bluuebunny/crossref_metadata_2025_split huggingface dataset:
Quercetin improves bone strength in experimental biliary cirrhosis
Authors: Derakhshanian Hoda , Ghadbeigi Sajad , Rezaian Maryam , Bahremand Arash , Javanbakht Mohammad Hassan , Golpaie Atefeh , Hosseinzadeh Payam , Tajik Narges , Dehpour Ahmad Reza 
Published: July 2012

Aim:  Metabolic bone disorders and reduced bone mass are common complications in patients with biliary cirrhosis. As a result of there being no clear etiology, no specific therapy has been established yet. Previous studies have reported that quercetin, a plant‐derived flavonoid, might improve bone quality. The present study was designed to investigate the effect of quercetin on bone strength of biliary cirrhotic rats.Methods:  Twenty‐four male Sprague–Dawley rats aged 6–7 months were randomized into three groups of eight. One group served as control (sham operated), while the other two groups underwent a complete bile duct ligation (BDL). Four weeks after the operation, serum bilirubin, alkaline phosphatase, alanine aminotransferase and aspartate aminotransferase were measured in animal blood samples to confirm the occurrence of cirrhosis in the BDL rats. Then, one of the BDL groups received placebo and the other one was injected once a day with 150 µmol/kg of quercetin for 4 weeks. At the end of the study, femora were removed and tested for bone strength and histomorphometric parameters. The serum levels of osteocalcin, C‐terminal cross‐linked telopeptide of type I collagen, calcium and phosphorus were determined as bone turnover markers.Results:  Femur breaking strength was dramatically lower in the BDL group compared with control. However, receiving quercetin could reverse the deteriorating effect of cirrhosis on bone strength of BDL rats. Quercetin could noticeably elevate osteocalcin as a bone formation marker.Conclusion:  These data suggest that quercetin can significantly improve bone strength particularly due to increasing bone formation in biliary cirrhosis.
VimA–dependent modulation of the secretome in Porphyromonas gingivalis
Authors: Osbourne D. , Wilson Aruni A. , Dou Y. , Perry C. , Boskovic D.S. , Roy F. , Fletcher H. M. 
Published: July 2012

SummaryThe VimA protein of Porphyromonas gingivalis is a multifunctional protein involved in cell surface biogenesis. To further determine if its acetyl coenzyme A (acetyl‐CoA) transfer and putative sorting functions can affect the secretome, its role in peptidoglycan biogenesis and effects on the extracellular proteins of P. gingivalis FLL92, a vimA‐defective mutant, were evaluated. There were structural and compositional differences in the peptidoglycan of P. gingivalis FLL92 compared with the wild‐type strain. Sixty‐eight proteins were present only in the extracellular fraction of FLL92. Fifteen proteins present in the extracellular fraction of the parent strain were missing in the vimA‐defective mutant. These proteins had protein sorting characteristics that included a C‐terminal motif with a common consensus Gly‐Gly–CTERM pattern and a polar tail consisting of aromatic amino acid residues. These observations suggest that the VimA protein is likely involved in peptidoglycan synthesis, and corroborates our previous report, which suggests a role in protein sorting.
Object habituation in horses: The effect of voluntary versus negatively reinforced approach to frightening stimuli
Authors: Christensen J. W. 
Published: July 2012

SummaryReasons for performing the study: The ability of horses to habituate to novel objects influences safety in the horse–human relationship. However, the effectiveness of different habituation techniques has not been investigated in detail.Objectives: 1) To investigate whether horses show increased stress responses when negatively reinforced to approach novel objects, compared with horses allowed to voluntarily explore the objects and 2) whether a negatively reinforced approach facilitates object habituation.Methods: Twenty‐two 2–3‐year‐old Danish Warmblood geldings were included. Half of the horses (NR group) were negatively reinforced by a familiar human handler to approach a collection of novel objects in a test arena. The other half were individually released in the arena and were free to explore the objects (VOL group). On the next day, the horses were exposed to the objects again without a human handler, to investigate the rate of habituation. Behavioural and heart rate responses were recorded.Results: All VOL horses initially avoided the unknown objects, whereas the handler was able to get all NR horses to approach and stand next to the objects within the first 2 min session. The NR horses had a significantly longer duration of alertness and a higher max heart rate in the first session. On the next day, however, NR horses spent significantly less time investigating the objects and had a shorter latency to approach a feed container, placed next to the objects, indicating increased habituation.Conclusion: A negatively reinforced approach to novel objects increases stress responses during the initial exposure but facilitates habituation in young horses.Potential relevance: Although a negatively reinforced approach appears beneficial for habituation, the procedure should be carefully managed due to increased stress responses in the horse, which may constitute a safety risk. Further experiments should aim to investigate differences in stimulus intensity.
Distribution of insulin receptor and insulin‐like growth factor‐1 receptor in the digital laminae of mixed‐breed ponies: An immunohistochemical study
Authors: Burns T. A. , Watts M. R. , Weber P. S. , Mccutcheon L. J. , Geor R. J. , Belknap J. K. 
Published: July 2012

