bluuebunny/crossref_metadata_2025_split huggingface dataset:
The cholesterol biosynthesis enzyme oxidosqualene cyclase is a new target to impair tumour angiogenesis and metastasis dissemination
Authors: Maione Federica , Oliaro-Bosso Simonetta , Meda Claudia , Di Nicolantonio Federica , Bussolino Federico , Balliano Gianni , Viola Franca , Giraudo Enrico 
Published: March 2015

AbstractAberrant cholesterol homeostasis and biosynthesis has been observed in different tumour types. This paper investigates the role of the post-squalenic enzyme of cholesterol biosynthesis, oxidosqualene cyclase (OSC), in regulating tumour angiogenesis and metastasis dissemination in mouse models of cancer. We showed that Ro 48-8071, a selective inhibitor of OSC, reduced vascular density and increased pericyte coverage, with a consequent inhibition of tumour growth in a spontaneous mouse model of pancreatic tumour (RIP-Tag2) and two metastatic mouse models of human colon carcinoma (HCT116) and pancreatic adenocarcinoma (HPAF-II). Remarkably, the inhibition of OSC hampered metastasis formation in HCT116 and HPAF-II models. Ro 48-8071 induced tumour vessel normalization and enhanced the anti-tumoral and anti-metastatic effects of 5-fluorouracil (5-FU) in HCT116 mice. Ro 48-8071 exerted a strong anti-angiogenic activity by impairing endothelial cell adhesion and migration and by blocking vessel formation in angiogenesis assays. OSC inhibition specifically interfered with the PI3K pathway. According to in vitro results, Ro 48-8071 specifically inhibited Akt phosphorylation in both cancer cells and tumour vasculature in all treated models. Thus, our results unveil a crucial role of OSC in the regulation of cancer progression and tumour angiogenesis and indicate Ro 48-8071 as a potential novel anti-angiogenic and anti-metastatic drug.
Characterization of the MCM homohexamer from the thermoacidophilic euryarchaeon Picrophilus torridus
Authors: Goswami Kasturi , Arora Jasmine , Saha Swati 
Published: March 2015

AbstractThe typical archaeal MCM exhibits helicase activity independently invitro. This study characterizes MCM from the euryarchaeon Picrophilus torridus. While PtMCM hydrolyzes ATP in DNA-independent manner, it displays very poor ability to unwind DNA independently and then too only under acidic conditions. The protein exists stably in complex with PtGINS in whole cell lysates, interacting directly with PtGINS under neutral and acidic conditions. GINS strongly activates MCM helicase activity, but only at low pH. In consonance with this, PtGINS activates PtMCM-mediated ATP hydrolysis only at low pH, with the amount of ATP hydrolyzed during the helicase reaction increasing more than fifty-fold in the presence of GINS. While the stimulation of MCM-mediated helicase activity by GINS has been reported in MCMs from P.furiosus, T.kodakarensis and very recently, T.acidophilum, to the best of our knowledge, this is the first report of an MCM helicase demonstrating DNA unwinding activity only at such acidic pH, across all archaea and eukaryotes. PtGINS may induce/stabilize a conducive conformation of PtMCM under acidic conditions, favouring PtMCM-mediated DNA unwinding coupled to ATP hydrolysis. Our findings underscore the existence of divergent modes of replication regulation among archaea and the importance of investigating replication events in more archaeal organisms.
Magnetic Resonance Imaging with Superparamagnetic Iron Oxide Fails to Track the Long-term Fate of Mesenchymal Stem Cells Transplanted into Heart
Authors: Ma Ning , Cheng Huaibing , Lu Minjie , Liu Qiong , Chen Xiuyu , Yin Gang , Zhu Hao , Zhang Lianfeng , Meng Xianmin , Tang Yue , Zhao Shihua 
Published: March 2015

