bluuebunny/crossref_metadata_2025_split huggingface dataset:
Radiation-Induced Erectile Dysfunction Using Prostate-Confined Modern Radiotherapy in a Rat Model
Authors: Kimura Masaki , Yan Hui , Rabbani Zahid , Satoh Takefumi , Baba Shiro , Yin Fang-fang , Polascik Thomas J. , Donatucci Craig F. , Vujaskovic Zeljko , Koontz Bridget F. 
Published: June 2011

ABSTRACT

Introduction
The mechanisms of radiation-induced erectile dysfunction (ED) are unclear, as clinical studies are limited, and previous animal models were based on wide-field irradiation, which does not model current radiotherapy (RT) techniques.

Aims
To perform functional and morphological analyses of erectile function (EF) utilizing image-guided stereotactic prostate-confined RT in a rat model.

Methods
Sixty young adult male rats aged 10–12 weeks old were divided into age-matched sham and RT groups. A single 20-Gy fraction to the prostate was delivered to RT animals. Penile bulb, shaft, and testes were excluded from treatment fields.

Main Outcome Measures
Bioassay and intracavernous pressure (ICP) measurements were conducted at 2, 4, and 9 weeks following RT. Perfusion analysis of the corpora cavernosa (CC) was conducted using Hoechst injected prior to sacrifice. Penile shaft and cavernous nerve (CN) were evaluated by immunohistochemistry. Plasma testosterone level was analyzed using a testosterone enzyme-linked immunosorbent assay (ELISA) assay kit.

Results
Irradiated animals demonstrated statistically significant time-dependent functional impairment of EF by bioassay and ICP measurement from 4 weeks. Neuronal nitric oxide synthase (NOS) expression was decreased in CN by 4 weeks. In CC, expression levels of anti-alpha smooth muscle actin and endothelial NOS were significantly decreased at 9 weeks. In penile dorsal vessels, smooth muscle/collagen ratio was significantly decreased at 4 and 9 weeks. Additionally, Hoechst perfusion showed time-dependent decrease in CC of RT animals, whereas CD31 expression was not affected. No toxicities were noted; testosterone levels were similar in both groups.

Conclusion
We demonstrated time-dependent ED following image-guided stereotactic RT. Our results imply that reduction of neuronal NOS expression in cavernous nerve could trigger consecutive reduction of smooth muscle content as well as blood perfusion in CC that resulted in corporal veno-occlusive dysfunction. Present study could be a cornerstone to future research that may bring comprehensive scientific understanding of radiation-induced ED.
Hyperthyroidism: A Risk Factor for Female Sexual Dysfunction
Authors: Atis Gokhan , Dalkilinc Ayhan , Altuntas Yuksel , Atis Alev , Gurbuz Cenk , Ofluoglu Yilmaz , Cil Esra , Caskurlu Turhan 
Published: June 2011

ABSTRACT

Introduction
Hyperthyroidism is a common hormonal disorder in women that may cause female sexual dysfunction (FSD).

Aim
To assess sexual function in women with hyperthyroidism.

Methods
A total of 40 women with clinical hyperthyroidism and 40 age-matched voluntary healthy women controls were included in the study. All the subjects were evaluated with a detailed medical and sexual history, including a Female Sexual Function Index (FSFI) questionnaire for sexual status and the Beck Depression Inventory (BDI) for psychiatric assessment.

Main Outcomes Measures
The levels of serum thyroid-stimulating hormone (TSH), thyroid hormones, sex hormone binding globulin (SHBG), total testosterone (tT), free testosterone (fT), prolactin, estradiol, follicle-stimulating hormone, and luteinizing hormone were measured.