SummaryReasons for performing study:Hyperinsulinaemia has been implicated in the pathogenesis of laminitis; however, laminar cell types responding to insulin remain poorly characterised.Objectives:To identify laminar cell types expressing insulin receptor (IRc) and/or insulin‐like growth factor‐1 receptor (IGF‐1R); and to evaluate the effect of dietary nonstructural carbohydrate (NSC) on their expression.Methods:Mixed‐breed ponies (n = 22) received a conditioning hay chop diet (NSC ∼6%); following acclimation, ponies were stratified into lean (n = 11, body condition score [BCS]≤4) or obese (n = 11, BCS ≥7) groups and each group further stratified to remain on the low NSC diet (n = 5 each for obese and lean) or receive a high NSC diet (total diet ∼42% NSC; n = 6 each for obese and lean) for 7 days. Laminar samples were collected at the end of the feeding protocol and stained immunohistochemically for IRc and IGF‐1R. The number of IRc(+) cells was quantified; distribution of IGF‐1R was qualitatively described. Laminar IRc content was assessed via immunoblotting.Results:The number of IRc(+) cells was greater in the laminae of high NSC ponies than low NSC ponies (P = 0.001); there was a positive correlation between the change in serum insulin concentration and number of IRc(+) cells (r2= 0.74; P<0.0001). No epithelial IRc(+) cells were observed; IRc(+) cells were absent from the deep dermis. Analysis of serial sections identified IRc(+) cells as endothelial cells. The distribution of IGF‐1R was more extensive than that of IRc, with signal in vascular elements, epithelial cells and fibroblasts.Conclusions:Increased dietary NSC results in increased laminar endothelial IRc expression. Laminar keratinocytes do not express IRc, suggesting that insulin signalling in laminar epithelial cells must be mediated through other receptors (such as IGF‐1R).Potential relevance:Manipulation of signalling downstream of IRc and IGF‐1R may aid in treatment and prevention of laminitis associated with hyperinsulinaemia.
Expression of cyclin-dependent kinase 2-associated protein 1 confers an independent prognosticator in nasopharyngeal carcinoma: a cohort study
Authors: Wu Li-Ching , Chen Yi-Ling , Wu Wen-Ren , Li Chien-Feng , Huang Hsuan-Ying , Lee Sung-Wei , Chang Shih-Lun , Lin Ching-Yih , Chen Yi-Hsien , Hsu Han-Ping , Lu Pei-Jung , Shiue Yow-Ling 
Published: July 2012

Background and aimLow expression of cyclin-dependent kinase 2-associated protein (CDK2AP1) is associated with tumour progression in oral and oesophageal carcinomas, but is not well studied in patients with head and neck cancer and nasopharyngeal carcinoma (NPC).MethodsA rabbit anti-human CDK2AP1 polyclonal antibody was prepared. Immunoblotting of CDK2AP1 was examined in three cell lines and immunoexpression was retrospectively assessed in biopsies of 124 consecutive NPC patients without initial distant metastasis and treated with consistent guidelines.ResultsHigher CDK2AP1 expression level was identified in dysplastic oral keratinocytes, compared with two NPC-derived HONE-1 and TW01 cell lines. Low expression of CDK2AP1 (50.8%) was correlated with advanced nodal status (p=0.002) and American Joint Committee on Cancer (AJCC) stage (p=0.004). In multivariate analyses, low CDK2AP1 expression emerged as an independent prognosticator for worse disease-specific survival (DSS; p=0.037) and local recurrence-free survival (LRFS; p=0.042), along with AJCC stage III–IV (p=0.034, DSS; p=0.029, LRFS).ConclusionsLow CDK2AP1 expression is common and associated with adverse prognosticators, conferring tumour aggressiveness through cycle cycle, cell growth or apoptosis cellular processes.
Longitudinal patterns in physical activity and sedentary behaviour from mid-life to early old age: a substudy of the Whitehall II cohort
Authors: Hamer Mark , Kivimaki Mika , Steptoe Andrew 
Published: July 2012

