bluuebunny/crossref_metadata_2025 huggingface dataset:
Transoral laser microsurgery followed by radiation therapy for oropharyngeal tumors: The mayo clinic arizona experience
Authors: Patel Samir H. , Hinni Michael L. , Hayden Richard E. , Wong William W. , Dueck Amylou C. , Zarka Matthew A. , Curtis Kelly K. , Halyard Michele Y.
Published: March 2013

Background

The purpose of this study was to report the treatment outcomes of patients with advanced oropharyngeal cancer treated with transoral laser microsurgery (TLM) followed by radiation therapy (RT) at Mayo Clinic in Arizona.

Methods

A retrospective study of 80 patients treated from January 1, 2000 to November 7, 2011 was performed. All patients had stage III/IV oropharyngeal tumors and underwent TLM with neck dissection. Adjuvant RT was then given. Thirty‐seven patients received concurrent adjuvant chemotherapy. The primary outcome was locoregional control.

Results

Median follow‐up was 47.3 months (range, 9.7–139.2 months). The 3‐year locoregional control, recurrence‐free survival, and overall survival rates were 98.6% (95% confidence interval [CI], 91% to 100%), 91.1% (95% CI, 81% to 96%), and 93.7% (95% CI, 84% to 98%), respectively. There were a total of 5 treatment failures, 1 regional and 4 distant. Twenty‐six patients underwent neck only RT with exclusion of the primary site.

Conclusion

TLM followed by RT for advanced oropharyngeal cancer results in excellent locoregional control rates. © 2013 Wiley Periodicals, Inc. Head Neck 36: 220–225, 2014
Synergism of Tapasin And Human Leukocyte Antigens in Resolving Hepatitis C Virus Infection
Authors: Ashraf Shirin , Nitschke Katja , Warshow Usama M. , Brooks Collin R. , Kim Arthur Y. , Lauer Georg M. , Hydes Theresa J. , Cramp Matthew E. , Alexander Graeme , Little Ann-Margaret , Thimme Robert , Neumann-Haefelin Christoph , Khakoo Salim I.
Published: March 2013

CD8+ T-cell responses to hepatitis C virus (HCV) are important in generating a successful immune response and spontaneously clearing infection. Human leukocyte antigen (HLA) class I presents viral peptides to CD8+ T cells to permit detection of infected cells, and tapasin is an important component of the peptide loading complex for HLA class I. We sought to determine if tapasin polymorphisms affected the outcome of HCV infection. Patients with resolved or chronic HCV infection were genotyped for the known G/C coding polymorphism in exon 4 of the tapasin gene. In a European, but not a US, Caucasian population, the tapasin G allele was significantly associated with the outcome of HCV infection, being found in 82.5% of resolvers versus 71.3% of persistently infected individuals (P = 0.02, odds ratio [OR] = 1.90 95% confidence interval [CI] = 1.11-3.23). This was more marked at the HLA-B locus at which heterozygosity of both tapasin and HLA-B was protective (P < 0.03). Individuals with an HLA-B allele with an aspartate at residue 114 and the tapasin G allele were more likely to spontaneously resolve HCV infection (P < 0.00003, OR = 3.2 95% CI = 1.6-6.6). Additionally, individuals with chronic HCV and the combination of an HLA-B allele with an aspartate at residue 114 and the tapasin G allele also had stronger CD8+ T-cell responses (P = 0.02, OR = 2.58, 95% CI-1.05-6.5). Conclusion: Tapasin alleles contribute to the outcome of HCV infection by synergizing with polymorphisms at HLA-B in a population-specific manner. This polymorphism may be relevant for peptide vaccination strategies against HCV infection. (Hepatology 2013;53:881–889)
Adenosine kinase is a key determinant for the anti-HCV activity of ribavirin
Authors: Mori Kyoko , Hiraoka Osamu , Ikeda Masanori , Ariumi Yasuo , Hiramoto Akiko , Wataya Yusuke , Kato Nobuyuki
Published: March 2013

Ribavirin (RBV) is often used in conjunction with interferon-based therapy for patients with chronic hepatitis C. There is a drastic difference in the anti–hepatitis C virus (HCV) activity of RBV between the HuH-7-derived assay system, OR6, possessing the RBV-resistant phenotype (50% effective concentration [EC50]: >100 μM) and the recently discovered Li23-derived assay system, ORL8, possessing the RBV-sensitive phenotype (EC50: 8 μM; clinically achievable concentration). This is because the anti-HCV activity of RBV was mediated by the inhibition of inosine monophosphate dehydrogenase in RBV-sensitive ORL8 cells harboring HCV RNA. By means of comparative analyses using RBV-resistant OR6 cells and RBV-sensitive ORL8 cells, we tried to identify host factor(s) determining the anti-HCV activity of RBV. We found that the expression of adenosine kinase (ADK) in ORL8 cells was significantly higher than that in RBV-resistant OR6 cells harboring HCV RNA. Ectopic ADK expression in OR6 cells converted them from an RBV-resistant to an RBV-sensitive phenotype, and inhibition of ADK abolished the activity of RBV. We showed that the differential ADK expression between ORL8 and OR6 cells was not the result of genetic polymorphisms in the ADK gene promoter region and was not mediated by a microRNA control mechanism. We found that the 5' untranslated region (UTR) of ADK messenger RNA in ORL8 cells was longer than that in OR6 cells, and that only a long 5' UTR possessed internal ribosome entry site (IRES) activity. Finally, we demonstrated that the long 5' UTR functioned as an IRES in primary human hepatocytes.

