yi-Chiung , Chan Hsun-Chuan
Published: June 2013

Wood debris is an important component of mountain streams. It causes serious damage and renders difficulty of water resource management in Taiwan. In this study, the quantity of wood debris and variation of migratory wood debris during flood events were examined. The downstream of Gaoshan Creek and Qijiawan Creek, located at Central Taiwan, was selected as the study area. The distribution and dynamic of wood debris in a high gradient headwater catchment were quantified using field surveys. A formula of critical depth for wood debris entrainment was used to evaluate the wood debris migration during three flooding events. In the study area, wood abundance and unit volume increased downstream, and wood density decreased downstream within a channel network. The channel morphology, riparian vegetation, and wood debris characteristics were found to influence the wood storage. As a result, the wood debris has an irregular accumulative distribution in the steep stream, and it migrates easily in the stream because of a high flow discharge. Strong relationships between the channel width and wood debris variables are discovered. Moreover, wood debris has a tendency to accumulate at sites with low stream power and wood debris dams, topographical notches, and unique geological structures. Our findings assist in the understanding of the effects of channel characteristics on distributions of wood debris in steep stream systems.
Physicochemical Properties, Volatile Compounds and Phospholipid Classes of Silver Carp Brain Lipids
Authors: Wang Caixia , Xia Wenshui , Xu Yanshun , Jang Qixing , Yu Peipie
Published: June 2013

Large amounts of utilizable by‐products are produced concomitant with silver carp processing. The lipids from fish brain contain considerable essential fatty acids which however have seldom been studied. In this study, the lipids extracted from the brain of silver carp exhibited good physicochemical properties. Forty volatile compounds were identified, of which hydrocarbons and aromatics predominated. The ratios of polar lipids and phospholipids to total lipids were 22.73 and 10.95 % respectively. Phosphatidylcholine (PC), phosphatidylethanolamine (PE) and phosphatidylserine (PS) accounted for 83.9 % of the phospholipids. Major fatty acids of neutral lipids, polar lipids, PC, PE and PS differed significantly. PE had the most polyunsaturated fatty acids (PUFA), while PC, PE and PS were rich in docosahexaenoic and eicosapentaenoic acids. Moreover, the ratios of fatty acids were considered to be reasonable due to high levels of n3 PUFA. The lipids from silver carp brain have been demonstrated to be healthy and nutritious. The results herein confirm that silver carp brain lipids are a commercially and industrially feasible prospect.
Redox modification of proteins as essential mediators of CNS autophagy and mitophagy
Authors: Lizama-Manibusan Britney , McLaughlin BethAnn
Published: June 2013

Production of cellular reactive oxygen species (ROS) is typically associated with protein and DNA damage, toxicity, and death. However, ROS are also essential regulators of signaling and work in concert with redox‐sensitive proteins to regulate cell homeostasis during stress. In this review, we focus on the redox regulation of mitophagy, a process that contributes to energetic tone as well as mitochondrial form and function. Mitophagy has been increasingly implicated in diseases including Parkinson's, Amyotrophic Lateral Sclerosis, and cancer. Although these disease states employ different genetic mutations, they share the common factors of redox dysregulation and autophagic signaling. This review highlights key redox sensitive signaling molecules which can enhance neuronal survival by promoting temporally and spatially controlled autophagic signaling and mitophagy.
Riluzole increases glutamate uptake by cultured C6 astroglial cells
Authors: Dall'Igna Oscar P. , Bobermin Larissa D. , Souza Diogo O. , Quincozes‐Santos André
Published: June 2013

Riluzole is a drug approved for the treatment of amyotrophic lateral sclerosis (ALS) and may be effective for the treatment of other neurodegenerative and neuropsychiatric disorders. Riluzole exerts diverse actions on the central nervous system, including altering glutamate release and uptake, and therefore act diminishing glutamate extracellular levels, but the underlying mechanism of these actions is still unknown. Here, we demonstrate that riluzole stimulated glutamate uptake and augmented the expression of the glutamate EAAC1 transporter in C6 astroglial cell cultures. The effect of riluzole on glutamate uptake was reduced to below controls when it was co‐administered with inhibitors of protein kinase C (PKC; bisindolylmaleimide II), phosphatidylinositol 3‐kinase (PI3K; wortmannin) and fibroblast growth factor receptor 1 (FGFR1; PD173074). Riluzole also decreased reactive oxygen species load with no effect on glutathione levels. This study investigates three independent intracellular pathways and the mechanism of action of riluzole on glutamate metabolism.
Through the open door: Preferential binding of dasatinib to the active form of BCR‐ABL unveiled by in silico experiments
Authors: Laurini Erik , Posocco Paola , Fermeglia Maurizio , Gibbons Don L. , Quintás-Cardama Alfonso , Pricl Sabrina
Published: June 2013