BackgroundThere are few longitudinal data on physical activity patterns from mid-life into older age. The authors examined associations of self-reported physical activity, adiposity and socio-demographic factors in mid-life with objectively assessed measures of activity in older age.MethodsParticipants were 394 healthy men and women drawn from the Whitehall II population-based cohort study. At the baseline assessment in 1997 (mean age 54 years), physical activity was assessed through self-report and quantified as metabolic equivalent of task hours/week. At the follow-up in 2010 (mean age 66 years), physical activity was objectively measured using accelerometers worn during waking hours for seven consecutive days (average daily wear time 891±68 min/day).ResultsSelf-reported physical activity at baseline was associated with objectively assessed activity at follow-up in various activity categories, including light-, moderate- and vigorous-intensity activity (all ps<0.04). Participants in the highest compared with lowest quartile of self-reported activity level at baseline recorded on average 64.1 (95% CI 26.2 to 102.1) counts per minute more accelerometer-assessed activity at follow-up and 9.0 (2.0–16.0) min/day more moderate-to-vigorous daily activity, after adjusting for baseline covariates. Lower education, obesity and self-perceived health status were also related to physical activity at follow-up. Only age and education were associated with objectively measured sedentary time at follow-up.ConclusionPhysical activity behaviour in middle age was associated with objectively measured physical activity in later life after 13 years of follow-up, suggesting that the habits in adulthood are partly tracked into older age.
Mechanical endovascular treatment of acute stroke due to cardiac myxoma
Authors: Garcia-Ptacek Sara , Matias-Guiu Jordi A , Valencia-Sánchez Cristina , Gil Alberto , Bernal-Becerra Israel , De las Heras-Revilla Virginia , Serna-Candel Carmen 
Published: July 2012

BackgroundMyxomas are rare cardiac tumors which often present with stroke caused by tumorous or thrombotic emboli. Treatment with intravenous recombinant tissue plasminogen activator (rtPA) and intra-arterial thrombolysis has been described previously but mechanical thrombectomy has not yet been reported, and treatment of myxoma-related ischemic stroke remains a clinical and technical challenge.MethodsTwo patients with ischemic stroke due to cardiac myxoma in which mechanical thrombectomy was performed are presented.ResultsEndovascular thrombectomy after intravenous rtPA (bridging therapy) was safely achieved in both cases, although with different clinical outcomes and degrees of recanalization.ConclusionsIn stroke secondary to cardiac myxoma, mechanical thrombectomy might represent a safe and effective treatment option. The authors suggest the use of histological examination of the clot for diagnosis as its composition may explain the differences in treatment outcome.
Ab initio calculation of the low-lying electronic states of the ZrN molecule
Authors: Farhat A. , Korek M. , Marques M.A.L. , Abdul-Al S.N. 
Published: July 2012

An ab initio calculation of the low-lying electronic states of zirconium nitride (ZrN) were performed by using a complete active space self-consistent field with multireference single and double excitation configuration interaction (MRSDCI). The potential energy curves of 21 low-lying electronic states of the ZrN molecule with different spin and spatial symmetries, in the representation 2s+1Λ(+/−) and below 30 000 cm–1, were identified. The harmonic frequency (ωe), the equilibrium internuclear distance (Re), the rotational constants (Be), the electronic energy with respect to the ground state (Te), and the permanent dipole moment (µ) were calculated for the considered electronic states. The comparison of these values with those available in the literature shows a very good agreement with either theoretical or experimental data. Fifteen new electronic states were studied here for the first time.
Where does transactional memory research stand and what challenges lie ahead?
Authors: Couceiro Maria , Romano Paolo 
Published: July 2012

