bluuebunny/crossref_metadata_2025_split huggingface dataset:
Theta‐related gating cells in hippocampal formation: In vivo and in vitro study
Authors: Kowalczyk Tomasz , Konopacki Jan , Bocian Renata , Caban Bartosz 
Published: June 2012

AbstractIn this study we extended our earlier in vitro findings concerning the discovery of a novel type of theta‐related cells, which we have termed gating cells. There were two main objectives of our present investigations. The first was to determine the distribution of theta gating cells in the separated CA1 and CA3 generators in three different pharmacological conditions: (i) the presence of a cholinergic agonist—carbachol, (ii) the presence of carbachol and GABAAergic antagonist—bicuculline, (iii) the presence of carbachol and GABABergic antagonist—2‐hydroxysaclofen. The second objective of our studies was to verify our earlier in vitro findings and to demonstrate, for the first time, gating cells in intact hippocampus during the generation of Type II theta in urethane anaesthetized rats. Two hundred ninety‐nine theta‐related cells were isolated and recorded from in vivo and in vitro hippocampal formation. Twenty out of all 299 neurons (6.6%) were classified as gating cells. The neuron was classified as a gating cell if it met one of the following criteria: (i) the cell discharges occurred precisely in the beginning and at the end of each theta epoch (gating cell A); (ii) the cell began to discharge just before the transition from non‐theta interval/LIA into the theta epoch (gating cell B); (iii) the cell began to discharge just after the transition from the theta epoch into non‐theta interval/LIA (gating cell C). Our data demonstrates that the appearance of theta epochs and their length, as well as the appearance of non‐theta states (in vivo recorded LIA or in vitro recorded intervals between theta epochs) and their length, may require the existence of a specific population of hippocampal neurons which we termed gating cells. © 2012 Wiley Periodicals, Inc.
The project organization as a policy tool in implementing welfare reforms in the public sector
Authors: Jensen Christian , Johansson Staffan , Löfström Mikael 
Published: June 2012

ABSTRACTOrganizational design is considered in policy literature as a forceful policy tool to put policy to action. However, previous research has not analyzed the project organization as a specific form of organizational design and, hence, has not given much attention to such organizations as a strategic choice when selecting policy tools. The purpose of the article is to investigate the project as a policy tool; how do such temporary organizations function as a specific form of organization when public policy is implemented? The article is based on a framework of policy implementation and is illustrated with two welfare reforms in the Swedish public sector, which were organized and implemented as project organizations. The case studies and the analysis show that it is crucial that a project organization fits into the overall governance structure when used as a policy tool. If not, the project will remain encapsulated and will not have sufficient impact on the permanent organizational structure. The concept of encapsulation indicates a need to protect the project from a potential hostile environment. The implication of this is that organizational design as a policy tool is a matter that deserves more attention in the strategic discussion on implementing public policies and on the suitability of using certain policy tools. Copyright © 2012 John Wiley & Sons, Ltd.
Valued ecosystem components for watershed cumulative effects: An analysis of environmental impact assessments in the South Saskatchewan River watershed, Canada
Authors: Ball Murray A , Noble Bram F , Dubé Monique G 
Published: June 2012