Dasatinib is a second‐generation BCR‐ABL inhibitor approved for the treatment of patients with chronic myeloid leukemia, both in the frontline and in the imatinib‐resistant/intolerant settings. The high affinity of dasatinib for the protein is currently assumed to result from its ability to bind both the active and inactive conformations of the BCR‐ABL kinase. In the present work, using state of the art molecular simulation techniques we prove that dasatinib exhibits a highly selective preference for the active (open) BCR‐ABL conformation. By using three different BCR‐ABL conformations (active, inactive, and intermediate inactive) we show that, from a thermodynamic standpoint, the affinity of dasatinib for BCR‐ABL drastically decreases in the order: active > alternative inactive > inactive, as a result of differential contributions from the single residues lining the kinase binding pocket and the concomitant stabilization/destabilization of the kinase hydrophobic spine. Molecule‐pulling experiments also corroborate this trend as significantly lower forces and smaller times are required to extract dasatinib from its inactive BCR‐ABL complexes with respect to the active complex counterparts. Importantly, our results support recent NMR solution results demonstrating no evidence of dasatinib bound to the inactive form of BCR‐ABL.
IKK epsilon kinase is crucial for viral G protein-coupled receptor tumorigenesis
Authors: Wang Yi , Lu Xiaolu , Zhu Lining , Shen Yan , Chengedza Shylet , Feng Hao , Wang Laiyee , Jung Jae U. , Gutkind J. Silvio , Feng Pinghui
Published: June 2013

G protein-coupled receptors (GPCRs) are seven-transmembrane proteins that transmit diverse extracellular signals across a membrane. Herpesvirus genomes encode multiple GPCRs implicated in viral pathogenesis. Kaposi sarcoma-associated herpesvirus GPCR (kGPCR) activates proliferative pathways and, when expressed in endothelium in mice, sufficiently induces angiogenic tumor resembling human Kaposi’s sarcoma. IKKε, an IκB kinase (IKK)-related kinase, is implicated in inflammation-driven tumorigenesis. We report here that IKKε is critically required for kGPCR tumorigenesis and links kGPCR to NF-κB activation. Using kGPCR-induced tumor models, we found that IKKε expression was drastically up-regulated in Kaposi sarcoma-like lesions and that loss of IKKε abolished tumor formation. Moreover, kGPCR interacted with and activated IKKε. Activated IKKε promoted NF-κB subunit RelA (also known as p65) phosphorylation, which correlated with NF-κB activation and inflammatory cytokine expression. The robust expression of IKKε and phosphorylated RelA was observed in human Kaposi sarcoma. Finally, a kinase-defective mutant of IKKε effectively abrogated NF-κB activation and tumorigenesis induced by kGPCR. Collectively, our findings uncover a critical IKKε in promoting NF-κB activation and tumorigenesis induced by a viral GPCR.
Consumer Response to “Contains” and “Free of” Labeling: Evidence from Lab Experiments
Authors: Liaukonyte Jura , Streletskaya Nadia A. , Kaiser Harry M. , Rickard Bradley J.
Published: June 2013

Using a lab experiment with 351 adult non‐student subjects, we investigate the impact of labels and secondary information on willingness to pay (WTP) for foods that use various ingredients and processes that have been the subject of food policy discussions. We find a distinct asymmetry of WTP sensitivity between “Contains X” and “Free of X” labels with negatively‐framed secondary information. The “Free of X” label has an impact only when secondary information is provided, and the negative impact of “Contains X” is mitigated by secondary information. We also consider how the results of our study can inform the ongoing debate about mandatory food labeling regulations in the United States: if mandatory labeling is adopted, providing additional information about what the product contains would significantly lessen the negative impact on demand.
AdvISER-PYRO: Amplicon Identification using SparsE Representation of PYROsequencing signal
Authors: Ambroise Jérôme , Piette Anne-Sophie , Delcorps Cathy , Rigouts Leen , de Jong Bouke C. , Irenge Leonid , Robert Annie , Gala Jean-Luc
Published: June 2013