Conclusion

: These results indicate that ADK acts as a determinant for the activity of RBV and provide new insight into the molecular mechanism underlying differential drug sensitivity. (Hepatology 2013;58:1236–1244)
Expression of Slc22a1 Variants May Affect the Response of Hepatocellular Carcinoma And Cholangiocarcinoma To Sorafenib
Authors: Herraez Elisa , Lozano Elisa , Macias Rocio I.R. , Vaquero Javier , Bujanda Luis , Banales Jesus M. , Marin Jose J.G. , Briz Oscar
Published: March 2013

Reduced drug uptake is an important mechanism of chemoresistance. Down-regulation of SLC22A1 encoding the organic cation transporter-1 (OCT1) may affect the response of hepatocellular carcinoma (HCC) and cholangiocarcinoma (CGC) to sorafenib, a cationic drug. Here we investigated whether SLC22A1 variants may contribute to sorafenib chemoresistance. Complete sequencing and selective variant identification were carried out to detect single nucleotide polymorphisms (SNPs) in SLC22A1 complementary DNA (cDNA). In HCC and CGC biopsies, in addition to previously described variants, two novel alternative spliced variants and three SNPs were identified. To study their functional consequences, these variants were mimicked by directed mutagenesis and expressed in HCC (Alexander and SK-Hep-1) and CGC (TFK1) cells. The two novel described variants, R61S fs*10 and C88A fs*16, encoded truncated proteins unable to reach the plasma membrane. Both variants abolished OCT1-mediated uptake of tetraethylammonium, a typical OCT1 substrate, and were not able to induce sorafenib sensitivity. In cells expressing functional OCT1 variants, OCT1 inhibition with quinine prevented sorafenib-induced toxicity. Expression of OCT1 variants in Xenopus laevis oocytes and determination of quinine-sensitive sorafenib uptake by high-performance liquid chromatography-dual mass spectrometry confirmed that OCT1 is able to transport sorafenib and that R61S fs*10 and C88A fs*16 abolish this ability. Screening of these SNPs in 23 HCC and 15 CGC biopsies revealed that R61S fs*10 was present in both HCC (17%) and CGC (13%), whereas C88A fs*16 was only found in HCC (17%). Considering all SLC22A1 variants, at least one inactivating SNP was found in 48% HCC and 40% CGC. Conclusion: Development of HCC and CGC is accompanied by the appearance of aberrant OCT1 variants that, together with decreased OCT1 expression, may dramatically affect the ability of sorafenib to reach active intracellular concentrations in these tumors. (Hepatology 2013;53:1065–1073)
Solid freeform fabrication of porous calcium polyphosphate structures for bone substitute applications: In vivo studies
Authors: Shanjani Yaser , Hu Youxin , Toyserkani Ehsan , Grynpas Marc , Kandel Rita A. , Pilliar Robert M.
Published: March 2013

Porous calcium polyphosphate (CPP) structures with 30 volume percent porosity and made by solid freeform fabrication (SFF) were implanted in rabbit femoral condyle sites for 6‐wk periods. Two forms of SFF implants with different stacked layer orientation were made in view of prior studies reporting on anisotropic/orthotropic mechanical properties of structures so formed. In addition, porous CPP implants of equal volume percent porosity made by conventional sintering and machining methods were prepared. Bone ingrowth and in vivo degradation of the three different implant types were compared using back‐scattered scanning electron microscopy (BS‐SEM) of implant samples and quantitative analysis of the images. The results indicated bone ingrowth with all samples resulting in 30–40% fill of available porosity by bone within the 6‐wk period. In the 6‐wk in vivo period, approximately 7–9% loss of CPP by degradation had occurred. © 2013 Wiley Periodicals, Inc. J Biomed Mater Res Part B: Appl Biomater, 2013.
Mechanical characterization of self‐assembling peptide hydrogels by microindentation
Authors: Hammond Nathan A. , Kamm Roger D.
Published: March 2013

Hydrogels formed from self‐assembling synthetic oligopeptides have been studied for almost 2 decades for use in tissue engineering and drug delivery. Although a great deal has been learned about the microstructure of these materials, there remain questions about how peptide filaments are ordered to form a gel. These unanswered questions leave a disconnect between our understanding of the observed nanoscale mechanical properties of peptide filaments and the macroscale properties of the gels they constitute. This study helps to bridge this gap by examining the role of filament length and interfilament crosslinks in determining bulk mechanical properties. Microindentation was used for mechanical characterization, and microstructure was observed using thin‐section transmission electron microscopy images of gels embedded in resin. Results suggest a gel structure in which filaments are not densely bundled as previously suggested and confirm that crosslinking can be an effective strategy to increase the stiffness of self‐assembling oligopeptide gels. © 2013 Wiley Periodicals, Inc. J Biomed Mater Res Part B: Appl Biomater, 2013.
Methylation of the PTPRO gene in human hepatocellular carcinoma and identification of VCP as its substrate
Authors: Hsu Shu‐hao , Motiwala Tasneem , Roy Satavisha , Claus Rainer , Mustafa Mufaddal , Plass Christoph , Freitas Michael A. , Ghoshal Kalpana , Jacob Samson T.
Published: March 2013