Abstract
The accumulating effects of human development are threatening water quality and availability. In recognition of the constraints to cumulative effects assessment (CEA) under traditional environmental impact assessment (EIA), there is an emerging body of research dedicated to watershed-based cumulative effects assessment (WCEA). To advance the science of WCEA, however, a standard set of ecosystem components and indicators is required that can be used at the watershed scale, to inform effects-based understanding of cumulative change, and at the project scale, to inform regulatory-based project based impact assessment and mitigation. A major challenge, however, is that it is not clear how such ecosystem components and indicators for WCEA can or should be developed. This study examined the use of aquatic ecosystem components and indicators in EIA practice in the South Saskatchewan River watershed, Canada, to determine whether current practice at the project scale could be “scaled up” to support ecosystem component and indicator development for WCEA. The hierarchy of assessment components and indicators used in a sample of 35 environmental impact assessments was examined and the factors affecting aquatic ecosystem component selection and indicator use were identified. Results showed that public environmental impact statements are not necessarily publically accessible, thus limiting opportunities for data and information sharing from the project to the watershed scale. We also found no consistent terminology across the sample of impact statements, thus making comparison of assessment processes and results difficult. Regulatory compliance was found to be the dominant factor influencing the selection of ecosystem components and indicators for use in project assessment, rather than scientific reasoning, followed by the mandate of the responsible government agency for the assessment, public input to the assessment process, and preexisting water licensing arrangements external to the assessment process. The current approach to project-based assessment offered little support for WCEA initiatives. It did not provide a standard set of aquatic ecosystem components and indicators or allow the sharing of information across projects and from the project to the watershed scale. We suggest that determining priority assessment parameters for WCEA requires adoption of a standardized framework of component and indicator terminology, which can then be populated for the watershed of concern based on both watershed-based priorities and project-specific regulatory requirements. Integr Environ Assess Manag 2013;9:469–479. © 2012 SETAC
Intratracheal and oral administration of SM‐276001: A selective TLR7 agonist, leads to antitumor efficacy in primary and metastatic models of cancer
Authors: Koga‐Yamakawa Erina , Dovedi Simon J. , Murata Masashi , Matsui Hiroyuki , Leishman Andrew J. , Bell John , Ferguson Douglas , Heaton Simon P. , Oki Toshihiro , Tomizawa Hideyuki , Bahl Ash , Takaku Haruo , Wilkinson Robert W. , Harada Hideyuki 
Published: June 2012

AbstractTopical TLR7 agonists such as imiquimod are highly effective for the treatment of dermatological malignancies; however, their efficacy in the treatment of nondermatological tumors has been less successful. We report that oral administration of the novel TLR7‐selective small molecule agonist; SM‐276001, leads to the induction of an inflammatory cytokine and chemokine milieu and to the activation of a diverse population of immune effector cells including T and B lymphocytes, NK and NKT cells. Oral administration of SM‐276001 leads to the induction of IFNα, TNFα and IL‐12p40 and a reduction in tumor burden in the Balb/c syngeneic Renca and CT26 models. Using the OV2944‐HM‐1 model of ovarian cancer which spontaneously metastasizes to the lungs following subcutaneous implantation, we evaluated the efficacy of intratracheal and oral administration of SM‐276001 in an adjuvant setting following surgical resection of the primary tumor. We show that both oral and intratracheal TLR7 therapy can reduce the frequency of pulmonary metastasis, and metastasis to the axillary lymph nodes. These results demonstrate that SM‐276001 is a potent selective TLR7 agonist that can induce antitumor immune responses when dosed either intratracheally or orally.
Identification of novel functional and spatial associations between sphingosine kinase 1, sphingosine 1‐phosphate receptors and other signaling proteins that affect prognostic outcome in estrogen receptor‐positive breast cancer
Authors: Ohotski Jan , Edwards Joanne , Elsberger Beatrix , Watson Carol , Orange Clare , Mallon Elizabeth , Pyne Susan , Pyne Nigel J. 
Published: June 2012

AbstractSphingosine kinase is an enzyme that catalyses the phosphorylation of sphingosine to form sphingosine 1‐phosphate. Sphingosine 1‐phosphate is a bioactive lipid, which has been shown to have an important role in promoting the survival, growth and invasiveness of cancer cells. Sphingosine 1‐phosphate binds to five different plasma membrane sphingosine 1‐phosphate receptors (S1P1–5) and can regulate intracellular target proteins. We have used immunohistochemical analysis to determine the concurrent expression levels of sphingosine kinase 1 or S1P receptors and other signaling proteins in estrogen receptor‐positive breast cancer tumors and have then assessed the impact of these combinations on clinical outcome. This approach has enabled identification of (i) novel biomarkers and (ii) several spatially controlled associations between either sphingosine kinase 1 or S1P1–3 and other signaling proteins whose combination affect prognosis. For instance, the translocation of sphingosine kinase 1 to the plasma membrane has been shown to be a critical determinant in cancer progression. However, our findings identify an additional novel role for the nuclear localization of sphingosine kinase 1 combined with either ERK‐1/2 or SFK or LYN or AKT or NF‐κB, which significantly shortens disease‐specific survival and/or recurrence. We also demonstrate that nuclear S1P2 receptor and c‐SRC are associated with improved prognosis and this is linked with a reduction in the nuclear localization of sphingosine kinase 1. These findings identify potential novel biomarker associations, which might serve as new targets for drug intervention designed to improve treatment of estrogen receptor‐positive breast cancer.
The Rec protein of HERV‐K(HML‐2) upregulates androgen receptor activity by binding to the human small glutamine‐rich tetratricopeptide repeat protein (hSGT)
Authors: Hanke Kirsten , Chudak Claudia , Kurth Reinhard , Bannert Norbert 
Published: June 2012