Motivation: Converting a pyrosequencing signal into a nucleotide sequence appears highly challenging when signal intensities are low (unitary peak heights ) or when complex signals are produced by several target amplicons. In these cases, the pyrosequencing software fails to provide correct nucleotide sequences. Accordingly, the objective was to develop the AdvISER-PYRO algorithm, performing an automated, fast and reliable analysis of pyrosequencing signals that circumvents those limitations.

Results: In the current mycobacterial amplicon genotyping application, AdvISER-PYRO performed much better than the pyrosequencing software in the following two situations: when converting Single Amplicon Sample (SAS) signals into a correct single sequence (97.2% versus 56.5%), and when translating Multiple Amplicon Sample (MAS) signals into the correct sequence pair (74.5%).

Availability: AdvISER-PYRO is implemented in an R package (http://sites.uclouvain.be/md-ctma/index.php/softwares) and can be used in broad range of clinical applications including multiplex pyrosequencing and oncogene re-sequencing in heterogeneous tumor cell samples.

Contact:  jerome.ambroise@uclouvain.be or jean-luc.gala@uclouvain.be
Porter, PaleAle 4.0: high-accuracy prediction of protein secondary structure and relative solvent accessibility
Authors: Mirabello Claudio , Pollastri Gianluca
Published: June 2013

Summary: Protein secondary structure and solvent accessibility predictions are a fundamental intermediate step towards protein structure and function prediction. We present new systems for the ab initio prediction of protein secondary structure and solvent accessibility, Porter 4.0 and PaleAle 4.0. Porter 4.0 predicts secondary structure correctly for 82.2% of residues. PaleAle 4.0’s accuracy is 80.0% for prediction in two classes with a 25% accessibility threshold. We show that the increasing training set sizes that come with the continuing growth of the Protein Data Bank keep yielding prediction quality improvements and examine the impact of protein resolution on prediction performances.

Availability: Porter 4.0 and PaleAle 4.0 are freely available for academic users at http://distillf.ucd.ie/porterpaleale/. Up to 64 kb of input in FASTA format can be processed in a single submission, with predictions now being returned to the user within a single web page and, optionally, a single email.

Contact:  gianluca.pollastri@ucd.ie
Feeding herring schools do not react to seismic air gun surveys
Authors: Peña Héctor , Handegard Nils Olav , Ona Egil
Published: June 2013

Peña, H., Handegard, N. O. and Ona, E. 2013. Feeding herring schools do not react to seismic air gun surveys. – ICES Journal of Marine Science, 70: 1174–1180. The real-time behaviour of herring schools exposed to a full-scale 3D seismic survey off Vesterålen, northern Norway, was observed using an omnidirectional fisheries sonar. Throughout the study period, the herring swam slowly against the predominant northeast current, with a net displacement along with the current. The mean swimming speed after subtracting the drift velocities was 0.35 m s−1, and the mean response speed in the direction away from the air gun array was 0.22 m s−1. No changes were observed in swimming speed, swimming direction, or school size that could be attributed to the transmitting seismic vessel as it approached from a distance of 27 to 2 km, over a 6 h period. The unexpected lack of a response to the seismic survey was interpreted as a combination of a strong motivation for feeding, a lack of suddenness of the air gun stimulus, and an increased level of tolerance to the seismic shooting.
Lung endothelial HO‐1 targeting in vivo using lentiviral miRNA regulates apoptosis and autophagy during oxidant injury
Authors: Zhang Yi , Jiang Ge , Sauler Maor , Lee Patty J.
Published: June 2013