Transactional Memory (TM) is a promising technology that aims to simplify parallel programming by providing a programmer friendly alternative to traditional lock-based concurrency. The past ten years have seen intense research work on software and hardware TM proposals, and has recently led to the first hardware TM implementation for a commodity high-performance microprocessor, and to the inclusion of TM support in the world's leading open source compiler.
EuroTM (COST Action IC1001), in collaboration with the CloudTM project1, organized the second edition of the EuroTM Workshop on Transactional Memory (WTM 2012). The objective of WTM was to discuss new developments for this era of maturing TM research.
The workshop took place on April 10, in Bern, Switzerland, in conjunction with Eurosys 2012. Below we give highlights on the topics discussed in the workshop.
CXCR3+ T Regulatory Cells Selectively Accumulate in Human Ovarian Carcinomas to Limit Type I Immunity
Authors: Redjimi Nassima , Raffin Caroline , Raimbaud Isabelle , Pignon Pascale , Matsuzaki Junko , Odunsi Kunle , Valmori Danila , Ayyoub Maha 
Published: July 2012

Abstract
Antitumor type I T-cell responses involving IFN-γ production are critical to control cancer, but the efficacy of this response is limited by a variety of immunosuppressive mechanisms that promote tumoral immune escape. One critical mechanism involves the accumulation of FOXP3+ T regulatory cells (Treg), a class of suppressive T cells that prevent excessive tissue destruction caused by unchecked immune responses. Recent studies have revealed that FOXP3+ Treg include distinct subsets specifically controlling over the corresponding effector subset. In particular, CXCR3+ Treg have been described as a subset specialized in the control of type I T-cell responses in vivo. Here, we show that CXCR3+ Treg are highly enriched in human ovarian carcinomas, particularly in solid tumor masses, where they represent the majority of Treg. Tumor-associated CXCR3+. Treg coexpress T-bet but do not secrete IFN-γ ex vivo and suppress proliferation and IFN-γ secretion of T effectors. In addition, they coexpress Helios, suggesting that they originate from natural Treg. Finally, we show that the proportion of CXCR3+ Treg at tumor sites is directly correlated with that of CXCR3+ T effectors, consistent with expression of CXCR3 ligands. Together, our findings support the concept that natural CXCR3+ T-bet+ Treg selectively accumulate in ovarian tumors to control type I T-cell responses, resulting in the collateral limitation of efficient antitumor immunity. Cancer Res; 72(17); 4351–60. ©2012 AACR.
Dual Targeting of the Cyclin/Rb/E2F and Mitochondrial Pathways in Mantle Cell Lymphoma with the Translation Inhibitor Silvestrol
Authors: Alinari Lapo , Prince Courtney J. , Edwards Ryan B. , Towns William H. , Mani Rajeswaran , Lehman Amy , Zhang Xiaoli , Jarjoura David , Pan Li , Kinghorn A. Douglas , Grever Michael R. , Baiocchi Robert A. , Lucas David M. 
Published: July 2012

Abstract
Purpose: During cell-cycle progression, D-cyclins activate cyclin-dependent kinases (CDKs) 4/6 to inactivate Rb, permitting E2F1-mediated S-phase gene transcription. This critical pathway is typically deregulated in cancer, and novel inhibitory strategies would be effective in a variety of tumors. The protein synthesis inhibitor silvestrol has potent activity in B-cell leukemias via the mitochondrial pathway of apoptosis, and also reduces cyclin D1 expression in breast cancer and lymphoma cell lines. We hypothesized that this dual activity of silvestrol would make it especially effective in malignancies driven by aberrant cyclin D1 expression.
Experimental Design: Mantle cell lymphoma (MCL), characterized by elevated cyclin D1, was used as a model to test this approach. The cyclin D/Rb/E2F1 pathway was investigated in vitro using MCL cell lines and primary tumor cells. Silvestrol was also evaluated in vivo using an aggressive model of MCL.
Results: Silvestrol showed low nanomolar potency both in MCL cell lines and primary MCL tumor cells. D-cyclins were depleted with just 10 nmol/L silvestrol at 16 hours, with subsequent reductions of phosphorylated Rb, E2F1 protein, and E2F1 target transcription. As showed in other leukemias, silvestrol caused Mcl-1 depletion followed by mitochondrial depolarization and caspase-dependent apoptosis, effects not related to inhibition of CDK4/6. Silvestrol significantly (P &lt; 0.0001) prolonged survival in a MCL xenograft model without detectable toxicity.
Conclusions: These data indicate that silvestrol effectively targets the cyclin/CDK/Rb pathway, and additionally induces cytotoxicity via intrinsic apoptosis. This dual activity may be an effective therapeutic strategy in MCL and other malignancies. Clin Cancer Res; 18(17); 4600–11. ©2012 AACR.
Systematic Kinome shRNA Screening Identifies CDK11 (PITSLRE) Kinase Expression Is Critical for Osteosarcoma Cell Growth and Proliferation
Authors: Duan Zhenfeng , Zhang Jianming , Choy Edwin , Harmon David , Liu Xianzhe , Nielsen Petur , Mankin Henry , Gray Nathanael S. , Hornicek Francis J. 
Published: July 2012