AbstractThe expression of endogenous retroviruses of the HERV‐K(HML‐2) family is strongly upregulated in germ cell tumors and several other cancers. Although the accessory Rec protein of HERV‐K(HML‐2) has been shown to induce carcinoma in situ in transgenic mice, to increase the activity of c‐myc and to interact with the androgen receptor (AR), whether or not Rec expression is indeed implicated causally in the initiation or progression of any human malignancies remains unclear. We used the yeast two‐hybrid system involving the Rec protein of a recently integrated HERV‐K(HML‐2) element in an effort to identify potential Rec‐related oncogenic mechanisms. This revealed the human small glutamine‐rich tetratricopeptide repeat (TPR)‐containing protein (hSGT) to be a cellular binding partner. The interaction of Rec with this known negative regulator of the AR was confirmed by coimmunoprecipitation, pull‐down assays and colocalization studies. The interaction involves the TPR motif of hSGT and takes place in the cytoplasm and in the nucleoli. Using an AR‐responsive promoter and gene we could demonstrate that Rec interference with hSGT resulted in an up to five‐fold increase in the activity of AR. Furthermore, in AR positive cells, Rec was shown to act as transactivator by enhancing AR‐mediated activation of the HERV‐K(HML‐2) LTR promoter. This is in line with previous observations of elevated HERV‐K(HML‐2) expression in steroid‐regulated tissues. On the basis of our findings we propose a “vicious cycle” model of Rec‐driven hyperactivation of the AR leading to increased cell proliferation, inhibition of apoptosis and eventually to tumor induction or promotion.
Antitumor effects of novel compound, guttiferone K, on colon cancer by p21Waf1/Cip1‐mediated G0/G1 cell cycle arrest and apoptosis
Authors: Kan Winnie Lai Ting , Yin Chun , Xu Hong Xi , Xu Gang , To Kenneth Kin Wah , Cho Chi Hin , Rudd John Anthony , Lin Ge 
Published: June 2012

AbstractLow selectivity is one of the major problems of currently used anticancer drugs, therefore, there is a high demand for novel, selective antitumor agents. In this study, the anticancer effects and mechanisms of guttiferone K (GUTK), a novel polyprenylated acylphloroglucinol derivative isolated from Garcinia cowa Roxb., were examined for its development as a novel drug targeting colon cancer. GUTK concentration‐ and time‐dependently reduced the viability of human colon cancer HT‐29 cells (IC50 value 5.39 ± 0.22 μM) without affecting the viability of normal human colon epithelial CCD 841 CoN cells and induced G0/G1 cell cycle arrest in HT‐29 cells by down‐regulating cyclins D1, D3 and cyclin‐dependent kinases 4 and 6, while selectively restoring p21Waf1/Cip1 and p27Kip1 to levels comparable to those observed in normal colon cells, without affecting their levels in normal cells. GUTK (10.0 μM) induced cleavage of PARP, caspases‐3, ‐8 and ‐9 and chromatin condensation to stimulate caspase‐3‐mediated apoptosis. The addition of a JNK inhibitor, SP600125, partially reversed GUTK‐induced caspase‐3 activity, indicating the possible involvement of JNK in GUTK‐induced apoptosis. Furthermore, GUTK (10 mg/kg, i.p.) significantly decreased the tumor volume in a syngeneic colon tumor model when used alone or in combination with 5‐fluorouracil without toxicity to the mice. Immunohistochemical staining of the tumor sections revealed a mechanism involving an increase in cleaved caspase‐3 and a decrease in cell proliferation marker Ki‐67. Our results support GUTK as a promising novel, potent and selective antitumor drug candidate for colon cancer.
Oncolytic Vaccinia virus safely and effectively treats skin tumors in mouse models of xeroderma pigmentosum
Authors: Brun Jan , Mahoney Douglas J. , Le Boeuf Fabrice , Lefebvre Charles , Sanaei Cina A. , Falls Theresa , Mccart J. Andrea , Stojdl David F. 
Published: June 2012