AbstractMRI for in vivo stem cell tracking remains controversial. Here we tested the hypothesis that MRI can track the long-term fate of the superparamagnetic iron oxide (SPIO) nanoparticles labelled mesenchymal stem cells (MSCs) following intramyocardially injection in AMI rats. MSCs (1 × 106) from male rats doubly labeled with SPIO and DAPI were injected 2 weeks after myocardial infarction. The control group received cell-free media injection. In vivo serial MRI was performed at 24 hours before cell delivery (baseline), 3 days, 1, 2 and 4 weeks after cell delivery, respectively. Serial follow-up MRI demonstrated large persistent intramyocardial signal-voids representing SPIO during the follow-up of 4 weeks and MSCs did not moderate the left ventricular dysfunction. The TUNEL analysis confirmed that MSCs engrafted underwent apoptosis. The histopathological studies revealed that the site of cell injection was infiltrated by inflammatory cells progressively and the iron-positive cells were macrophages identified by CD68 staining, but very few or no DAPI-positive stem cells at 4 weeks after cells transplantation. The presence of engrafted cells was confirmed by real-time PCR, which showed that the amount of Y-chromosome-specific SRY gene was consistent with the results. MRI may not reliably track the long-term fate of SPIO-labeled MSCs engraftment in heart.
The Nuclear Receptor Nr4a1 Controls CD8 T Cell Development Through Transcriptional Suppression of Runx3
Authors: Nowyhed Heba N. , Huynh Tridu R. , Blatchley Amy , Wu Runpei , Thomas Graham D. , Hedrick Catherine C. 
Published: March 2015

AbstractThe NR4A nuclear receptor family member Nr4a1 is strongly induced in thymocytes undergoing selection and has been shown to control the development of Treg cells; however the role of Nr4a1 in CD8+ T cells remains undefined. Here we report a novel role for Nr4a1 in regulating the development and frequency of CD8+ T cells through direct transcriptional control of Runx3. We discovered that Nr4a1 recruits the corepressor, CoREST to suppress Runx3 expression in CD8+ T cells. Loss of Nr4a1 results in increased Runx3 expression in thymocytes which consequently causes a 2-fold increase in the frequency and total number of intrathymic and peripheral CD8+ T cells. Our findings establish Nr4a1 as a novel and critical player in the regulation of CD8 T cell development through the direct suppression of Runx3.
Multiple strategies of oxygen supply in Drosophila malignancies identify tracheogenesis as a novel cancer hallmark
Authors: Grifoni Daniela , Sollazzo Manuela , Fontana Elisabetta , Froldi Francesca , Pession Annalisa 
Published: March 2015

AbstractAngiogenesis is the term used to describe all the alterations in blood vessel growth induced by a tumour mass following hypoxic stress. The occurrence of multiple strategies of vessel recruitment favours drug resistance, greatly complicating the treatment of certain tumours. In Drosophila, oxygen is conveyed to the internal organs by the tracheal system, a closed tubular network whose role in cancer growth is so far unexplored. We found that, as observed in human cancers, Drosophila malignant cells suffer from oxygen shortage, release pro-tracheogenic factors, co-opt nearby vessels and get incorporated into the tracheal walls. We also found that the parallelisms observed in cellular behaviours are supported by genetic and molecular conservation. Finally, we identified a molecular circuitry associated with the differentiation of cancer cells into tracheal cells. In summary, our findings identify tracheogenesis as a novel cancer hallmark in Drosophila, further expanding the power of the fly model in cancer research.
Strong magnetic field-assisted growth of carbon nanofibers and its microstructural transformation mechanism
Authors: Luo Chengzhi , Fu Qiang , Pan Chunxu 
Published: March 2015

AbstractIt is well-known that electric and magnetic fields can control the growth direction, morphology and microstructure of one-dimensional carbon nanomaterials (1-DCNMs), which plays a key role for its potential applications in micro-nano-electrics and devices. In this paper, we introduce a novel process for controlling growth of carbon nanofibers (CNFs) with assistance of a strong magnetic field (up to 0.5 T in the center) in a chemical vapor deposition (CVD) system. The results reveal that: 1) The CNFs get bundled when grown in the presence of a strong magnetic field and slightly get aligned parallel to the direction of the magnetic field; 2) The CNFs diameter become narrowed and homogenized with increase of the magnetic field; 3) With the increase of the magnetic field, the microstructure of CNFs is gradually changed, i.e., the strong magnetic field makes the disordered “solid-cored” CNFs transform into a kind of bamboo-liked carbon nanotubes; 4) We propose a mechanism that the reason for these variations and transformation is due to diamagnetic property of carbon atoms, so that it has direction selectivity in the precipitation process.
Structure, Function and Inhibition of the Phosphoethanolamine Methyltransferases of the Human Malaria Parasites Plasmodium vivax and Plasmodium knowlesi
Authors: Garg Aprajita , Lukk Tiit , Kumar Vidya , Choi Jae-Yeon , Augagneur Yoann , Voelker Dennis R. , Nair Satish , Mamoun Choukri Ben 
Published: March 2015