We have previously reported that the gene encoding protein tyrosine phosphatase receptor type‐O (PTPRO) is suppressed by promoter methylation in a rat model of hepatocellular carcinoma (HCC) and it functions as tumor suppressor in leukemia and lung cancer. Here, we explored the methylation and expression of PTPRO as well as its function in human HCC. MassARRAY analysis of primary human HCC and matching liver samples (n = 24) revealed significantly higher (P = 0.004) methylation density at the promoter CGI in tumors. Combined bisulfite restriction analysis (COBRA) of another set of human HCC samples (n = 17) demonstrated that the CGI was methylated in 29% of tumors where expression of PTPRO was lower than that in corresponding matching livers. A substrate‐trapping mutant of PTPRO that stabilizes the bound substrates was used to identify its novel substrate(s). VCP/p97 was found to be a PTPRO substrate by mass spectrometry of the peptides pulled down by the substrate‐trapping mutant of PTPRO. Tyrosyl dephosphorylation of VCP following ectopic expression of wild‐type PTPRO in H293T and HepG2 cells confirmed that it is a bona fide substrate of PTPRO. Treatment of PTPRO overexpressing HepG2 cells with Doxorubicin, a DNA damaging drug commonly used in therapy of primary HCC, sensitized these cells to this potent anticancer drug that correlated with dephosphorylation of VCP. Taken together, these results demonstrate methylation and downregulation of PTPRO in a subset of primary human HCC and establish VCP as a novel functionally important substrate of this tyrosine phosphatase that could be a potential molecular target for HCC therapy. J. Cell. Biochem. 114: 1810–1818, 2013. © 2013 Wiley Periodicals, Inc.
Effects of exposure to estradiol and estradiol plus testosterone on the mongolian gerbil (Meriones unguiculatus) female prostate
Authors: Da Silva Diego Augusto Lopes , Zanatelli Marianna , Shinohara Filipe Zardini , Góes Rejane Maira , Dos Santos Fernanda Cristina Alcântara , Vilamaior Patricia Simone Leite , Taboga Sebastião Roberto
Published: March 2013

The female prostate is a differentiated organ found in several mammal species, including humans and rodents. This gland has been related to important functions on female reproductive biology. Although the factors, which regulate prostate's development and activity are not well known, its functionality has been related to steroid hormones. It is well established that cyclic changes of estradiol and progesterone levels promote histophysiological adaptations of the whole female body. In contrast, only a few is found about those adaptations in female prostate. Thus, this study aimed to evaluate the effect of estradiol and estradiol + testosterone association on gerbil female prostate in order to verify, which hormonal associations are necessary to its homeostasis. For this, adult females had the ovaries surgically removed. After recovering, they received estradiol and estradiol + testosterone doses through 30 days, each 48 h. The prostatic tissue underwent morphological and morphometric‐estereological analysis. Hormonal restriction caused great gland involution and decreased secretory activity, aspects that were reverted by exposure to estradiol and estradiol + testosterone. However, these hormones were not able to re‐establish the normal prostate histoarchitecture. The immunoreaction of steroid receptors (ER‐α, ER‐β, and AR) responded differently among the experimental and control groups, and PCNA assay showed a decrease in epithelial cell proliferation within groups that had hormone privation. Therefore, we conclude that estradiol and testosterone are able to influence prostate morphophysiology and the maintenance of gland homeostasis depends on a balance among these and other hormones. Microsc. Res. Tech. 76:486–495, 2013. © 2013 Wiley Periodicals, Inc.
Gas‐phase fragmentation of the protonated benzyl ester of proline: intramolecular electrophilic substitution versus hydride transfer
Authors: Li Fei , Zhang Xiaoping , Zhang Huarong , Jiang Kezhi
Published: March 2013

In this study, the gas phase chemistry of the protonated benzyl esters of proline has been investigated by electrospray ionization mass spectrometry and theoretical calculation. Upon collisional activation, the protonated molecules undergo fragmentation reactions via three primary channels: (1) direct decomposition to the benzyl cation (m/z 91), (2) formation of an ion‐neutral complex of [benzyl cation + proline]+, followed by a hydride transfer to generate the protonated 4,5‐dihydro‐3H‐pyrrole‐2‐carboxylic acid (m/z 114), and (3) electrophilic attack at the amino by the transferring benzyl cation, and the subsequent migration of the activated amino proton leading to the simultaneous loss of (H2O + CO). Interestingly, no hydrogen/deuterium exchange for the fragment ion m/z 114 occurs in the d‐labeling experiments, indicating that the transferring hydride in path‐b comes from the methenyl hydrogen rather than the amino hydrogen. For para‐substituted benzyl esters, the presence of electron‐donating substituents significantly promotes the direct decomposition (path‐a), whereas the presence of electron‐withdrawing ones distinctively inhibits that channel. For the competing channels of path‐b and path‐c, the presence of electron‐donating substituents favors path‐b rather than path‐c, whereas the presence of electron‐withdrawing ones favors path‐c rather than path‐b. Copyright © 2013 John Wiley & Sons, Ltd.
Large mixed complexes involving uracil, cytosine, thymine and/or 1‐methyl uracil around Ca2+ ions: an electrospray ionization/MS study
Authors: Emilie‐Laure Zins
Published: March 2013

We investigated the possible formation of mixed BnB′n′Ca2+ complexes where B and B′ are two different nucleobases. Electrospray ionization (ESI) mass spectrometric experiments from solutions containing two different kinds of nucleobases and calcium ions were carried out to investigate the formation of magic number clusters that may be relevant in a biological point of view. The results presented here clearly show that mixed complexes can be formed and are stable in the gas phase. This represents an important step toward more complex solutions in which several nucleobases are present simultaneously and may compete in the formation of cationized clusters. We believe that thorough investigations on such systems may help understanding biological processes that may effect the tridimensional structure of the DNA macromolecule.