AbstractXeroderma pigmentosum (XP) is an orphan autosomal recessive disorder of DNA repair. When exposed to genotoxic stress, XP patients have reduced capacity to remove bulky adducts by nucleotide excision repair and are thus greatly predisposed to cancer. Unfortunately, given the nature of their underlying genetic defect, tumor‐bearing XP patients cannot be treated with conventional DNA damaging therapies. Engineered strains of the poxvirus Vaccinia have been shown to cure cancer in numerous preclinical models, and based on promising Phase I/II clinical trials have recently been approved for late phase evaluation in humans. As poxviruses are nongenotoxic, we investigated whether clinical‐candidate strains of Vaccinia can safely and effectively treat cancers arising from XP. In vitro, Vaccinia virus was highly cytotoxic against tumor‐derived cells from XP patients, on average 10‐ to 100‐fold more so than on nontumor derived control cells from similar patients. In vivo, local or systemic administration of Vaccinia virus led to durable tumor resolution in both xenograft and genetic models of XP. Importantly, Vaccinia virus was well tolerated in the genetic models, which are each null for a critical component of the DNA repair process. Taken together, our data suggest that oncolytic Vaccinia virus may be a safe and effective therapy for cancers arising from XP, and raise the possibility of similar therapeutic potential against tumors that arise in patients with other DNA repair disorders.
Colorectal cancer and RASSF family—A special emphasis on RASSF1A
Authors: Fernandes Maria Sofia , Carneiro Fátima , Oliveira Carla , Seruca Raquel 
Published: June 2012

AbstractThe RAS‐association domain family, commonly referred to as RASSF, is a family of 10 members (RASSF1‐10) implicated in a variety of key biological processes, including cell cycle regulation, apoptosis and microtubule stability. Furthermore, RASSFs have been implicated in tumorigenesis and several family members are now thought to be tumor suppressors. As opposed to the KRAS oncogene, for which mutational activation is frequent in colorectal cancer (CRC), RASSFs are found to be silenced mainly by aberrant promoter methylation. In particular, RASSF1A, RASSF2 and RASSF5 methylation has been associated with CRC development, though the mechanisms of action remain poorly understood. This review focus on the current knowledge of RASSF inactivation in CRC, particularly RASSF1A, and on the implications RASSFs may have as potential biomarkers and for the development of new targeted therapies for CRC.
α‐Catulin downregulates E‐cadherin and promotes melanoma progression and invasion
Authors: Kreiseder Birgit , Orel Lukas , Bujnow Constantin , Buschek Stefan , Pflueger Maren , Schuett Wolfgang , Hundsberger Harald , de Martin Rainer , Wiesner Christoph 
Published: June 2012