AbstractPhosphoethanolamine methyltransferases (PMTs) catalyze the three-step methylation of phosphoethanolamine to form phosphocholine, a critical step in the synthesis of phosphatidylcholine in a select number of eukaryotes including human malaria parasites, nematodes and plants. Genetic studies in the malaria parasite Plasmodium falciparum have shown that the methyltransferase PfPMT plays a critical function in parasite development and differentiation. The presence of PMT orthologs in other malaria parasites that infect humans and their absence in mammals make them ideal targets for the development of selective antimalarials with broad specificity against different Plasmodium species. Here we describe the X-ray structures and biochemical properties of PMT orthologs from Plasmodium vivax and Plasmodium knowlesi and show that both enzymes are inhibited by amodiaquine and NSC158011, two drugs with potent antimalarial activity. Metabolic studies in a yeast mutant that relies on PkPMT or PvPMT for survival demonstrated that these compounds inhibit phosphatidylcholine biosynthesis from ethanolamine. Our structural and functional data provide insights into the mechanism of catalysis and inhibition of PMT enzymes and set the stage for a better design of more specific and selective antimalarial drugs.
A Taxonomy of Voice Therapy
Authors: Van Stan Jarrad H. , Roy Nelson , Awan Shaheen , Stemple Joseph , Hillman Robert E. 
Published: March 2015

Purpose
Voice therapy practice and research, as in most types of rehabilitation, is currently limited by the lack of a taxonomy describing what occurs during a therapy session (with enough precision) to determine which techniques/components contribute most to treatment outcomes. To address this limitation, a classification system of voice therapy is proposed that integrates descriptions of therapeutic approaches from the clinical literature into a framework that includes relevant theoretical constructs.

Method
Literature searches identified existing rehabilitation taxonomies/therapy classification schemes to frame an initial taxonomic structure. An additional literature search and review of clinical documentation provided a comprehensive list of therapy tasks. The taxonomy's structure underwent several iterations to maximize accuracy, intuitive function, and theoretical underpinnings while minimizing redundancy. The taxonomy was then used to classify established voice therapy programs.

Results
The taxonomy divided voice therapy into direct and indirect interventions delivered using extrinsic and/or intrinsic methods, and Venn diagrams depicted their overlapping nature. A dictionary was developed of the taxonomy's terms, and 7 established voice therapy programs were successfully classified.

Conclusion
The proposed taxonomy represents an important initial step toward a standardized voice therapy classification system expected to facilitate outcomes research and communication among clinical stakeholders.
Child Modifiability as a Predictor of Language Abilities in Deaf Children Who Use American Sign Language
Authors: Mann Wolfgang , Peña Elizabeth D. , Morgan Gary 
Published: March 2015

PurposeThis research explored the use of dynamic assessment (DA) for language-learning abilities in signing deaf children from deaf and hearing families.MethodThirty-seven deaf children, aged 6 to 11 years, were identified as either stronger (n= 26) or weaker (n= 11) language learners according to teacher or speech-language pathologist report. All children received 2 scripted, mediated learning experience sessions targeting vocabulary knowledge—specifically, the use of semantic categories that were carried out in American Sign Language. Participant responses to learning were measured in terms of an index of child modifiability. This index was determined separately at the end of the 2 individual sessions. It combined ratings reflecting each child's learning abilities and responses to mediation, including social–emotional behavior, cognitive arousal, and cognitive elaboration.ResultsGroup results showed that modifiability ratings were significantly better for stronger language learners than for weaker language learners. The strongest predictors of language ability were cognitive arousal and cognitive elaboration.ConclusionMediator ratings of child modifiability (i.e., combined score of social-emotional factors and cognitive factors) are highly sensitive to language-learning abilities in deaf children who use sign language as their primary mode of communication. This method can be used to design targeted interventions.
Spinal Metastases from a Primary Fallopian Tube Serous Adenocarcinoma: A Case Report
Authors: Eskander Jonathan P. , Kuris Eren O. , Younghein Andrew J. , Landsman Samuel , Japko Leonard , Eskander Mark S. 
Published: March 2015