The formation of mixed hexamers, decamers, dodecamers and tetradecamers are clearly favored from solution containing uracil (Ura), thymine (Thy) and Ca2+, whereas mixed octamers are preferred from 1‐methyl uracil (MeU), uracil and Ca2+ mixtures. Cytosine (Cyto) can form mixed complexes with either uracil or 1‐methyl uracil or thymine. On the other hand, the main species formed in these latter cases are mixed tetramers. Copyright © 2013 John Wiley & Sons, Ltd.
The sequential dissociation of protonated polyethylene glycols
Authors: Hester Thomas H. , McCraney Kendra K. , Castillo Daniel E. , Goebbert Daniel J.
Published: March 2013

Early investigations of protonated polyethylene glycol fragmentation suggested the dissociation mechanism includes both direct and sequential processes. Experiments designed to study the proposed mechanisms of sequential dissociation are absent from the literature. In order to obtain additional experimental details about the fragmentation reactions, the dissociation of protonated polyethylene glycol was studied by energy‐dependent collision‐induced dissociation (CID). Key fragment ions were separated by mass differences corresponding to the loss of single monomer units. Several fragment ions were also generated by in‐source fragmentation and studied by CID. These experiments indicate the primary ions undergo sequential dissociation by the loss of either one or two monomer units. The results suggest that at least two different mechanisms must be considered to explain the sequential dissociation of protonated polyethylene glycols. The reaction involving the elimination of two subunits suggests the loss of a six‐membered 1,4‐dioxane product, while the elimination of a single subunit involves the loss of acetaldehyde by a 1,2‐hydride shift rearrangement. Copyright © 2013 John Wiley & Sons, Ltd.
Prospective clinical trial of diagnostic peritoneal lavage to detect positive peritoneal cytology in patients with gastric cancer
Authors: Mezhir James J. , Posner Mitchell C. , Roggin Kevin K.
Published: March 2013

Background and Objectives

Positive peritoneal cytology equates M1 disease in patients with gastric cancer. Diagnostic peritoneal lavage (DPL) is a proven test to detect occult visceral injury in trauma patients. The objective of this study is to determine whether DPL can be used to assess peritoneal cytology in patients with gastric cancer.

Methods

Patients with gastric adenocarcinoma were prospectively enrolled to undergo DPL prior to diagnostic laparoscopy (DL). Saline was instilled through a percutaneous catheter and fluid was collected for cytology (DPL‐cyt). Washings obtained during DL were used as controls (DL‐cyt).

Results

DPL was successful in 22/27 patients (81.5%). Among the 22 successful DPLs, 12 had positive cytology (54.5%). Positive DPL‐cyt specimens matched DL‐cyt specimens in 12/12 cases (specificity = 100%). One of 10 cases with negative DPL‐cyt was positive on the final DL‐cyt (sensitivity = 92%). There were six patients with negative DPL‐cyt who had visible M1 disease diagnosed with DL (DPL evaluation of M1 disease, sensitivity 54.5%, specificity = 100%).

Conclusions

DPL is a safe method of detecting positive cytology in patients with gastric cancer, however gross M1 disease may be missed without visual inspection. The specific role of DPL in the staging workup of patients with gastric cancer remains to be determined. J. Surg. Oncol. 2013;107:794–798. © 2013 Wiley Periodicals, Inc.
Deviated nose correction
Authors: Cho Gye Song , Jang Yong Ju
Published: March 2013

Objectives/Hypothesis

The present study analyzed 631 deviated nose cases to determine the overall success rate of correction, the treatment outcomes according to the different types of deviation, and the revision rate.

Study Design

Case series study.

Methods

We reviewed 631 patients who underwent rhinoplasty for correction of a deviated nose with a minimum follow‐up of 18 months. Surgical outcomes were classified as excellent, good, fair, or no change. Deviations were classified into five types: type I, a straight tilted bony pyramid with straight tilted cartilaginous vault in the opposite direction; type II, a straight tilted bony pyramid with concavely or convexly bent cartilaginous vault; type III, a straight bony pyramid with tilted cartilaginous vault; type IV, a straight bony pyramid with bent cartilaginous vault, and type V, a straight tilted bony pyramid and tilted cartilaginous dorsum in the same direction.

Results

Postoperative assessment showed that 80.2% of the 631 patients had successful (excellent or good) outcomes, and 19.8% had unsuccessful (fair or no change) outcomes. Deformities of types I through V occurred in 169 (26.8%), 139 (22.0%), 150 (23.8%), 101 (16.0%), and 72 (11.4%) patients, respectively, of whom 34 (20.1%), 39 (28.1%), 11 (7.3%), 11 (10.9%), and 30 (41.7%) had unsuccessful outcomes. Analysis showed that the frequency of unsuccessful outcomes differed according to the deviation type (P < .001). Forty‐one patients (6.5%) required revision rhinoplasty owing to dissatisfaction.

Conclusions

An unsatisfactory surgical outcome is a significant risk following surgical correction of a deviated nose. The type of deviation affects the likelihood of a successful outcome.

Level of Evidence

4.
Tolerance and toxicity of primary radiation therapy in the management of seropositive HIV patients with squamous cell carcinoma of the head and neck
Authors: Mourad Waleed F. , Hu Kenneth S. , Ishihara Dan , Shourbaji Rania A. , Lin Wilson , Kumar Mahesh , Jacobson Adam S. , Tran Theresa , Manolidis Spiros , Urken Mark , Persky Mark , Harrison Louis
Published: March 2013

Objectives/Hypothesis

To report tolerance and toxicity of radiotherapy (RT) with or without chemotherapy in HIV seropositive patients with squamous cell carcinoma of the head and neck (SCCHN).

Methods

This is a single institution retrospective study of 73 HIV seropositive patients with SCCHN treated from January 1997 through 2010. Stages I, II, III, and IV were 8%, 10%, 24%, and 58%, respectively. The median age at RT, HIV diagnosis. and the duration of HIV seropositive were 51 (32–72), 34 (25–50), and 11 (6–20) years, respectively. Patients were treated definitively with RT alone (35%) or concurrent chemo‐RT (65%). Median dose of 70 Gy (66–70) was delivered to the gross disease. Median duration of treatment was 52 (49–64) days. Fifty patients (70%) were on HAART.