Results
The mean total FSFI scores were 24.2 ± 9.96 in the hyperthyroidic group and 29 ± 10.4 in the control group (P &lt; 0.0001). Desire (P &lt; 0.040), arousal (P &lt; 0.0001), lubrication (P &lt; 0.0001), orgasm (P &lt; 0.0001), satisfaction (P &lt; 0.0001), and pain (P &lt; 0.007) domain scores were also significantly lower in women with hyperthyroidism. The mean BDI score for hyperthyroidic patients was significantly greater than the score for the control group (P &lt; 0.0001). The mean SHBG level in the hyperthyroidic group was found to be significantly higher than the level in the controls (P &lt; 0.0001), whereas the mean fT level in the hyperthyroidic group was lower than in the control group (P &lt; 0.0001). The FSFI score showed a significant negative correlation with the serum SHBG (r = −0.309, P = 0.005), free triiodothyronine (r = −0.353, P = 0.006) and free tetraiodothyronine (r = −0.305, P = 0.018) levels, BDI scores (r = −0.802, P = 0.0001) and positive correlation with tT (r = 0.284, P = 0.011), fT (r = 0.407, P = 0.001), and TSH (r = 0.615, P = 0.0001) levels.

Conclusions
A significant percentage of women with clinical hyperthyroidism had sexual dysfunction. Increased depressive symptoms, increased SHBG level, and decreased fT levels were all found to be associated with FSD in clinical hyperthyroidism.
NEAR WELL‐SCALE HETEROGENEITIES IN A KHUFF OUTCROP EQUIVALENT (SAIQ PLATEAU, AL JABAL AL AKHDAR, SULTANATE OF OMAN)
Authors: Zeller M. , Koehrer B. , Adams E. W. , Pöppelreiter M. , Aigner T. 
Published: June 2011

The Middle Permian to Lower Triassic Khuff Formation is one of the world's most prolific hydrocarbon reservoirs. This study is part of a research project on Khuff outcrop equivalents whose overall aim is to investigate the reservoir architecture on different scales. The present paper focuses on heterogeneities in Khuff‐equivalent grainstones at the near well scale.An outcrop in the Oman Mountains, where the Khuff‐equivalent Saiq and Mahil Formations are exposed in an area 1800 m long by 100 m high, was studied to map lateral and vertical depositional heterogeneities. The investigated section represents parts of three third‐order sequences: the upper part of Khuff sequence (KS)3 (grain‐dominated), the whole of KS2 (mud‐dominated), and the lower part of KS1 (grain‐dominated). Real‐Time Kinematic GPS, satellite imagery, outcrop gamma‐ray and digitized sedimentary logs were used for outcrop description and were integrated into a three‐dimensional digital outcrop model.The resulting 3D facies model indicates that the apparently simple, layer‐cake geometry of the grainstone reservoir facies shows pinching and swelling with a standard deviation of 12.75% of bed thickness. These thickness variations may influence volume calculations during reservoir assessments. The heterogeneities of grainstone bodies are represented by compositional (ooid, peloid or intraclast‐dominated) and grain‐size variations.Muddy event beds at the cm‐scale were mapped out in detail in a 200 × 40 m outcrop window and together form a dense network of potential baffles to fluid flow. The thickness of these beds varies significantly due to syndepositional erosion.An important conclusion of this near well‐scale study is that the perceived simple, layer‐cake Khuff‐equivalent succession in the study area is in fact heterogeneous in mud‐rich deposits, while grain‐rich deposits extend over a wide area with some thickness variations. These findings can be directly applied in Khuff subsurface correlation and modelling attempts.
GEOCHEMISTRY AND ORIGIN OF CRUDE OILS AND CONDENSATES FROM THE CENTRAL PERSIAN GULF, OFFSHORE IRAN
Authors: Mobarakabad A. Fathi , Bechtel A. , Gratzer R. , Mohsenian E. , Sachsenhofer R.F. 
Published: June 2011