Study Design Case report. Objective This case exemplifies the importance of a high index of suspicion when dealing with intractable pain and neurologic symptoms in patients with a history of cancer. Fallopian tube cancer is relatively uncommon, accounting for less than 0.2% of all female malignancies. Because of a low index of suspicion, it is often detected at an advanced stage. From an orthopedic perspective, osseous metastasis from primary fallopian tube malignancies is rare with only a few documented cases in the medical literature. Methods This case report documents a 68-year-old woman who developed back pain and leg weakness after undergoing surgical resection with adjuvant therapy of a primary fallopian tube adenocarcinoma. Her hospital course and follow-up are documented. Results Imaging revealed a compression fracture in the L1 vertebral body that when a biopsy confirmed a soft tissue diagnosis of a high-grade serous papillary adenocarcinoma of fallopian tube origin. The patient underwent a surgical decompression, posterior stabilization, and tumor debulking with postoperative resolution of her symptoms. Conclusions This is the first reported case of a spine metastasis from a fallopian tube serous carcinoma in a living patient. This case documents the diagnosis of a pathologic vertebral fracture due to metastasis of an atypical cancer.
Risk Prediction for Development of Traumatic Cervical Spinal Cord Injury without Spinal Instability
Authors: Lee Soo Eon , Chung Chun Kee 
Published: March 2015

Study Design Retrospective comparative study. Objective A narrow spinal canal is an important risk factor for predicting a spinal cord injury (SCI); however, the radiologic parameters have not been fully established. The authors conducted a comparative study to forecast SCI risk by determining a predictive spinal canal diameter (SCD) cutoff value from magnetic resonance image (MRI) in the Korean population. Methods On T2-weighted MRI of the cervical spine, the SCD at the pedicle (SCDpedicle) and the intervertebral disk level (SCDdisk) were measured in patients with SCI without spinal instability and in healthy subjects. Additionally, the vertebral body diameter (Dvertebral body) and intervertebral disk diameter (Dintervertebral disk) were measured, and the two ratios (SCDpedicle to Dvertebral body and SCDdisk to Dintervertebral disk) were calculated. In the SCI group, the extent of high signal intensity on the T2-weighted midsagittal MRI was determined. Results The data obtained from 20 patients in the SCI group (18 men, mean age 61.35 years) and 65 individuals in the control group (47 men, mean age 57.05 years) was compared. All the parameters including the SCD and the calculated ratios were significantly smaller in the SCI group than in the control group. Among them, the area under the receiver operating curve (AUC) value for the SCDdisk-to-Dintervertebral disk ratio at C2–C3, with a cutoff ratio value of 0.59, provided the greatest positive predictive value. A low SCDdisk-to-Dintervertebral disk ratio at C4–C5 and the presence of >40 mm of high signal intensity on the MRI were related with the presence of complete SCI. Conclusion Because the C2–C3 level is relatively wide compared with the subaxial cervical spine, a small ratio at C2–C3 provided the greatest positive predictive value in SCI. Complete SCI is associated with a small SCDdisk-to-Dintervertebral disk ratio at C4–C5 and with extensive high signal intensity on MRI.
Selection and identification of ligand peptides targeting a model of castrate-resistant osteogenic prostate cancer and their receptors
Authors: Mandelin Jami , Cardó-Vila Marina , Driessen Wouter H. P. , Mathew Paul , Navone Nora M. , Lin Sue-Hwa , Logothetis Christopher J. , Rietz Anna Cecilia , Dobroff Andrey S. , Proneth Bettina , Sidman Richard L. , Pasqualini Renata , Arap Wadih 
Published: March 2015

Significance
This study shows how phage display technology can be applied successfully to in vivo models and can advance molecular oncology through the identification of tumor-homing peptides and their target receptors. Treatment options are still limited for prostate cancer patients who have progressed to develop castrate-resistant osteoblastic bone metastases. The peptides identified in this study may lead to breakthroughs in fighting metastatic androgen-independent prostate cancer by enabling drug targeting and nanotechnology-based therapeutic strategies and may lead to significant advances in the management and therapy of this frequently lethal disease.
Ex Post Use Restriction and Benefit‐sharing Provisions for Access to Non‐plant Genetic Materials for Public Research
Authors: Seyoum Aseffa , Welch Eric W. 
Published: March 2015