Results

RT± chemotherapy induced acute toxicity was: median weight loss 20 pounds (6–40), 100% developed dysgeusia and xerostomia (grades 1–3). Acute mucositis and dysphagia/odynophagia grades ≤2 and 3 were 83% and 17%, respectively. Treatment breaks in excess of 10, 7, and 3 days were found in 5%, 13%, and 15% of patients, respectively. With a median follow‐up of 4 years (2–12) the RT ±chemotherapy induced late dysphagia and xerostomia grades >2 were 26% and 23% of patients, respectively.

Conclusion

Our data show that primary RT ±chemotherapy for HIV seropositive SCCHN is less tolerated compared to the historical data for SCCHN without HIV.

Level of Evidence

2b.
Radiation therapy for benign lymphoepithelial cysts of parotid glands in HIV patients
Authors: Mourad Waleed F. , Hu Kenneth S. , Shourbaji Rania A. , Lin Wilson , Harrison Louis B.
Published: March 2013

Objectives/Hypothesis

To report the long‐term outcomes of radiation therapy (RT), and the impact of fractionation size and RT duration on HIV patients with Benign Lymphoepithelial Cysts (BLEC) of the parotid glands.

Methods

From January 2000 to 2011, 30 patients were eligible for our single institution retrospective study. Both parotids were treated with 24Gy via RT. The median age at RT, HIV diagnosis, and duration of HIV seropositive was 45 years (28–64), 38 years (23–53), and 11 years (6–35), respectively. Patients were stratified into two groups. Group A and B received 2Gyx12 and 1.5Gyx16, respectively.

Results

After a median follow‐up of 66 months (12–141), the overall response (OvR) was 93% of the patients. Specifically, complete response (CR) and partial response (PR) were 80% and 13%, respectively. In group A, 100% had CR. Treatment failure was 7% and all were in group B, which was mainly due to poor compliance. A Chi‐square test showed significant relationship between OvR and RT duration (P <0.001), and a positive trend between CR and fraction size of 2Gy (P = 0.053). All acute toxicities were grade ≤2, specifically mucositis (48%), xerostomia (45%), skin erythema (41%), and altered taste (14%). Two patients (6.7%) experienced long‐term grade 1 xerostomia.

Conclusion

RT provides a sustained long‐term cosmetic control for BLEC of the parotid glands in HIV patients. Failures are uncommon, and the late side effects have been negligible.
Characterization of Aphanizomenon ovalisporum amidinotransferase involved in cylindrospermopsin synthesis
Authors: Barón‐Sola Ángel , Gutiérrez‐Villanueva Miguel A. , del Campo Francisca F. , Sanz‐Alférez Soledad
Published: March 2013

An increasing abundance of Aphanizomenon ovalisporum in water bodies from diverse world regions has been reported in the last few years, with the majority of the isolated strains producing the toxin cylindrospermopsin (CYN), leading to a rise in ecological and health risks. The understanding of CYN synthesis is crucial in the control of CYN production. An amidinotransferase (AMDT) seems to be the first enzyme involved in the synthesis of CYN. In this study, we have cloned and overexpressed the aoaA gene from the constitutive CYN producer A. ovalisporum UAM‐MAO. The recombinant purified AoaA was characterized, confirming that it is an l‐arginine:glycine AMDT. It shows an optimal activity between 32 and 37°C, at pH from 8 to 9. The activity exhibits a mixed (ping‐pong/sequential) kinetic mechanism, and is inhibited by the reaction product guanidine acetate (GAA) in a noncompetitive manner. Mg2+ stimulates AoaA activity while Co2+ and Mn2+ inhibit it. AoaA conserves the critical residues of the catalytic site and substrate specificity of AMDTs, as the previously reported AMDT from Cylindrospermopsis raciborskii Cyr. Both proteins can be included in a new group of prokaryotic AMDTs involved in CYN production.
Gonad differentiation and puberty onset in the zebrafish: Evidence for the dependence of puberty onset on body growth but not age in females
Authors: Chen Weiting , Ge Wei
Published: March 2013

Puberty is the period in the vertebrate life cycle that marks the transition from sexual immaturity to maturity, enabling an animal to acquire adult reproductive functions. Puberty, an important point in vertebrate reproductive life, has been under extensive study in the past decades. It has been known for a long time that the initiation of puberty in mammals is closely associated with body growth and metabolism; however, there has been no equivalent report in small model teleosts such as the zebrafish. Using morphological and histological analysis, this study was undertaken to examine the timing of gonad differentiation and female maturation (puberty) in the zebrafish, with particular emphasis on the potential impact of body growth on the onset of puberty. Our data showed that gonad differentiation in the zebrafish completed around 35 days post‐fertilization (dpf) in females and 45 dpf in males. Puberty in females is initiated at around 45 dpf. Our experiments provided clear evidence that the initiation of puberty in female zebrafish was strongly correlated with body size but not age, supporting the importance of the growth axis in the onset of puberty. This study provides essential information on basic characteristics of growth and reproduction in zebrafish. Mol. Reprod. Dev. 80: 384–392, 2013. © 2013 Wiley Periodicals, Inc.
Four‐channel surface coil array for 300‐MHz pulsed EPR imaging: Proof‐of‐concept experiments
Authors: Enomoto Ayano , Hirata Hiroshi , Matsumoto Shingo , Saito Keita , Subramanian Sankaran , Krishna Murali C. , Devasahayam Nallathamby
Published: March 2013