Biomarker‐ and compound‐specific carbon isotope analyses were used to compare oil samples recovered from Late Jurassic and Early to Middle Cretaceous reservoirs at South Pars and nearby fields in the Iranian portion of the Persian Gulf, and condensate samples associated with the super‐giant gas accumulation in Permo‐Triassic reservoirs at South Pars.The results indicate that all of the oil samples, including heavy oil from South Pars and oil from the Salman, Reshadat, Resalat and Balal fields, are genetically related. The most probable source rocks for these oils are Jurassic marine limestones or marls deposited under anoxic conditions. Based on the methyl phenanthrene index, source rock maturity was inferred to be equivalent to vitrinite reflectance values of about 0.8% Rc. The distribution and maturity pattern of the source rocks suggest migration from a depocentre located to the south, with inferred migration distances of up to 250 km.There is no genetic relationship between the heavy oil which has accumulated in Mesozoic reservoirs at South Pars and condensates which are associated with the super‐giant gas accumulation in Permo‐Triassic reservoirs there. Based on biomarker compositions, the condensates at South Pars appear to be derived from shaly marine or lacustrine source rocks deposited under dysoxic conditions. The δ13C values of short‐chain n‐alkanes and isoprenoids in condensate samples suggest a common source and an equal maturity for the source rocks. Pristane/n‐C17 versus phytane/n‐C18 characteristics are in agreement with published data for Silurian‐sourced condensates. High thermal maturities equivalent to 1.7% Rc are also consistent with a Palaeozoic (Silurian) source rock.
Multiplexed microsatellite recovery using massively parallel sequencing
Authors: JENNINGS T. N. , KNAUS B. J. , MULLINS T. D. , HAIG S. M. , CRONN R. C. 
Published: June 2011

AbstractConservation and management of natural populations requires accurate and inexpensive genotyping methods. Traditional microsatellite, or simple sequence repeat (SSR), marker analysis remains a popular genotyping method because of the comparatively low cost of marker development, ease of analysis and high power of genotype discrimination. With the availability of massively parallel sequencing (MPS), it is now possible to sequence microsatellite‐enriched genomic libraries in multiplex pools. To test this approach, we prepared seven microsatellite‐enriched, barcoded genomic libraries from diverse taxa (two conifer trees, five birds) and sequenced these on one lane of the Illumina Genome Analyzer using paired‐end 80‐bp reads. In this experiment, we screened 6.1 million sequences and identified 356 958 unique microreads that contained di‐ or trinucleotide microsatellites. Examination of four species shows that our conversion rate from raw sequences to polymorphic markers compares favourably to Sanger‐ and 454‐based methods. The advantage of multiplexed MPS is that the staggering capacity of modern microread sequencing is spread across many libraries; this reduces sample preparation and sequencing costs to less than $400 (USD) per species. This price is sufficiently low that microsatellite libraries could be prepared and sequenced for all 1373 organisms listed as ‘threatened’ and ‘endangered’ in the United States for under $0.5 M (USD).
E6 and E7 from Human Papillomavirus Type 16 Cooperate To Target the PDZ Protein Na/H Exchange Regulatory Factor 1
Authors: Accardi Rosita , Rubino Rosa , Scalise Mariafrancesca , Gheit Tarik , Shahzad Naveed , Thomas Miranda , Banks Lawrence , Indiveri Cesare , Sylla Bakary S. , Cardone Rosa A. , Reshkin Stephan J. , Tommasino Massimo 
Published: June 2011