Abstract
Purpose: Identification of new targeted therapies is critical to improving the survival rate of patients with osteosarcoma. The goal of this study is to identify kinase based potential therapeutic target in osteosarcomas.
Experimental Design: We used a lentiviral-based shRNA kinase library to screen for kinases which play a role in osteosarcoma cell survival. The cell proliferation assay was used to evaluate cell growth and survival. siRNA assays were applied to confirm the observed phenotypic changes resulting from the loss of kinase gene expression. CDK11 (PITSLRE) was identified as essential for the survival of osteosarcoma cells, and its expression was confirmed by Western blot analysis and immunohistochemistry. Overall patient survival was correlated with the CDK11 expression and its prognosis. The role of CDK11 expression in sustaining osteosarcoma growth was further evaluated in an osteosarcoma xenograft model in vivo.
Results: Osteosarcoma cells display high levels of CDK11 expression. CDK11 expression knocked down by either lentiviral shRNA or siRNA inhibit cell growth and induce apoptosis in osteosarcoma cells. Immunohistochemical analysis showed that patients with osteosarcoma with high CDK11 tumor expression levels were associated with significantly shorter survival than patients with osteosarcoma with low level of tumor CDK11 expression. Systemic in vivo administration of in vivo ready siRNA of CDK11 reduced the tumor growth in an osteosarcoma subcutaneous xenograft model.
Conclusions: We show that CDK11 signaling is essential in osteosarcoma cell growth and survival, further elucidating the regulatory mechanisms controlling the expression of CDK11 and ultimately develop a CDK11 inhibitor that may provide therapeutic benefit against osteosarcoma. Clin Cancer Res; 18(17); 4580–8. ©2012 AACR.
Group I p21-Activated Kinases (PAKs) Promote Tumor Cell Proliferation and Survival through the AKT1 and Raf–MAPK Pathways
Authors: Menges Craig W. , Sementino Eleonora , Talarchek Jacqueline , Xu Jinfei , Chernoff Jonathan , Peterson Jeffrey R. , Testa Joseph R. 
Published: July 2012

Abstract
Group I p21–activated kinases (PAK) are important effectors of the small GTPases Rac and Cdc42, which regulate cell motility/migration, survival, proliferation, and gene transcription. Hyperactivation of these kinases have been reported in many tumor types, making PAKs attractive targets for therapeutic intervention. PAKs are activated by growth factor–mediated signaling and are negatively regulated by the tumor suppressor neurofibromatosis type 2 (NF2)/Merlin. Thus, tumors characterized by NF2 inactivation would be expected to show hyperactivated PAK signaling. On the basis of this rationale, we evaluated the status of PAK signaling in malignant mesothelioma, an aggressive neoplasm that is resistant to current therapies and shows frequent inactivation of NF2. We show that group I PAKs are activated in most mesotheliomas and mesothelioma cell lines and that genetic or pharmacologic inhibition of PAKs is sufficient to inhibit mesothelioma cell proliferation and survival. We also identify downstream effectors and signaling pathways that may contribute mechanistically to PAK-related tumorigenesis. Specifically, we show that inhibition of PAK results in attenuation of AKT and Raf–MAPK signaling and decreased tumor cell viability. Collectively, these data suggest that pharmacologic inhibition of group I PAKs may have therapeutic efficacy in tumors characterized by PAK activation. Mol Cancer Res; 10(9); 1178–88. ©2012 AACR.