Time‐domain electron paramagnetic resonance imaging is currently a useful preclinical molecular imaging modality in experimental animals such as mice and is capable of quantitatively mapping hypoxia in tumor implants. The microseconds range relaxation times (T1 and T2) of paramagnetic tracers and the large bandwidths (tens of MHz) to be excited by electron paramagnetic resonance pulses for spatial encoding makes imaging of large objects a challenging task. The possibility of using multiple array coils to permit studies on large sized object is the purpose of the present work. Toward this end, the use of planar array coils in different configurations to image larger objects than cannot be fully covered by a single resonator element is explored. Multiple circular surface coils, which are arranged in a plane or at suitable angles mimicking a volume resonator, are used in imaging a phantom and a tumor‐bearing mouse leg. The image was formed by combining the images collected from the individual coils with suitable scaling. The results support such a possibility. By multiplexing or interleaving the measurements from each element of such array resonators, one can scale up the size of the subject and at the same time reduce the radiofrequency power requirements and increase the sensitivity. Magn Reson Med 71:853–858, 2014. © 2013 Wiley Periodicals, Inc.
High‐resolution magic angle spinning 1H MRS in prostate cancer
Authors: Decelle Emily A. , Cheng Leo L.
Published: March 2013

Prostate cancer (PCa) is the most frequently diagnosed malignancy in men worldwide, largely as a result of the increased use of the annual serum prostate‐specific antigen (PSA) screening test for detection. PSA screening has saved lives, but it has also resulted in the overtreatment of many patients with PCa because of a limited ability to accurately localize and characterize PCa lesions through imaging. High‐resolution magic angle spinning (HRMAS) 1H MRS has proven to be a strong potential clinical tool for PCa diagnosis and prognosis. The HRMAS technique allows valuable metabolic information to be obtained from ex vivo intact tissue samples and also enables the performance of histopathology on the same tissue specimens. Studies have found that the quantification of individual metabolite levels and metabolite ratios, as well as metabolomic profiles, shows strong potential to improve accuracy in PCa detection, diagnosis and monitoring. Ex vivo HRMAS is also a valuable tool for the interpretation of in vivo results, including the localization of tumors, and thus has the potential to improve in vivo diagnostic tests used in the clinic. Here, we primarily review publications of HRMAS 1H MRS and its use for the study of intact human prostate tissue. Copyright © 2013 John Wiley & Sons, Ltd.
Feasibility of a nurse‐led in‐home cognitive behavioral program to manage concerns about falls in frail older people: A process evaluation
Authors: Dorresteijn Tanja A.C. , Rixt Zijlstra G.A. , Van Haastregt Jolanda C.M. , Vlaeyen Johan W.S. , Kempen Gertrudis I.J.M.
Published: March 2013

Concerns about falls and related avoidance of activities are common problems among older people living in the community. In this study we examined the feasibility and acceptability of AMB‐Home (the Dutch in‐home version of A Matter of Balance), a nurse‐led in‐home cognitive behavioral program developed for frail community‐living older people with concerns about falls and related activity avoidance. The multicomponent program consisted of seven individual sessions, including three home visits and four telephone contacts. Data were collected from eight nurses and 194 participants. Generally, the program was considered acceptable and feasible by both the nurses and the participants. When AMB‐Home turns out to be effective, the implementation of a fine‐tuned version of this in‐home program in regular health care, would be a natural next step. © 2013 Wiley Periodicals, Inc. Res Nurs Health 36:257–270, 2013
Synthesis and photovoltaic performance of donor–acceptor polymers containing benzo[1,2‐b:4,5‐b′]dithiophene with thienyl substituents
Authors: Sista Prakash , Kularatne Ruvini S. , Mulholland Michael E. , Wilson Mitchell , Holmes Natalie , Zhou Xiaojing , Dastoor Paul C. , Belcher Warwick , Rasmussen Seth C. , Biewer Michael C. , Stefan Mihaela C.
Published: March 2013

Three alternating donor–acceptor copolymers have been synthesized by Stille coupling polymerization of 2,6‐(trimethyltin)−4,8‐bis(5‐dodecylthiophene‐2‐yl)benzo[1,2‐b:4,5‐b′]dithiophene with 1,3‐dibromo‐5‐hexylthieno[3,4‐c]pyrrole‐4,6‐dione, 4,7‐dibromo‐1,3‐benzothiadiazole, and 5,7‐dibromo‐2,3‐didodecylthieno[3,4‐b]pyrazine, respectively. The synthesized polymers were tested in bulk heterojunction solar cells as blends with the acceptor [6,6]‐phenyl‐C61‐butyric acid methyl ester (PCBM). The thienopyrroledione copolymer displayed a power conversion efficiency of 3.00% which was increased to 3.86% by application of the additive 1,8‐diiodooctane (DIO). Tapping mode atomic force microscopy analysis indicated that there was an increase in the phase separation between polymer and PCBM, leading to an improvement in the performance upon the addition of DIO. © 2013 Wiley Periodicals, Inc. J. Polym. Sci., Part A: Polym. Chem. 2013, 51, 2622–2630
Cyclotrimerization of diisocyanates toward high‐performance networked polymers with rigid isocyanurate structure: Combination of aromatic and aliphatic diisocyanates for tunable flexibility
Authors: Moritsugu Masaki , Sudo Atsushi , Endo Takeshi
Published: March 2013

A series of networked polymers bearing isocyanurate moiety was synthesized by cyclotrimerization of diisocyanates, with employing methylenediphenyl 4,4′‐diisocyanate and 1,6‐hexamethylenediisocyanate (HMDI) in several feed ratios. In spite of the large difference in intrinsic reactivity between these two diisocyanates, their coannulation proceeded efficiently by using sodium p‐toluenesulfinate (pTolSO2Na) and 1,3‐dimethyl‐2‐imidazolidinone as a catalyst and a solvent, respectively. The resulting networked polymers were transparent and exhibited excellent thermal stability. In addition, HMDI‐rich feed ratios allowed for the formation of networked polymers with increased flexibility. © 2013 Wiley Periodicals, Inc. J. Polym. Sci., Part A: Polym. Chem. 2013, 51, 2631–2637
Synthesis and photoproperties of Eu(III)‐bearing star polymers as luminescent materials
Authors: Kusumaatmaja Ahmad , Ando Tsuyoshi , Terada Kayo , Hirohara Shiho , Nakashima Takuya , Kawai Tsuyoshi , Terashima Takaya , Tanihara Masao
Published: March 2013