ABSTRACT

Previous studies have shown that the PDZ-binding motif of the E6 oncoprotein from the mucosal high-risk (HR) human papillomavirus (HPV) types plays a key role in HPV-mediated cellular transformation in
in vitro
and
in vivo
experimental models. HR HPV E6 oncoproteins have the ability to efficiently degrade members of the PDZ motif-containing membrane-associated guanylate kinase (MAGUK) family; however, it is possible that other PDZ proteins are also targeted by E6. Here, we describe a novel interaction of HPV type 16 (HPV16) E6 with a PDZ protein, Na
+
/H
+
exchange regulatory factor 1 (NHERF-1), which is involved in a number of cellular processes, including signaling and transformation. HPV16 E6 associates with and promotes the degradation of NHERF-1, and this property is dependent on the C-terminal PDZ-binding motif of E6. Interestingly, HPV16 E7, via the activation of the cyclin-dependent kinase complexes, promoted the accumulation of a phosphorylated form of NHERF-1, which is preferentially targeted by E6. Thus, both oncoproteins appear to cooperate in targeting NHERF-1. Notably, HPV18 E6 is not able to induce NHERF-1 degradation, indicating that this property is not shared with E6 from all HR HPV types. Downregulation of NHERF-1 protein levels was also observed in HPV16-positive cervical cancer-derived cell lines, such as SiHa and CaSki, as well as HPV16-positive cervical intraepithelial neoplasia (CIN). Finally, our data show that HPV16-mediated NHERF-1 degradation correlates with the activation of the phosphatidylinositol-3′-OH kinase (PI3K)/AKT signaling pathway, which is known to play a key role in carcinogenesis.
Construction of a Full Transcription Map of Human Papillomavirus Type 18 during Productive Viral Infection
Authors: Wang Xiaohong , Meyers Craig , Wang Hsu-Kun , Chow Louise T. , Zheng Zhi-Ming 
Published: June 2011

ABSTRACTHuman papillomavirus type 18 (HPV18) is the second most common oncogenic HPV genotype, responsible for ∼15% of cervical cancers worldwide. In this study, we constructed a full HPV18 transcription map using HPV18-infected raft tissues derived from primary human vaginal or foreskin keratinocytes. By using 5′ rapid amplification of cDNA ends (RACE), we mapped two HPV18 transcription start sites (TSS) for early transcripts at nucleotide (nt) 55 and nt 102 and the HPV18 late TSS frequently at nt 811, 765, or 829 within the E7 open reading frame (ORF) of the virus genome. HPV18 polyadenylation cleavage sites for early and late transcripts were mapped to nt 4270 and mainly to nt 7299 or 7307, respectively, by using 3′ RACE. Although all early transcripts were cleaved exclusively at a single cleavage site, HPV18 late transcripts displayed the heterogeneity of 3′ ends, with multiple minor cleavage sites for late RNA polyadenylation. HPV18 splice sites/splice junctions for both early and late transcripts were identified by 5′ RACE and primer walking techniques. Five 5′ splice sites (donor sites) and six 3′ splice sites (acceptor sites) that are highly conserved in other papillomaviruses were identified in the HPV18 genome. HPV18 L1 mRNA translates a L1 protein of 507 amino acids (aa), smaller than the 568 aa residues previously predicted. Collectively, a full HPV18 transcription map constructed from this report will lead us to further understand HPV18 gene expression and virus oncogenesis.
Nucleolin Interacts with the Feline Calicivirus 3′ Untranslated Region and the Protease-Polymerase NS6 and NS7 Proteins, Playing a Role in Virus Replication
Authors: Cancio-Lonches Clotilde , Yocupicio-Monroy Martha , Sandoval-Jaime Carlos , Galvan-Mendoza Iván , Ureña Luis , Vashist Surender , Goodfellow Ian , Salas-Benito Juan , Gutiérrez-Escolano Ana Lorena 
Published: June 2011

ABSTRACT

Cellular proteins play many important roles during the life cycle of all viruses. Specifically, host cell nucleic acid-binding proteins interact with viral components of positive-stranded RNA viruses and regulate viral translation, as well as RNA replication. Here, we report that nucleolin, a ubiquitous multifunctional nucleolar shuttling phosphoprotein, interacts with the Norwalk virus and feline calicivirus (FCV) genomic 3′ untranslated regions (UTRs). Nucleolin can also form a complex
in vitro
with recombinant Norwalk virus NS6 and -7 (NS6/7) and can be copurified with the analogous protein from feline calicivirus (p76 or NS6/7) from infected feline kidney cells. Nucleolin RNA levels or protein were not modified during FCV infection; however, as a consequence of the infection, nucleolin was seen to relocalize from the nucleoli to the nucleoplasm, as well as to the perinuclear area where it colocalizes with the feline calicivirus NS6/7 protein. In addition, antibodies to nucleolin were able to precipitate viral RNA from feline calicivirus-infected cells, indicating a direct or indirect association of nucleolin with the viral RNA during virus replication. Small interfering RNA (siRNA)-mediated knockdown of nucleolin resulted in a reduction of the cytopathic effect and virus yield in CrFK cells. Taken together, these results demonstrate that nucleolin is a nucleolar component that interacts with viral RNA and NS6/7 and is required for feline calicivirus replication.
Peptidyl-Prolyl Isomerase Pin1 Is a Cellular Factor Required for Hepatitis C Virus Propagation
Authors: Lim Yun-Sook , Tran Huong T. L. , Park Soo-Je , Yim Seung-Ae , Hwang Soon B. 
Published: June 2011