The lung endothelium is a major target for inflammatory and oxidative stress. Heme oxygenase‐1 (HO‐1) induction is a crucial defense mechanism during oxidant challenges, such as hyperoxia. The role of lung endothelial HO‐1during hyperoxia in vivo is not well defined. We engineered lentiviral vectors with microRNA (miRNA) sequences controlled by vascular endothelium cadherin (VE‐cad) to study the specific role of lung endothelial HO‐1. Wild‐type (WT) murine lung endothelial cells (MLECs) or WT mice were treated with lentivirus and exposed to hyperoxia (95% oxygen). We detected HO‐1 knockdown (~55%) specifically in the lung endothelium. MLECs and lungs showed approximately a 2‐fold increase in apoptosis and ROS generation after HO‐1 silencing. We also demonstrate for the first time that silencing endothelial HO‐1 has the same effect on lung injury and survival as silencing HO‐1 in multiple lung cell types and that HO‐1 regulates caspase 3 activation and autophagy in endothelium during hyperoxia. These studies demonstrate the utility of endothelial‐targeted gene silencing in vivo using lentiviral miRNA constructs to assess gene function and that endothelial HO‐1 is an important determinant of survival during hyperoxia.—Zhang, Y., Jiang, G., Sauler, M., Lee, P. J., Lung endothelial HO‐1 targeting in vivo using lentiviral miRNA regulates apoptosis and autophagy during oxidant injury. FASEB J. 27, 4041–4058 (2013). www.fasebj.org
Isoflurane, a Commonly Used Volatile Anesthetic, Enhances Renal Cancer Growth and Malignant Potential via the Hypoxia-inducible Factor Cellular Signaling Pathway In Vitro
Authors: Benzonana Laura L. , Perry Nicholas J. S. , Watts Helena R. , Yang Bob , Perry Iain A. , Coombes Charles , Takata Masao , Ma Daqing
Published: June 2013

Background:

Growing evidence indicates that perioperative factors, including choice of anesthetic, affect cancer recurrence after surgery although little is known about the effect of anesthetics on cancer cells themselves. Certain anesthetics are known to affect hypoxia cell signaling mechanisms in healthy cells by up-regulating hypoxia-inducible factors (HIFs). HIFs are also heavily implicated in tumorigenesis and high levels correlate with poor prognosis.

Methods:

Renal cell carcinoma (RCC4) cells were exposed to isoflurane for 2 h at various concentrations (0.5–2%). HIF-1α, HIF-2α, phospho-Akt, and vascular endothelial growth factor A levels were measured by immunoblotting at various time points (0–24 h). Cell migration was measured across various components of extracellular matrix, and immunocytochemistry was used to analyze proliferation rate and cytoskeletal changes.

Results:

Isoflurane up-regulated levels of HIF-1α and HIF-2α and intensified expression of vascular endothelial growth factor A. Exposed cultures contained significantly more cells (1.81 ± 0.25 vs. 1.00 of control; P = 0.03) and actively proliferating cells (89.4 ± 2.80 vs. 64.74 ± 7.09% of control; P = 0.016) than controls. These effects were abrogated when cells were pretreated with the Akt inhibitor, LY294002. Exposed cells also exhibited greater migration on tissue culture–coated (F = 16.89; P = 0.0008), collagen-coated (F = 20.99; P = 0.0003), and fibronectin-coated wells (F = 8.21; P = 0.011) as along with dramatic cytoskeletal rearrangement, with changes to both filamentous actin and α-tubulin.

Conclusions:

These results provide evidence that a frequently used anesthetic can exert a protumorigenic effect on a human cancer cell line. This may represent an important contributory factor to high recurrence rates observed after surgery.
Rehaibacterium terrae gen. nov., sp. nov. isolated from a geothermally heated soil sample
Authors: Yu Tian-Tian , Yao Ji-Cheng , Yin Yi-Rui , Dong Lei , Liu Ruo-Fei , Ming Hong , Zhou En-Min , Li Wen-Jun
Published: June 2013