Water‐soluble luminescent material was developed by introducing europium (Eu(III)) ions into the core of a star polymer. Living radical polymerization was used to obtain the star polymer. The strategy to introduce Eu(III) ions into the star polymer was studied using poly(methyl methacrylate) as an arm. The best Eu(III) ion introduction was obtained by simultaneous introduction, resulting in about 30 µmol/g‐polymer, which needed only one step for synthesis. The utilization of a hydrophilic polymer such as poly(ethylene oxide) (PEO) as an arm produced a water‐soluble star polymer. The Eu(III)‐bearing PEO star polymer obtained in this study was water soluble and showed fluorescence. In addition, it was stable in water after 1 month. The Eu(III)‐bearing star polymer exhibited luminescent properties under UV light irradiation with relatively high quantum yields of 60% in organic solution and 19% in aqueous solution. © 2013 Wiley Periodicals, Inc. J. Polym. Sci., Part A: Polym. Chem. 2013, 51, 2527–2535
Political Inequality and State Policy Adoption: Predatory Lending, Children's Health Care, and Minimum Wage
Authors: Franko William W.
Published: March 2013

This article argues that considering the economic status of various politically active groups in society is an important and often overlooked aspect of representation. Economic status is linked closely with economic need, which is especially important for the disadvantaged. Income affects the types of government programs people are influenced by and rely on; for example, government health care and public housing policies are more likely to directly influence the poor while those with higher economic status may never have an experience with these programs. This suggests that different levels of political activity by various groups in society can have an influence on lawmakers' decisions regarding how to address certain issues. Using a relative index of economic inequalities in participation for each of the 50 states over time, I examine whether housing, health care, and wage equity policies are more beneficial to the disadvantaged when levels of participation inequality are low. Time‐series cross‐sectional (TSCS) analyses are used to understand the relationship between state participation bias and the favorability of policy outcomes for the poor. The results of this study have important implications for how political power can be used to control the policy process.
Androgen deprivation and androgen receptor competition by bicalutamide induce autophagy of hormone‐resistant prostate cancer cells and confer resistance to apoptosis
Authors: Boutin Benoît , Tajeddine Nicolas , Vandersmissen Patrick , Zanou Nadège , Van Schoor Monique , Mondin Ludivine , Courtoy Pierre J. , Tombal Bertrand , Gailly Philippe
Published: March 2013

BACKGROUND

Treatment of advanced prostate cancer (PCa) relies on pharmacological or surgical androgen deprivation. However, it is only temporarily efficient. After a few months or years, the tumor relapses despite the absence of androgenic stimulation: a state referred to as hormone‐refractory prostate cancer (HRPCa). Although autophagy confers chemoresistance in some cancers, its role in the development of HRPCa remains unknown.

METHODS

Autophagic flux was assayed by GFP‐LC3 clustering, by LC3‐I to LC3‐II conversion and transmission electron microscopy. Cell death was detected by sub‐G1 quantification and concomitant measurement of transmembrane mitochondrial potential and plasma membrane permeabilization. Inhibition of autophagy was achieved by siRNAs and pharmacological inhibitors.

RESULTS

Androgen deprivation or treatment with the anti‐androgen bicalutamide promoted autophagy in HRPCa‐derived LNCaP cells. This effect was dramatically reduced after depletion of Atg5 and Beclin‐1, two canonical autophagy genes, and was associated with an inhibition of the androgen‐induced mTOR pathway. The depletion of Atg5 and Beclin‐1 significantly increased the level of cell death induced by androgen deprivation or bicalutamide. Finally, the safe anti‐malarial drug chloroquine, an inhibitor of autophagy, dramatically increased cell death after androgen deprivation or bicalutamide treatment.

CONCLUSION

Taken together, our data suggest that autophagy is a protective mechanism against androgen deprivation in HRPCa cells and that chloroquine could restore hormone dependence. This set of data could lead to the development of new therapeutic strategy against HRPCa. Prostate 73: 1090–1102, 2013. © 2013 Wiley Periodicals, Inc.
Obesity‐induced diabetes and lower urinary tract fibrosis promote urinary voiding dysfunction in a mouse model
Authors: Gharaee‐Kermani Mehrnaz , Rodriguez‐Nieves Jose A. , Mehra Rohit , Vezina Chad A. , Sarma Aruna V. , Macoska Jill A.
Published: March 2013

BACKGROUND

Progressive aging‐ and inflammation‐associated fibrosis effectively remodels the extracellular matrix (ECM) to increase prostate tissue stiffness and reduce urethral flexibility, resulting in urinary flow obstruction and lower urinary tract symptoms (LUTS). In the current study, we sought to test whether senescence‐accelerated mouse prone (SAMP)6 mice, which were reported to develop prostatic fibrosis, would also develop LUTS, and whether these symptoms would be exacerbated by diet‐induced obesity and concurrent Type 2 Diabetes Mellitus (T2DM).

METHODS

To accomplish this, SAMP6 and AKR/J background strain mice were fed regular mouse chow, low fat diet chow, or high fat diet chow for 8 months, then subjected to glucose tolerance tests, assessed for plasma insulin levels, evaluated for urinary voiding function, and assessed for lower urinary tract fibrosis.

RESULTS

The results of these studies show that SAMP6 mice and AKR/J background strain mice develop diet‐induced obesity and T2DM concurrent with urinary voiding dysfunction. Moreover, urinary voiding dysfunction was more severe in SAMP6 than AKR/J mice and was associated with pronounced prostatic and urethral tissue fibrosis.