ABSTRACT

The life cycle of hepatitis C virus (HCV) is highly dependent on cellular factors. Using small interfering RNA (siRNA) library screening, we identified peptidyl-prolyl
cis-trans
isomerase NIMA-interacting 1 (Pin1) as a host factor involved in HCV propagation. Here we demonstrated that silencing of Pin1 expression resulted in decreases in HCV replication in both HCV replicon cells and cell culture-grown HCV (HCVcc)-infected cells, whereas overexpression of Pin1 increased HCV replication. Pin1 interacted with both the NS5A and NS5B proteins. However, Pin1 expression was increased only by the NS5B protein. Both the protein binding and isomerase activities of Pin1 were required for HCV replication. Juglone, a natural inhibitor of Pin1, inhibited HCV propagation by inhibiting the interplay between the Pin1 and HCV NS5A/NS5B proteins. These data indicate that Pin1 modulates HCV propagation and may contribute to HCV-induced liver pathogenesis.
Circulating Tumor Cells as Biomarkers in Prostate Cancer
Authors: Danila Daniel C. , Fleisher Martin , Scher Howard I. 
Published: June 2011

Abstract
Unmet needs in prostate cancer drug development and patient management are the ability to monitor treatment effects and to identify therapeutic targets in a tumor at the time treatment is being considered. This review focuses on establishing analytically valid biomarkers for specific contexts of use in patients with castration-resistant prostate cancer (CRPC), emphasizing a biomarker currently in clinical use, circulating tumor cells (CTC). The FDA Critical Path provides a road map for these investigations, which, if followed, will facilitate the incorporation of these types of assays into clinical decision-making. CTC enumeration at baseline and post-treatment is prognostic of survival, with no threshold effect, and the shedding of cells into the circulation represents an intrinsic property of the tumor, distinct from extent of disease. The clinical utility of monitoring CTC changes with treatment, as an efficacy-response surrogate biomarker of survival, is currently being tested in large phase III trials, with the novel antiandrogen therapies abiraterone acetate and MDV3100. Molecular determinants can be identified and characterized in CTCs as potential predictive biomarkers of tumor sensitivity to a therapeutic modality. Additionally, we discuss novel technologies to enrich and characterize CTCs from more patients, the potential clinical uses of CTCs in determining prognosis and monitoring treatment effects, and CTCs as a source of tissue to identify predictive markers of drug sensitivity to guide treatment selection. Prospective studies, designed around the biomarker itself and the specific clinical context for which it is applied, are needed to further assess the role of these and novel markers in clinical practice. Clin Cancer Res; 17(12); 3903–12. ©2011 AACR.
Emerging Roles of Protein Kinase D1 in Cancer
Authors: Sundram Vasudha , Chauhan Subhash C. , Jaggi Meena 
Published: June 2011

Abstract
Protein kinase D1 (PKD1) is a serine-threonine kinase that regulates various functions within the cell, including cell proliferation, apoptosis, adhesion, and cell motility. In normal cells, this protein plays key roles in multiple signaling pathways by relaying information from the extracellular environment and/or upstream kinases and converting them into a regulated intracellular response. The aberrant expression of PKD1 is associated with enhanced cancer phenotypes, such as deregulated cell proliferation, survival, motility, and epithelial mesenchymal transition. In this review, we summarize the structural and functional aspects of PKD1 and highlight the pathobiological roles of this kinase in cancer. Mol Cancer Res; 9(8); 985–96. ©2011 AACR.
Inactivation of AR/TMPRSS2-ERG/Wnt Signaling Networks Attenuates the Aggressive Behavior of Prostate Cancer Cells
Authors: Li Yiwei , Kong Dejuan , Wang Zhiwei , Ahmad Aamir , Bao Bin , Padhye Subhash , Sarkar Fazlul H. 
Published: June 2011