AbstractMetastasis is associated with poor prognosis for melanoma responsible for about 90% of skin cancer‐related mortality. To metastasize, melanoma cells must escape keratinocyte control, invade across the basement membrane and survive in the dermis by resisting apoptosis before they can intravasate into the circulation. α‐Catulin (CTNNAL1) is a cytoplasmic molecule that integrates the crosstalk between nuclear factor‐kappa B and Rho signaling pathways, binds to β‐catenin and increases the level of both α‐catenin and β‐catenin and therefore has potential effects on inflammation, apoptosis and cytoskeletal reorganization. Here, we show that α‐catulin is highly expressed in melanoma cells. Expression of α‐catulin promoted melanoma progression and occurred concomitantly with the downregulation of E‐cadherin and the upregulation of expression of mesenchymal genes such as N‐cadherin, Snail/Slug and the matrix metalloproteinases 2 and 9. Knockdown of α‐catulin promoted adhesion to and inhibited migration away from keratinocytes in an E‐cadherin‐dependent manner and decreased the transmigration through a keratinocyte monolayer, as well as in Transwell assays using collagens, laminin and fibronectin coating. Moreover, knockdown promoted homotypic spheroid formation and concomitantly increased E‐cadherin expression along with downregulation of transcription factors implicated in its repression (Snail/Slug, Twist and ZEB). Consistent with the molecular changes, α‐catulin provoked invasion of melanoma cells in a three‐dimensional culture assay by the upregulation of matrix metalloproteinases 2 and 9 and the activation of ROCK/Rho. As such, α‐catulin may represent a key driver of the metastatic process, implicating potential for therapeutic interference.
Proteomic analysis of oropharyngeal carcinomas reveals novel HPV‐associated biological pathways
Authors: Slebos Robbert J.C. , Jehmlich Nico , Brown Brandee , Yin Zhirong , Chung Christine H. , Yarbrough Wendell G. , Liebler Daniel C. 
Published: June 2012

AbstractOropharyngeal carcinoma (OPC) can be classified into two equally prevalent subtypes depending on the presence of human papillomavirus (HPV). Patients with HPV‐positive (HPV+) OPC represent a unique cohort with a distinct tumor biology and clinical behavior compared to HPV‐negative (HPV−) OPC. Genetic studies have demonstrated chromosomal and gene expression changes associated with distinct subclasses of OPC; however, the proteomic consequences of HPV infection are not known. We analyzed sets of ten HPV+ and ten HPV− OPCs and ten normal adult oral epithelia using a standardized global proteomic analysis platform. This analysis yielded a total of 2,653 confidently identified proteins from which we chose 31 proteins on the basis of expression differences between HPV+, HPV− and normal epithelium for targeted protein quantitation. Analysis of differentially expressed proteins by HPV status revealed enrichment of proteins involved in epithelial cell development, keratinization and extracellular matrix organization in HPV− OPC, whereas enrichment of proteins in DNA initiation and replication and cell cycle control was found for HPV+ OPC. Enrichment analysis for transcription factor targets identified transcription factors E2F1 and E2F4 to be highly expressed in HPV+ OPC. We also found high expression of argininosuccinate synthase 1 in HPV+ OPC, suggesting that HPV+ OPC is more dependent on conditionally essential amino acid, arginine, and this was confirmed on a OPC‐specific tissue microarray. These identified proteomic changes reveal novel driving molecular pathways for HPV+ and HPV− OPCs that may be pertinent in therapeutic strategies and outcomes of OPC.
Psychotherapy groups and individual support to enhance mental health and early dyadic interaction among drug‐abusing mothers
Authors: Belt Ritva H. , Flykt Marjo , Punamäki Raija‐Leena , Pajulo Marjukka , Posa Tiina , Tamminen Tuula 
Published: June 2012

AbstractThe purpose of this controlled study was to examine the outcome of psychodynamic mother–infant group psychotherapy (PGT) outpatient intervention for drug‐abusing perinatal mother–infant dyads. PGT comprised 20 to 24 weekly 3‐hr sessions with 3 to 5 months of follow‐up. A comparison intervention group was formed of mothers participating in individually tailored psychosocial support (PSS) lasting, on average, 12 months and providing mother–infant support and practical counseling. We hypothesized that positive changes would occur in maternal drug abuse, mental health, and mother–infant interaction, especially in the PGT group due to its more intensive therapeutic focus. Participants were 26 drug‐abusing dyads in PGT, 25 in PSS, and 50 dyads in a non‐drug‐abusing comparison group. Assessments were pre‐intervention and at 4 and 12 months' follow‐up, including maternal depressive symptoms and mother–child interaction assessed by the Emotional Availability Scales (EA). As hypothesized, in dyadic interaction maternal hostility decreased significantly in the PGT group, and intrusiveness decreased in both intervention groups, but especially in the PTG group. However, both interventions showed a general improvement in the quality of mother–infant interaction. They also succeeded in sustaining high maternal abstinence, treatment retention, and alleviating depressive symptoms. The findings are discussed in relation to preventing negative transgenerational interaction patterns in the high‐risk dyads.