CONCLUSIONS

Taken together, these studies suggest that obesity, T2DM, lower urinary tract fibrosis, and urinary voiding dysfunction are inextricably and biologically linked. Prostate 73: 1123–1133, 2013. © 2013 Wiley Periodicals, Inc.
High‐pressure synthesis of crystalline boron in B–H system
Authors: Ekimov E. A. , Lebed J. B. , Sidorov V. A. , Lyapin S. G.
Published: March 2013

An experimental P–T‐phase diagram was proposed for boron produced by pyrolysis of decaborane B10H14 in the temperature range 1000–2100 K and pressure range 2–8 GPa. It was found that decaborane decomposes at temperatures above 1100–1400 K with a formation of either β‐rhombohedral boron at pressures of 2–3 GPa or α‐tetragonal boron at higher pressures. The electrical resistivity of α‐tetragonal boron was measured as a function of temperature under pressures up to 5 GPa and in the temperature range 300–600 K. The energy gap between the valence and the conduction bands of α‐tetragonal boron was found to be 1.52 eV. The gap decreases slightly under pressure.
Lateral boundary conditions for limited area models
Authors: Davies Terry
Published: March 2013

Limited area models (LAMs) are widely used in numerical weather prediction and regional climate modelling to obtain high‐resolution results that would be too expensive computationally to be obtained with a global model. To run LAMs requires lateral boundary conditions (LBCs) which are normally obtained from a global model or another (lower‐resolution) LAM containing the domain of the smaller LAM. It is widely thought that the LBCs are a source of significant errors in LAMs but in the Meteorological Office Unified Model (UM) LBC errors are shown to be a tiny part of the overall error. The source of LBC errors is explained and the LBC procedure employed in the UM is described. The UM LBC procedure is effectively transparent for a nested LAM with the same resolution and grid points as a LAM providing its LBCs.
A crossed random effects modeling approach for estimating diagnostic accuracy from ordinal ratings without a gold standard
Authors: Xie Yunlong , Chen Zhen , Albert Paul S.
Published: March 2013

In diagnostic studies without a gold standard, the assumption on the dependence structure of the multiple tests or raters plays an important role in model performance. In case of binary disease status, both conditional independence and crossed random effects structure have been proposed and their performance investigated. Less attention has been paid to the situation where the true disease status is ordinal. In this paper, we propose crossed subject‐specific and rater‐specific random effects to account for the dependence structure and assess the robustness of the proposed model to misspecification in the random effects distributions. We applied the models to data from the Physician Reliability Study, which focuses on assessing the diagnostic accuracy in a population of raters for the staging of endometriosis, a gynecological disorder in women. Using this new methodology, we estimate the probability of a correct classification and show that regional experts can more easily classify the intermediate stage than resident physicians. Copyright © 2013 John Wiley & Sons, Ltd.
Tumorigenic Potential of miR-18A* in Glioma Initiating Cells Requires NOTCH-1 Signaling
Authors: Turchi Laurent , Debruyne David N. , Almairac Fabien , Virolle Virginie , Fareh Mohamed , Neirijnck Yasmine , Burel-Vandenbos Fanny , Paquis Philippe , Junier Marie-Pierre , Van Obberghen-Schilling Ellen , Chneiweiss Hervé , Virolle Thierry
Published: March 2013

Stem cell-like properties of glioma initiating cells (GiCs) fuel glioblastoma (GBM) development by providing the different cell types that comprise the tumor. It is therefore likely that the molecular circuitries that regulate their decision to self-renew or commit to a more differentiated state may offer targets for future innovative therapies. In previous micro-RNA profiling studies to search for regulators of stem cell plasticity, we identified miR-18a* as a potential candidate and its expression correlated with the stemness state. Here, using human GiCs we found that miR-18a* expression promotes clonal proliferation in vitro and tumorigenicity in vivo. Mechanistically, ERK-dependent induction of miR-18a* directly represses expression of DLL3, an autocrine inhibitor of NOTCH, thus enhancing the level of activated NOTCH-1. Activated NOTCH-1 in turn is required for sustained ERK activation. This feed-forward loop, driven by miR-18a*, is required to turn on the SHH-GLI-NANOG network, essential for GiC self-renewal. Hence, by tightly regulating expression of DLL3, miR-18a* constitutes an important signaling mediator for fine tuning the level of GiC self-renewal.
Native Adipose Stromal Cells Egress from Adipose Tissue In Vivo: Evidence During Lymph Node Activation
Authors: Gil-Ortega Marta , Garidou Lucile , Barreau Corinne , Maumus Marie , Breasson Ludovic , Tavernier Geneviève , García-Prieto Concha F. , Bouloumié Anne , Casteilla Louis , Sengenès Coralie
Published: March 2013

Adipose tissue (AT) has become accepted as a source of multipotent progenitor cells, the adipose stromal cells (ASCs). In this regard, considerable work has been performed to harvest and characterize this cell population as well as to investigate the mechanisms by which transplanted ASCs mediate tissue regeneration. In contrast the endogenous release of native ASCs by AT has been poorly investigated. In this work, we show that native ASCs egress from murine AT. Indeed, we demonstrated that the release of native ASCs from AT can be evidenced both using an ex vivo perfusion model that we set up and in vivo. Such a mobilization process is controlled by CXCR4 chemokine receptor. In addition, once mobilized from AT, circulating ASCs were found to navigate through lymph fluid and to home into lymph nodes (LN). Therefore, we demonstrated that, during the LN activation, the fat depot encapsulating the activated LN releases native ASCs, which in turn invade the activated LN. Moreover, the ASCs invading the LN were visualized in close physical interaction with podoplanin and ER-TR7 positive structures corresponding to the stromal network composing the LN. This dynamic was impaired with CXCR4 neutralizing antibody. Taken together, these data provide robust evidences that native ASCs can traffic in vivo and that AT might provide stromal cells to activated LNs.