AbstractThis study investigates the tradeoffs that providers of genetic materials make between constructing a benefits arrangement and establishing use restrictions. The analysis makes use of individual‐ and project‐level data collected from university and government researchers in the United States. Results show, for instance, that although most genetic resources are exchanged without up‐front payments, when up‐front payments are required for transfer, recipients are less likely to be expected to contribute monetary or non‐monetary benefits after receipt of material. Recipients are also less likely to be subjected to ex post restrictions on the use of the materials they receive. Conversely, when recipients are expected to provide information from project results, up‐front payments for genetic materials are less likely to be assessed. The paper concludes that up‐front payments can be applied in ways that avoid complex restrictions and obligations that may hinder the exchange of genetic materials, public research, and further innovation.
LCZ696, Angiotensin II Receptor-Neprilysin Inhibitor, Ameliorates High-Salt-Induced Hypertension and Cardiovascular Injury More Than Valsartan Alone
Authors: Kusaka Hiroaki , Sueta Daisuke , Koibuchi Nobutaka , Hasegawa Yu , Nakagawa Takashi , Lin BoWen , Ogawa Hisao , Kim-Mitsuyama Shokei 
Published: March 2015

BACKGROUND
LCZ696, an angiotensin receptor-neprilysin inhibitor, has recently been demonstrated to exert more beneficial effects on hypertensive or heart failure patients than conventional renin-angiotensin system blockers. However, the mechanism underlying the benefit of LCZ696 remains to be understood. The present study was undertaken to examine the effect of LCZ696 compared with valsartan on hypertension and cardiovascular injury.

METHODS
(i) Using telemetry, we compared the hypotensive effect of LCZ696 and valsartan in spontaneously hypertensive rats (SHR) that were fed a high-salt diet followed by a low-salt diet. (ii) We also examined the comparative effect of LCZ696 and valsartan on salt loaded SHRcp, a model of metabolic syndrome.

RESULTS
(i) LCZ696 exerted a greater blood pressure (BP) lowering effect than valsartan in SHR regardless of high-salt or low-salt intake. Additive BP reduction by LCZ696 was associated with a significant increase in urinary sodium excretion and sympathetic activity suppression. (ii) LCZ696 significantly ameliorated cardiac hypertrophy and inflammation, coronary arterial remodeling, and vascular endothelial dysfunction in high-salt loaded SHRcp compared with valsartan.

CONCLUSIONS
LCZ696 caused greater BP reduction than valsartan in SHR regardless of the degree of salt intake, which was associated with a significant enhancement in urinary sodium excretion and sympathetic activity suppression. Furthermore, an additive BP lowering effect of LCZ696 led to greater cardiovascular protection in hypertensive rats.
A simple technical measure to reduce bycatch and discard of skates and sharks in mixed-species bottom-trawl fisheries
Authors: Kynoch R. J. , Fryer R. J. , Neat F. C. 
Published: March 2015

AbstractDue to global declines, skates and sharks have become a focus of marine conservation in recent years. Despite protective measures, they remain vulnerable to bycatch by fisheries, especially bottom-trawls and pose a problem for fisheries management measures that aim to eliminate discards in the future. In the mixed-species bottom-trawl fisheries of the North Atlantic catches can be increased by fitting a length of chain known as a “tickler” in front of the groundgear of the trawl. It was hypothesized that the tickler is especially effective at catching skates and rays that may otherwise escape beneath the net. A trial was undertaken with paired tows with and without the tickler chain. The trial demonstrated that the catch rate of skates and sharks can be significantly lowered by removing the tickler. A set of secondary nets (groundgear bags) attached behind the groundgear of the main net allowed the number of fish escaping under the net to be estimated and showed that the reduction of skates and sharks in the main net was accompanied by an increase in number in the groundgear bags. This suggests that prohibition of the use of tickler chains in areas that are known to be especially important to skates and sharks could have conservation benefits. The removal of the tickler chain had little effect on catch rates of haddock, whiting, and flatfish, but caused a marked decrease in the catch rate of commercially valuable anglerfish.