A thermotolerant, alkalitolerant, Gram-stain-negative and strictly aerobic bacterium, designated strain YIM 77974T, was isolated from a geothermally heated soil sample collected at Rehai National Park, Tengchong, Yunnan province, south-west China. Cells of the strain were rod-shaped and colonies were light brown and circular. The strain grew in the presence of 0–3 % (w/v) NaCl (optimum, 0–1 %) and at pH 7.0–10.0 (optimum, pH 8.0) and 30–55 °C (optimum, 45 °C). The only quinone was Q-8 and the genomic DNA G+C content was 68.3 mol%. Major fatty acids (>10 %) were iso-C16 : 0, iso-C17 : 0, iso-C15 : 0 and iso-C11 : 0. The polar lipids consisted of diphosphatidylglycerol, phosphatidylethanolamine, phosphatidylglycerol, phosphatidylcholine, an unidentified aminophospholipid, three unidentified phospholipids and two unidentified polar lipids. On the basis of the morphological and chemotaxonomic characteristics as well as genotypic data, it is proposed that this strain should be classified as a representative of a novel genus and species, Rehaibacterium terrae gen. nov., sp. nov., in the family

Xanthomonadaceae

. The type strain is strain YIM 77974T ( = DSM 25897T = CCTCC AB 2012062T).
Bacillus songklensis sp. nov., isolated from soil
Authors: Kang Hyeonji , Weerawongwiwat Veeraya , Kim Jong-Hwa , Sukhoom Ampaitip , Kim Wonyong
Published: June 2013

A Gram-stain-positive, spore-forming, rod-shaped, motile, strictly aerobic bacterial strain, designated CAU 1033T, was isolated from soil and its taxonomic position was investigated using a polyphasic approach. Phylogenetic analysis based on 16S rRNA gene sequences revealed that strain CAU 1033T formed a distinct lineage within the genus

Bacillus

and was most closely related to

Bacillus drentensis

KCTC 13025T (similarity 95.9 %). CAU 1033T contained MK-7 as the only isoprenoid quinone and iso-C15 : 0 and anteiso-C15 : 0 as the major fatty acids. The cell wall peptidoglycan of strain CAU 1033T contained meso-diaminopimelic acid and the major whole-cell sugars were arabinose, sucrose and ribose. The polar lipids were composed of diphosphatidylglycerol, phosphatidylglycerol, phosphatidylethanolamine, two unidentified phospholipids, four unidentified aminophospholipids, an unidentified aminolipid, two unidentified glycolipids and another unidentified polar lipid. The DNA G+C content was 41.4 mol%. On the basis of phenotypic data and phylogenetic inference, strain CAU 1033T was classified as a representative of a novel species in the genus

Bacillus

for which the name Bacillus songklensis sp. nov. is proposed. The type strain is CAU 1033T ( = KCTC 13881T = CCUG 61889T).
Arenicella chitinivorans sp. nov., a gammaproteobacterium isolated from the sea urchin Strongylocentrotus intermedius
Authors: Nedashkovskaya Olga I. , Cleenwerck Ilse , Zhukova Natalia V. , Kim Seung Bum , de Vos Paul
Published: June 2013

A strictly aerobic, Gram-stain-negative, rod-shaped, non-motile and yellow-pigmented bacterial strain, designated KMM 6208T, was isolated from a sea urchin. Phylogenetic analysis based on 16S rRNA gene sequencing revealed that this novel isolate was affiliated to the class

Gammaproteobacteria

and formed a robust cluster with

Arenicella xantha

KMM 3895T with 98.2 % 16S rRNA gene sequence similarity. Strain KMM 6208T grew in the presence of 0.5–5 % NaCl and at a temperature range of 4–38 °C. The isolate was oxidase-positive and hydrolysed aesculin, casein, chitin, gelatin, starch and Tweens 40 and 80. The prevalent fatty acids of strain KMM 6208T were C16 : 1ω7c, iso-C16 : 0, iso-C18 : 0, C18 : 1ω7c and C16 : 0. The polar lipids consisted of phosphatidylethanolamine, phosphatidylglycerol, diphosphatidylglycerol and an unidentified aminophospholipid, and the major isoprenoid quinone was Q-8. The DNA G+C content of strain KMM 6208T was 46.3 mol%. The DNA–DNA relatedness value of strain KMM 6208T with

Arenicella xantha

KMM 3895T was 5 %. Molecular data in a combination with phenotypic findings strongly suggest inclusion of this novel strain in the genus

Arenicella

as a representative of a novel species for which the name Arenicella chitinivorans sp. nov. is proposed. The type strain is KMM 6208T ( = KCTC 12711T = LMG 26983T).