AbstractThe development of prostate cancer and its progression to castrate-resistant prostate cancer (CRPC) after antiandrogen ablation therapy are driven by persistent biological activity of androgen receptor (AR) signaling. Moreover, studies have shown that more than 50% of human prostate cancers overexpress ERG (v-ets avian erythroblastosis virus E26 oncogene related gene) due to AR-regulated TMPRSS2-ERG fusion gene. However, the reported roles of TMPRSS2-ERG fusion in cancer progression are not clear. In this study, we investigated the signal transduction in the AR/TMPRSS2-ERG/Wnt signaling network for studying the aggressive behavior of prostate cancer cells and further assessed the effects of BR-DIM and CDF [natural agents-derived synthetic formulation and analogue of 3,3′-diindolylmethane (DIM) and curcumin, respectively, with improved bioavailability] on the regulation of AR/TMPRSS2-ERG/Wnt signaling. We found that activation of AR resulted in the induction of ERG expression through TMPRSS2-ERG fusion. Moreover, we found that ERG overexpression and nuclear translocation activated the activity of Wnt signaling. Furthermore, forced overexpression of ERG promoted invasive capacity of prostate cancer cells. More important, we found that BR-DIM and CDF inhibited the signal transduction in the AR/TMPRSS2-ERG/Wnt signaling network, leading to the inactivation of Wnt signaling consistent with inhibition of prostate cancer cell invasion. In addition, BR-DIM and CDF inhibited proliferation of prostate cancer cells and induced apoptotic cell death. On the basis of our findings, we conclude that because BR-DIM and CDF downregulate multiple signaling pathways including AR/TMPRSS2-ERG/Wnt signaling, these agents could be useful for designing novel strategies for the prevention and/or treatment of prostate cancer. Cancer Prev Res; 4(9); 1495–506. ©2011 AACR.
Phase I Randomized, Double-Blind Pilot Study of Micronized Resveratrol (SRT501) in Patients with Hepatic Metastases—Safety, Pharmacokinetics, and Pharmacodynamics
Authors: Howells Lynne M. , Berry D.P. , Elliott P.J. , Jacobson E.W. , Hoffmann E. , Hegarty B. , Brown K. , Steward W.P. , Gescher A.J. 
Published: June 2011

Abstract
The phytochemical resveratrol has undergone extensive preclinical investigation for its putative cancer chemopreventive properties. Low systemic availability of the parent compound due to rapid and extensive metabolism may confound its usefulness as a potential agent to prevent malignancies in organs remote from the site of absorption. Micronization allows increased drug absorption, thus increasing availability. Here we describe a pilot study of SRT501, micronized resveratrol, given as 5.0 g daily for 14 days, to patients with colorectal cancer and hepatic metastases scheduled to undergo hepatectomy. The purpose of the study was to assess the safety, pharmacokinetics, and pharmacodynamics of the formulation. SRT501 was found to be well tolerated. Mean plasma resveratrol levels following a single dose of SRT501 administration were 1,942 ± 1,422 ng/mL, exceeding those published for equivalent doses of nonmicronized resveratrol by 3.6-fold. Resveratrol was detectable in hepatic tissue following SRT501 administration (up to 2,287 ng/g). Cleaved caspase-3, a marker of apoptosis, significantly increased by 39% in malignant hepatic tissue following SRT501 treatment compared with tissue from the placebo-treated patients. SRT501 warrants further clinical exploration to assess its potential clinical utility. Cancer Prev Res; 4(9); 1419–25. ©2011 AACR.